Embryology - User contributions [en-gb]

User:Z3279511

2011-10-23T12:49:00Z

Z3279511:

{{2011Student}}

--[[User:Z3279511|Z3279511]] 12:55, 28 July 2011 (EST)

'''Lab 1: Assessment'''

'''1.''' The origin of In Vitro Fertilization (IVF) lies in 1950s, where Dr. Robert G. Edwards started to work on his idea for the treatment of infertility. He was the first to show, that the human oocyte can undergo fertilization, grow into an embryo and blastocyst ''in vitro'' and then be implanted into the mothers womb to develop into a healthy infant. On the 25th of July 1987 Louise Joy Brown, the first child conceived via IVF was born. Dr. Robert G. Edwards received the 2010 Nobel Prize in Physiology or Medicine for the discovery of IVF.

'''2.''' Özer ''et al.'' showed in their study published in the Turk Arch Pediatri, that children conceived through assisted reproductive techniques (ART) have a higher risk of premature birth and multiple gestation in comparison to children conceived naturally. The study evaluated neonatal morbidity, mortality, congenital abnormalities, prematurity and multiple pregnancies in 123 ART babies. It was found that ART babies in comparison to normal babies have higher rates of mortality and abnormalities and lower birth weight.

Reference: Özer, E. A., Türko?lu E., Ball?, T., Sütçüo?, S., Erdemir, A., Co?ar, H., Kahramaner, Z., Kan?k, A., Men, G., Yaprak, I., Neonatal mortality and short term prognosis in newborns born after assisted reproductive techniques. ''Turk Arch Pediatri'' (2011), 46, pp. 37-38.

'''3.''' Congenital abnormalities are conditions existing at birth, for example trisomy 21 and spina bifida. Trisomy 21 is an genetic abnormality where the chromosome 21 exists in three copies instead of the normal two. These children have a number of physical and mental symptoms collectively called Down's Syndrome. Spina bifida is a neural tube defect which occurs when the neural tube fails to close at the caudal end during embryonic development. There are several subclasses of spina bifida. For example spina bifida cystica and spina bifida occulta. In spina bifida cystica either the meninges only herniate through the opening of the spinal canal (meningocele) or the spinal cord as well (myelomeningocele). These herniations do not occur in spina bifida occulta and it is therefore less severe.

--[[User:Z3279511|Z3279511]] 20:18, 2 August 2011 (EST)

'''Lab 2: Assessment'''

The capacitated spermatozoa binds to the zona pellucida glycoprotein 3 (ZP 3). ZP 3 functions as receptor and induces the acrosome reaction. In the acrosome reaction the spermatozoa releases enzymes from the acrosome which facilitate the penetration of the zona pellucida. ZP 2 acts as second spermatozoa receptor. Once membrane fusion occurs, where the spermatozoa and oocyte membranes fuse allowing the sperm nuclei to enter into the oocytes cytoplasm, membrane depolarization functions to prevent polyspermy. This is facilitated by enzymes that alter ZP3, which in turn will no longer bind to spermatozoa.

--[[User:Z3279511|Z3279511]] 12:38, 4 August 2011 (EST)
--z3279511 15:38, 4 August 2011 (EST)

--Z3279511 12:17, 11 August 2011 (EST)

[[File:Differentially expressed RefSeq genes in human trisomy 21.jpg| 250px]]

--Z3279511 13:02, 11 August 2011 (EST)

'''Lab 3: Assessment'''

'''1.''' An important maternal dietary requirement for neural development is foliate. The incident of spina bifida and anencephali became much less since foliate is a component of the normal diet in Australia. Another maternal dietary requirement, particular in late neural development, is iodine. It is for the prevention of congenital hypothyrodism.

'''2.''' Facial manifestations of patient with DiGeorge Syndrome

[[File:Facial manifestations of patient with DiGeorge Syndrome.jpg| 250px]]

File:Facial manifestations of patient with DiGeorge Syndrome

--z3279511 21:00, 17 August 2011 (EST)

--z3279511 11:21, 18 August 2011 (EST)

'''Lab 4: Assessment'''

'''1.''' The allantois is an invagination of endoderm and surrounding extra-embryonic mesoderm into the connecting stalk. It forms an extension of the yolk sac into the connecting stalk (umbilical cord). In the human fetus, the fetal bladder is connected to the allantois via the urachus, which aids as passage for nitrogenous waist from the bladder.

'''2.''' The three vascular shunts are:

1) Ductus venosus: it connects the portal and umbilical vein to the inferior vena cava

2) Foramen ovale: it connects the right and the left atrium

3) Ductus arteriosus: it connects the left pulmonary artery with the arch of the aorta

'''3.''' Group project plan - DiGeorge Syndrome: I will be working on the following:

1) Clinical manifestation and explanations of these

2) Treatment options

3) Drawing of images

The distribution of the tasks to the individual group members can be found on the group discussion page under project plan.
--Anna Marx 16:09, 21 August 2011 (EST)

--Anna Marx 11:18, 25 August 2011 (EST)

'''Lab 5: Assessment'''

Diaphragmatic hernia occur if there is a failure in closure of the peusoperitoneal foramen, which separates the thoracic cavity from that abdominal cavity.The most common diaphragmatic hernia occurs on the left hand side. During development in the embryo the right pleuroperitoneal folds closes before the left and the left is more prone to fail to close completely.In the even of a diaphragmatic hernia abdominal organs can move up into the thoracic cavity.--Anna Marx 10:55, 1 September 2011 (EST)

--Anna Marx 12:45, 1 September 2011 (EST)

'''Lab 6: Assessment'''

1) The palatal shelves fuse in week 9 of human development. The preparation process for this in the early embryonic development is growth, elevation, and fusion of palatal shelves.

2) The quail-chick chimera helps to study the neural crest origin and migration.

3) Tetralogy of Fallot is an abnormality that results the failure of neural crest cells to migrate into the cardiac outflow tract.

Lab 7 Attendance: --Anna Marx 12:05, 15 September 2011 (EST)

'''Lab 7: Assessmaent'''

1) Satellite cells are not a requirement for skeletal muscle fiber hypertrophy but satellite cells are necessary for both the formation of new fibers (hyperplasia) and fiber regeneration.

2) Cellular destruction and regeneration occurs after chronic low frequency stimulation (CLFS). Satellite cells are recruited and differentiate from fast fibre type to slow fibre type. Long-term stimulation increases aerobic capacity, decreases relaxation time and makes the muscle more resistant to fatigue. The change from fast to slow fibre type is an adaptive mechanism to prevent damage of the muscle fibres.

'''Peer review for trisomy 21'''

INTRODUCTION: An introduction is a brief summary of the content of the page, should only contain information that will be discussed in more detail below and not be confusing. Furthermore it should raise the interest to keep on reading. This introduction did not have this effect for me. Try to explain what trisomy 21 is about, what the characteristics are and quickly introduce the sections that will be talked about on this page. Trisomy 21 is a very common condition and we have all seen people with it on the street, it would be nice to have a picture of a person with trisomy 21 for recognition. They are lovely people and it would engage the reader. The image "Chromosome- trisomy" is a repetition of the image "Trisomy 21 (Down Syndrome) Karyotypes" and fits much better in an "etiology/pathogenesis" section, which I am hoping to find below. Links to websites with further information or to a glossary are great when they are actually directly related to the section and relevant to it. However, the introduction is rather an invitation to read more on the actual page, where the content will be discussed in detail and where links to external pages and to the glossary can be used for further information. The text itself needs proper referencing (1st and 3rd paragraph).

SOME RECENT FINDINGS: The title "recent findings" would be more appropriate under the assumption that the most recent and most relevant research is discussed here. Recent findings should rather be placed in the end of the project. The image "Trisomy 21 newborn" has no copyright information and has also no relation to this section. It neither has to do with the recent findings discussed nor is it mentioned or referred to in the text.

TRISOMY 21 (DONW SYNDROME) KARYOTYPES: The image a good illustration of what the genetic difference of an individual with trisomy 21 and a normal person is. However it could be explained more in detail. First of all if "Karyotypes" appears in the title, it should as well be explained directly in the section and not via a link to an external glossary. Secondly it would be nice to see an etiology/pathogenesis section on the page. Some one who is interested in finding out more about trisomy 21 would want to know how it is caused, what the risk factors are (eg.: the age of the mother plays and important role), and how it happens, that the genes do not separate. A suggestion would be to make an etiology/pathogenesis section and to discuss the "Trisomy 21 karyotypes" and "Meiosis I and Meiosis II" in this section.
Additioinally, in the introduction it has been explained that trisomy 21 and Down's syndrome are two names for the same abnormality. Hence from that point on chose one of the names and stick with it rather that mixing them up or having the both in the same heading. The spelling in the heading is wrong (Down Syndrome, should be Down's Syndrome).

ASSOCIATED CONGENITAL ABNORMALITIES: The associated congenital abnormalities are important because they have an impact on the life of individuals with trisomy 21. Hence the section could be a little more complex. It might be worth writing an introducing paragraph, in which the most common associated abnormalities and the prevalence is mentioned. Not to forget, that the clinical picture of trisomy 21 individuals varies highly. For example there is a person that even made it into university while in more severe cases individuals only speak a few words lifelong - some individuals present with congenital heart defects some have perfectly normal hearts and no problems lifelong, etc. May be each of the relevant abnormalities could be explained in a table as under "limb defects".

AMERICAN COLLEGE: Instead of this section it would be nice to see a "diagnostic test" section. In this the "ACOG" could be incorporated as external link. The tests mentioned here for example: measuring features of the back of the neck and ultrasound are not diagnostic test for trisomy 21. Trisomy 21 is detected by sampling the amniotic fluid and by genetic testing. Abnormalities of the back of the neck and ultrasound are techniques to detect other abnormalities. Hence these are not directly relevant to trisomy 21. I have noticed that there is a complex section about screening - which discusses the detection of trisomy 21 somewhat. However I find it a little confusing. A table is a good idea but maternal age is not a procedure and what are all the tests for? Trisomy 21? How do they work? A diagram is as well and excellent idea but what does it all mean? How is a buccal swap done? And again is that all relevant to trisomy 21? If I was for example a pregnant woman with the concern that my baby has trisomy 21, I would like to know what the commonly used test is, how it is done, what the risk factors are and how accurate it is.

PREVALENCE these section would be more appropriate after the introduction, may be as "epidemiology" section. Furthermore it would be interesting the see some figures that are more recent and worldwide.

SCREENING: See comment under AMERICAN COLLEGE. Also about "SCREENING BY COUNTRY" One sentence does not need and extra heading. Either this information is not important or there could perhaps be some more information about other countries as well and about the difference such an screening makes.

MEIOSIS I AND MEIOSIS II: See comment under TRISOMY 21 (DONW SYNDROME) KARYOTYPES
ANEUPLOIDY: Aneuploidy has been explained before and this section has as such no relevance to the topic.

GROWTH CHARTS: May be this information could be presented under "Clinical presentation". From this section on its own I cannot derive weather children with trisomy 21 show abnormalities in growth or not and why it should be relevant.

REFERENCES: The first part of the references does not have a subheading but the rest does. May be it could be structured a bid differently. The first part contains articles, so why is it not under articles?

TERMS: It would be good to have a more terms in the glossary. Basically all words used in the sections above that would be new to a person with no scientific background should be explained here.

NOTE IN THE END:
* You have already collected lot's of the information needed, the page just need good structuring, and try to make sure that information is relevant to the topic.
* The images "Chromosome- trisomy", "Trisomy 21 newborn", "Trisomy 21 (Down Syndrome) Karyotypes", "Human idiogram-chromosome 21" "Trisomy 21 hand features", and "John Langdon Down (1828 – 1896) was a British physician who in 1866 was first to describe the syndrome." have no copyright information.
* An Idea: The 2009 Tropfest winner was Genevieve Clay with the short movie "My brother". This is a very sweet movie, which describes the personality of a person with trisomy 21 better than words can do. May be you like to integrate a link to the youtube video (http://www.youtube.com/watch?v=8d-7IFN4DKA) on you page. I am not sure if it is appropriate though.

Lab 8 attendance --Anna Marx 11:26, 22 September 2011 (EST)

'''Peer Assessment'''

Group 1: Peer Assessment
* An image would make your introduction more engaging
* The second paragraph of the introduction is already quite explanatory and might fit better into aetiology/pathogenesis. Instead one or two simple but engaging sentences would be goo.
* The epidemiology section is good but if I wouldn't have learned about chromosomes I would feel a little confused.
* There are writing mistakes and there is no copyright information in the table in the epidemiology section
* The direct links to the glossary (blue words) in the aetiology section are great. If you would have those for all sections it would make your page look more whole
* There are too few references in the aetiology section
* Clinical Manifestations contain useful information, however it's also good to have a more detailed description. May be you could outline the most common clinical presentation a bid more explanatory.
* The tables in the diagnostic section are great, just a different format, so that you don't have huge white gaps would be better
* The treatment and research section are good. May be you could put a little introduction into the treatment section before you go straight into the subheadings.
* Overall, your page has a good structure and is informative. The links to the glossary are great but should be used through the whole page. A few more pictures would make your page more engaging.

Group 3: Peer Assessment
* You have constructed an informative page about an interesting syndrome
* At this stage it's a little text heavy, so may be you can cut it down and add some pictures instead
* In the history section it would be great to see these dates from the table with the text blended in, so it's on chronologic flow.
* You seem to take it very serious with the mitosis or not communicating with each other because you have four pictures of mitosis in three different sections. One picture and a good explanation would be sufficient. Then you could use the rest of the space for other pictures.
* The table for signs ad symptoms is great, but looks a bid empty. So may be you can change the format or add some more pictures.
* May be you could write a bid more about therapeutic options. I would find that more important then "similar abnormalities"
* Good referencing through the section. Just change the "double referencing"
* Overall, you page has a lot of information, may be you can balance it a little more out, communicate so you don't have "double" information and a few more pictures would be great.

Group 4: Peer Assessment
* Your page has a good balance of text, images and tables
* I like that your introduction is brief and to the point
* You history section is the best one have seen so far, it looks good and it easy to read
* The image in the pathogenesis has no copyright information
* In clinical manifestations are quite important I think and your section seems a little weak in comparison to the rest
* Treatment: I'm sure the table was a lot of work but it is quite complex ad all the drug names make me a bid dizzy. May be you can shorten it to the most relevant?

*Overall the page has a good content and it's fun to read. The diagrams and drawings are great

Group 5: Peer Assessment
* Your page looks a bid 80's with all the different pinks in your table. Not a bad thing, however may be just one colour per table would be enough
* The introduction is too brief and written a little careless and lacks referencing.
* The history table is good in the way that it's chronologic and easy to read but you could write a bid more about the relevance of these events.
* Your drawing needs some copyright information and if the writing would have more contrast it would come more into account.
* The aetiology section is informative overall but some long sentences could be separated and more explanatory. Put the pictures on the same side may be to give it a bid more shape.
* The development of the disease section and signs and symptoms section read well and there is good use of subheadings.
* Is there some current research you could talk about?
* Your glossary and your references clearly need some editing and fixing up
* Overall your page seems to be written a bid careless but there are bids of interesting information in there.

Group 6: Peer Assessment
* It would be good to see more images
* The introduction would be more engaging if it had an image
* The history section is informative however would be nicer in a chronologic fashion. May be a table?
* The extra surgical history makes it clear that surgery plays an important role. Good
* Signs and Symptoms and genetic abnormalities are good overall. Many of the terms need to be added to the glossary though and it might be better to put aetiology first.
* It's a quite big and text heavy table in your diagnostic section. May be you can make it shorter, put pictures in

* I found quite a few words that should be in the glossary
* There is no title for your reference section and it looks like you should have more references for the amount of text that you have written
* Overall your page is very informative, good content. You need more images, appropriate referencing and a more complex glossary.

Group 7: Peer Assessment
* The introduction is brief and informative and makes me want to read the rest.
* May be you can add an image in the introduction or history or both to make it even more engaging
* You history section is nicely to ready and captures my interest.
* While it is good to come straight to the point, your epidemiology section is really short
* The pathogenesis section is very informative and very good especially for people who are really looking to understand the disorder. May be a few subheadings on the way, just to make this text heavy section a little lighter.
* Diagnostic techniques would be nice in a table
* You still got some "double referencing", we have the same problem;)
* You glossary in comparison to most other projects seams to be relatively complex. Great
* The student images are well done!
* You have got a lot of information and I find it quite interesting. It seems a little text heavy overall.

Group 8: Peer Assessment
* Overall you page is well structured, has relevant content and is written nicely. It also fits nicely together, good group work.
* May be you could put a picture of a person with this disorder in?
* Structure and content of the introduction and history is good. What happened between 1907 and 1988?
* Good use of subheadings in the epidemiology section
* You aetiology section is informative and nicely balanced
* "The fraxtaxin gene on chromosome 9": can you get a better contrast for that image?
* The aetiology, neuropathology, clinical presentations and diagnosis sections are all well written, interesting and have the right amount of text and images
* The current research section looks rather unfinished in comparison to the rest. May be you can put the information into a few paragraphs instead of bullet points.
* The current research section is interesting, just lacks dates
* Glossary, References and External links are fine

Group 9: Peer assessment
* The introduction is good
* The history section is informative but may be could be kept a little shorter
* The start of the page is quite text heavy, may be you can brake it up with a picture
* Rearrange you page, so that you have the epidemiology section right after the history section
* Genetic and aetiology sections are well done
* There are no references in the Phenotype section
* May be the detail in the foundations is a little over the top. Why not put a simple link to their web side instead?
* The research section could be a little more detailed
* It would be good to put more of the terms used into your glossary
* Overall the page is interesting to read. A few more images would be nice.

Group 10: Peer Assessment
* Your page is relatively short overall and could use some more pictures, especially in the first few sections.
* You have forgotten to put a title on you page
* The introduction is good
* You have got quite a bid of text in the history section, may be you can make a bid lighter with a time line?
* Epidemiology is nice to read and relevant
* Signs and symptoms belong into the clinical manifestation section
* Diagnostics could be more in detail
* The green and blue in the table is a bid too much colour all on a sudden. May be you can have some more colour overall or do the table in just one colour?
* It would be great to have more terms in the glossary
* I would put the diagnosis section right after pathogenesis
* Overall you have got good information on your page. May be you can work on the overall structure and some references.

Group 11: Peer Assessment
* You have picked an interesting topic, surely you can write a more engaging introduction
* Some of you headings and subheadings need rearrangement
* The history section is good but takes a bid too much space. May be you can compress it a bid, make it a little shorter?
* Some of you information is double
* The neuroembryology and functional anatomy of craniofacial cleft is interesting and well written
* Good diagnostic section. An image would be nice
* Some more references in the treatment and associated problems section are needed
* You could put some more words into the glossary
* You have some "double referencing"
* Overall, you have an interesting page. Good work. You just need a little more formatting, referencing and fixing here and there.

'''Attendance Lab 10''': --Anna Marx 11:19, 6 October 2011 (EST)
Questions lab 10:
1) Tertogens can also lead to hearing loss
2) three factors that contribute to poor drainage: 1) auditori tube is nearly horizontal, the auditory tube is narrow, auditory tube only opens with one single muscle

==Lab 11 Questions==

1) Componentsthat give rise to the interatrial vessel: Septum primium and septum secundum
Passages that connect the right and left atria: Foramen ovale and foramen secundum

2) Cardiac defects that arise due to abnormalities in the development of the outflow tract are:
*Tetrallogy of fallot
*Pulmonary stenosis
*aortic stenosis
* Transposition of great vessels
*Pulmonary artresis
*Patient ductus arteriosus
*Interrupted aortic arch
*Hypoplastic left heart syndrome
*Coarctation of aorta

==Lab 12 Questions==

Give three examples of systems that continue to develop postnatally
* Respiratory system
* Neurological system
* Reproductive system

Identify the abnormalities detected by the Gutherie test and link to one abnormelity listed in OMIM

* Congenital Toxoplasmosis

* Homocystinuria

* Biotinidase Deficiency

* Cystic Fibrosis (CF)

* Congenital Adrenal Hyperplasia (CAH)

* Congenital Hypothyroidism (CH)

* Maple Syrup Urine Disease (MSUD) ([http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=248600 OMIM])

User:Z3279511

2011-10-14T07:56:14Z

Z3279511:

User:Z3279511

2011-10-13T00:22:41Z

Z3279511:

{{2011Student}}

--[[User:Z3279511|Z3279511]] 12:55, 28 July 2011 (EST)

'''Lab 1: Assessment'''

'''1.''' The origin of In Vitro Fertilization (IVF) lies in 1950s, where Dr. Robert G. Edwards started to work on his idea for the treatment of infertility. He was the first to show, that the human oocyte can undergo fertilization, grow into an embryo and blastocyst ''in vitro'' and then be implanted into the mothers womb to develop into a healthy infant. On the 25th of July 1987 Louise Joy Brown, the first child conceived via IVF was born. Dr. Robert G. Edwards received the 2010 Nobel Prize in Physiology or Medicine for the discovery of IVF.

'''2.''' Özer ''et al.'' showed in their study published in the Turk Arch Pediatri, that children conceived through assisted reproductive techniques (ART) have a higher risk of premature birth and multiple gestation in comparison to children conceived naturally. The study evaluated neonatal morbidity, mortality, congenital abnormalities, prematurity and multiple pregnancies in 123 ART babies. It was found that ART babies in comparison to normal babies have higher rates of mortality and abnormalities and lower birth weight.

Reference: Özer, E. A., Türko?lu E., Ball?, T., Sütçüo?, S., Erdemir, A., Co?ar, H., Kahramaner, Z., Kan?k, A., Men, G., Yaprak, I., Neonatal mortality and short term prognosis in newborns born after assisted reproductive techniques. ''Turk Arch Pediatri'' (2011), 46, pp. 37-38.

'''3.''' Congenital abnormalities are conditions existing at birth, for example trisomy 21 and spina bifida. Trisomy 21 is an genetic abnormality where the chromosome 21 exists in three copies instead of the normal two. These children have a number of physical and mental symptoms collectively called Down's Syndrome. Spina bifida is a neural tube defect which occurs when the neural tube fails to close at the caudal end during embryonic development. There are several subclasses of spina bifida. For example spina bifida cystica and spina bifida occulta. In spina bifida cystica either the meninges only herniate through the opening of the spinal canal (meningocele) or the spinal cord as well (myelomeningocele). These herniations do not occur in spina bifida occulta and it is therefore less severe.

--[[User:Z3279511|Z3279511]] 20:18, 2 August 2011 (EST)

'''Lab 2: Assessment'''

The capacitated spermatozoa binds to the zona pellucida glycoprotein 3 (ZP 3). ZP 3 functions as receptor and induces the acrosome reaction. In the acrosome reaction the spermatozoa releases enzymes from the acrosome which facilitate the penetration of the zona pellucida. ZP 2 acts as second spermatozoa receptor. Once membrane fusion occurs, where the spermatozoa and oocyte membranes fuse allowing the sperm nuclei to enter into the oocytes cytoplasm, membrane depolarization functions to prevent polyspermy. This is facilitated by enzymes that alter ZP3, which in turn will no longer bind to spermatozoa.

--[[User:Z3279511|Z3279511]] 12:38, 4 August 2011 (EST)
--z3279511 15:38, 4 August 2011 (EST)

--Z3279511 12:17, 11 August 2011 (EST)

[[File:Differentially expressed RefSeq genes in human trisomy 21.jpg| 250px]]

--Z3279511 13:02, 11 August 2011 (EST)

'''Lab 3: Assessment'''

'''1.''' An important maternal dietary requirement for neural development is foliate. The incident of spina bifida and anencephali became much less since foliate is a component of the normal diet in Australia. Another maternal dietary requirement, particular in late neural development, is iodine. It is for the prevention of congenital hypothyrodism.

'''2.''' Facial manifestations of patient with DiGeorge Syndrome

[[File:Facial manifestations of patient with DiGeorge Syndrome.jpg| 250px]]

File:Facial manifestations of patient with DiGeorge Syndrome

--z3279511 21:00, 17 August 2011 (EST)

--z3279511 11:21, 18 August 2011 (EST)

'''Lab 4: Assessment'''

'''1.''' The allantois is an invagination of endoderm and surrounding extra-embryonic mesoderm into the connecting stalk. It forms an extension of the yolk sac into the connecting stalk (umbilical cord). In the human fetus, the fetal bladder is connected to the allantois via the urachus, which aids as passage for nitrogenous waist from the bladder.

'''2.''' The three vascular shunts are:

1) Ductus venosus: it connects the portal and umbilical vein to the inferior vena cava

2) Foramen ovale: it connects the right and the left atrium

3) Ductus arteriosus: it connects the left pulmonary artery with the arch of the aorta

'''3.''' Group project plan - DiGeorge Syndrome: I will be working on the following:

1) Clinical manifestation and explanations of these

2) Treatment options

3) Drawing of images

The distribution of the tasks to the individual group members can be found on the group discussion page under project plan.
--Anna Marx 16:09, 21 August 2011 (EST)

--Anna Marx 11:18, 25 August 2011 (EST)

'''Lab 5: Assessment'''

Diaphragmatic hernia occur if there is a failure in closure of the peusoperitoneal foramen, which separates the thoracic cavity from that abdominal cavity.The most common diaphragmatic hernia occurs on the left hand side. During development in the embryo the right pleuroperitoneal folds closes before the left and the left is more prone to fail to close completely.In the even of a diaphragmatic hernia abdominal organs can move up into the thoracic cavity.--Anna Marx 10:55, 1 September 2011 (EST)

--Anna Marx 12:45, 1 September 2011 (EST)

'''Lab 6: Assessment'''

1) The palatal shelves fuse in week 9 of human development. The preparation process for this in the early embryonic development is growth, elevation, and fusion of palatal shelves.

2) The quail-chick chimera helps to study the neural crest origin and migration.

3) Tetralogy of Fallot is an abnormality that results the failure of neural crest cells to migrate into the cardiac outflow tract.

Lab 7 Attendance: --Anna Marx 12:05, 15 September 2011 (EST)

'''Lab 7: Assessmaent'''

1) Satellite cells are not a requirement for skeletal muscle fiber hypertrophy but satellite cells are necessary for both the formation of new fibers (hyperplasia) and fiber regeneration.

2) Cellular destruction and regeneration occurs after chronic low frequency stimulation (CLFS). Satellite cells are recruited and differentiate from fast fibre type to slow fibre type. Long-term stimulation increases aerobic capacity, decreases relaxation time and makes the muscle more resistant to fatigue. The change from fast to slow fibre type is an adaptive mechanism to prevent damage of the muscle fibres.

'''Peer review for trisomy 21'''

INTRODUCTION: An introduction is a brief summary of the content of the page, should only contain information that will be discussed in more detail below and not be confusing. Furthermore it should raise the interest to keep on reading. This introduction did not have this effect for me. Try to explain what trisomy 21 is about, what the characteristics are and quickly introduce the sections that will be talked about on this page. Trisomy 21 is a very common condition and we have all seen people with it on the street, it would be nice to have a picture of a person with trisomy 21 for recognition. They are lovely people and it would engage the reader. The image "Chromosome- trisomy" is a repetition of the image "Trisomy 21 (Down Syndrome) Karyotypes" and fits much better in an "etiology/pathogenesis" section, which I am hoping to find below. Links to websites with further information or to a glossary are great when they are actually directly related to the section and relevant to it. However, the introduction is rather an invitation to read more on the actual page, where the content will be discussed in detail and where links to external pages and to the glossary can be used for further information. The text itself needs proper referencing (1st and 3rd paragraph).

SOME RECENT FINDINGS: The title "recent findings" would be more appropriate under the assumption that the most recent and most relevant research is discussed here. Recent findings should rather be placed in the end of the project. The image "Trisomy 21 newborn" has no copyright information and has also no relation to this section. It neither has to do with the recent findings discussed nor is it mentioned or referred to in the text.

TRISOMY 21 (DONW SYNDROME) KARYOTYPES: The image a good illustration of what the genetic difference of an individual with trisomy 21 and a normal person is. However it could be explained more in detail. First of all if "Karyotypes" appears in the title, it should as well be explained directly in the section and not via a link to an external glossary. Secondly it would be nice to see an etiology/pathogenesis section on the page. Some one who is interested in finding out more about trisomy 21 would want to know how it is caused, what the risk factors are (eg.: the age of the mother plays and important role), and how it happens, that the genes do not separate. A suggestion would be to make an etiology/pathogenesis section and to discuss the "Trisomy 21 karyotypes" and "Meiosis I and Meiosis II" in this section.
Additioinally, in the introduction it has been explained that trisomy 21 and Down's syndrome are two names for the same abnormality. Hence from that point on chose one of the names and stick with it rather that mixing them up or having the both in the same heading. The spelling in the heading is wrong (Down Syndrome, should be Down's Syndrome).

ASSOCIATED CONGENITAL ABNORMALITIES: The associated congenital abnormalities are important because they have an impact on the life of individuals with trisomy 21. Hence the section could be a little more complex. It might be worth writing an introducing paragraph, in which the most common associated abnormalities and the prevalence is mentioned. Not to forget, that the clinical picture of trisomy 21 individuals varies highly. For example there is a person that even made it into university while in more severe cases individuals only speak a few words lifelong - some individuals present with congenital heart defects some have perfectly normal hearts and no problems lifelong, etc. May be each of the relevant abnormalities could be explained in a table as under "limb defects".

AMERICAN COLLEGE: Instead of this section it would be nice to see a "diagnostic test" section. In this the "ACOG" could be incorporated as external link. The tests mentioned here for example: measuring features of the back of the neck and ultrasound are not diagnostic test for trisomy 21. Trisomy 21 is detected by sampling the amniotic fluid and by genetic testing. Abnormalities of the back of the neck and ultrasound are techniques to detect other abnormalities. Hence these are not directly relevant to trisomy 21. I have noticed that there is a complex section about screening - which discusses the detection of trisomy 21 somewhat. However I find it a little confusing. A table is a good idea but maternal age is not a procedure and what are all the tests for? Trisomy 21? How do they work? A diagram is as well and excellent idea but what does it all mean? How is a buccal swap done? And again is that all relevant to trisomy 21? If I was for example a pregnant woman with the concern that my baby has trisomy 21, I would like to know what the commonly used test is, how it is done, what the risk factors are and how accurate it is.

PREVALENCE these section would be more appropriate after the introduction, may be as "epidemiology" section. Furthermore it would be interesting the see some figures that are more recent and worldwide.

SCREENING: See comment under AMERICAN COLLEGE. Also about "SCREENING BY COUNTRY" One sentence does not need and extra heading. Either this information is not important or there could perhaps be some more information about other countries as well and about the difference such an screening makes.

MEIOSIS I AND MEIOSIS II: See comment under TRISOMY 21 (DONW SYNDROME) KARYOTYPES
ANEUPLOIDY: Aneuploidy has been explained before and this section has as such no relevance to the topic.

GROWTH CHARTS: May be this information could be presented under "Clinical presentation". From this section on its own I cannot derive weather children with trisomy 21 show abnormalities in growth or not and why it should be relevant.

REFERENCES: The first part of the references does not have a subheading but the rest does. May be it could be structured a bid differently. The first part contains articles, so why is it not under articles?

TERMS: It would be good to have a more terms in the glossary. Basically all words used in the sections above that would be new to a person with no scientific background should be explained here.

NOTE IN THE END:
* You have already collected lot's of the information needed, the page just need good structuring, and try to make sure that information is relevant to the topic.
* The images "Chromosome- trisomy", "Trisomy 21 newborn", "Trisomy 21 (Down Syndrome) Karyotypes", "Human idiogram-chromosome 21" "Trisomy 21 hand features", and "John Langdon Down (1828 – 1896) was a British physician who in 1866 was first to describe the syndrome." have no copyright information.
* An Idea: The 2009 Tropfest winner was Genevieve Clay with the short movie "My brother". This is a very sweet movie, which describes the personality of a person with trisomy 21 better than words can do. May be you like to integrate a link to the youtube video (http://www.youtube.com/watch?v=8d-7IFN4DKA) on you page. I am not sure if it is appropriate though.

Lab 8 attendance --Anna Marx 11:26, 22 September 2011 (EST)

'''Peer Assessment'''

Group 1: Peer Assessment
* An image would make your introduction more engaging
* The second paragraph of the introduction is already quite explanatory and might fit better into aetiology/pathogenesis. Instead one or two simple but engaging sentences would be goo.
* The epidemiology section is good but if I wouldn't have learned about chromosomes I would feel a little confused.
* There are writing mistakes and there is no copyright information in the table in the epidemiology section
* The direct links to the glossary (blue words) in the aetiology section are great. If you would have those for all sections it would make your page look more whole
* There are too few references in the aetiology section
* Clinical Manifestations contain useful information, however it's also good to have a more detailed description. May be you could outline the most common clinical presentation a bid more explanatory.
* The tables in the diagnostic section are great, just a different format, so that you don't have huge white gaps would be better
* The treatment and research section are good. May be you could put a little introduction into the treatment section before you go straight into the subheadings.
* Overall, your page has a good structure and is informative. The links to the glossary are great but should be used through the whole page. A few more pictures would make your page more engaging.

Group 3: Peer Assessment
* You have constructed an informative page about an interesting syndrome
* At this stage it's a little text heavy, so may be you can cut it down and add some pictures instead
* In the history section it would be great to see these dates from the table with the text blended in, so it's on chronologic flow.
* You seem to take it very serious with the mitosis or not communicating with each other because you have four pictures of mitosis in three different sections. One picture and a good explanation would be sufficient. Then you could use the rest of the space for other pictures.
* The table for signs ad symptoms is great, but looks a bid empty. So may be you can change the format or add some more pictures.
* May be you could write a bid more about therapeutic options. I would find that more important then "similar abnormalities"
* Good referencing through the section. Just change the "double referencing"
* Overall, you page has a lot of information, may be you can balance it a little more out, communicate so you don't have "double" information and a few more pictures would be great.

Group 4: Peer Assessment
* Your page has a good balance of text, images and tables
* I like that your introduction is brief and to the point
* You history section is the best one have seen so far, it looks good and it easy to read
* The image in the pathogenesis has no copyright information
* In clinical manifestations are quite important I think and your section seems a little weak in comparison to the rest
* Treatment: I'm sure the table was a lot of work but it is quite complex ad all the drug names make me a bid dizzy. May be you can shorten it to the most relevant?

*Overall the page has a good content and it's fun to read. The diagrams and drawings are great

Group 5: Peer Assessment
* Your page looks a bid 80's with all the different pinks in your table. Not a bad thing, however may be just one colour per table would be enough
* The introduction is too brief and written a little careless and lacks referencing.
* The history table is good in the way that it's chronologic and easy to read but you could write a bid more about the relevance of these events.
* Your drawing needs some copyright information and if the writing would have more contrast it would come more into account.
* The aetiology section is informative overall but some long sentences could be separated and more explanatory. Put the pictures on the same side may be to give it a bid more shape.
* The development of the disease section and signs and symptoms section read well and there is good use of subheadings.
* Is there some current research you could talk about?
* Your glossary and your references clearly need some editing and fixing up
* Overall your page seems to be written a bid careless but there are bids of interesting information in there.

Group 6: Peer Assessment
* It would be good to see more images
* The introduction would be more engaging if it had an image
* The history section is informative however would be nicer in a chronologic fashion. May be a table?
* The extra surgical history makes it clear that surgery plays an important role. Good
* Signs and Symptoms and genetic abnormalities are good overall. Many of the terms need to be added to the glossary though and it might be better to put aetiology first.
* It's a quite big and text heavy table in your diagnostic section. May be you can make it shorter, put pictures in

* I found quite a few words that should be in the glossary
* There is no title for your reference section and it looks like you should have more references for the amount of text that you have written
* Overall your page is very informative, good content. You need more images, appropriate referencing and a more complex glossary.

Group 7: Peer Assessment
* The introduction is brief and informative and makes me want to read the rest.
* May be you can add an image in the introduction or history or both to make it even more engaging
* You history section is nicely to ready and captures my interest.
* While it is good to come straight to the point, your epidemiology section is really short
* The pathogenesis section is very informative and very good especially for people who are really looking to understand the disorder. May be a few subheadings on the way, just to make this text heavy section a little lighter.
* Diagnostic techniques would be nice in a table
* You still got some "double referencing", we have the same problem;)
* You glossary in comparison to most other projects seams to be relatively complex. Great
* The student images are well done!
* You have got a lot of information and I find it quite interesting. It seems a little text heavy overall.

Group 8: Peer Assessment
* Overall you page is well structured, has relevant content and is written nicely. It also fits nicely together, good group work.
* May be you could put a picture of a person with this disorder in?
* Structure and content of the introduction and history is good. What happened between 1907 and 1988?
* Good use of subheadings in the epidemiology section
* You aetiology section is informative and nicely balanced
* "The fraxtaxin gene on chromosome 9": can you get a better contrast for that image?
* The aetiology, neuropathology, clinical presentations and diagnosis sections are all well written, interesting and have the right amount of text and images
* The current research section looks rather unfinished in comparison to the rest. May be you can put the information into a few paragraphs instead of bullet points.
* The current research section is interesting, just lacks dates
* Glossary, References and External links are fine

Group 9: Peer assessment
* The introduction is good
* The history section is informative but may be could be kept a little shorter
* The start of the page is quite text heavy, may be you can brake it up with a picture
* Rearrange you page, so that you have the epidemiology section right after the history section
* Genetic and aetiology sections are well done
* There are no references in the Phenotype section
* May be the detail in the foundations is a little over the top. Why not put a simple link to their web side instead?
* The research section could be a little more detailed
* It would be good to put more of the terms used into your glossary
* Overall the page is interesting to read. A few more images would be nice.

Group 10: Peer Assessment
* Your page is relatively short overall and could use some more pictures, especially in the first few sections.
* You have forgotten to put a title on you page
* The introduction is good
* You have got quite a bid of text in the history section, may be you can make a bid lighter with a time line?
* Epidemiology is nice to read and relevant
* Signs and symptoms belong into the clinical manifestation section
* Diagnostics could be more in detail
* The green and blue in the table is a bid too much colour all on a sudden. May be you can have some more colour overall or do the table in just one colour?
* It would be great to have more terms in the glossary
* I would put the diagnosis section right after pathogenesis
* Overall you have got good information on your page. May be you can work on the overall structure and some references.

Group 11: Peer Assessment
* You have picked an interesting topic, surely you can write a more engaging introduction
* Some of you headings and subheadings need rearrangement
* The history section is good but takes a bid too much space. May be you can compress it a bid, make it a little shorter?
* Some of you information is double
* The neuroembryology and functional anatomy of craniofacial cleft is interesting and well written
* Good diagnostic section. An image would be nice
* Some more references in the treatment and associated problems section are needed
* You could put some more words into the glossary
* You have some "double referencing"
* Overall, you have an interesting page. Good work. You just need a little more formatting, referencing and fixing here and there.

'''Attendance Lab 10''': --Anna Marx 11:19, 6 October 2011 (EST)
Questions lab 110:
1) Tertogens can also lead to hearing loss
2) three factors that contribute to poor drainage: 1) auditori tube is nearly horizontal, the auditory tube is narrow, auditory tube only opens with one single muscle

User:Z3279511

2011-10-06T00:19:49Z

Z3279511:

Talk:2011 Group Project 2

2011-10-02T10:02:15Z

Z3279511:

[[2011_Group_Project_2|'''Group 2''']]: [[User:z3279511]] | [[User:z3288196]] | [[User:z3288729]] | [[User:z3288827]]

{{2011GroupDiscussionMH}}

'''Page Edits 30 Sep'''
<gallery>
File:2011_Project_Group_2_edits.jpg|Project Page
File:2011_Project_Group_1-11_edits.jpg|All Groups (1-11) Project
File:2011_Talk_Group_2_edits.jpg|Discussion Page
File:2011 Talk Group 1-11 edits.jpg|All Groups (1-11) Discussion
</gallery>

Hello,

I have DiGeorge and DGS to DiGeorge Syndrome for all of us. This way there is a better flow through the page. Great work guys. i think our page looks great. --Anna Marx 21:02, 2 October 2011 (EST)

==Question==

Hi Leonard, it's actually hard to find good pictures that are actually useful. I had the same problem for the treatment section. I like your pictures but I guess if you wanted to you could draw them again with straight line or so... ;) But it's a bid hard to make them all happy anyway. I had about 75% of people saying that the table in clinical manifestations is really informative and great and 25% said it's to text heavy. I would say 75% win... Anna

Hi, does someone know how I can change my table in clinical manifestations in the way that there is a space in between each section? --Anna Marx 16:23, 2 October 2011 (EST)
Hi Anna, not too sure but if you check in the shortcuts section with editing basics then you might be able to find something in there that'll help. I'm going to add all my words to the glossary and fix up my referencing now! In general I think we got pretty good reviews, just take heed of what the people said and we'll finish up :) --[[User:Z3288827|Leonard Tiong]] 17:05, 2 October 2011 (EST) Hi, yeah I couldn't find the trick in the shortcut tut. But it should be ok just like that....

btw guys i can't actually find an image/graph for the epidemiology section and that's one of the things that a lot of people have commented on. have you found anything in your research that has something like that that I could use? Thanks guys--[[User:Z3288827|Leonard Tiong]] 17:14, 2 October 2011 (EST)
hey all, just finished doing my sections for the glossary linking and fixing of the references. Just read through each of your sections again to make sure that your sentence structure all make sense, alright? I'll do the duplicated references later, going to take a break from this now. by the way, if it's possible, can anyone help me with my two pubmed reference between 46 and 52? I have the formatting of the pubmed reference correct but it's not working in the reference section.

Thanks guys :) --[[User:Z3288827|Leonard Tiong]] 18:36, 2 October 2011 (EST)

==The Final Fix up==

hey not sure what you guys think but what if we take the advice we got on our own sections and focus on fixing them up? I can go through and link the terms to the glossary if someone else wants to fix up the references?

Hi, sounds like a good idea! Will do my part over the week end. anna

Group 2 Critique:
*What Can I say, well researched, nicely sub headed.
*Historical Background shows amazing work. The only 2 things I noticed are the “ 22q11 is in purple” is that on purpose? And the second thing is the image has a source but no reference.
*Epidmiology and Etiology may need some images to balance the words. Also, some spacing between the paragraphs would make it more readable.
* Nice illustration via drawings in the Pathophysiology sections . well structured.
* This section is well established, it has colours and few paragraphs. You might want to consider the size of images probably into something bigger like (Based on symptoms, Ultrasound) and add one more photo in the last two sections (Amniocentesis, BACS- on beads technology)
* one of the best sections on this page is Clinical manifestations. Great work on the table. Perhaps more images along with the abnormality would make a more presentable table. Also, you may consider re-phrasing ( the sub-heading “ How it is caused”) into something with one word. Fabulous work on Heart Drawings.
* in the Section of “ Current and Future research”, allocation of each would be more organised.
The large number of references show how much you guys spent on the page. Some of the references may need to be formatted ( 1,2,3,4,5, etc) note: reference 33,40,47,49, are empty . Overall Great Job.
z3284061

'''Group 2'''

* Well researched and set out page
* An image is needed in either Epidemiology or Etiology would be good
* Diagnostic section tests section is good, however, images are needed for BAC and Amniocentesis
* Glossary is well set out, maybe links to the glossary would be helpful
* Subheadings might be useful in the Current/future research section
* some of the referencing will need to be fixed such as double references
--[[User:Z3292953|z3292953]] 11:11, 29 September 2011 (EST)

'''''DiGeorge Syndrome (Group 2) Peer Review:'''''

Introduction: Well introduced topic. Picture needs description at bottom. Seems to be referenced appropriately.

Historical Background: Extensive timeline which is good. Try to be a little bit more consistent with the colon – either place it after the date or not. Also, picture seems a bit random and needs to have a description at the bottom so that the reader knows what it encompasses.

Epidemiology: Could be a bit more spaced out to make it easier for the reader to read through.

Etiology: Good information and referencing. Try to include a picture in this section as it would help the reader visualize what you are conveying in words.

Pathogenesis/ Pathophysiology: This section is well done. Information is good and images are well-drawn and also contain a relevant description at the bottom. Well done!

Diagnostic Tests: Very extensive. Great use of images. Could you possible also find an image for amniocentesis and BACS? Some image references are not in the correct format and images in this section need to have a label at the bottom.

Clinical Manifestations: This section is well done as well. Possibly too much information which may overwhelm the reader though.

Treatment: Slight inconsistency with the formatting, but otherwise no major dramas. Also possibly more images needed in this section.

Current and Future Research: This section is quite interesting. Research is extensive and images are good – however, they lack correct referencing format and the student template in the information section.

Glossary: Extensive. Well done.

Overall, good job! --[[User:Z3290808|z3290808]] 10:40, 29 September 2011 (EST)

Group 2:

There seems to be a lot of references, almost an excessive amount.

A picture for epidemiology and aetiology would be good.

Diagnostic tests was done well

Clinical manifestations should include some info on what the normal structure and function of the heart.

There is a very large amount of written information and this is reflected in the reference section that takes up alot of space on the page. There are slabs of writing which makes it hard to read the page. It’s boring to see long slabs of writing. The long glossary reflects the long slabs of writing. It’ll be hard to read through. Its not that clear and concise.

z3332178 =]

'''Group 2:'''

*Intro: the first sentence is a little vague. Rather joining sentence 1 and 2 together and defining congenital disorder and explaining it at the same time would be better. I liked the pictures but the trio in that arrangement left the section looking a little unfinished.

*Historical background: image is not explained, a little confused as to why it is there.

*epidemiology: good section, good referencing

*etiology: its a little awkward in flow as you jump from talking about one study, and after one sentence talk about what another study said. Maybe work on building it into an actual paragraph instead of making them merely sentences.

*pathogenesis: the images would look better if they were larger so you get the vague image of it at a glance. Good section, flows nicely

*diagnosis: great section. Layout made it easy to read. Maybe increase the size of the image in the symptoms part, this was harder to see.

*clinical manifestation: good section. Maybe with the last set of images with the heart, leave a space or include a pink heading like you did for the table above it to indicate another table. This was hard to see

*treatment: good section. Maybe change the colour of the bit that you highlighted in that pale orange/skin colour thing. It’d be nice to have that stand out a little more so those headings can actually be seen and not seen as random words.

--[[User:Z3290558|z3290558]] 09:55, 29 September 2011 (EST)

'''Peer review'''
WOW!
This page looks fantastic. The editing is great. All of the information is presented neatly and concisely.
However, just look in "historical background" and make sure all of the lines are edited uniformly. Some have ":" some don't.
Obviously that is nothing major, I'm just nit-picking.
I think you may want to redraw your "pathology of Di George syndrome". It seems quite cluttered.

Overall: Excellent. There really isn't much to say about this page.

--[[User:Z3290618|Ziggy Harrison-Tikisci]] 10:29, 29 September 2011 (EST)

'''Group 2 peer review'''

Introduction: Please explain what the images is about.

Historical background: Please be careful that you type 'DiGeorge syndrome' throughout the section. For example, the point about the 1981 event has 'diGeorge syndrome'. There are also some spelling errors. Furthermore, a legend for the image would clarify.

Epidemiology: Breaking up the segments with images will make understanding the content easier for the reader.

Diagnositic test: Information on the ultrasound test, particularly the second paragraph, is repetitive. The layout is great and the images breaks up the text nicely. A legend for the image will be good. In particular, please clarify what is abnormal with the male face.

Treatment: Are 'Hypocalcaemia' and 'Psychiatric illness' a late occuring feature or an observable condition in newborns.

--[[User:Z3289301|z3289301]] 09:42, 29 September 2011 (EST)

'''Peer Review'''

:*The first three sentences about congenital disease is misplaced. This should be in your glossary, not in your very first sentences.

:*The common symptoms could be left out of the introduction and discussed in the appropriate section.

:*Written like an essay rather than a webpage. Language such as “for example” not necessary.

:*Clinical Diagnosis was well structured and good use of pictures.

:*Clinical Manifestations could be simplified slightly in the table.

:*Some references need to be adjusted rather than just a web address.

--[[User:Z3217043|z3217043]] 08:42, 29 September 2011 (EST)

'''Peer Review'''

This wiki has obviously been given a lot of time and effort and it shows. The text isn't too heavy and I've learnt a few things about DeGeorge Syndrome. Very thoroughly researched and overall, looks and feels very neat and concise. A few points to be made:

:*No need to define congenital disorder. I recommend just leaving it out entirely.

:*Some pictures still need to be captioned even after addressed by Mark Hill. Who is that person in the History section? Angelo DiGeorge? Which one is he?

:*The student drawn images are the let-down. They look very rushed and haven't been given enough effort. The student drawn images on the wiki is also small, so to read the accompanying text by expanding the image, breaks up the flow of reading the wiki. It also hasn't followed the referencing format.

:*BACS- on beads technology image is a pdf file. Either put a picture in the designated area or remove the reference.

:*Amniocentesis doesn't have an image.

:*You should refrain from using the words "mental retardation" as this could be deemed offensive. Use "intellectual disability" as that is a more common term now used in Australia. Also use "learning difficulty" or "developmental delay". We should also encourage the use of person-first language e.g., "a child with an intellectual disability" rather than "intellectually disabled child". This promotes the idea that a person comes before their disability.

:*References section needs attention. Some referencing are not present at all in some casees.

--[[User:Z3293267|z3293267]] 07:12, 29 September 2011 (EST)

'''Group 2 Peer Review'''

• Your overall structure and layout of the page is really good! It’s really neat and all the images and text seem to be in proportion.

• All your pictures, graphs and tables show that you have a good understanding of this abnormality.

• The introduction gives a really good summary of the disease, however I think you should introduce the disease first and then go onto
to explain ‘congenital disorders’.

• Epidemiology could probably be broken down into sections, to make it an easier read and more interesting.

• The aetiology section needs an image to break up a large amount of text also to make it more interesting and informative.

• Good use of subheadings in the pathogenesis, very relevant! Student drawn images are good, could they be a little neater?

• Diagnostics test is really nice and clear, however consistency with the colour of the tables would be good.

• Clinical manifestations section has really good information, I think it could be structured better though, for example; only have the table describing each sign and symptom and then have another sub-heading related abnormalities where you could include ‘Teratology of Fallot as an example...’ (Just an idea).

• Current future research is obviously researched thoroughly, breaking it down into relevant subheadings would really improve it though.

• Make sure you fix up your repeated references. But good work overall!

--[[User:Z3289829|z3289829]] 02:40, 29 September 2011 (EST)

*Intro: Great intro, the picture is excellent and grabs your attention. Perhaps don’t start with a definition of congenital disorders. You can put that in the glossary or mention it after you have initially began discussing the disease.

*History: Love the timeline, clear, easy to follow.

*Epidemiology: Very word heavy which is not necessary for this section. Dot pints or some sort of visual representation would make it more appealing.

*Etiolgy: “ mentioned previously it has a prevalence of 1/2000 to 1/4000” This part is not necessary. Image of the gene would look good in this section. You refer to the disease as DGS (which is perfectly fine) but repeatedly refer to it as DiGeorge syndrome in the previous section, which can get a little confusing. Either use its full name or just the abbreviation.

*Pathogenesis:“As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion” probably unnecessary.
Excellent image, perhaps make it a bit bigger so that you can refer to it whilst reading.

*Diagnosis: The formatting of the text against it’s visual representation is fantastic and love the use of colour – refreshing! The use of colour can be expanded to the rest of the page to make it more cohesive. There is a an image heading with no image under the “ Amniocentesis” heading. There is also an image missing in the BAC’s image column replaced with a link- should fix this.

*Clinical manifestations: Once again great use of colour, but VERY word heavy. It shows that you have done a lot of research but it’s a lot to take in, you can definitely make it more compact.

*Treatment: I quite like this section. It’s informative and is formatted in a way that won’t bore you. The sections which have big blocks of text could benefit from this format. You need to choose a different colour for the block highlights though because you can barely see it.

*Research: Thorough research, very informative but again too much text. If you feel it’s necessary to keep the text you can break it down with word highlights/ bolding or dot points.

*Text/image: Great ratio except a few sections where the text can be cut down a little bit.

*Overall, very thorough, loved the colour and formatting and the student drawn image. Excellent work.

--[[User:Z3290270|z3290270]] 02:37, 29 September 2011 (EST)

'''Peer Review for Group 2'''

'''Peer Review'''
* Many of the pictures do not have a legend/explanation associated with them. However, the hand-drawn picture is underscored by a legend.
* The introduction is rather abrupt; definition of "congenital disorder" could have been a simple hyperlink or a note in the glossary.
* Is the historical background necessary? In the section, the photo of the two people is not explained.
* Section on epidemiology seems to cross over significantly with clinical manifestations.
* Thorough referencing throughout. However, some of the references appear strangely in the references section (could be a vestige of that crash a few weeks earlier?)
* The table in clinical manifestations is strangely.....implied. Section on Tetralogy of Fallot can be cleaned up in terms of layout.
* Inclusion of current and future research is noted, and well set out/referenced.
* Glossary is thorough.
* Overall, a very thorough and broad exploration of the topic.
--[[User:Z3290689|z3290689]] 00:11, 29 September 2011 (EST)

*I don’t think it would be necessary to start the intro with clarifying what congenital diseases are. It would be better if it starts with, ‘Di George Syndrome is a …’ sentence.
*In the intro, fix this sentence as it needs punctuation, ‘As there is currently no treatment education is vital to the wellbeing of those affected, directly or indirectly by this condition’
*Nice picture of Angelo, and also the history is presented well as it makes easy to read and follow.
*Information presented in the epidemiology section is interesting but not organised properly so it flows. Please fix this up.
*Etiology has some technical jargon that is not explained or put in the glossary. Please do so
*Thumb picture of the area where 22q deletion occurred doesn’t show when viewing the page.
*The first line of the Pathogenesis section is, I believe, not necessary as the section just before it just mentioned that fact.
*Punctuation needed for ‘ ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud’
*Pathogenesis/physiology easy to read and has good drawn diagram
*The diagnostics section has good information of how the tool works, what it detects and an image refering to the tool. However Amniocentesis section has no image and yet has a column for it. Please fix this if there is no image for it. Also the Ultrasound section should include what DiGeorge patients would have on Ultrasound scans.
*It is good that the clinical Manifestations section is presented in that way in the table as it explains the abnormalities really well.
*The four images in the Tetralogy of Fallot section may make the reader seem that one of these problems may occur, whilst all four problems are present in the TOF heart.
*The treatment section has information in regards to symptoms. This be under another subheading altogether and not under the treatment section
*Current and Future Research section provides the reader with a good image of the current status of this disease in regards to research.
*References are not properly formatted as repetition in the referencing could be seen. Please fix this.
*Please balance the text to image ratio as the page is text heavy and can be hard to read unless it is complemented with more images.
*Other than that good page.

--[[User:Z3291317|Z3291317]] 23:46, 28 September 2011 (EST)

'''Group 2 peer evaluation'''
*The introduction is done quite well. It is succinct and brief. You have done a very good introduction to the topics that your page is about to explore. Unfortunately you did fail to introduce some of the headings that your page have, like the diagnostic section. Aside from this it is a good introduction overall.
*Historical background is done very well. It has enough detail to see the ongoing achievements on the disease.
*The epidemiology was excellent. You have covered the demography of the disease and properly cited some of the facts that you try to get across. Revision of some of the sentences may be needed because some sentences are not expressed properly. Also it would have been really nice if you could incorporate some of the data that was mentioned in a more summarized form, like a table, dot points, or something. It just makes reading easier and less likely to get lost in the words
*I really like how concise yet very informative your etiology section. What would make this section better than what it is at the moment is an image that would complement the information, and also a bit of an explanation about some of the terms that is in there, like “hemizygous”.
*The Pathogenesis section is very well done. It contains enough detail that we get an in-depth knowledge about the development of the disease, and the images that were used are very helpful. One thing that would improve it though is that if you can elaborate further on the function of the TBX1 gene and how affecting the expression of this gene results to DiGeorge.
*The Diagnostic test section I think is perfect. The way the test works was described, and at the same time they were all related back to how this aids in the detection of the disease. The layout of the information is also very engaging.
*Clinical manifestation is very nicely done. The information was very descriptive and informative. It is also presented very well. Just one thing though is that there is no clear separation between two clinical outcomes, so it tends to get confusing sometimes when someone is reading it. I guess adding more space between would be a good idea.
*Treatments section is done quite well. If you could add a video of some of these treatments or even just a link to a video of it that would really make this section perfect.
*The research section is also very good, especially your insight to future direction of research on this disease. I guess it wouldn’t hurt to drop some current research articles within this section, which shows the readers that the information that they have just read is up-to-date.
*Glossary is a good idea, not really a big fan of it but good idea anyway.
--[[User:Z3290841|z3290841]] 10:20, 29 September 2011 (EST)

'''Group 2'''

Introduction: Introduction is good. The pictures look great.

Historical background: I like the timeline. I think the picture needs a caption underneath explaining who the people are.

Epidemiology: Needs some pictures to break up the text.

Etiology: This section is quite difficult to understand. I think a lot of terms need explaining eg. hemizygous deletion, microdeletion and halpingoinsufficiency.

Pathophysiology: This section is much easier to understand and flows quite well. The pictures should be bigger though.

Diagnostic tests: great section! Good layout and easy to read. The symptoms picture could be a bit bigger and it would be good if there were pictures for the bottom two.

Clinical manifestations: Again, great section. The table could use some more pictures though to balance out all the text.

Treatment: Needs some more pictures.

Current and future research: This section is quite well explained and has a good level of detail.
--[[User:Z3291324|z3291324]] 23:18, 28 September 2011 (EST)

'''Group 2:'''

•I’m not sure if you need the definition and explanation of congenital disorders at the very beginning of the page. The third sentence beginning with DiGeorge syndrome would make more sense as the beginning of the introduction.

•I like the use of images in the introduction and at the beginning of the page, but they are not referred to in the text and do not include captions. Perhaps you should include a brief caption under each image explaining what the image is portraying and why it is relevant.

•Be careful with the wording of some things, particularly in the introduction, i think some parts need to be edited and reworded as they are a little confusing to read.

•The fact that the timetable in the history goes all the way up to 2011 is good and this section seems to be referenced well.

•The student drawn image of the heart defects do not include the correct template that is required for proper copyright information.

•Good use of tables to break up the text, although the different colours is a bit distracting, i would recommend choosing one colour and using that throughout the page.

•The referencing needs to be fixed up as many references appear multiple times in the reference list.

--[[User:Z3332183|z3332183]] 21:24, 28 September 2011 (EST)

'''Peer Assessment Group 2-DiGeorge Syndrome'''
*The introduction and history look good with great use of images which makes for an interesting start.
*There could be at least one other picture in 'Epidemiology' and 'Etiology', otherwise it just looks like a big block of text
*The 'Diagnostic Tests' look good-the image for BACS still need to be uploaded
*The student drawn images are colorful however doesn't have copyright information-just states who drew them
*Some sentences seem incomplete or doesn't seem to convey a message e.g. "Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists".
*'Current and Future Research' has a lot of information however is it possible to condense it and give a basic summary instead. I understand that you have tried to do your best but it is just a lot of information. You might also wnat to consider using sub headings.
*The references need a bit of attention-you have a lot of links there which need to be changed to proper references
--[[User:Z3308968|Tahmina Lata]] 21:13, 28 September 2011 (EST)

'''Group 2 Peer Assessment'''
*Good introduction. Like the use of the image to grab the reader's attention but it might be a good idea to include one or two sentences in the text explaining the characteristic appearance of the patients and give the image a title (just to link the image to text straightway at first glance without having to click on the image to understand it's significance).
*Not sure if you need to explain the term 'congenital' in the introduction. Might be better to start straight away on the actual syndrome.
*Great job on the "Historical background" section. Maybe have small title for the image of Angelo DiGeorge.
*Good explanations in the 'epidemiology' and 'etiology' sections but the text is a bit too heavy. Try breaking it up with an image.
*Good use of images, table and the general arrangement and layout of information in the 'Diagnostic test" section. (Small spelling error in section name). Try to include an image in the "Amniocentesis" section as well to complete the table.
*Needs to explain the link in the "BACS- on beads technology" section and why it has been inserted.
*Like the student drawings in the 'tetralogy of fallout' section and good explanations of what is happening. Small grammatical error in the title (on instead of an).
*Good job on the 'treatment' and 'current/future research' sections.
--[[User:Z3291622|Z3291622]] 16:17, 28 September 2011 (EST)

'''Group 2'''

*The whole page is very nicely formatted
*Introduction is clear and concise although would it be more efficient to start talking about DiGeorge straight away rather then define congenital abnormalities?
*Historical background is obviously well researched
*There needs to be an image in epidemiology and/or etiology to break up the text or present some of the information in a table
*The pathogenesis section flows nicely although a few words need to be added to the glossary
*Great table for diagnostic tests- this makes it easy to follow
*A few more pictures would be great for clinical manifestation and maybe this would be better in dot points?
*Student drawn images of tetralogy of fallot were excellent
*Subheadings are needed for Current/future research
*Good project overall, obviously a lot of effort has been put into this.

'''Group 2 - Peer assessment'''

*The introduction is easy to read and understand. Maybe one thing you could improve on is the organization of the paragraphs because it looks abit too choppy as of now.
*The history looks amazing and well researched AND well referenced! Makes me believe and trust your project even more. Furthermore the picture on the right just makes the section more appealing.
*Epidemiology - the information flows well and examples are also mentioned which is nice to see
*Etiology - The information is ok but maybe it could be better explained with explanation of the technical terms within your texts
*Pathogenesis/Pathophysiology - the student drawn images look amazing! And the organisation of information is good. Maybe a suggestion would be to hyperlink some of the terms in the text because there was alot of technical terms to be scrolling down and up for.
*Diagnostic Tests - The layout is very appealing and consistent with the rest of the page. The spelling of the heading is wrong!
*Maybe for the glossary it would be a good idea to include headings such as "A", "B" etc
*Fixing up double referencing would be a good idea aswell

--[[User:Z3330313|z3330313]] 19:36, 28 September 2011 (EST)

'''Peer Assessment Group2'''

*Epidemiology – hyperlink technical terms to glossary?
*The pathophysiology/pathogenesis sections (pharyngeal arches onwards) needs to be linked back to the syndrome. You list it in the “genes” section then describe the normal development, but it needs to be described to what happens in the syndrome/abnormal development.
*Don’t forget to add in the missing images in the diagnostic techniques
*You have several (excellent) summary tables – I think the format should be consistent in each, would make it look/flow better
*Typical symptoms: Newborn section can be condensed
*Current and future research could benefit by being broken up a bit – maybe use subheadings, colour or bold main points – it just is a big slab of text and looks daunting to read.
*References: some just have the PMID number and need to be fixed so it reads the whole reference (just for consistency)
--[[User:Z3332824|z3332824]] 23:18, 27 September 2011 (EST)

GROUP 2: DiGeorge Syndrome
*I don't know if the congenital disorder definition is needed in the intro, maybe you can included in the glossary instead
*The image in the intro could use a legend
*Info in the intro is comprehensive and informative
*History section has got good, succinct information and i like the fact that it goes up to 2011, however maybe you can consider putting the timeline in a table. Image could also have a legend
*Epidemiology has been researched relatively well, info is comprehensive and flows well, however, could be improved with a graph of some sort to accompany info with a visual
*Etiology contains very descriptive, informative info, could be improved with an image of the chromosome and the area of deletion
*It would be a good idea if the acronyms are included in the glossary
*It is evident that the Pathogenesis/Pathophysiology section has been very well researched, maybe the "genes involved in DiGeorge syndrome" section could be formatted in a table
*The use of a table in Diagnostic tests is succinct and informative. You should check for spelling mistakes (Dianostic Tests is spelt wrong), images to accompany these tests are useful, however, again a legend for each of these would be help
*Image missing in the Amniocentesis part of diagnosis
*I don't know if the image link for BACS- on beads technology is really helpful
*Clinical manifestations has clearly been researched extesively, however, this section is very overwhelming,too much text in my opinion. It would be easier to read if it was summarised more, a graph may be helpful
*Treatment section is comprehensive and summarised well
*I have found that incidence has been mentioned in quite a few sections, is this really necessary? Can it just be mentioned in epidemiology?
*Current and future has got some good info but it is quite lengthy and could be better to summerise it a bit more so u don't lose the reader
*The last two images need to be referenced properly, with the template and correct referencing

Overall:
*The whole project has been researched very well
*Some of the images could use legends to describe what they are about and you could also consider moving the images around a bit so there's variety and making some of them a little bigger so their features can be seen
*Maybe acronyms could be included in the glossary
*some sections could be reviewed and info could be condensed
*references need to be reviewed and correctly structured (some work on this is required)
*You could improve this project by also linking the glossary terms to the text to make it easier to access, also some graphs could be used

--[[User:Z3331556|z3331556]] 22:51, 27 September 2011 (EST)

'''Group 2: DiGeorge Syndrome'''
*initial browse through the webpage: well balanced use of text, image, colour and table format.
*introduction: well summarised and good use of image. It is interesting and provides a good overview to the syndrome. Minor adjustment: give one or two examples of symptoms rather than providing a list.
*Historical background: good use of timeline, and layout.
* Epidemiology & Etiology: needs to define terms in glossary such as velocardial syndrome.
*I appreciate the subheadings used in the pathogensis section... it breaks up the mass of information, creates flow and also shows understanding. Needs to define a few terms in glossary such as: hypoplasia, hypoparathyroidism, parturition etc.
*Diagnostic tests: well set out, I think the use of colour is aesthetically pleasing and adds to the overall presentation of the webpage.
*Clinical Manifestations: well set out and good use of images. Table could benefit from use of borders, just to clearly separate the rows where the information appears to overlap.
*Current&Future Research: could benefit from formatting of previous headings. That is, in a table to break up the information, or by using subheadings
--[[User:Z3332327|z3332327]] 15:42, 27 September 2011 (EST)

'''Peer Assessment group 2'''
*Introduction is clear cut and enters the topic with easy understanding though should incorporate the image more, where the image has no description of what its suppose to explain where symptoms would link to the image would help a lot.
*Timeline used correctly in displaying the increased understanding of the disorder, image used was does not have a description so don’t know who is the discover right or left and what is the image suppose to show.
*Etiology refers to a lot of studies or research which is not clearly explained how the research shows the causation of the disorder with various results showing different reasons for causation
*athogenesis clearly links image to the common deletion of gene with clear explanations of genetics component of Digeorge syndrome. Though would become more fluid with introduction of embryological effects instead of leading to pharyngeal defects.
*Embryological component didn’t expand the defects of the pharyngeal arches as well not much of the parathyroid which is major component of calcium levels also poorly linked to the image without any mention of the figure.
*Diagnostic tests require an introduction onto the topic and techniques, where heading directly states the techniques without any understanding of what these means.
*Clinical manifestations describes information clearly though the congenital heart defects images would work better below the information, so text and information with image below.
*Treatment has image relating to plastic surgery could have a description even though it’s a example of surgery.
*Current and future research should be more organised instead of paragraphs have dot points to know the difference between new research and current also images not place in correct manner but in between the glossary as well.
*Referencing has not been done correctly with only links, repeats and some are even blank.
*Glossary not linked to the term or bolded to note that it’s in the glossary so while reading its confusing if you have no pathology background.
z3332250 23:42, 26 September 2011 (EST)

Group 2 Peer Review

*Well structured page in terms of headings, good choice of topics covered
*Do not need to define congenital abnormality. If you want to define it perhaps add it to the glossary instead?
*Symptoms in introduction would probably be best in another section
*Great images. Some need to be made bigger in order to easily read the detail on it
*Most images are on the right side of the page. Could you move them around a bit to make it visually more appealing?
*Faint colour highlighting under treatment needs to be made darker or deleted
*Some duplication in referencing
*Well researched-great
*Overall, an informative and well presented page. Just some minor details which need to be adjusted to finalise page
--[[User:Z3308965|Fleur McGregor]] 16:55, 26 September 2011 (EST)

===Comments on Group Project 2===

Group 2

*By looking at your page it’s clear you’ve performed extensive research on DiGeorge Syndrome, well done on the effort
*Spelling needs to be attended to....’Diagnostic Tests’
*The image included in the introduction could use a legend. Maybe you could refer to it in the introduction, but to me it’s just a picture of 3 babies
*Nice work on the historical background, grammar could be attended to easily, just some minor things really. This timeline could be better formatted though, maybe in a table. The image included here doesn’t have a legend or some form of description. Just a picture of two old-timers shaking hands.
*Epidemiology is great although it might be useful to include an image of some sort if possible (I’ve got the same problem) as it’s just a block of text
*Etiology is good, very descriptive and evidence of a well researched sub-heading.
*Diagnostic Tests – clever heading, clever formatting and great information. The images included definitely need legends and descriptions
*Current and Future Research heading could be broken up with some sub-headings
*Glossary looks great

--[[User:Z3331469|z3331469]] 06:57, 29 September 2011 (EST)

'''Strengths:'''
*Good placement of sub-headings and headings.
*I like how the introduction gives an overview of the syndrome.
*All images have copyright statements.
'''Weaknesses:'''
*The epidemiology and etiology sections seem like really wordy, overwhelming to read. It is paragraphed but maybe the paragraphs could be more distinct.
*It would be good to link the words that is defined the glossary to the glossary.
*Some of the references are not formatted properly.
'''Specific corrections:'''
*It would be good if introduction immediately started with what is DiGeorge Syndrome instead of leading up with the definition/characteristic of congenital disorder. This definition can be shifted to the glossary
*Just curious, it will be interesting to hear how different the first sound of a DiGeorge baby differs from a normal one.
*”Dianostic Tests” is spelt incorrectly.
*Instead of the sub-heading “Based on symptoms”, it could be “Symptomatic diagnosis”.
*What is “clinodactyly” in the description of the image under “based on symptoms”?
*The link under images for BAC subheading could go under external links section?
*Maybe the table under “Tetralogy of Fallot...in DiGeorge Syndrome” could be vertical instead of horizontal? It will look neater.

--Z3389806 06:40, 26 September 2011 (EST)

'''Group 2'''

*Introduction: good content, but the symptoms do not really belong there.

*Very nice historical section, nice to read

*Epidemiology and etiology seem almost like one big section. Maybe separate the content a bit more (no repetitions), and break it done with subheadings.

*Pathogenesis: includes helpful explanations and information, good use of reasonable subheadings. The drawn images could have been done with more
accuracy.

*Diagnostic tests: very nice informative section, good use of images to visualize the content. I think the choice of colour for the table could be
better, maybe another shade of the pink (darker, red...) that has been used for clinical manifestations. The green disrupts the flow of the entire page.

*Clinical manifestations: very nice section, precise information, good structure, useful images.

*Treatment: lots of information in a nice form, but the image would look better on the right edge (like the ones in ” research” ). Good use of subheadings.

*Research: good content, but would be easier to follow if you would break it down with subheadings.

*Glossary: looks good, but explanations like “malformation: see dysmorphia” should be avoided. It would be better to define every term separately.
--[[User:Z3387190|Z3387190]] 11:34, 25 September 2011 (EST)

'''Group 2 Critique'''

#• The introduction needs to be re-written in proper English. Some of the sentences don’t make proper sense. Also, the introduction should focus primarily on DiGeorge’s Syndrome and not explain what a congenital abnormality is
#• Historical background was good
#• Epidemiology should not explain clinical features, such as the baby making a noise which is nasally in tone
#• Aetiology is ok
#• Pathogenesis is quite detailed, however genes should be explained a little more clearly
#• Diagnostic tests section was impressive
#• Clinical manifestations was good
#• Treatment was good
#• Future research was good
#• Glossary was good

Images were appropriately used. --[[User:Z3289991|Robert Klein]] 18:36, 24 September 2011 (EST)

Group 2

Hey Group 2, firstly, well done on putting in the effort to create this page, it really shows your dedication and cooperation as a team! Here are some points I thought you could improve on to take this page to that extra level

#The key points relating to the topic that your group allocated are clearly described.
#* Introduction: Good overview. Image would look better with a border or as a thumb
#* History: Image too large, again maybe a border?
#* Epidemiology: Need to define velocardiofacial syndrome in glossary, also break it down into subheadings, eg. Incidence, Sex, etc
#* Etiology: Maybe better if in a table
#* Pathogenesis: I liked how you broke it doen into relevant subheadings. However, on a slightly negative note, the DG Pathophysiology Diagram looks rushed; I think it would've looked better if it was neater and easier to read.
#* Diagnosis: I felt citing was done poorly in this section, eg. the last 4/5 sentences in the FISH technique was not referenced at all, but again, this is very easily fixed. But good to see you have put in the effort and time
#* Clinical: Image of normal and cleft palate, if based on a textbook, I think you still need permission to adapt it (not quite sure, please ask Mark)? Table with 'How it is caused' would be better by itself as pathophysiology. Tetralogy of Fallot needs to be fitted into this section more smoothly, at the moment, it makes this section look very cramped. Also, the image regarding Tetralogy needs the correct format for student drawn images (ie. 'I (student no.)....)
#* Research: Maybe break it down into subheadings
#The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
#* Good images used with a nice range of self drawn images. However, no where in the page is there any reference to the images within the text.
#Content is correctly cited and referenced.
#* I feel citation needs to be improved overall. Lots of the sections have missing citations, especially Diagnostic Tests. Also in the reference list, refs 33,40,47, 49 have nothing in it (is it meant to be like this?)
#The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
#* Nice drawings, though some could've done better with more effort
#Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
#* Nice range of references used
#Relates the topic and content of the Wiki entry to learning aims of embryology.
#Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
#Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
#The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
#* It's very clear to me that you guys have worked together well and there has been good team work going on here to create this page, so well done
#Develops and edits the wiki entries in accordance with the above guidelines

"What would improve this project...."

* I feel your page is too heavy with the text, although there's a lot of images as well, it just doesn't quite balance out with the text.
* Also felt the different colours used for the tables, although adding a splash of colour to your page, brought down the overall quality of the page. However, please keep in mind that others might really like this approach of table formatting, it's just that personally, I think you could benefit from keeping all table colours consistent.
* Sometimes you refer to DiGeorge Syndrome as DGS and also as DS. Small and easy to fix, adds consistency
* Please don't forget to add the {template} for student uploaded images
* Definitely needs more words in the Glossary, such as Meiosis, de novo, microarray

--[[User:Z3291643|z3291643]] 16:02, 24 September 2011 (EST)

'''DiGeorge Syndrome'''

*The page has a really nice setout, the introduction and history looks really good. It has a nice flow.
*There could be at least one other picture in 'Epidemiology' and 'Etiology', otherwise it just looks like a big block of text
*The second last paragraph in 'Epidemiology' would be better suited in 'Clinical Manifestations'
*There's a bit of repetition between 'Etiology' and 'Pathology', it could be better to combine these
*The 'Diagnostic Tests' look really good, fantastic table and images
*I love the ultrasound picture
*The table in 'Clinical Manifestations' is really great with lots of detail
*I understand it's difficult to find, but more images in 'Clinical Manifestations' to give a visual representation would be fantastic
*"Teratoogy of Fallot as ''an'' example...."
*"Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists" This doesn't make muhc sense, that was from the 'Treatment' section.
*You had a lot of good information in 'Current and Future Research', but I found myself getting lost in all the text. Maybe subheadings would help?
*Don't forget to fix up the references, we don't want to see webpages as a reference even if it leads you to the paper
*Overall your page looks very good, some minor formatting would be useful

* A very clear format has been used. The mixed use of dot points and paragraph form were used appropriately in most sections and made your web-page easy to read and follow
* Good use of self drawn images, however the large image of Angelo DiGeorge seemed slightly irrelevant and took up a large portion of your page. Your first two images should probably have small heading below the image, just to make them a bit more clear to the reader.
* A coherent history/timeline was used.
* You’re referencing needs to be tidied up; there are multiple entries from the same source that tends to clutter your reference section. Some references are incompletely, or have no linking information such as reference 49.
* Your current research section was good but perhaps could have been tabulated just for easier reading and to really draw out the main points.
* Your table for clinical manifestations could have been summarised otherwise it should maybe just be written in paragraph form.
* Your page definitely reflects the time and effort you have placed into the assignment. I really liked the range of formatting you used and the use of colour made your page easy to read and follow. Another great feature was the section based on the example of Tetralogy of fallot. It was interesting to read how other defects that we have discussed in class, linked in with your studied abnormality.
--[[User:Z3332629|z3332629]] 15:21, 22 September 2011 (EST)

'''Group 2'''
* Structure- headings, subheadings and tables make this a very readable page with a nice flow.
* It may be nice to have the colours of the tables continuous throughout the page. eg only yellow.
* Ensure all your pictures are correctly referenced, it would be a shame if Mark deleted them, as they add a lot to your page and aid in read ability.
* not to text heavy which is good!
* Intro well written an gives a good scope to the syndrome.
* Dianostic Tests: I like this section and that the images accompany the text.
* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome: Very interesting example, great pictures!! very well drawn. maybe you could put the pictures vertically down the page.
* Current and Future Research section it might be nice to add subheadings of what the research is.
* Good use of citing/ referencing it gives your page authority/ believability, just beware of the doubling in your reference list.
* It might nice to collate all the genetic info into one section.

*'''Introduction''': Good in general. Last paragraph needs a slight revision in sentence structure. "The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality" - significant in what way? As in they have a big impact? And also, poor quality of what? Life?
*'''Historical Background''' : Very detailed, which is nice. The layout isn't quite 100% consistent, which should be easily fixed. Some findings could do with further explanations to show how this lead to progress. Also, some terms should be linked to the glossary, or in some cases, a mention that subsequent paragraphs will provide more detail.
*'''Epidemiology''': Seems fine to me, though a figure would be nice to break up the text.
*'''Etiology''': Links to glossary needed. This part contains many technical terms that aren't explained. Also, is it known why this region is specially prone to rearrangements?
*'''Pathogenesis''': Seems to repeat what was said in etiology, but in more detail. Well written and explained.
*'''Diagnosis''': There's a typo in the title - Dianostic instead of Diagnostic. You might want to split your table into prenatal and postnatal, as otherwise it is a bit confusing to read "ultrasound" as a diagnostic tool. It does become obvious very quickly that it is prenatal, but just for clarity's sake, splitting the table could help, especially as you mix pre- and postnatal tools throughout the table. Also, just be careful about using capitals - in the beginning you say BACS, and later you say BACs. BACs is the plural of BAC, which is what Bacterial Artificial Chromosome stands for, not BACS. Your explanations in this part of the table are quite technical - you might want to explain more terms in the glossary at least.
*'''Clinical Manifestations''': Very thorough and detailed, which is good. I like the table, but including some more figures might help break up the long bits of text.
*'''Treatment''': Also quite thorough, well explained.
*'''Current and Future Research''': Very good and detailed, well explained. Maybe include headings for the different sections, so it's easier to see what each is talking about?
*'''Glossary''': More terms need explanations.
*'''References''': Seem fine in general, though there are a few links that probably should be cited differently. Also, some references link to emptiness?
*General: All the tables are slightly differently formatted, you might want to get that more uniform.

'''Group 2 Critique'''

*Do the symptoms need to be listed in the introduction, or is that repetitive since it’s also in the etiology portion?
*Historical Background- Overall this section looks good, but each bullet needs to be consistent. Ie:
-only the first few bullets have a colon after the date while the others don’t. I think either a colon or a – mark should be used after the date to show a better separation.
-some sentences don’t end with periods.
*The Etiology and Epidemiology sections have good content, but it looks rather wordy from an aesthetic viewpoint. A picture or some bullet points for separation might be helpful to solve this.
*For the image Chromosome22DGS.jpg, surely you didn’t know this layout from your own knowledge… Wouldn’t you have had to copy this image from another source, and wouldn’t that source also need to be cited as well?
*For terms that are in the glossary, it would be good to format the words in the wiki so that when you click on them it takes the reader directly to that term in the glossary.
*Several of the references aren’t formatted correctly, or are missing entirely.
*This might be a bit nit-picky, but for the references given throughout the wiki, there isn’t any consistency. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
--[[User:Z3391078|Ashley Smith]] 11:05, 27 September 2011 (EST)

'''Peer Assessment: Group Project 2'''
*The information in the introduction is good, however you may want to introduce the syndrome in the first sentence and then explain what congenital abnormalities are.
*The timeline is clearly set out, maybe decide whether you want to put a colon or not after the date to keep consistency.
*The diagnostic tests section has a good balance between being informative through pictures and text. It would be good to place an image for amniocentesis and also replace the link on BACS technology to either have an image and use the paper as an extra link or to replace the heading of 'image' to 'additional information' or some such title.
*Maybe an image could be inserted in the section on etiology or epidemiology. An graph to accompany some of the statistics might make the information more accessible.
*Under the information of the images you have uploaded, you need put <nowiki>{{Template:2011 Student Image}}</nowiki>.
*In the glossary writing "A" above the group of A words and so on and so forth for the rest of it, would make it easier for the reader to quickly find the desired word.
*Some of the references should have more information in them (references 1, 2, 3, 4, 5, 46, 47, 48, 49 and others).
*The references should not be duplicated and can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.

--[[User:Z3217345|z3217345]] 12:43, 27 September 2011 (EST)

'''Group 2:'''
* The introduction is very easy to read and is accompanied by a great image, although this image should include a legend. It would be beneficial to link the image with the symptoms mentioned in the intro and to only mention a couple of important symptoms instead of listing them all here and having to repeat yourself later on.
* Very extensive historical background. Very impressive and well referenced. Image needs to include a legend.
* Epidemiology needs to be proof read as there are a couple of little mistakes that lessen the value of what is a really well researched section; “Due to the fact that 22q11.2 deletions can also resulting in signs that...”, “It has been well documented that there individuals who...” and “which may be resultant form a learning dysfunction or heart disease.”
* Etiology is also done well and is very comprehensive, however there is a spelling mistake “interstital deletions of chromosome 22” so make sure you re-read this section too.
*An image either in epidemiology or etiology would help break up a huge chunk of text.
* Pathogenesis/Pathophysiology section is very strong with great student drawn images relevant to the text. Only suggestion is to hyperlink glossary terms since there are a lot of terms in this section which need to be explained further.
* Diagnostic Test section is done well with a well formatted table making it easy to read. Some images are missing as I’m sure you’re aware of and make sure to include <nowiki>“{{Template:2011 Student Image}}”</nowiki> for these images.
* Clinical manifestations; perhaps the table describing the symptoms could immediately proceed after “The most common signs and symptoms include:” instead of having the symptoms in dot points and repeated twice. The student drawn image may benefit from pointing out that A is at rest and B is during normal speech – just to clarify. I also noticed a spelling mistake “In more severs cases..” so just make sure you go over this section with a fine comb.
* Treatment also had a couple of little mistakes for example “and consult various specialists, from example a cardiologist”. A legend for the images here would improve this section.
*Current and future research is very extensive and well researched.
Hats off to you guys!

Peer Assessment

* interesting layout
* pictures were good examples
* maybe need a touch up with the referencing
* i liked it how it was worded in a way that could be understood for a wide audience however the structure and format could not be read so easily

--[[User:Z3060621|z3060621]] 20:37, 28 September 2011 (EST)

--z3290815 14:09, 28 September 2011 (EST)

'''Group 2'''

'''*The key points relating to the topic that your group allocated are clearly described.'''
Well described, but very hard to follow at points due to volume of text.

'''*The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'''
Tables include too much information. it should summarise the main points, for large chunks of text put it in the body of the wiki.

'''*Content is correctly cited and referenced.'''
Fix up some references - there is duplication and links provided in place of a reference as well as missing references. reference for Chest PA 1.jpeg, DiGeorge-Intra Operative XRay.jpg and FISH for DiGeorge Syndrome.jpg should be fixed. also include {{Template:2011 Student Image}} in all images.

'''*The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.'''
Good diagram explaining pathophysiology but it can be neaten up by doing the text on a program (paint would suffice).

'''*Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'''
Very high research volume put into the page but there is too much text going on. Try using some sub-headings to break up the information into easily digestible sections. It also allows for easy location of specific sections.

'''*Relates the topic and content of the Wiki entry to learning aims of embryology.'''
Good information on genetics but if possible say how the deletion occurs?

'''*Develops and edits the wiki entries in accordance with the above guidelines.
Apart from small things, the wiki has been edited well.

--z3329495 21:09, 28 September 2011 (EST)

==The final Pimp==

Hi guys, how is your week end? Thursday is the due date for our side and I think it's looking great already. I just read through it all and noticed the following.

1) I changed 1/4000 to 1/2000 to 1/4000 in the introduction (hope that's ok) this way we are all saying the same.

2) I think we should still change what Mark Hill suggested for the "Historical Background" section: date first and picture not within the text. I'm happy to do it, just thought I should check with you Sarah...

3) There are still some references that need to be fixed

4) Do you guys want to add some of the scientific words that you used to the glossary, otherwise that would be incomplete

and 5) Mark Hill wanted to help me with the tetrallogy of fallot picture but I think he forgot, so I'll ask him again after the lecture and than it's going to be a fancy scenic view picture.

So, let's do the final pimp: I wouldn't leave it until Wednesday because the system is probably going to crash on that day;)
Let me know if you need any help and let us know if you think something els should be changed/edited as well.--Anna Marx 16:40, 18 September 2011 (EST)

Hi Anna, yup, 1) sounds fine; we still have that issue with the ultrasound image and removing the text from the background don't we? I'll have a trawl through the references later and see what I can do, and for most of the scientific words I know the sections that I've done have their wording in there; everyone else just has to go through it a bit?

btw guys it looks fantastic :D --[[User:Z3288827|Leonard Tiong]] 10:51, 20 September 2011 (EST)

hey i changed up the history and put the tables in different colours so they dont look like they ar all the same thing if you know what i mean?? anyway... hope its ok :) --[[User:Z3288729|Sarah Jenkins]] 13:20, 21 September 2011 (EST)

Cool, looks good. I like the colours :) --Anna Marx 11:47, 22 September 2011 (EST)

==Question==

Hi Sarah, I have a question, do you think we can split the baby pictures that you used in you introduction. Sounds super lazy of me, I know. But my problem is, that I would like to put one in my section about facial abnormalities and I couldn't find one that shows these abnormalities well and that has copyright. I wanted to use the one that is in the epidemiology section but I think Leonard wants to keep it there??? Don't really know. Any way, if we would split yours, you could get one baby and I would use the other one. What do you think? --Anna Marx 22:01, 10 September 2011 (EST)

Hey Anna, I wouldnt have a problem doing that but it is one image within the journal and im not sure if we are allowed to manipulate the images? I will talk to Mark about it and if it is ok then i will cut it up for you and put one of them in your section :) Hope this helps. --[[User:Z3288729|Sarah Jenkins]] 08:54, 11 September 2011 (EST)

Hi anna, I SAID down there that you could use the image! :D '''Feel free to take it because I also think it would assist in that section'''. I'm just squabbling over the image filename with Mark because it's not descriptive. There's another one there that has a picture of another fellow whose facial abnormalities are quite apparent so I was thinking to use them as they've got a pretty strong contrast between the two of them. What do you think? I've also uploaded my drawings, they took ages and they look so crap :( But I've been scrolling through some of the other groups and we're in good shape guys! It looks really great :) I'll sort out my glossary terms tomorrow morning. Excellent work over the break guys. --[[User:Z3288827|Leonard Tiong]] 21:42, 11 September 2011 (EST)

==Update==

Hey, how are you holidays coming along? I just wanted to let you know four things;):

1. I am "done" with clinical manifestations. So you can have a look if you like it... I'll still upload at least three images of which two are drawings.

2. So we have got the drawings covered. I just have to scan them.

3. I'll still work on the treatment section tomorrow.

4. For the matching up of our individual sections, Sarah would you mind to change the typical symptoms in your introduction to the same ones I talked about in detail. I think it would look good. Anyway...It would be the following ones:
* Congenital heart defects
* Defects of the palate/velopharyngeal insufficiency
* Recurrent infections due to immunodeficiency
* Hypocalcaemia due to hypoparathyrodism
* Learning difficulties
* Abnormal facial features
Have a good brake guys, --Anna Marx 2--[[User:Z3288827|Leonard Tiong]] 10:45, 8 September 2011 (EST)0:22, 3 September 2011 (EST)

Hi, so I have done my treatment section as well including references and glossary. --Anna Marx 21:43, 6 September 2011 (EST)

Thanks Anna :) I will change it all up now. I know you are doing the drawings but the rest of us need to get some pictures up if possible? --[[User:Z3288729|Sarah Jenkins]] 08:55, 7 September 2011 (EST)

Hey guys, i have a few pictures to load up, so will get onto that..

Was also going to ask if anyone came across anything good under the future research heading? I have found a bit, struggling a little though, and i feel like there should be more.. Just wondering if anyone came across any interesting points/areas when doing your own research.. Also had the suggestion that maybe pathogenesis/etiology could fall under the same heading, as they are both very similar topics, and maybe I/we could write something up more focussing on the pathophysiology as another heading... I know Anna does talk about this a bit in her clinical manifestations, but thought there was room to potentially cover pathophysiology in a bit more detail under anther heading, and we could maybe reduce the detail in her table as a result, make it a little less large.. let me know what you think..

--[[User:Z3288196|Timothy Ellwood]] 09:21, 7 September 2011 (EST)

really good job with everything at the moment it looks really fantastic. tomorrow is my allocated day to get through this work, so I'll be sure to get a large chunk of my sections "done". Anna, excellent work done so far, it looks really fantastic. Umm tim, as for your struggles at the moment, I'll be sure to keep that in mind when I'm looking at my other papers; just having a look at the moment and I'll get a little more help for you tomorrow, if possible. looking great so far guys! --[[User:Z3288827|Leonard Tiong]] 14:23, 7 September 2011 (EST)

hey tim, another idea is to change the heading to 'current and future research' that way you can look into what is being down now and very recently. that will give you heaps :) --[[User:Z3288729|Sarah Jenkins]] 07:13, 8 September 2011 (EST)

ps. i used a wikipedia image so we cant put another one up now... hope this isnt a problem --[[User:Z3288729|Sarah Jenkins]] 07:14, 8 September 2011 (EST)

By the way Anna, I'll probably draw my image and upload it later this evening; I can't find any images that best match what I want without having to go through all of the copyright information, so I'll just draw it :D slowly trawling through my sections. Epidemiology might be a bit short (as there's not that much you can write on it) but the pathophysiology section should be quite lengthy (Hopefully :) ) --[[User:Z3288827|Leonard Tiong]] 10:45, 8 September 2011 (EST)

Slowly going through pathophysl now. by the way guys, '''Mark Hill has put something at the top of our page if you haven't already seen it. I think it would be best to implement the points that he has noted; they're relatively minor, if you guys haven't gotten round to doing it by say, tomorrow (?) then i'll see if I can change it :) '''
I'm finding this INCREDIBLY FRUSTRATING that I can't save the material but no one else seems to be online. :(

Hello! I just thought let you know that I did two drawings which I plan to put into the table under clinical manifestations. And I also have images on my computer, that also go into the table. I just have trouble uploading them (may be it's because I have a mac... not sure). But in case I don't manage I'm sure one of you could help me on Thursday. I'll also try to make the tables a bid lighter. --Anna Marx 17:15, 8 September 2011 (EST)

ALL RIGHT, so I have change my tables. I have tried to explain it in a way so that people with no science background should understand it. Some words I had to leave in because that is just what it's called... Any way I think it'll be even better once I have the pictures in as well. If you like to have some thing changed let me know. --Anna Marx 19:12, 8 September 2011 (EST)

Hi Anna, just asking what have you done in your drawings? I drew the chromosome and the area in which deletions were most common, it's not the greatest drawing but I leave it up; and, I was thinking of drawing the presenting symptoms of DiGeorge (there aren't that many anyway). What do you think? Let me know what you've gotten down :) --[[User:Z3288827|Leonard Tiong]] 23:06, 8 September 2011 (EST)

Hey guys I will fix up what is wrong with my bits tomorrow afternoon sorry. I have had other things to do this week as well. Mark's comments are valid and relatively simple to fix luckily. --[[User:Z3288729|Sarah Jenkins]] 00:55, 9 September 2011 (EST)

Hey guys. Looks like Dr Hill's criticism was relatively minor which is great. Should be easy for us to fix. As for the future research I have found a heap more stuff, seems as if alot of current research on this deletion is in relation to schizophrenia, but have found alot more stuff relating to Digeorge. Suggestions still welcome of course. Sarah your suggestion is fanatastic, more relevant as well. I will change that now. As for my last section and images I will get to that tonight hopefully, just have been working full time over the break..
--[[User:Z3288196|Timothy Ellwood]] 10:24, 9 September 2011 (EST)

Hi, I have changed my table even more - hope you like it. In the end we might have to match the colours but we cna do that together in the lab. How is doing epidemiology, I planned on using exact the picture for clinical section where I describe facial abnormalities. That was the best one I found - that other children looked so said. Any way, may be I can steal it or I try to find another one.
Tim, I also thought I suggest, if you still can's find enough you could look into more specific stuff. For example into research of how to improve cardiac surgery, treatment for immunodeficiency etc... there should be loads out there. Any way, we are doing great team! --Anna Marx 16:40, 9 September 2011 (EST)

Hey guys,

Yeah, just have to put in a couple of images to help break things up. I've been looking at the things that the other groups have produced from the previous years and it looks really great, I think our project is beginning to look somewhat like that (which I feel will do us good!). I'm still trawling through some of the references and images; as for the epidemiology section, I've written all that I can find on that... if you guys want to put anything else in there feel free too but I feel there's a lot of repetition throughout the literature and what I've written covers epidemiology quite well. Having looked at some of the other groups we've done a really great job, anna, feel free to upload those pictures so that we can all have a look :)--[[User:Z3288827|Leonard Tiong]] 22:09, 9 September 2011 (EST)

Hi yeah, I will on Monday. I am sorry that I can't do it earlier! --Anna Marx 21:42, 10 September 2011 (EST)

==week 6==

hey awseome work with the page but u have to put references on your work asap or we will get done for plagiarism --[[User:Z3288729|Sarah Jenkins]] 07:18, 23 August 2011 (EST)

Yep, I'm working on it now. Is tim still working on the project with us? He hasn't written anything for his sections yet.. --[[User:Z3288827|Leonard Tiong]] 08:50, 1 September 2011 (EST)

Hey guys. Yeh im working on my sections, havnt posted anything up at all coz have been sick for the last week or so, and then working all weekend. I plan to have the majority of mine done by tonight though, then will start the editing process overall later in the week i guess. Sorry to hold things up.
--[[User:Z3288196|Timothy Ellwood]] 08:57, 5 September 2011 (EST)

== Discussion==

Hey sorry I missed the lab class today, im having some family troubles but will be back in sydney on the weekend. If somebody could let me know what happened etc I would really appreciate it. Are we still doing Duchennes or did another group choose it too?

Hello,
I hope that you family gets better soon. So, we had to flip a coin with another group about Duchennes and unfortunately lost. We decided that we'll all think about what else we would find interesting until Sunday and post our suggestions here so that we can make a decision about it on Sunday or early this week. If I understand right, it would be the best if we find a disorder that is really caused during embryonic development. Hence Duchennes and Thalassamia for example are not the best ones any way.
Have a good week end guys.
--Anna Marx 18:51, 11 August 2011 (EST)

Thanks Anna, I will have a look at some now and see what I can find :) --[[User:Z3288729|Sarah Jenkins]] 15:20, 12 August 2011 (EST)

== New Ideas==

* Conjoined twins. It results from abnormalities in the original process of cell division.

http://www.ncbi.nlm.nih.gov/pubmed/15278382

* Spina Bifida is due to incomplete closing of the neural tube

http://www.ncbi.nlm.nih.gov/pubmed/19918803

http://www.ncbi.nlm.nih.gov/pubmed/21790891

* Cri Du chat syndrome

http://www.ncbi.nlm.nih.gov/pubmed/21112524

http://www.health.medicbd.com/wiki/Cri_du_chat

* Ectodermal dysplasia

http://www.health.medicbd.com/wiki/Ectodermal%20dysplasia

http://www.ncbi.nlm.nih.gov/pubmed/21814340

== Another Idea ==

Hi! I think there are so many interesting congenital diseases/abnormalities which we could choose. I have had a look around and I think that [[DiGeorge Syndrome]] would be a good topic! First, it is due to some abnormalities in the chromosome 22, hence there is a genetic component. Second, it occurs in 1 of 4000 people and there are lots of variations from person to person, hence there will be a lot of research and a lot of information that we can use. Third, a defect in the migration of neural crest cells is included, which means it happens during embryonic development. So, may be you can have a look into it and let me know what you think.
Have a good week end, Anna
--Anna Marx 15:03, 13 August 2011 (EST)

I had a quick look and this looks like a good one. I'm happy to do DiGeorge if everyone else is?? --[[User:Z3288729|Sarah Jenkins]] 10:40, 14 August 2011 (EST)

Ok, sounds good! What about the rest of the group? Do you guys like DiGeorge too? I am open for any other suggestion, however I would suggest, that we make our decision soon, so that we can start our research about it. So I'll open a little "Agree with you signature" box and wait what happens :) --Anna Marx 17:41, 14 August 2011 (EST)

== DiGeorge Syndrome ==

If you like to make DiGeorge Syndrome to our team project, sign below.

--Anna Marx 17:43, 14 August 2011 (EST)
--[[User:Z3288729|Sarah Jenkins]] 19:09, 15 August 2011 (EST)
--[[User:Z3288196|Timothy Ellwood]] 09:30, 16 August 2011 (EST)
--[[User:Z3288827|Leonard Tiong]] 00:21, 17 August 2011 (EST)

==Project Plan==

I think it is important to keep moving on with the project. We need to quickly agree on things and get the job done. From previous experience, getting the work done early is a benefit to everyone involved. The project needs to be broken down into subheadings. I have listed some below which need to be covered without doubt, and I am open to other ideas as well. If everyone could pick 2 that they are happy to take on it means that everyone will have a round about even job. I spoke to [[Anna]] Earlier and she said she was willing to do the drawings. Is that still ok? If so I think its fair that you only have to do one subheading of theory work.

* Introduction (Sarah)

* Historical background of the disease and its research (Sarah)

* Epidemiology (Leonard)

* Etiology (Tim)

* Pathogenesis (Leonard)

* Clinical manifestations (and explanations of these) (Anna)

* Treatment options if available (Anna)

* Diagnosis of the disease, pre and post natally (Sarah)

* Further research possibilities (Tim)

* Image (Anna)

I would prefer it if i could do the introduction, historical background and diagnosis. I am willing to do 3 because the introduction is a pretty easy one. If anyone has a problem with this let me know. I also think first in best dressed to picking topics. I only think its fair and if not, we can sort it out later.
--[[User:Z3288729|Sarah Jenkins]] 19:09, 15 August 2011 (EST)

Hi, thank you for the layout. I think it is a good start!
I an still happy to do the drawings. So let me know if you have specific wishes or if you have suggestions of what we/I need to draw. I can also do Clinical manifestations and treatment options, which would make it three as well. However I thought pathogenesis will be a big one because that would include all the genetics. May be it will be enough if one person on it's own. Otherwise etiology would go well with it, leaving epidemiology and further research for the last one;) Further research might be big too... However, I am open to adjust. --Anna Marx 21:03, 15 August 2011 (EST)

Hey guys, sorry I haven't been in touch, just been busy with some orchestra stuff outside of uni. The stuff so far sounds great, I'll get to work tomorrow getting some papers together and seeing what I can find out about the condition. I wouldn't mind doing the epidemiology and pathogenesis sections - Anna, I think he said we only had to submit one self-drawn picture but I wouldn't mind doing some either, since I draw everything for anatomy :D either way, let me know what you think! So far things sound really great, thanks for getting so much done and once again my apologies for not having chucked in my two cents earlier!
--[[User:Z3288827|Leonard Tiong]] 23:02, 15 August 2011 (EST)

Awesome, now that we are on the way there it should be easier to focus our reading. We also need to do a glossary, and i think its easier if we do it as we go. so when we come across words that need a definition (to non science people) just chuck it in the glossary. even if we define it later, having it there is easier than having to go through and pick them out later. :) thanks for being so enthusiastic. :) --[[User:Z3288729|Sarah Jenkins]] 07:13, 16 August 2011 (EST)

Hey guys, sorry for the late addition, busy with various other things as I'm sure most of you are! Im happy to take the two headings that are left over. Also it looks like some of the other headings might contain alot more work than the two I've got, i think the further research one could potentially contain alot but unsure at this stage.so i would be happy to share another one and help out if anyone would like?? It was suggested above that Pathogenesis and etiology could go well together.... Let me know. Glossary sounds like a great idea!

Also i thought it would be a good idea if before the lab on Thursday if we could each try to find say 2 articles that relate to the heading we have selected.. Similar to what Dr Hill asked us to do for last week but now we have our topics etc. it should help to get us up and running.
--[[User:Z3288196|Timothy Ellwood]] 09:29, 16 August 2011 (EST)

I have set up sections below for us to put any references we find. it makes it easy to find the ones we need, and if other people come across good references for a topic other than their own it allows us to share :)--[[User:Z3288729|Sarah Jenkins]] 15:22, 16 August 2011 (EST)

Hey tim, more then happy to switch doing etiology with you but I wouldn't mind doing both together either. We'd better tell Mark to change our title over to DiGeorge's syndrome, I'll get some papers up in the mean time but will be really busy until thursday! :(

Update - Hey guys, just found a rather general article on DiGeorge but thought it was interesting, will leave the link here, if you guys got a moment have a trawl through :) I don't know what I'm still doing up at this hour :\ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954737/?tool=pmcentrez I'll have a read of it tomorrow morning :)
--[[User:Z3288827|Leonard Tiong]] 23:55, 16 August 2011 (EST)

Assuming that was Leonard above? I dont mind at all, maybe we can talk about it on thursday and sort something out. In the meantime i guess ill try find whatever articles I can on both topics.

Also just thought i would point out this resource [http://www.nationwidechildrens.org/22q11-deletion-syndrome], as it says that DiGeorge Syndrome (DGS) falls under the the title of 22q11.2 Deletion Syndrome, which apparently includes a number of other very similar disorders such as Velocardiofacial Syndrome, Conotruncal Anomoly Syndrome, Autosomal Dominant Opitz G/BBB Syndrome, Cayler Cardiofacial Syndrome and Shprintzen Syndrome. Not sure if we wanted to include these in our research, but worth considering I think as there could be alot more research under one of these titles and allow us for a broader and more accurate picture of the disorder as a whole.

--[[User:Z3288196|Timothy Ellwood]] 15:21, 17 August 2011 (EST)

Good work guys, our project has taken shape already. I have now changed our project title, hence we should be safe and good to go! See you tomorrow in the lab --Anna Marx 20:19, 17 August 2011 (EST)

Things are looking really splendid guys, I'm starting my sections now but it doesn't seem like there's that much for me to write on. I'll try to see if i can spruce things up a little bit more. Referring to several textbooks (anyone got any suggestions?) for some of my basic info, and I'll find original sources later. But yeah, difficulties in trying to find specific information. Especially since there's so much overlap at the moment with the other different names. So far the four major ones that I got (I know you guys have included them) but four definite names involve (obviously) DiGeorge syndrome, Velocardiofacial Syndrome (VCFS), Conotrunchal anomalies facie syndrome (CTAF) Syndrome, and CATCH22. I don't think CATCH22 is a diagnostic name but rather a mnemonic that helps them remember the symptons of DiGeorge. Onto my writing! Just another thing that I'm well aware of, I haven't put many references into my work as of yet, still trying to find the best sources for the information. I've got a bunch of them written down and need to just go through them to make sure that I've the right sources from the right place but my laptops out of battery at the moment :( I'll try to get that done by tonight or tomorrow. :) --[[User:Z3288827|Leonard Tiong]] 18:25, 22 August 2011 (EST)

== Review Article ==
Hey guys, just found a review article that I thought was rather interesting, it's an animal model for Duchenne's muscular dystrophy[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022202/]. I also found a primary journal article that discusses drug delivery for the condition [http://www.jstage.jst.go.jp/article/bpb/34/5/712/_pdf]. I will print these articles for myself tonight and give them a quick read tomorrow and then paste a quick summary of the articles here just for you guys to consider :)

'''Review''' [http://www.ncbi.nlm.nih.gov/pubmed/21274260 Mammalian models of Duchenne Muscular Dystrophy: pathological characteristics and therapeutic applications.]

'''Primary''' [http://www.ncbi.nlm.nih.gov/pubmed/21681700 Detection of duchenne/becker muscular dystrophy carriers in a group of Iranian families by linkage analysis.]

--[[User:Z3288729|Sarah Jenkins]] 10:00, 6 August 2011 (EST)

'''Primary''' http://www.ncbi.nlm.nih.gov/pubmed/15991868 Diagnosis and management of Duchenne muscular dystrophy in a developing country over a 10-year period.

'''Review''' http://www.ncbi.nlm.nih.gov/pubmed/14526374 Advances in Duchenne muscular dystrophy gene therapy.

--Anna Marx 12:52, 8 August 2011 (EST)

----

'''Duchennes Muscular dystrophy'''

----
--[[User:Z3288827|z3288827]] 21:53, 8 August 2011 (EST)

== Review Article ==
Hey guys, just found a review article that I thought was rather interesting, it's an animal model for Duchenne's muscular dystrophy[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022202/]. I also found a primary journal article that discusses drug delivery for the condition [http://www.jstage.jst.go.jp/article/bpb/34/5/712/_pdf]. I will print these articles for myself tonight and give them a quick read tomorrow and then paste a quick summary of the articles here just for you guys to consider :)

== References ==
[1] Nakamura A., Takeda S.; Mammalian Models of Duchenne Muscular Dystrophy: Pathological Characteristics and Therapeutic Applications, J. Biomedicine and Biotechnology Vol. 2011, Article ID 184393

[2] Yukihara et al; Effective Drug Delivery System for Duchenne Muscular Dystrophy Using Hybrid Liposomes Including Gentamicin along with Reduced Toxicity, J. Biol. Pharm. Bull, Volume 34, No. 5 pp. 712-716

== Found References==

===Introduction===

[http://www.ncbi.nlm.nih.gov/books/NBK22179/ DiGeorge]

[http://emedicine.medscape.com/article/135711-overview DiGeorge Anomaly]

===Historical Background===

=== Epidemiology===

[http://emedicine.medscape.com/article/886526-overview#a0199 Epidemiology]

===Etiology===

A Genetic etiology for DiGeorge syndrome [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682598/]

Inactivation of TGF􏰀 signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome [http://genesdev.cshlp.org/content/19/5/530.full.pdf]

A deletion in chromosome 22 can cause digeorge syndrome [http://www.springerlink.com/content/r85p0r5q05rj6w88/]

DiGeorge syndrome phenotype in mice mutant for the T-box gene [http://webcourse.cs.technion.ac.il/234523/Winter2002-2003/hw/WCFiles/DiGeorge.pdf]

=== Pathogenesis===

[[http://www.ncbi.nlm.nih.gov/pubmed/20833244 Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: patterning, proliferation, and mitochondrial functions of 22q11 genes]]

[http://emedicine.medscape.com/article/886526-overview#a0104 Pathophysiology]

===Diagnosis===

[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=10600329&ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Diagnostic Criteria]

===Clinical===

{http://www.ncbi.nlm.nih.gov/pubmed/19665396 Seizures and EEG findings in an adult patient with DiGeorge syndrome: a case report and review of the literature.]

http://www.chw.org/display/PPF/DocID/23047/router.asp

===Treatment===

===Research===

This looks like an excellent resource, listing over 100 research papers on nearly every aspect of DiGeorge from the 70's to present. [http://omim.org/entry/188400]

Deciphering DiGeorge Syndrome: Big Advances In Understanding Microdeletions [http://www.sciencedaily.com/releases/2005/03/050308134838.htm]

== Images==

FISH carried out to detect DiGeorge syndrome. FISH is abbreviated as fluorescent in-situ hybridisation and is carried out to detect abnormalities whilst babies are still developing in the womb. --
[[Image:FISH_for_DiGeorge_Syndrome.jpg|400px|left|FISH to detect DiGeorge syndrome[1]]]
[[User:Z3288827|Leonard Tiong]] 00:17, 17 August 2011 (EST)

[[File:DiGeorge T cell receptor Diversity post thymus transplant.jpg|400px|left]]

--[[User:Z3288729|Sarah Jenkins]] 08:54, 18 August 2011 (EST)

Facial manifestations of patient with DiGeorge Syndrome

[[File:Facial manifestations of patient with DiGeorge Syndrome.jpg|left]]

--z3279511 21:18, 17 August 2011 (EST)

2011 Group Project 2

2011-10-02T09:56:56Z

Z3279511: /* Current and Future Research */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DiGeorge Syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DiGeorge Syndrome on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge Syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DiGeorge Syndrome are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DiGeorge Syndrome is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DiGeorge Syndrome until later in life. DiGeorge Syndrome may only be suspected when learning dysfunction and heart problems arise. DiGeorge Syndrome frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge Syndrome, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge Syndrome (up to 50 years of age).

==Etiology==

DiGeorge Syndrome is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS and DiGeorge Syndrome are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DiGeorge Syndrome, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DiGeorge Syndrome.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DiGeorge Syndrome have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DiGeorge Syndrome symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge Syndrome critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge Syndrome is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DiGeorge Syndrome can present in families that have no previous history of DiGeorge Syndrome. However, DiGeorge Syndrome can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge Syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge Syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge Syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge Syndrome below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge syndrome diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge syndrome. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge syndrome patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge syndrome, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge syndrome has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge syndrome cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge syndrome. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge syndrome over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2 deletion sydnrome. It is known that patients with 22q11.2 deletion sydnrome have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2 deletion sydnrome will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2 deletion sydnrome.

As there is no known cure for DiGeorge syndrome, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge syndrome research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 deletion syndrome. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 deletion sydnrome is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:51:52Z

Z3279511: /* Treatment */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DiGeorge Syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DiGeorge Syndrome on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge Syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DiGeorge Syndrome are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DiGeorge Syndrome is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DiGeorge Syndrome until later in life. DiGeorge Syndrome may only be suspected when learning dysfunction and heart problems arise. DiGeorge Syndrome frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge Syndrome, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge Syndrome (up to 50 years of age).

==Etiology==

DiGeorge Syndrome is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS and DiGeorge Syndrome are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DiGeorge Syndrome, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DiGeorge Syndrome.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DiGeorge Syndrome have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DiGeorge Syndrome symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge Syndrome critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge Syndrome is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DiGeorge Syndrome can present in families that have no previous history of DiGeorge Syndrome. However, DiGeorge Syndrome can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge Syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge Syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge Syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge Syndrome below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge syndrome diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge syndrome. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge syndrome patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge syndrome, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge syndrome has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge syndrome cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge syndrome. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge syndrome over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:48:04Z

Z3279511: /* Clinical Manifestations */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DiGeorge Syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DiGeorge Syndrome on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge Syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DiGeorge Syndrome are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DiGeorge Syndrome is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DiGeorge Syndrome until later in life. DiGeorge Syndrome may only be suspected when learning dysfunction and heart problems arise. DiGeorge Syndrome frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge Syndrome, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge Syndrome (up to 50 years of age).

==Etiology==

DiGeorge Syndrome is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS and DiGeorge Syndrome are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DiGeorge Syndrome, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DiGeorge Syndrome.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DiGeorge Syndrome have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DiGeorge Syndrome symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge Syndrome critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge Syndrome is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DiGeorge Syndrome can present in families that have no previous history of DiGeorge Syndrome. However, DiGeorge Syndrome can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge Syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge Syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge Syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge Syndrome below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge syndrome diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge syndrome. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge syndrome patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge syndrome, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge syndrome has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge syndrome cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge syndrome. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:44:29Z

Z3279511: /* Diagnostic Tests */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DiGeorge Syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DiGeorge Syndrome on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge Syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DiGeorge Syndrome are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DiGeorge Syndrome is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DiGeorge Syndrome until later in life. DiGeorge Syndrome may only be suspected when learning dysfunction and heart problems arise. DiGeorge Syndrome frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge Syndrome, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge Syndrome (up to 50 years of age).

==Etiology==

DiGeorge Syndrome is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS and DiGeorge Syndrome are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DiGeorge Syndrome, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DiGeorge Syndrome.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DiGeorge Syndrome have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DiGeorge Syndrome symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge Syndrome critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge Syndrome is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DiGeorge Syndrome can present in families that have no previous history of DiGeorge Syndrome. However, DiGeorge Syndrome can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge Syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge Syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge Syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge Syndrome below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge syndrome diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge syndrome. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge syndrome patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge syndrome, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge syndrome has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:40:04Z

Z3279511: /* Pathogenesis/Pathophysiology */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DiGeorge Syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DiGeorge Syndrome on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge Syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DiGeorge Syndrome are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DiGeorge Syndrome is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DiGeorge Syndrome until later in life. DiGeorge Syndrome may only be suspected when learning dysfunction and heart problems arise. DiGeorge Syndrome frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge Syndrome, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge Syndrome (up to 50 years of age).

==Etiology==

DiGeorge Syndrome is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS and DiGeorge Syndrome are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DiGeorge Syndrome, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DiGeorge Syndrome.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DiGeorge Syndrome have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DiGeorge Syndrome symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge Syndrome critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge Syndrome is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DiGeorge Syndrome can present in families that have no previous history of DiGeorge Syndrome. However, DiGeorge Syndrome can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge Syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge Syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge Syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge Syndrome below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:36:56Z

Z3279511: /* Pathogenesis/Pathophysiology */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DiGeorge Syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DiGeorge Syndrome on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge Syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DiGeorge Syndrome are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DiGeorge Syndrome is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DiGeorge Syndrome until later in life. DiGeorge Syndrome may only be suspected when learning dysfunction and heart problems arise. DiGeorge Syndrome frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge Syndrome, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge Syndrome (up to 50 years of age).

==Etiology==

DiGeorge Syndrome is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS and DiGeorge Syndrome are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DiGeorge Syndrome, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DiGeorge Syndrome.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DiGeorge Syndrome have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DiGeorge Syndrome symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge Syndrome critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge Syndrome is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DGS can present in families that have no previous history of DiGeorge Syndrome. However, DiGeorge Syndrome can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge Syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DGS presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge Syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge Syndrome below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:33:12Z

Z3279511: /* Etiology */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DiGeorge Syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DiGeorge Syndrome on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge Syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DiGeorge Syndrome are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DiGeorge Syndrome is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DiGeorge Syndrome until later in life. DiGeorge Syndrome may only be suspected when learning dysfunction and heart problems arise. DiGeorge Syndrome frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge Syndrome, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge Syndrome (up to 50 years of age).

==Etiology==

DiGeorge Syndrome is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS and DiGeorge Syndrome are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DiGeorge Syndrome, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DiGeorge Syndrome.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DiGeorge Syndrome have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DiGeorge Syndrome symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge Syndrome critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DGS can present in families that have no previous history of DGS. However, DGS can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DGS is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DGS presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DGS.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:28:18Z

Z3279511: /* Epidemiology */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DiGeorge Syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DiGeorge Syndrome on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge Syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DiGeorge Syndrome are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DiGeorge Syndrome is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DiGeorge Syndrome until later in life. DiGeorge Syndrome may only be suspected when learning dysfunction and heart problems arise. DiGeorge Syndrome frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge Syndrome, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge Syndrome (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DGS can present in families that have no previous history of DGS. However, DGS can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DGS is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DGS presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DGS.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:24:21Z

Z3279511: /* Historical Background */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge syndrome could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge syndrome was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge syndrome <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in DiGeorge syndrome patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge syndrome <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge syndrome prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in DiGeorge syndrome patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome (DGS) has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DGS; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DGS on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DGS is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DGS are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DGS is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DGS until later in life. DGS may only be suspected when learning dysfunction and heart problems arise. DGS frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DGS, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DGS (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DGS can present in families that have no previous history of DGS. However, DGS can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DGS is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DGS presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DGS.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-10-02T09:19:40Z

Z3279511: /* Introduction */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge syndrome is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge syndrome is a complex abnormality and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge syndrome can affect many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amniocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge Syndrome (DGS) has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking as the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also result in signs that are predictive of velocardiofacial syndrome, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. It is therefore difficult to generate an exact figure for the epidemiology of DGS; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of whom had [[#Glossary|'''ventricular septal defects''']]. This study, performed by directly examining the infants, produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DGS, such as the study performed by Devriendt et al, have referred to birth defect registries and produce an average incidence of 1 in 6935. However, this incidence is specific to Belgium, and may not represent the true incidence of DGS on a global scale <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DGS is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DGS includes [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary | '''dysmorphic''']] features, [[#Glossary | '''renal abnormalities''']] and possibly [[#Glossary | '''cardiac''']] defects<ref> <pubmed> 9875047 </pubmed> </ref>. [[#Glossary | '''Cardiac''']] defects are present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. A telltale sign that raises suspicion of DGS would be if the infant has a very nasal tone when he/she produces her first noise. Other indications of DGS are an unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

However, whilst these above points have discussed incidences in which DGS is recognisable at birth, it has been well documented that there individuals who have relatively minor [[#Glossary | '''cardiac''']] malformations and normal immune function, and may show no signs or symptoms of DGS until later in life. DGS may only be suspected when learning dysfunction and heart problems arise. DGS frequently presents with cleft palate, as well as [[#Glossary | '''congenital''']] heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be expected, [[#Glossary | '''cardiac''']] complications are the largest causes of mortality. Infants also face constant recurrent infection as a secondary result of [[#Glossary | '''T-cell''']] immunodeficiency, caused by the [[#Glossary | '''hypoplastic''']] thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DGS, it may be diagnosed at varying age. Those that present with [[#Glossary | '''cardiac''']] symptoms will most likely be diagnosed at birth; others may present much later in life and be diagnosed with DGS (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to [[#Glossary | '''microdeletions''']], which usually occur during [[#Glossary | '''meiosis''']]. These [[#Glossary | '''microdeletions''']] also tend to be new, hence DGS can present in families that have no previous history of DGS. However, DGS can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple [[#Glossary | '''genes''']] responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 [[#Glossary | '''microdeletion''']] syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DGS is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies face (CTAF) syndrome, as well as CATCH-22 syndrome <ref> <pubmed> 17950858 </pubmed> </ref>. The acronym of CATCH-22 also describes many signs of which DGS presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific [[#Glossary | '''gene''']] that is critical in development of DiGeorge Syndrome when deleted is the ''TBX1'' gene <ref> <pubmed> 20301696 </pubmed> </ref>. The ''TBX1'' chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include [[#Glossary | '''thymic hypoplasia''']], [[#Glossary | '''hypoparathyroidism''']], recurrent susceptibility to infection, as well as congenital [[#Glossary | '''cardiac''']] abnormalities, [[#Glossary | '''craniofacial dysmorphology''']] and learning dysfunctions<ref> <pubmed> 17950858 </pubmed> </ref>. These symptoms are also accompanied by [[#Glossary | '''hypocalcemia''']] as a direct result of the [[#Glossary | '''hypoparathyroidism''']]; however, this may resolve within the first year of life. ''TBX1'' is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ''TBX1'' results in the [[#Glossary | '''cardiac malformations''']] that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioural and [[#Glossary | '''cognitive''']] disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DGS.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory [[#Glossary | '''T-cells''']].
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
[[#Glossary | '''Hypocalcemia''']] is a result of the parathyroid [[#Glossary | '''hypoplasia''']]. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the [[#Glossary | '''parathyroid glands''']] results in a lack of the hormone PTH, resulting in the observed [[#Glossary | '''hypocalcemia''']]<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
[[#Glossary | '''Hypoplasia''']] of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of [[#Glossary | '''T-cells''']] in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these [[#Glossary | '''lymphocytes''']] that have been sensitised do not react to any antigens presented by the body’s own tissue, and ensures that they only recognise foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is [[#Glossary | '''hypoplasia''']] of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
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| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' - the sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' - a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' - first part of the aorta (major blood vessel from heart)

'''Autoimmune''' - of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' - caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' - a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Cardiac''' - relating to the heart

'''Chromosome''' - genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' - refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' - preset from birth

'''Ductus arteriosus''' - duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' - refers to the abnormal formation of parts of the body.

'''Echocardiography''' - the use of ultrasound waves to investigate the action of the heart

'''Graves disease''' - symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Genes''' - a specific nucleotide sequence on a chromosome that determines an observed characteristic

'''Haemapoietic stem cells''' - multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' - deficiency of calcium in the blood stream

'''Hypoparathyrodism''' - diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' - refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' - insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' - anatomical expression meaning of, at towards, or from the side or sides

'''Lymphocytes''' - specialised white blood cells involved in the specific immune response and the development of immunity

'''Malformation''' - see dysmorphia

'''Mediastinum''' - the membranous portion between the two pleural cavities, in which the heart and thymus reside

'''Meiosis''' - the process of cell division that results in four daughter cells with half the number of chromosomes of the parent cell

'''Microdeletions''' - the loss of a tiny piece of chromosome which is not apparent upon ordinary examination of the chromosome and requires special high-resolution testing to detect

'''Palate''' - the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' - four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' - regulates calcium levels in the body

'''Pharynx''' - part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' - set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' - round and flat fragments found in blood, involved in blood clotting

'''Posterior''' - anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' - health care given to pregnant women.

'''Renal''' - of or relating to the kidneys

'''Rheumatoid arthritis''' - a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' - a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' - a fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' - an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' - a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' - group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' - a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' - is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Velocardiofacial Syndrome''' - another congenitalsyndrome quite similar in presentation to DiGeorge syndrome, which has abnormalities to the heart and face.

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

Talk:2011 Group Project 2

2011-10-02T09:14:42Z

Z3279511: /* Question */

[[2011_Group_Project_2|'''Group 2''']]: [[User:z3279511]] | [[User:z3288196]] | [[User:z3288729]] | [[User:z3288827]]

{{2011GroupDiscussionMH}}

'''Page Edits 30 Sep'''
<gallery>
File:2011_Project_Group_2_edits.jpg|Project Page
File:2011_Project_Group_1-11_edits.jpg|All Groups (1-11) Project
File:2011_Talk_Group_2_edits.jpg|Discussion Page
File:2011 Talk Group 1-11 edits.jpg|All Groups (1-11) Discussion
</gallery>

==Question==

Hi Leonard, it's actually hard to find good pictures that are actually useful. I had the same problem for the treatment section. I like your pictures but I guess if you wanted to you could draw them again with straight line or so... ;) But it's a bid hard to make them all happy anyway. I had about 75% of people saying that the table in clinical manifestations is really informative and great and 25% said it's to text heavy. I would say 75% win... Anna

Hi, does someone know how I can change my table in clinical manifestations in the way that there is a space in between each section? --Anna Marx 16:23, 2 October 2011 (EST)
Hi Anna, not too sure but if you check in the shortcuts section with editing basics then you might be able to find something in there that'll help. I'm going to add all my words to the glossary and fix up my referencing now! In general I think we got pretty good reviews, just take heed of what the people said and we'll finish up :) --[[User:Z3288827|Leonard Tiong]] 17:05, 2 October 2011 (EST) Hi, yeah I couldn't find the trick in the shortcut tut. But it should be ok just like that....

btw guys i can't actually find an image/graph for the epidemiology section and that's one of the things that a lot of people have commented on. have you found anything in your research that has something like that that I could use? Thanks guys--[[User:Z3288827|Leonard Tiong]] 17:14, 2 October 2011 (EST)
hey all, just finished doing my sections for the glossary linking and fixing of the references. Just read through each of your sections again to make sure that your sentence structure all make sense, alright? I'll do the duplicated references later, going to take a break from this now. by the way, if it's possible, can anyone help me with my two pubmed reference between 46 and 52? I have the formatting of the pubmed reference correct but it's not working in the reference section.

Thanks guys :) --[[User:Z3288827|Leonard Tiong]] 18:36, 2 October 2011 (EST)

==The Final Fix up==

hey not sure what you guys think but what if we take the advice we got on our own sections and focus on fixing them up? I can go through and link the terms to the glossary if someone else wants to fix up the references?

Hi, sounds like a good idea! Will do my part over the week end. anna

Group 2 Critique:
*What Can I say, well researched, nicely sub headed.
*Historical Background shows amazing work. The only 2 things I noticed are the “ 22q11 is in purple” is that on purpose? And the second thing is the image has a source but no reference.
*Epidmiology and Etiology may need some images to balance the words. Also, some spacing between the paragraphs would make it more readable.
* Nice illustration via drawings in the Pathophysiology sections . well structured.
* This section is well established, it has colours and few paragraphs. You might want to consider the size of images probably into something bigger like (Based on symptoms, Ultrasound) and add one more photo in the last two sections (Amniocentesis, BACS- on beads technology)
* one of the best sections on this page is Clinical manifestations. Great work on the table. Perhaps more images along with the abnormality would make a more presentable table. Also, you may consider re-phrasing ( the sub-heading “ How it is caused”) into something with one word. Fabulous work on Heart Drawings.
* in the Section of “ Current and Future research”, allocation of each would be more organised.
The large number of references show how much you guys spent on the page. Some of the references may need to be formatted ( 1,2,3,4,5, etc) note: reference 33,40,47,49, are empty . Overall Great Job.
z3284061

'''Group 2'''

* Well researched and set out page
* An image is needed in either Epidemiology or Etiology would be good
* Diagnostic section tests section is good, however, images are needed for BAC and Amniocentesis
* Glossary is well set out, maybe links to the glossary would be helpful
* Subheadings might be useful in the Current/future research section
* some of the referencing will need to be fixed such as double references
--[[User:Z3292953|z3292953]] 11:11, 29 September 2011 (EST)

'''''DiGeorge Syndrome (Group 2) Peer Review:'''''

Introduction: Well introduced topic. Picture needs description at bottom. Seems to be referenced appropriately.

Historical Background: Extensive timeline which is good. Try to be a little bit more consistent with the colon – either place it after the date or not. Also, picture seems a bit random and needs to have a description at the bottom so that the reader knows what it encompasses.

Epidemiology: Could be a bit more spaced out to make it easier for the reader to read through.

Etiology: Good information and referencing. Try to include a picture in this section as it would help the reader visualize what you are conveying in words.

Pathogenesis/ Pathophysiology: This section is well done. Information is good and images are well-drawn and also contain a relevant description at the bottom. Well done!

Diagnostic Tests: Very extensive. Great use of images. Could you possible also find an image for amniocentesis and BACS? Some image references are not in the correct format and images in this section need to have a label at the bottom.

Clinical Manifestations: This section is well done as well. Possibly too much information which may overwhelm the reader though.

Treatment: Slight inconsistency with the formatting, but otherwise no major dramas. Also possibly more images needed in this section.

Current and Future Research: This section is quite interesting. Research is extensive and images are good – however, they lack correct referencing format and the student template in the information section.

Glossary: Extensive. Well done.

Overall, good job! --[[User:Z3290808|z3290808]] 10:40, 29 September 2011 (EST)

Group 2:

There seems to be a lot of references, almost an excessive amount.

A picture for epidemiology and aetiology would be good.

Diagnostic tests was done well

Clinical manifestations should include some info on what the normal structure and function of the heart.

There is a very large amount of written information and this is reflected in the reference section that takes up alot of space on the page. There are slabs of writing which makes it hard to read the page. It’s boring to see long slabs of writing. The long glossary reflects the long slabs of writing. It’ll be hard to read through. Its not that clear and concise.

z3332178 =]

'''Group 2:'''

*Intro: the first sentence is a little vague. Rather joining sentence 1 and 2 together and defining congenital disorder and explaining it at the same time would be better. I liked the pictures but the trio in that arrangement left the section looking a little unfinished.

*Historical background: image is not explained, a little confused as to why it is there.

*epidemiology: good section, good referencing

*etiology: its a little awkward in flow as you jump from talking about one study, and after one sentence talk about what another study said. Maybe work on building it into an actual paragraph instead of making them merely sentences.

*pathogenesis: the images would look better if they were larger so you get the vague image of it at a glance. Good section, flows nicely

*diagnosis: great section. Layout made it easy to read. Maybe increase the size of the image in the symptoms part, this was harder to see.

*clinical manifestation: good section. Maybe with the last set of images with the heart, leave a space or include a pink heading like you did for the table above it to indicate another table. This was hard to see

*treatment: good section. Maybe change the colour of the bit that you highlighted in that pale orange/skin colour thing. It’d be nice to have that stand out a little more so those headings can actually be seen and not seen as random words.

--[[User:Z3290558|z3290558]] 09:55, 29 September 2011 (EST)

'''Peer review'''
WOW!
This page looks fantastic. The editing is great. All of the information is presented neatly and concisely.
However, just look in "historical background" and make sure all of the lines are edited uniformly. Some have ":" some don't.
Obviously that is nothing major, I'm just nit-picking.
I think you may want to redraw your "pathology of Di George syndrome". It seems quite cluttered.

Overall: Excellent. There really isn't much to say about this page.

--[[User:Z3290618|Ziggy Harrison-Tikisci]] 10:29, 29 September 2011 (EST)

'''Group 2 peer review'''

Introduction: Please explain what the images is about.

Historical background: Please be careful that you type 'DiGeorge syndrome' throughout the section. For example, the point about the 1981 event has 'diGeorge syndrome'. There are also some spelling errors. Furthermore, a legend for the image would clarify.

Epidemiology: Breaking up the segments with images will make understanding the content easier for the reader.

Diagnositic test: Information on the ultrasound test, particularly the second paragraph, is repetitive. The layout is great and the images breaks up the text nicely. A legend for the image will be good. In particular, please clarify what is abnormal with the male face.

Treatment: Are 'Hypocalcaemia' and 'Psychiatric illness' a late occuring feature or an observable condition in newborns.

--[[User:Z3289301|z3289301]] 09:42, 29 September 2011 (EST)

'''Peer Review'''

:*The first three sentences about congenital disease is misplaced. This should be in your glossary, not in your very first sentences.

:*The common symptoms could be left out of the introduction and discussed in the appropriate section.

:*Written like an essay rather than a webpage. Language such as “for example” not necessary.

:*Clinical Diagnosis was well structured and good use of pictures.

:*Clinical Manifestations could be simplified slightly in the table.

:*Some references need to be adjusted rather than just a web address.

--[[User:Z3217043|z3217043]] 08:42, 29 September 2011 (EST)

'''Peer Review'''

This wiki has obviously been given a lot of time and effort and it shows. The text isn't too heavy and I've learnt a few things about DeGeorge Syndrome. Very thoroughly researched and overall, looks and feels very neat and concise. A few points to be made:

:*No need to define congenital disorder. I recommend just leaving it out entirely.

:*Some pictures still need to be captioned even after addressed by Mark Hill. Who is that person in the History section? Angelo DiGeorge? Which one is he?

:*The student drawn images are the let-down. They look very rushed and haven't been given enough effort. The student drawn images on the wiki is also small, so to read the accompanying text by expanding the image, breaks up the flow of reading the wiki. It also hasn't followed the referencing format.

:*BACS- on beads technology image is a pdf file. Either put a picture in the designated area or remove the reference.

:*Amniocentesis doesn't have an image.

:*You should refrain from using the words "mental retardation" as this could be deemed offensive. Use "intellectual disability" as that is a more common term now used in Australia. Also use "learning difficulty" or "developmental delay". We should also encourage the use of person-first language e.g., "a child with an intellectual disability" rather than "intellectually disabled child". This promotes the idea that a person comes before their disability.

:*References section needs attention. Some referencing are not present at all in some casees.

--[[User:Z3293267|z3293267]] 07:12, 29 September 2011 (EST)

'''Group 2 Peer Review'''

• Your overall structure and layout of the page is really good! It’s really neat and all the images and text seem to be in proportion.

• All your pictures, graphs and tables show that you have a good understanding of this abnormality.

• The introduction gives a really good summary of the disease, however I think you should introduce the disease first and then go onto
to explain ‘congenital disorders’.

• Epidemiology could probably be broken down into sections, to make it an easier read and more interesting.

• The aetiology section needs an image to break up a large amount of text also to make it more interesting and informative.

• Good use of subheadings in the pathogenesis, very relevant! Student drawn images are good, could they be a little neater?

• Diagnostics test is really nice and clear, however consistency with the colour of the tables would be good.

• Clinical manifestations section has really good information, I think it could be structured better though, for example; only have the table describing each sign and symptom and then have another sub-heading related abnormalities where you could include ‘Teratology of Fallot as an example...’ (Just an idea).

• Current future research is obviously researched thoroughly, breaking it down into relevant subheadings would really improve it though.

• Make sure you fix up your repeated references. But good work overall!

--[[User:Z3289829|z3289829]] 02:40, 29 September 2011 (EST)

*Intro: Great intro, the picture is excellent and grabs your attention. Perhaps don’t start with a definition of congenital disorders. You can put that in the glossary or mention it after you have initially began discussing the disease.

*History: Love the timeline, clear, easy to follow.

*Epidemiology: Very word heavy which is not necessary for this section. Dot pints or some sort of visual representation would make it more appealing.

*Etiolgy: “ mentioned previously it has a prevalence of 1/2000 to 1/4000” This part is not necessary. Image of the gene would look good in this section. You refer to the disease as DGS (which is perfectly fine) but repeatedly refer to it as DiGeorge syndrome in the previous section, which can get a little confusing. Either use its full name or just the abbreviation.

*Pathogenesis:“As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion” probably unnecessary.
Excellent image, perhaps make it a bit bigger so that you can refer to it whilst reading.

*Diagnosis: The formatting of the text against it’s visual representation is fantastic and love the use of colour – refreshing! The use of colour can be expanded to the rest of the page to make it more cohesive. There is a an image heading with no image under the “ Amniocentesis” heading. There is also an image missing in the BAC’s image column replaced with a link- should fix this.

*Clinical manifestations: Once again great use of colour, but VERY word heavy. It shows that you have done a lot of research but it’s a lot to take in, you can definitely make it more compact.

*Treatment: I quite like this section. It’s informative and is formatted in a way that won’t bore you. The sections which have big blocks of text could benefit from this format. You need to choose a different colour for the block highlights though because you can barely see it.

*Research: Thorough research, very informative but again too much text. If you feel it’s necessary to keep the text you can break it down with word highlights/ bolding or dot points.

*Text/image: Great ratio except a few sections where the text can be cut down a little bit.

*Overall, very thorough, loved the colour and formatting and the student drawn image. Excellent work.

--[[User:Z3290270|z3290270]] 02:37, 29 September 2011 (EST)

'''Peer Review for Group 2'''

'''Peer Review'''
* Many of the pictures do not have a legend/explanation associated with them. However, the hand-drawn picture is underscored by a legend.
* The introduction is rather abrupt; definition of "congenital disorder" could have been a simple hyperlink or a note in the glossary.
* Is the historical background necessary? In the section, the photo of the two people is not explained.
* Section on epidemiology seems to cross over significantly with clinical manifestations.
* Thorough referencing throughout. However, some of the references appear strangely in the references section (could be a vestige of that crash a few weeks earlier?)
* The table in clinical manifestations is strangely.....implied. Section on Tetralogy of Fallot can be cleaned up in terms of layout.
* Inclusion of current and future research is noted, and well set out/referenced.
* Glossary is thorough.
* Overall, a very thorough and broad exploration of the topic.
--[[User:Z3290689|z3290689]] 00:11, 29 September 2011 (EST)

*I don’t think it would be necessary to start the intro with clarifying what congenital diseases are. It would be better if it starts with, ‘Di George Syndrome is a …’ sentence.
*In the intro, fix this sentence as it needs punctuation, ‘As there is currently no treatment education is vital to the wellbeing of those affected, directly or indirectly by this condition’
*Nice picture of Angelo, and also the history is presented well as it makes easy to read and follow.
*Information presented in the epidemiology section is interesting but not organised properly so it flows. Please fix this up.
*Etiology has some technical jargon that is not explained or put in the glossary. Please do so
*Thumb picture of the area where 22q deletion occurred doesn’t show when viewing the page.
*The first line of the Pathogenesis section is, I believe, not necessary as the section just before it just mentioned that fact.
*Punctuation needed for ‘ ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud’
*Pathogenesis/physiology easy to read and has good drawn diagram
*The diagnostics section has good information of how the tool works, what it detects and an image refering to the tool. However Amniocentesis section has no image and yet has a column for it. Please fix this if there is no image for it. Also the Ultrasound section should include what DiGeorge patients would have on Ultrasound scans.
*It is good that the clinical Manifestations section is presented in that way in the table as it explains the abnormalities really well.
*The four images in the Tetralogy of Fallot section may make the reader seem that one of these problems may occur, whilst all four problems are present in the TOF heart.
*The treatment section has information in regards to symptoms. This be under another subheading altogether and not under the treatment section
*Current and Future Research section provides the reader with a good image of the current status of this disease in regards to research.
*References are not properly formatted as repetition in the referencing could be seen. Please fix this.
*Please balance the text to image ratio as the page is text heavy and can be hard to read unless it is complemented with more images.
*Other than that good page.

--[[User:Z3291317|Z3291317]] 23:46, 28 September 2011 (EST)

'''Group 2 peer evaluation'''
*The introduction is done quite well. It is succinct and brief. You have done a very good introduction to the topics that your page is about to explore. Unfortunately you did fail to introduce some of the headings that your page have, like the diagnostic section. Aside from this it is a good introduction overall.
*Historical background is done very well. It has enough detail to see the ongoing achievements on the disease.
*The epidemiology was excellent. You have covered the demography of the disease and properly cited some of the facts that you try to get across. Revision of some of the sentences may be needed because some sentences are not expressed properly. Also it would have been really nice if you could incorporate some of the data that was mentioned in a more summarized form, like a table, dot points, or something. It just makes reading easier and less likely to get lost in the words
*I really like how concise yet very informative your etiology section. What would make this section better than what it is at the moment is an image that would complement the information, and also a bit of an explanation about some of the terms that is in there, like “hemizygous”.
*The Pathogenesis section is very well done. It contains enough detail that we get an in-depth knowledge about the development of the disease, and the images that were used are very helpful. One thing that would improve it though is that if you can elaborate further on the function of the TBX1 gene and how affecting the expression of this gene results to DiGeorge.
*The Diagnostic test section I think is perfect. The way the test works was described, and at the same time they were all related back to how this aids in the detection of the disease. The layout of the information is also very engaging.
*Clinical manifestation is very nicely done. The information was very descriptive and informative. It is also presented very well. Just one thing though is that there is no clear separation between two clinical outcomes, so it tends to get confusing sometimes when someone is reading it. I guess adding more space between would be a good idea.
*Treatments section is done quite well. If you could add a video of some of these treatments or even just a link to a video of it that would really make this section perfect.
*The research section is also very good, especially your insight to future direction of research on this disease. I guess it wouldn’t hurt to drop some current research articles within this section, which shows the readers that the information that they have just read is up-to-date.
*Glossary is a good idea, not really a big fan of it but good idea anyway.
--[[User:Z3290841|z3290841]] 10:20, 29 September 2011 (EST)

'''Group 2'''

Introduction: Introduction is good. The pictures look great.

Historical background: I like the timeline. I think the picture needs a caption underneath explaining who the people are.

Epidemiology: Needs some pictures to break up the text.

Etiology: This section is quite difficult to understand. I think a lot of terms need explaining eg. hemizygous deletion, microdeletion and halpingoinsufficiency.

Pathophysiology: This section is much easier to understand and flows quite well. The pictures should be bigger though.

Diagnostic tests: great section! Good layout and easy to read. The symptoms picture could be a bit bigger and it would be good if there were pictures for the bottom two.

Clinical manifestations: Again, great section. The table could use some more pictures though to balance out all the text.

Treatment: Needs some more pictures.

Current and future research: This section is quite well explained and has a good level of detail.
--[[User:Z3291324|z3291324]] 23:18, 28 September 2011 (EST)

'''Group 2:'''

•I’m not sure if you need the definition and explanation of congenital disorders at the very beginning of the page. The third sentence beginning with DiGeorge syndrome would make more sense as the beginning of the introduction.

•I like the use of images in the introduction and at the beginning of the page, but they are not referred to in the text and do not include captions. Perhaps you should include a brief caption under each image explaining what the image is portraying and why it is relevant.

•Be careful with the wording of some things, particularly in the introduction, i think some parts need to be edited and reworded as they are a little confusing to read.

•The fact that the timetable in the history goes all the way up to 2011 is good and this section seems to be referenced well.

•The student drawn image of the heart defects do not include the correct template that is required for proper copyright information.

•Good use of tables to break up the text, although the different colours is a bit distracting, i would recommend choosing one colour and using that throughout the page.

•The referencing needs to be fixed up as many references appear multiple times in the reference list.

--[[User:Z3332183|z3332183]] 21:24, 28 September 2011 (EST)

'''Peer Assessment Group 2-DiGeorge Syndrome'''
*The introduction and history look good with great use of images which makes for an interesting start.
*There could be at least one other picture in 'Epidemiology' and 'Etiology', otherwise it just looks like a big block of text
*The 'Diagnostic Tests' look good-the image for BACS still need to be uploaded
*The student drawn images are colorful however doesn't have copyright information-just states who drew them
*Some sentences seem incomplete or doesn't seem to convey a message e.g. "Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists".
*'Current and Future Research' has a lot of information however is it possible to condense it and give a basic summary instead. I understand that you have tried to do your best but it is just a lot of information. You might also wnat to consider using sub headings.
*The references need a bit of attention-you have a lot of links there which need to be changed to proper references
--[[User:Z3308968|Tahmina Lata]] 21:13, 28 September 2011 (EST)

'''Group 2 Peer Assessment'''
*Good introduction. Like the use of the image to grab the reader's attention but it might be a good idea to include one or two sentences in the text explaining the characteristic appearance of the patients and give the image a title (just to link the image to text straightway at first glance without having to click on the image to understand it's significance).
*Not sure if you need to explain the term 'congenital' in the introduction. Might be better to start straight away on the actual syndrome.
*Great job on the "Historical background" section. Maybe have small title for the image of Angelo DiGeorge.
*Good explanations in the 'epidemiology' and 'etiology' sections but the text is a bit too heavy. Try breaking it up with an image.
*Good use of images, table and the general arrangement and layout of information in the 'Diagnostic test" section. (Small spelling error in section name). Try to include an image in the "Amniocentesis" section as well to complete the table.
*Needs to explain the link in the "BACS- on beads technology" section and why it has been inserted.
*Like the student drawings in the 'tetralogy of fallout' section and good explanations of what is happening. Small grammatical error in the title (on instead of an).
*Good job on the 'treatment' and 'current/future research' sections.
--[[User:Z3291622|Z3291622]] 16:17, 28 September 2011 (EST)

'''Group 2'''

*The whole page is very nicely formatted
*Introduction is clear and concise although would it be more efficient to start talking about DiGeorge straight away rather then define congenital abnormalities?
*Historical background is obviously well researched
*There needs to be an image in epidemiology and/or etiology to break up the text or present some of the information in a table
*The pathogenesis section flows nicely although a few words need to be added to the glossary
*Great table for diagnostic tests- this makes it easy to follow
*A few more pictures would be great for clinical manifestation and maybe this would be better in dot points?
*Student drawn images of tetralogy of fallot were excellent
*Subheadings are needed for Current/future research
*Good project overall, obviously a lot of effort has been put into this.

'''Group 2 - Peer assessment'''

*The introduction is easy to read and understand. Maybe one thing you could improve on is the organization of the paragraphs because it looks abit too choppy as of now.
*The history looks amazing and well researched AND well referenced! Makes me believe and trust your project even more. Furthermore the picture on the right just makes the section more appealing.
*Epidemiology - the information flows well and examples are also mentioned which is nice to see
*Etiology - The information is ok but maybe it could be better explained with explanation of the technical terms within your texts
*Pathogenesis/Pathophysiology - the student drawn images look amazing! And the organisation of information is good. Maybe a suggestion would be to hyperlink some of the terms in the text because there was alot of technical terms to be scrolling down and up for.
*Diagnostic Tests - The layout is very appealing and consistent with the rest of the page. The spelling of the heading is wrong!
*Maybe for the glossary it would be a good idea to include headings such as "A", "B" etc
*Fixing up double referencing would be a good idea aswell

--[[User:Z3330313|z3330313]] 19:36, 28 September 2011 (EST)

'''Peer Assessment Group2'''

*Epidemiology – hyperlink technical terms to glossary?
*The pathophysiology/pathogenesis sections (pharyngeal arches onwards) needs to be linked back to the syndrome. You list it in the “genes” section then describe the normal development, but it needs to be described to what happens in the syndrome/abnormal development.
*Don’t forget to add in the missing images in the diagnostic techniques
*You have several (excellent) summary tables – I think the format should be consistent in each, would make it look/flow better
*Typical symptoms: Newborn section can be condensed
*Current and future research could benefit by being broken up a bit – maybe use subheadings, colour or bold main points – it just is a big slab of text and looks daunting to read.
*References: some just have the PMID number and need to be fixed so it reads the whole reference (just for consistency)
--[[User:Z3332824|z3332824]] 23:18, 27 September 2011 (EST)

GROUP 2: DiGeorge Syndrome
*I don't know if the congenital disorder definition is needed in the intro, maybe you can included in the glossary instead
*The image in the intro could use a legend
*Info in the intro is comprehensive and informative
*History section has got good, succinct information and i like the fact that it goes up to 2011, however maybe you can consider putting the timeline in a table. Image could also have a legend
*Epidemiology has been researched relatively well, info is comprehensive and flows well, however, could be improved with a graph of some sort to accompany info with a visual
*Etiology contains very descriptive, informative info, could be improved with an image of the chromosome and the area of deletion
*It would be a good idea if the acronyms are included in the glossary
*It is evident that the Pathogenesis/Pathophysiology section has been very well researched, maybe the "genes involved in DiGeorge syndrome" section could be formatted in a table
*The use of a table in Diagnostic tests is succinct and informative. You should check for spelling mistakes (Dianostic Tests is spelt wrong), images to accompany these tests are useful, however, again a legend for each of these would be help
*Image missing in the Amniocentesis part of diagnosis
*I don't know if the image link for BACS- on beads technology is really helpful
*Clinical manifestations has clearly been researched extesively, however, this section is very overwhelming,too much text in my opinion. It would be easier to read if it was summarised more, a graph may be helpful
*Treatment section is comprehensive and summarised well
*I have found that incidence has been mentioned in quite a few sections, is this really necessary? Can it just be mentioned in epidemiology?
*Current and future has got some good info but it is quite lengthy and could be better to summerise it a bit more so u don't lose the reader
*The last two images need to be referenced properly, with the template and correct referencing

Overall:
*The whole project has been researched very well
*Some of the images could use legends to describe what they are about and you could also consider moving the images around a bit so there's variety and making some of them a little bigger so their features can be seen
*Maybe acronyms could be included in the glossary
*some sections could be reviewed and info could be condensed
*references need to be reviewed and correctly structured (some work on this is required)
*You could improve this project by also linking the glossary terms to the text to make it easier to access, also some graphs could be used

--[[User:Z3331556|z3331556]] 22:51, 27 September 2011 (EST)

'''Group 2: DiGeorge Syndrome'''
*initial browse through the webpage: well balanced use of text, image, colour and table format.
*introduction: well summarised and good use of image. It is interesting and provides a good overview to the syndrome. Minor adjustment: give one or two examples of symptoms rather than providing a list.
*Historical background: good use of timeline, and layout.
* Epidemiology & Etiology: needs to define terms in glossary such as velocardial syndrome.
*I appreciate the subheadings used in the pathogensis section... it breaks up the mass of information, creates flow and also shows understanding. Needs to define a few terms in glossary such as: hypoplasia, hypoparathyroidism, parturition etc.
*Diagnostic tests: well set out, I think the use of colour is aesthetically pleasing and adds to the overall presentation of the webpage.
*Clinical Manifestations: well set out and good use of images. Table could benefit from use of borders, just to clearly separate the rows where the information appears to overlap.
*Current&Future Research: could benefit from formatting of previous headings. That is, in a table to break up the information, or by using subheadings
--[[User:Z3332327|z3332327]] 15:42, 27 September 2011 (EST)

'''Peer Assessment group 2'''
*Introduction is clear cut and enters the topic with easy understanding though should incorporate the image more, where the image has no description of what its suppose to explain where symptoms would link to the image would help a lot.
*Timeline used correctly in displaying the increased understanding of the disorder, image used was does not have a description so don’t know who is the discover right or left and what is the image suppose to show.
*Etiology refers to a lot of studies or research which is not clearly explained how the research shows the causation of the disorder with various results showing different reasons for causation
*athogenesis clearly links image to the common deletion of gene with clear explanations of genetics component of Digeorge syndrome. Though would become more fluid with introduction of embryological effects instead of leading to pharyngeal defects.
*Embryological component didn’t expand the defects of the pharyngeal arches as well not much of the parathyroid which is major component of calcium levels also poorly linked to the image without any mention of the figure.
*Diagnostic tests require an introduction onto the topic and techniques, where heading directly states the techniques without any understanding of what these means.
*Clinical manifestations describes information clearly though the congenital heart defects images would work better below the information, so text and information with image below.
*Treatment has image relating to plastic surgery could have a description even though it’s a example of surgery.
*Current and future research should be more organised instead of paragraphs have dot points to know the difference between new research and current also images not place in correct manner but in between the glossary as well.
*Referencing has not been done correctly with only links, repeats and some are even blank.
*Glossary not linked to the term or bolded to note that it’s in the glossary so while reading its confusing if you have no pathology background.
z3332250 23:42, 26 September 2011 (EST)

Group 2 Peer Review

*Well structured page in terms of headings, good choice of topics covered
*Do not need to define congenital abnormality. If you want to define it perhaps add it to the glossary instead?
*Symptoms in introduction would probably be best in another section
*Great images. Some need to be made bigger in order to easily read the detail on it
*Most images are on the right side of the page. Could you move them around a bit to make it visually more appealing?
*Faint colour highlighting under treatment needs to be made darker or deleted
*Some duplication in referencing
*Well researched-great
*Overall, an informative and well presented page. Just some minor details which need to be adjusted to finalise page
--[[User:Z3308965|Fleur McGregor]] 16:55, 26 September 2011 (EST)

===Comments on Group Project 2===

Group 2

*By looking at your page it’s clear you’ve performed extensive research on DiGeorge Syndrome, well done on the effort
*Spelling needs to be attended to....’Diagnostic Tests’
*The image included in the introduction could use a legend. Maybe you could refer to it in the introduction, but to me it’s just a picture of 3 babies
*Nice work on the historical background, grammar could be attended to easily, just some minor things really. This timeline could be better formatted though, maybe in a table. The image included here doesn’t have a legend or some form of description. Just a picture of two old-timers shaking hands.
*Epidemiology is great although it might be useful to include an image of some sort if possible (I’ve got the same problem) as it’s just a block of text
*Etiology is good, very descriptive and evidence of a well researched sub-heading.
*Diagnostic Tests – clever heading, clever formatting and great information. The images included definitely need legends and descriptions
*Current and Future Research heading could be broken up with some sub-headings
*Glossary looks great

--[[User:Z3331469|z3331469]] 06:57, 29 September 2011 (EST)

'''Strengths:'''
*Good placement of sub-headings and headings.
*I like how the introduction gives an overview of the syndrome.
*All images have copyright statements.
'''Weaknesses:'''
*The epidemiology and etiology sections seem like really wordy, overwhelming to read. It is paragraphed but maybe the paragraphs could be more distinct.
*It would be good to link the words that is defined the glossary to the glossary.
*Some of the references are not formatted properly.
'''Specific corrections:'''
*It would be good if introduction immediately started with what is DiGeorge Syndrome instead of leading up with the definition/characteristic of congenital disorder. This definition can be shifted to the glossary
*Just curious, it will be interesting to hear how different the first sound of a DiGeorge baby differs from a normal one.
*”Dianostic Tests” is spelt incorrectly.
*Instead of the sub-heading “Based on symptoms”, it could be “Symptomatic diagnosis”.
*What is “clinodactyly” in the description of the image under “based on symptoms”?
*The link under images for BAC subheading could go under external links section?
*Maybe the table under “Tetralogy of Fallot...in DiGeorge Syndrome” could be vertical instead of horizontal? It will look neater.

--Z3389806 06:40, 26 September 2011 (EST)

'''Group 2'''

*Introduction: good content, but the symptoms do not really belong there.

*Very nice historical section, nice to read

*Epidemiology and etiology seem almost like one big section. Maybe separate the content a bit more (no repetitions), and break it done with subheadings.

*Pathogenesis: includes helpful explanations and information, good use of reasonable subheadings. The drawn images could have been done with more
accuracy.

*Diagnostic tests: very nice informative section, good use of images to visualize the content. I think the choice of colour for the table could be
better, maybe another shade of the pink (darker, red...) that has been used for clinical manifestations. The green disrupts the flow of the entire page.

*Clinical manifestations: very nice section, precise information, good structure, useful images.

*Treatment: lots of information in a nice form, but the image would look better on the right edge (like the ones in ” research” ). Good use of subheadings.

*Research: good content, but would be easier to follow if you would break it down with subheadings.

*Glossary: looks good, but explanations like “malformation: see dysmorphia” should be avoided. It would be better to define every term separately.
--[[User:Z3387190|Z3387190]] 11:34, 25 September 2011 (EST)

'''Group 2 Critique'''

#• The introduction needs to be re-written in proper English. Some of the sentences don’t make proper sense. Also, the introduction should focus primarily on DiGeorge’s Syndrome and not explain what a congenital abnormality is
#• Historical background was good
#• Epidemiology should not explain clinical features, such as the baby making a noise which is nasally in tone
#• Aetiology is ok
#• Pathogenesis is quite detailed, however genes should be explained a little more clearly
#• Diagnostic tests section was impressive
#• Clinical manifestations was good
#• Treatment was good
#• Future research was good
#• Glossary was good

Images were appropriately used. --[[User:Z3289991|Robert Klein]] 18:36, 24 September 2011 (EST)

Group 2

Hey Group 2, firstly, well done on putting in the effort to create this page, it really shows your dedication and cooperation as a team! Here are some points I thought you could improve on to take this page to that extra level

#The key points relating to the topic that your group allocated are clearly described.
#* Introduction: Good overview. Image would look better with a border or as a thumb
#* History: Image too large, again maybe a border?
#* Epidemiology: Need to define velocardiofacial syndrome in glossary, also break it down into subheadings, eg. Incidence, Sex, etc
#* Etiology: Maybe better if in a table
#* Pathogenesis: I liked how you broke it doen into relevant subheadings. However, on a slightly negative note, the DG Pathophysiology Diagram looks rushed; I think it would've looked better if it was neater and easier to read.
#* Diagnosis: I felt citing was done poorly in this section, eg. the last 4/5 sentences in the FISH technique was not referenced at all, but again, this is very easily fixed. But good to see you have put in the effort and time
#* Clinical: Image of normal and cleft palate, if based on a textbook, I think you still need permission to adapt it (not quite sure, please ask Mark)? Table with 'How it is caused' would be better by itself as pathophysiology. Tetralogy of Fallot needs to be fitted into this section more smoothly, at the moment, it makes this section look very cramped. Also, the image regarding Tetralogy needs the correct format for student drawn images (ie. 'I (student no.)....)
#* Research: Maybe break it down into subheadings
#The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
#* Good images used with a nice range of self drawn images. However, no where in the page is there any reference to the images within the text.
#Content is correctly cited and referenced.
#* I feel citation needs to be improved overall. Lots of the sections have missing citations, especially Diagnostic Tests. Also in the reference list, refs 33,40,47, 49 have nothing in it (is it meant to be like this?)
#The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
#* Nice drawings, though some could've done better with more effort
#Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
#* Nice range of references used
#Relates the topic and content of the Wiki entry to learning aims of embryology.
#Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
#Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
#The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
#* It's very clear to me that you guys have worked together well and there has been good team work going on here to create this page, so well done
#Develops and edits the wiki entries in accordance with the above guidelines

"What would improve this project...."

* I feel your page is too heavy with the text, although there's a lot of images as well, it just doesn't quite balance out with the text.
* Also felt the different colours used for the tables, although adding a splash of colour to your page, brought down the overall quality of the page. However, please keep in mind that others might really like this approach of table formatting, it's just that personally, I think you could benefit from keeping all table colours consistent.
* Sometimes you refer to DiGeorge Syndrome as DGS and also as DS. Small and easy to fix, adds consistency
* Please don't forget to add the {template} for student uploaded images
* Definitely needs more words in the Glossary, such as Meiosis, de novo, microarray

--[[User:Z3291643|z3291643]] 16:02, 24 September 2011 (EST)

'''DiGeorge Syndrome'''

*The page has a really nice setout, the introduction and history looks really good. It has a nice flow.
*There could be at least one other picture in 'Epidemiology' and 'Etiology', otherwise it just looks like a big block of text
*The second last paragraph in 'Epidemiology' would be better suited in 'Clinical Manifestations'
*There's a bit of repetition between 'Etiology' and 'Pathology', it could be better to combine these
*The 'Diagnostic Tests' look really good, fantastic table and images
*I love the ultrasound picture
*The table in 'Clinical Manifestations' is really great with lots of detail
*I understand it's difficult to find, but more images in 'Clinical Manifestations' to give a visual representation would be fantastic
*"Teratoogy of Fallot as ''an'' example...."
*"Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists" This doesn't make muhc sense, that was from the 'Treatment' section.
*You had a lot of good information in 'Current and Future Research', but I found myself getting lost in all the text. Maybe subheadings would help?
*Don't forget to fix up the references, we don't want to see webpages as a reference even if it leads you to the paper
*Overall your page looks very good, some minor formatting would be useful

* A very clear format has been used. The mixed use of dot points and paragraph form were used appropriately in most sections and made your web-page easy to read and follow
* Good use of self drawn images, however the large image of Angelo DiGeorge seemed slightly irrelevant and took up a large portion of your page. Your first two images should probably have small heading below the image, just to make them a bit more clear to the reader.
* A coherent history/timeline was used.
* You’re referencing needs to be tidied up; there are multiple entries from the same source that tends to clutter your reference section. Some references are incompletely, or have no linking information such as reference 49.
* Your current research section was good but perhaps could have been tabulated just for easier reading and to really draw out the main points.
* Your table for clinical manifestations could have been summarised otherwise it should maybe just be written in paragraph form.
* Your page definitely reflects the time and effort you have placed into the assignment. I really liked the range of formatting you used and the use of colour made your page easy to read and follow. Another great feature was the section based on the example of Tetralogy of fallot. It was interesting to read how other defects that we have discussed in class, linked in with your studied abnormality.
--[[User:Z3332629|z3332629]] 15:21, 22 September 2011 (EST)

'''Group 2'''
* Structure- headings, subheadings and tables make this a very readable page with a nice flow.
* It may be nice to have the colours of the tables continuous throughout the page. eg only yellow.
* Ensure all your pictures are correctly referenced, it would be a shame if Mark deleted them, as they add a lot to your page and aid in read ability.
* not to text heavy which is good!
* Intro well written an gives a good scope to the syndrome.
* Dianostic Tests: I like this section and that the images accompany the text.
* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome: Very interesting example, great pictures!! very well drawn. maybe you could put the pictures vertically down the page.
* Current and Future Research section it might be nice to add subheadings of what the research is.
* Good use of citing/ referencing it gives your page authority/ believability, just beware of the doubling in your reference list.
* It might nice to collate all the genetic info into one section.

*'''Introduction''': Good in general. Last paragraph needs a slight revision in sentence structure. "The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality" - significant in what way? As in they have a big impact? And also, poor quality of what? Life?
*'''Historical Background''' : Very detailed, which is nice. The layout isn't quite 100% consistent, which should be easily fixed. Some findings could do with further explanations to show how this lead to progress. Also, some terms should be linked to the glossary, or in some cases, a mention that subsequent paragraphs will provide more detail.
*'''Epidemiology''': Seems fine to me, though a figure would be nice to break up the text.
*'''Etiology''': Links to glossary needed. This part contains many technical terms that aren't explained. Also, is it known why this region is specially prone to rearrangements?
*'''Pathogenesis''': Seems to repeat what was said in etiology, but in more detail. Well written and explained.
*'''Diagnosis''': There's a typo in the title - Dianostic instead of Diagnostic. You might want to split your table into prenatal and postnatal, as otherwise it is a bit confusing to read "ultrasound" as a diagnostic tool. It does become obvious very quickly that it is prenatal, but just for clarity's sake, splitting the table could help, especially as you mix pre- and postnatal tools throughout the table. Also, just be careful about using capitals - in the beginning you say BACS, and later you say BACs. BACs is the plural of BAC, which is what Bacterial Artificial Chromosome stands for, not BACS. Your explanations in this part of the table are quite technical - you might want to explain more terms in the glossary at least.
*'''Clinical Manifestations''': Very thorough and detailed, which is good. I like the table, but including some more figures might help break up the long bits of text.
*'''Treatment''': Also quite thorough, well explained.
*'''Current and Future Research''': Very good and detailed, well explained. Maybe include headings for the different sections, so it's easier to see what each is talking about?
*'''Glossary''': More terms need explanations.
*'''References''': Seem fine in general, though there are a few links that probably should be cited differently. Also, some references link to emptiness?
*General: All the tables are slightly differently formatted, you might want to get that more uniform.

'''Group 2 Critique'''

*Do the symptoms need to be listed in the introduction, or is that repetitive since it’s also in the etiology portion?
*Historical Background- Overall this section looks good, but each bullet needs to be consistent. Ie:
-only the first few bullets have a colon after the date while the others don’t. I think either a colon or a – mark should be used after the date to show a better separation.
-some sentences don’t end with periods.
*The Etiology and Epidemiology sections have good content, but it looks rather wordy from an aesthetic viewpoint. A picture or some bullet points for separation might be helpful to solve this.
*For the image Chromosome22DGS.jpg, surely you didn’t know this layout from your own knowledge… Wouldn’t you have had to copy this image from another source, and wouldn’t that source also need to be cited as well?
*For terms that are in the glossary, it would be good to format the words in the wiki so that when you click on them it takes the reader directly to that term in the glossary.
*Several of the references aren’t formatted correctly, or are missing entirely.
*This might be a bit nit-picky, but for the references given throughout the wiki, there isn’t any consistency. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
--[[User:Z3391078|Ashley Smith]] 11:05, 27 September 2011 (EST)

'''Peer Assessment: Group Project 2'''
*The information in the introduction is good, however you may want to introduce the syndrome in the first sentence and then explain what congenital abnormalities are.
*The timeline is clearly set out, maybe decide whether you want to put a colon or not after the date to keep consistency.
*The diagnostic tests section has a good balance between being informative through pictures and text. It would be good to place an image for amniocentesis and also replace the link on BACS technology to either have an image and use the paper as an extra link or to replace the heading of 'image' to 'additional information' or some such title.
*Maybe an image could be inserted in the section on etiology or epidemiology. An graph to accompany some of the statistics might make the information more accessible.
*Under the information of the images you have uploaded, you need put <nowiki>{{Template:2011 Student Image}}</nowiki>.
*In the glossary writing "A" above the group of A words and so on and so forth for the rest of it, would make it easier for the reader to quickly find the desired word.
*Some of the references should have more information in them (references 1, 2, 3, 4, 5, 46, 47, 48, 49 and others).
*The references should not be duplicated and can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.

--[[User:Z3217345|z3217345]] 12:43, 27 September 2011 (EST)

'''Group 2:'''
* The introduction is very easy to read and is accompanied by a great image, although this image should include a legend. It would be beneficial to link the image with the symptoms mentioned in the intro and to only mention a couple of important symptoms instead of listing them all here and having to repeat yourself later on.
* Very extensive historical background. Very impressive and well referenced. Image needs to include a legend.
* Epidemiology needs to be proof read as there are a couple of little mistakes that lessen the value of what is a really well researched section; “Due to the fact that 22q11.2 deletions can also resulting in signs that...”, “It has been well documented that there individuals who...” and “which may be resultant form a learning dysfunction or heart disease.”
* Etiology is also done well and is very comprehensive, however there is a spelling mistake “interstital deletions of chromosome 22” so make sure you re-read this section too.
*An image either in epidemiology or etiology would help break up a huge chunk of text.
* Pathogenesis/Pathophysiology section is very strong with great student drawn images relevant to the text. Only suggestion is to hyperlink glossary terms since there are a lot of terms in this section which need to be explained further.
* Diagnostic Test section is done well with a well formatted table making it easy to read. Some images are missing as I’m sure you’re aware of and make sure to include <nowiki>“{{Template:2011 Student Image}}”</nowiki> for these images.
* Clinical manifestations; perhaps the table describing the symptoms could immediately proceed after “The most common signs and symptoms include:” instead of having the symptoms in dot points and repeated twice. The student drawn image may benefit from pointing out that A is at rest and B is during normal speech – just to clarify. I also noticed a spelling mistake “In more severs cases..” so just make sure you go over this section with a fine comb.
* Treatment also had a couple of little mistakes for example “and consult various specialists, from example a cardiologist”. A legend for the images here would improve this section.
*Current and future research is very extensive and well researched.
Hats off to you guys!

Peer Assessment

* interesting layout
* pictures were good examples
* maybe need a touch up with the referencing
* i liked it how it was worded in a way that could be understood for a wide audience however the structure and format could not be read so easily

--[[User:Z3060621|z3060621]] 20:37, 28 September 2011 (EST)

--z3290815 14:09, 28 September 2011 (EST)

'''Group 2'''

'''*The key points relating to the topic that your group allocated are clearly described.'''
Well described, but very hard to follow at points due to volume of text.

'''*The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'''
Tables include too much information. it should summarise the main points, for large chunks of text put it in the body of the wiki.

'''*Content is correctly cited and referenced.'''
Fix up some references - there is duplication and links provided in place of a reference as well as missing references. reference for Chest PA 1.jpeg, DiGeorge-Intra Operative XRay.jpg and FISH for DiGeorge Syndrome.jpg should be fixed. also include {{Template:2011 Student Image}} in all images.

'''*The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.'''
Good diagram explaining pathophysiology but it can be neaten up by doing the text on a program (paint would suffice).

'''*Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'''
Very high research volume put into the page but there is too much text going on. Try using some sub-headings to break up the information into easily digestible sections. It also allows for easy location of specific sections.

'''*Relates the topic and content of the Wiki entry to learning aims of embryology.'''
Good information on genetics but if possible say how the deletion occurs?

'''*Develops and edits the wiki entries in accordance with the above guidelines.
Apart from small things, the wiki has been edited well.

--z3329495 21:09, 28 September 2011 (EST)

==The final Pimp==

Hi guys, how is your week end? Thursday is the due date for our side and I think it's looking great already. I just read through it all and noticed the following.

1) I changed 1/4000 to 1/2000 to 1/4000 in the introduction (hope that's ok) this way we are all saying the same.

2) I think we should still change what Mark Hill suggested for the "Historical Background" section: date first and picture not within the text. I'm happy to do it, just thought I should check with you Sarah...

3) There are still some references that need to be fixed

4) Do you guys want to add some of the scientific words that you used to the glossary, otherwise that would be incomplete

and 5) Mark Hill wanted to help me with the tetrallogy of fallot picture but I think he forgot, so I'll ask him again after the lecture and than it's going to be a fancy scenic view picture.

So, let's do the final pimp: I wouldn't leave it until Wednesday because the system is probably going to crash on that day;)
Let me know if you need any help and let us know if you think something els should be changed/edited as well.--Anna Marx 16:40, 18 September 2011 (EST)

Hi Anna, yup, 1) sounds fine; we still have that issue with the ultrasound image and removing the text from the background don't we? I'll have a trawl through the references later and see what I can do, and for most of the scientific words I know the sections that I've done have their wording in there; everyone else just has to go through it a bit?

btw guys it looks fantastic :D --[[User:Z3288827|Leonard Tiong]] 10:51, 20 September 2011 (EST)

hey i changed up the history and put the tables in different colours so they dont look like they ar all the same thing if you know what i mean?? anyway... hope its ok :) --[[User:Z3288729|Sarah Jenkins]] 13:20, 21 September 2011 (EST)

Cool, looks good. I like the colours :) --Anna Marx 11:47, 22 September 2011 (EST)

==Question==

Hi Sarah, I have a question, do you think we can split the baby pictures that you used in you introduction. Sounds super lazy of me, I know. But my problem is, that I would like to put one in my section about facial abnormalities and I couldn't find one that shows these abnormalities well and that has copyright. I wanted to use the one that is in the epidemiology section but I think Leonard wants to keep it there??? Don't really know. Any way, if we would split yours, you could get one baby and I would use the other one. What do you think? --Anna Marx 22:01, 10 September 2011 (EST)

Hey Anna, I wouldnt have a problem doing that but it is one image within the journal and im not sure if we are allowed to manipulate the images? I will talk to Mark about it and if it is ok then i will cut it up for you and put one of them in your section :) Hope this helps. --[[User:Z3288729|Sarah Jenkins]] 08:54, 11 September 2011 (EST)

Hi anna, I SAID down there that you could use the image! :D '''Feel free to take it because I also think it would assist in that section'''. I'm just squabbling over the image filename with Mark because it's not descriptive. There's another one there that has a picture of another fellow whose facial abnormalities are quite apparent so I was thinking to use them as they've got a pretty strong contrast between the two of them. What do you think? I've also uploaded my drawings, they took ages and they look so crap :( But I've been scrolling through some of the other groups and we're in good shape guys! It looks really great :) I'll sort out my glossary terms tomorrow morning. Excellent work over the break guys. --[[User:Z3288827|Leonard Tiong]] 21:42, 11 September 2011 (EST)

==Update==

Hey, how are you holidays coming along? I just wanted to let you know four things;):

1. I am "done" with clinical manifestations. So you can have a look if you like it... I'll still upload at least three images of which two are drawings.

2. So we have got the drawings covered. I just have to scan them.

3. I'll still work on the treatment section tomorrow.

4. For the matching up of our individual sections, Sarah would you mind to change the typical symptoms in your introduction to the same ones I talked about in detail. I think it would look good. Anyway...It would be the following ones:
* Congenital heart defects
* Defects of the palate/velopharyngeal insufficiency
* Recurrent infections due to immunodeficiency
* Hypocalcaemia due to hypoparathyrodism
* Learning difficulties
* Abnormal facial features
Have a good brake guys, --Anna Marx 2--[[User:Z3288827|Leonard Tiong]] 10:45, 8 September 2011 (EST)0:22, 3 September 2011 (EST)

Hi, so I have done my treatment section as well including references and glossary. --Anna Marx 21:43, 6 September 2011 (EST)

Thanks Anna :) I will change it all up now. I know you are doing the drawings but the rest of us need to get some pictures up if possible? --[[User:Z3288729|Sarah Jenkins]] 08:55, 7 September 2011 (EST)

Hey guys, i have a few pictures to load up, so will get onto that..

Was also going to ask if anyone came across anything good under the future research heading? I have found a bit, struggling a little though, and i feel like there should be more.. Just wondering if anyone came across any interesting points/areas when doing your own research.. Also had the suggestion that maybe pathogenesis/etiology could fall under the same heading, as they are both very similar topics, and maybe I/we could write something up more focussing on the pathophysiology as another heading... I know Anna does talk about this a bit in her clinical manifestations, but thought there was room to potentially cover pathophysiology in a bit more detail under anther heading, and we could maybe reduce the detail in her table as a result, make it a little less large.. let me know what you think..

--[[User:Z3288196|Timothy Ellwood]] 09:21, 7 September 2011 (EST)

really good job with everything at the moment it looks really fantastic. tomorrow is my allocated day to get through this work, so I'll be sure to get a large chunk of my sections "done". Anna, excellent work done so far, it looks really fantastic. Umm tim, as for your struggles at the moment, I'll be sure to keep that in mind when I'm looking at my other papers; just having a look at the moment and I'll get a little more help for you tomorrow, if possible. looking great so far guys! --[[User:Z3288827|Leonard Tiong]] 14:23, 7 September 2011 (EST)

hey tim, another idea is to change the heading to 'current and future research' that way you can look into what is being down now and very recently. that will give you heaps :) --[[User:Z3288729|Sarah Jenkins]] 07:13, 8 September 2011 (EST)

ps. i used a wikipedia image so we cant put another one up now... hope this isnt a problem --[[User:Z3288729|Sarah Jenkins]] 07:14, 8 September 2011 (EST)

By the way Anna, I'll probably draw my image and upload it later this evening; I can't find any images that best match what I want without having to go through all of the copyright information, so I'll just draw it :D slowly trawling through my sections. Epidemiology might be a bit short (as there's not that much you can write on it) but the pathophysiology section should be quite lengthy (Hopefully :) ) --[[User:Z3288827|Leonard Tiong]] 10:45, 8 September 2011 (EST)

Slowly going through pathophysl now. by the way guys, '''Mark Hill has put something at the top of our page if you haven't already seen it. I think it would be best to implement the points that he has noted; they're relatively minor, if you guys haven't gotten round to doing it by say, tomorrow (?) then i'll see if I can change it :) '''
I'm finding this INCREDIBLY FRUSTRATING that I can't save the material but no one else seems to be online. :(

Hello! I just thought let you know that I did two drawings which I plan to put into the table under clinical manifestations. And I also have images on my computer, that also go into the table. I just have trouble uploading them (may be it's because I have a mac... not sure). But in case I don't manage I'm sure one of you could help me on Thursday. I'll also try to make the tables a bid lighter. --Anna Marx 17:15, 8 September 2011 (EST)

ALL RIGHT, so I have change my tables. I have tried to explain it in a way so that people with no science background should understand it. Some words I had to leave in because that is just what it's called... Any way I think it'll be even better once I have the pictures in as well. If you like to have some thing changed let me know. --Anna Marx 19:12, 8 September 2011 (EST)

Hi Anna, just asking what have you done in your drawings? I drew the chromosome and the area in which deletions were most common, it's not the greatest drawing but I leave it up; and, I was thinking of drawing the presenting symptoms of DiGeorge (there aren't that many anyway). What do you think? Let me know what you've gotten down :) --[[User:Z3288827|Leonard Tiong]] 23:06, 8 September 2011 (EST)

Hey guys I will fix up what is wrong with my bits tomorrow afternoon sorry. I have had other things to do this week as well. Mark's comments are valid and relatively simple to fix luckily. --[[User:Z3288729|Sarah Jenkins]] 00:55, 9 September 2011 (EST)

Hey guys. Looks like Dr Hill's criticism was relatively minor which is great. Should be easy for us to fix. As for the future research I have found a heap more stuff, seems as if alot of current research on this deletion is in relation to schizophrenia, but have found alot more stuff relating to Digeorge. Suggestions still welcome of course. Sarah your suggestion is fanatastic, more relevant as well. I will change that now. As for my last section and images I will get to that tonight hopefully, just have been working full time over the break..
--[[User:Z3288196|Timothy Ellwood]] 10:24, 9 September 2011 (EST)

Hi, I have changed my table even more - hope you like it. In the end we might have to match the colours but we cna do that together in the lab. How is doing epidemiology, I planned on using exact the picture for clinical section where I describe facial abnormalities. That was the best one I found - that other children looked so said. Any way, may be I can steal it or I try to find another one.
Tim, I also thought I suggest, if you still can's find enough you could look into more specific stuff. For example into research of how to improve cardiac surgery, treatment for immunodeficiency etc... there should be loads out there. Any way, we are doing great team! --Anna Marx 16:40, 9 September 2011 (EST)

Hey guys,

Yeah, just have to put in a couple of images to help break things up. I've been looking at the things that the other groups have produced from the previous years and it looks really great, I think our project is beginning to look somewhat like that (which I feel will do us good!). I'm still trawling through some of the references and images; as for the epidemiology section, I've written all that I can find on that... if you guys want to put anything else in there feel free too but I feel there's a lot of repetition throughout the literature and what I've written covers epidemiology quite well. Having looked at some of the other groups we've done a really great job, anna, feel free to upload those pictures so that we can all have a look :)--[[User:Z3288827|Leonard Tiong]] 22:09, 9 September 2011 (EST)

Hi yeah, I will on Monday. I am sorry that I can't do it earlier! --Anna Marx 21:42, 10 September 2011 (EST)

==week 6==

hey awseome work with the page but u have to put references on your work asap or we will get done for plagiarism --[[User:Z3288729|Sarah Jenkins]] 07:18, 23 August 2011 (EST)

Yep, I'm working on it now. Is tim still working on the project with us? He hasn't written anything for his sections yet.. --[[User:Z3288827|Leonard Tiong]] 08:50, 1 September 2011 (EST)

Hey guys. Yeh im working on my sections, havnt posted anything up at all coz have been sick for the last week or so, and then working all weekend. I plan to have the majority of mine done by tonight though, then will start the editing process overall later in the week i guess. Sorry to hold things up.
--[[User:Z3288196|Timothy Ellwood]] 08:57, 5 September 2011 (EST)

== Discussion==

Hey sorry I missed the lab class today, im having some family troubles but will be back in sydney on the weekend. If somebody could let me know what happened etc I would really appreciate it. Are we still doing Duchennes or did another group choose it too?

Hello,
I hope that you family gets better soon. So, we had to flip a coin with another group about Duchennes and unfortunately lost. We decided that we'll all think about what else we would find interesting until Sunday and post our suggestions here so that we can make a decision about it on Sunday or early this week. If I understand right, it would be the best if we find a disorder that is really caused during embryonic development. Hence Duchennes and Thalassamia for example are not the best ones any way.
Have a good week end guys.
--Anna Marx 18:51, 11 August 2011 (EST)

Thanks Anna, I will have a look at some now and see what I can find :) --[[User:Z3288729|Sarah Jenkins]] 15:20, 12 August 2011 (EST)

== New Ideas==

* Conjoined twins. It results from abnormalities in the original process of cell division.

http://www.ncbi.nlm.nih.gov/pubmed/15278382

* Spina Bifida is due to incomplete closing of the neural tube

http://www.ncbi.nlm.nih.gov/pubmed/19918803

http://www.ncbi.nlm.nih.gov/pubmed/21790891

* Cri Du chat syndrome

http://www.ncbi.nlm.nih.gov/pubmed/21112524

http://www.health.medicbd.com/wiki/Cri_du_chat

* Ectodermal dysplasia

http://www.health.medicbd.com/wiki/Ectodermal%20dysplasia

http://www.ncbi.nlm.nih.gov/pubmed/21814340

== Another Idea ==

Hi! I think there are so many interesting congenital diseases/abnormalities which we could choose. I have had a look around and I think that [[DiGeorge Syndrome]] would be a good topic! First, it is due to some abnormalities in the chromosome 22, hence there is a genetic component. Second, it occurs in 1 of 4000 people and there are lots of variations from person to person, hence there will be a lot of research and a lot of information that we can use. Third, a defect in the migration of neural crest cells is included, which means it happens during embryonic development. So, may be you can have a look into it and let me know what you think.
Have a good week end, Anna
--Anna Marx 15:03, 13 August 2011 (EST)

I had a quick look and this looks like a good one. I'm happy to do DiGeorge if everyone else is?? --[[User:Z3288729|Sarah Jenkins]] 10:40, 14 August 2011 (EST)

Ok, sounds good! What about the rest of the group? Do you guys like DiGeorge too? I am open for any other suggestion, however I would suggest, that we make our decision soon, so that we can start our research about it. So I'll open a little "Agree with you signature" box and wait what happens :) --Anna Marx 17:41, 14 August 2011 (EST)

== DiGeorge Syndrome ==

If you like to make DiGeorge Syndrome to our team project, sign below.

--Anna Marx 17:43, 14 August 2011 (EST)
--[[User:Z3288729|Sarah Jenkins]] 19:09, 15 August 2011 (EST)
--[[User:Z3288196|Timothy Ellwood]] 09:30, 16 August 2011 (EST)
--[[User:Z3288827|Leonard Tiong]] 00:21, 17 August 2011 (EST)

==Project Plan==

I think it is important to keep moving on with the project. We need to quickly agree on things and get the job done. From previous experience, getting the work done early is a benefit to everyone involved. The project needs to be broken down into subheadings. I have listed some below which need to be covered without doubt, and I am open to other ideas as well. If everyone could pick 2 that they are happy to take on it means that everyone will have a round about even job. I spoke to [[Anna]] Earlier and she said she was willing to do the drawings. Is that still ok? If so I think its fair that you only have to do one subheading of theory work.

* Introduction (Sarah)

* Historical background of the disease and its research (Sarah)

* Epidemiology (Leonard)

* Etiology (Tim)

* Pathogenesis (Leonard)

* Clinical manifestations (and explanations of these) (Anna)

* Treatment options if available (Anna)

* Diagnosis of the disease, pre and post natally (Sarah)

* Further research possibilities (Tim)

* Image (Anna)

I would prefer it if i could do the introduction, historical background and diagnosis. I am willing to do 3 because the introduction is a pretty easy one. If anyone has a problem with this let me know. I also think first in best dressed to picking topics. I only think its fair and if not, we can sort it out later.
--[[User:Z3288729|Sarah Jenkins]] 19:09, 15 August 2011 (EST)

Hi, thank you for the layout. I think it is a good start!
I an still happy to do the drawings. So let me know if you have specific wishes or if you have suggestions of what we/I need to draw. I can also do Clinical manifestations and treatment options, which would make it three as well. However I thought pathogenesis will be a big one because that would include all the genetics. May be it will be enough if one person on it's own. Otherwise etiology would go well with it, leaving epidemiology and further research for the last one;) Further research might be big too... However, I am open to adjust. --Anna Marx 21:03, 15 August 2011 (EST)

Hey guys, sorry I haven't been in touch, just been busy with some orchestra stuff outside of uni. The stuff so far sounds great, I'll get to work tomorrow getting some papers together and seeing what I can find out about the condition. I wouldn't mind doing the epidemiology and pathogenesis sections - Anna, I think he said we only had to submit one self-drawn picture but I wouldn't mind doing some either, since I draw everything for anatomy :D either way, let me know what you think! So far things sound really great, thanks for getting so much done and once again my apologies for not having chucked in my two cents earlier!
--[[User:Z3288827|Leonard Tiong]] 23:02, 15 August 2011 (EST)

Awesome, now that we are on the way there it should be easier to focus our reading. We also need to do a glossary, and i think its easier if we do it as we go. so when we come across words that need a definition (to non science people) just chuck it in the glossary. even if we define it later, having it there is easier than having to go through and pick them out later. :) thanks for being so enthusiastic. :) --[[User:Z3288729|Sarah Jenkins]] 07:13, 16 August 2011 (EST)

Hey guys, sorry for the late addition, busy with various other things as I'm sure most of you are! Im happy to take the two headings that are left over. Also it looks like some of the other headings might contain alot more work than the two I've got, i think the further research one could potentially contain alot but unsure at this stage.so i would be happy to share another one and help out if anyone would like?? It was suggested above that Pathogenesis and etiology could go well together.... Let me know. Glossary sounds like a great idea!

Also i thought it would be a good idea if before the lab on Thursday if we could each try to find say 2 articles that relate to the heading we have selected.. Similar to what Dr Hill asked us to do for last week but now we have our topics etc. it should help to get us up and running.
--[[User:Z3288196|Timothy Ellwood]] 09:29, 16 August 2011 (EST)

I have set up sections below for us to put any references we find. it makes it easy to find the ones we need, and if other people come across good references for a topic other than their own it allows us to share :)--[[User:Z3288729|Sarah Jenkins]] 15:22, 16 August 2011 (EST)

Hey tim, more then happy to switch doing etiology with you but I wouldn't mind doing both together either. We'd better tell Mark to change our title over to DiGeorge's syndrome, I'll get some papers up in the mean time but will be really busy until thursday! :(

Update - Hey guys, just found a rather general article on DiGeorge but thought it was interesting, will leave the link here, if you guys got a moment have a trawl through :) I don't know what I'm still doing up at this hour :\ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954737/?tool=pmcentrez I'll have a read of it tomorrow morning :)
--[[User:Z3288827|Leonard Tiong]] 23:55, 16 August 2011 (EST)

Assuming that was Leonard above? I dont mind at all, maybe we can talk about it on thursday and sort something out. In the meantime i guess ill try find whatever articles I can on both topics.

Also just thought i would point out this resource [http://www.nationwidechildrens.org/22q11-deletion-syndrome], as it says that DiGeorge Syndrome (DGS) falls under the the title of 22q11.2 Deletion Syndrome, which apparently includes a number of other very similar disorders such as Velocardiofacial Syndrome, Conotruncal Anomoly Syndrome, Autosomal Dominant Opitz G/BBB Syndrome, Cayler Cardiofacial Syndrome and Shprintzen Syndrome. Not sure if we wanted to include these in our research, but worth considering I think as there could be alot more research under one of these titles and allow us for a broader and more accurate picture of the disorder as a whole.

--[[User:Z3288196|Timothy Ellwood]] 15:21, 17 August 2011 (EST)

Good work guys, our project has taken shape already. I have now changed our project title, hence we should be safe and good to go! See you tomorrow in the lab --Anna Marx 20:19, 17 August 2011 (EST)

Things are looking really splendid guys, I'm starting my sections now but it doesn't seem like there's that much for me to write on. I'll try to see if i can spruce things up a little bit more. Referring to several textbooks (anyone got any suggestions?) for some of my basic info, and I'll find original sources later. But yeah, difficulties in trying to find specific information. Especially since there's so much overlap at the moment with the other different names. So far the four major ones that I got (I know you guys have included them) but four definite names involve (obviously) DiGeorge syndrome, Velocardiofacial Syndrome (VCFS), Conotrunchal anomalies facie syndrome (CTAF) Syndrome, and CATCH22. I don't think CATCH22 is a diagnostic name but rather a mnemonic that helps them remember the symptons of DiGeorge. Onto my writing! Just another thing that I'm well aware of, I haven't put many references into my work as of yet, still trying to find the best sources for the information. I've got a bunch of them written down and need to just go through them to make sure that I've the right sources from the right place but my laptops out of battery at the moment :( I'll try to get that done by tonight or tomorrow. :) --[[User:Z3288827|Leonard Tiong]] 18:25, 22 August 2011 (EST)

== Review Article ==
Hey guys, just found a review article that I thought was rather interesting, it's an animal model for Duchenne's muscular dystrophy[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022202/]. I also found a primary journal article that discusses drug delivery for the condition [http://www.jstage.jst.go.jp/article/bpb/34/5/712/_pdf]. I will print these articles for myself tonight and give them a quick read tomorrow and then paste a quick summary of the articles here just for you guys to consider :)

'''Review''' [http://www.ncbi.nlm.nih.gov/pubmed/21274260 Mammalian models of Duchenne Muscular Dystrophy: pathological characteristics and therapeutic applications.]

'''Primary''' [http://www.ncbi.nlm.nih.gov/pubmed/21681700 Detection of duchenne/becker muscular dystrophy carriers in a group of Iranian families by linkage analysis.]

--[[User:Z3288729|Sarah Jenkins]] 10:00, 6 August 2011 (EST)

'''Primary''' http://www.ncbi.nlm.nih.gov/pubmed/15991868 Diagnosis and management of Duchenne muscular dystrophy in a developing country over a 10-year period.

'''Review''' http://www.ncbi.nlm.nih.gov/pubmed/14526374 Advances in Duchenne muscular dystrophy gene therapy.

--Anna Marx 12:52, 8 August 2011 (EST)

----

'''Duchennes Muscular dystrophy'''

----
--[[User:Z3288827|z3288827]] 21:53, 8 August 2011 (EST)

== Review Article ==
Hey guys, just found a review article that I thought was rather interesting, it's an animal model for Duchenne's muscular dystrophy[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022202/]. I also found a primary journal article that discusses drug delivery for the condition [http://www.jstage.jst.go.jp/article/bpb/34/5/712/_pdf]. I will print these articles for myself tonight and give them a quick read tomorrow and then paste a quick summary of the articles here just for you guys to consider :)

== References ==
[1] Nakamura A., Takeda S.; Mammalian Models of Duchenne Muscular Dystrophy: Pathological Characteristics and Therapeutic Applications, J. Biomedicine and Biotechnology Vol. 2011, Article ID 184393

[2] Yukihara et al; Effective Drug Delivery System for Duchenne Muscular Dystrophy Using Hybrid Liposomes Including Gentamicin along with Reduced Toxicity, J. Biol. Pharm. Bull, Volume 34, No. 5 pp. 712-716

== Found References==

===Introduction===

[http://www.ncbi.nlm.nih.gov/books/NBK22179/ DiGeorge]

[http://emedicine.medscape.com/article/135711-overview DiGeorge Anomaly]

===Historical Background===

=== Epidemiology===

[http://emedicine.medscape.com/article/886526-overview#a0199 Epidemiology]

===Etiology===

A Genetic etiology for DiGeorge syndrome [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682598/]

Inactivation of TGF􏰀 signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome [http://genesdev.cshlp.org/content/19/5/530.full.pdf]

A deletion in chromosome 22 can cause digeorge syndrome [http://www.springerlink.com/content/r85p0r5q05rj6w88/]

DiGeorge syndrome phenotype in mice mutant for the T-box gene [http://webcourse.cs.technion.ac.il/234523/Winter2002-2003/hw/WCFiles/DiGeorge.pdf]

=== Pathogenesis===

[[http://www.ncbi.nlm.nih.gov/pubmed/20833244 Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: patterning, proliferation, and mitochondrial functions of 22q11 genes]]

[http://emedicine.medscape.com/article/886526-overview#a0104 Pathophysiology]

===Diagnosis===

[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=10600329&ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Diagnostic Criteria]

===Clinical===

{http://www.ncbi.nlm.nih.gov/pubmed/19665396 Seizures and EEG findings in an adult patient with DiGeorge syndrome: a case report and review of the literature.]

http://www.chw.org/display/PPF/DocID/23047/router.asp

===Treatment===

===Research===

This looks like an excellent resource, listing over 100 research papers on nearly every aspect of DiGeorge from the 70's to present. [http://omim.org/entry/188400]

Deciphering DiGeorge Syndrome: Big Advances In Understanding Microdeletions [http://www.sciencedaily.com/releases/2005/03/050308134838.htm]

== Images==

FISH carried out to detect DiGeorge syndrome. FISH is abbreviated as fluorescent in-situ hybridisation and is carried out to detect abnormalities whilst babies are still developing in the womb. --
[[Image:FISH_for_DiGeorge_Syndrome.jpg|400px|left|FISH to detect DiGeorge syndrome[1]]]
[[User:Z3288827|Leonard Tiong]] 00:17, 17 August 2011 (EST)

[[File:DiGeorge T cell receptor Diversity post thymus transplant.jpg|400px|left]]

--[[User:Z3288729|Sarah Jenkins]] 08:54, 18 August 2011 (EST)

Facial manifestations of patient with DiGeorge Syndrome

[[File:Facial manifestations of patient with DiGeorge Syndrome.jpg|left]]

--z3279511 21:18, 17 August 2011 (EST)

Talk:2011 Group Project 2

2011-10-02T05:23:38Z

Z3279511:

[[2011_Group_Project_2|'''Group 2''']]: [[User:z3279511]] | [[User:z3288196]] | [[User:z3288729]] | [[User:z3288827]]

{{2011GroupDiscussionMH}}

'''Page Edits 30 Sep'''
<gallery>
File:2011_Project_Group_2_edits.jpg|Project Page
File:2011_Project_Group_1-11_edits.jpg|All Groups (1-11) Project
File:2011_Talk_Group_2_edits.jpg|Discussion Page
File:2011 Talk Group 1-11 edits.jpg|All Groups (1-11) Discussion
</gallery>

==Question==
Hi, does someone know how I can change my table in clinical manifestations in the way that there is a space in between each section? --Anna Marx 16:23, 2 October 2011 (EST)

==The Final Fix up==

hey not sure what you guys think but what if we take the advice we got on our own sections and focus on fixing them up? I can go through and link the terms to the glossary if someone else wants to fix up the references?

Hi, sounds like a good idea! Will do my part over the week end. anna

Group 2 Critique:
*What Can I say, well researched, nicely sub headed.
*Historical Background shows amazing work. The only 2 things I noticed are the “ 22q11 is in purple” is that on purpose? And the second thing is the image has a source but no reference.
*Epidmiology and Etiology may need some images to balance the words. Also, some spacing between the paragraphs would make it more readable.
* Nice illustration via drawings in the Pathophysiology sections . well structured.
* This section is well established, it has colours and few paragraphs. You might want to consider the size of images probably into something bigger like (Based on symptoms, Ultrasound) and add one more photo in the last two sections (Amniocentesis, BACS- on beads technology)
* one of the best sections on this page is Clinical manifestations. Great work on the table. Perhaps more images along with the abnormality would make a more presentable table. Also, you may consider re-phrasing ( the sub-heading “ How it is caused”) into something with one word. Fabulous work on Heart Drawings.
* in the Section of “ Current and Future research”, allocation of each would be more organised.
The large number of references show how much you guys spent on the page. Some of the references may need to be formatted ( 1,2,3,4,5, etc) note: reference 33,40,47,49, are empty . Overall Great Job.
z3284061

'''Group 2'''

* Well researched and set out page
* An image is needed in either Epidemiology or Etiology would be good
* Diagnostic section tests section is good, however, images are needed for BAC and Amniocentesis
* Glossary is well set out, maybe links to the glossary would be helpful
* Subheadings might be useful in the Current/future research section
* some of the referencing will need to be fixed such as double references
--[[User:Z3292953|z3292953]] 11:11, 29 September 2011 (EST)

'''''DiGeorge Syndrome (Group 2) Peer Review:'''''

Introduction: Well introduced topic. Picture needs description at bottom. Seems to be referenced appropriately.

Historical Background: Extensive timeline which is good. Try to be a little bit more consistent with the colon – either place it after the date or not. Also, picture seems a bit random and needs to have a description at the bottom so that the reader knows what it encompasses.

Epidemiology: Could be a bit more spaced out to make it easier for the reader to read through.

Etiology: Good information and referencing. Try to include a picture in this section as it would help the reader visualize what you are conveying in words.

Pathogenesis/ Pathophysiology: This section is well done. Information is good and images are well-drawn and also contain a relevant description at the bottom. Well done!

Diagnostic Tests: Very extensive. Great use of images. Could you possible also find an image for amniocentesis and BACS? Some image references are not in the correct format and images in this section need to have a label at the bottom.

Clinical Manifestations: This section is well done as well. Possibly too much information which may overwhelm the reader though.

Treatment: Slight inconsistency with the formatting, but otherwise no major dramas. Also possibly more images needed in this section.

Current and Future Research: This section is quite interesting. Research is extensive and images are good – however, they lack correct referencing format and the student template in the information section.

Glossary: Extensive. Well done.

Overall, good job! --[[User:Z3290808|z3290808]] 10:40, 29 September 2011 (EST)

Group 2:

There seems to be a lot of references, almost an excessive amount.

A picture for epidemiology and aetiology would be good.

Diagnostic tests was done well

Clinical manifestations should include some info on what the normal structure and function of the heart.

There is a very large amount of written information and this is reflected in the reference section that takes up alot of space on the page. There are slabs of writing which makes it hard to read the page. It’s boring to see long slabs of writing. The long glossary reflects the long slabs of writing. It’ll be hard to read through. Its not that clear and concise.

z3332178 =]

'''Group 2:'''

*Intro: the first sentence is a little vague. Rather joining sentence 1 and 2 together and defining congenital disorder and explaining it at the same time would be better. I liked the pictures but the trio in that arrangement left the section looking a little unfinished.

*Historical background: image is not explained, a little confused as to why it is there.

*epidemiology: good section, good referencing

*etiology: its a little awkward in flow as you jump from talking about one study, and after one sentence talk about what another study said. Maybe work on building it into an actual paragraph instead of making them merely sentences.

*pathogenesis: the images would look better if they were larger so you get the vague image of it at a glance. Good section, flows nicely

*diagnosis: great section. Layout made it easy to read. Maybe increase the size of the image in the symptoms part, this was harder to see.

*clinical manifestation: good section. Maybe with the last set of images with the heart, leave a space or include a pink heading like you did for the table above it to indicate another table. This was hard to see

*treatment: good section. Maybe change the colour of the bit that you highlighted in that pale orange/skin colour thing. It’d be nice to have that stand out a little more so those headings can actually be seen and not seen as random words.

--[[User:Z3290558|z3290558]] 09:55, 29 September 2011 (EST)

'''Peer review'''
WOW!
This page looks fantastic. The editing is great. All of the information is presented neatly and concisely.
However, just look in "historical background" and make sure all of the lines are edited uniformly. Some have ":" some don't.
Obviously that is nothing major, I'm just nit-picking.
I think you may want to redraw your "pathology of Di George syndrome". It seems quite cluttered.

Overall: Excellent. There really isn't much to say about this page.

--[[User:Z3290618|Ziggy Harrison-Tikisci]] 10:29, 29 September 2011 (EST)

'''Group 2 peer review'''

Introduction: Please explain what the images is about.

Historical background: Please be careful that you type 'DiGeorge syndrome' throughout the section. For example, the point about the 1981 event has 'diGeorge syndrome'. There are also some spelling errors. Furthermore, a legend for the image would clarify.

Epidemiology: Breaking up the segments with images will make understanding the content easier for the reader.

Diagnositic test: Information on the ultrasound test, particularly the second paragraph, is repetitive. The layout is great and the images breaks up the text nicely. A legend for the image will be good. In particular, please clarify what is abnormal with the male face.

Treatment: Are 'Hypocalcaemia' and 'Psychiatric illness' a late occuring feature or an observable condition in newborns.

--[[User:Z3289301|z3289301]] 09:42, 29 September 2011 (EST)

'''Peer Review'''

:*The first three sentences about congenital disease is misplaced. This should be in your glossary, not in your very first sentences.

:*The common symptoms could be left out of the introduction and discussed in the appropriate section.

:*Written like an essay rather than a webpage. Language such as “for example” not necessary.

:*Clinical Diagnosis was well structured and good use of pictures.

:*Clinical Manifestations could be simplified slightly in the table.

:*Some references need to be adjusted rather than just a web address.

--[[User:Z3217043|z3217043]] 08:42, 29 September 2011 (EST)

'''Peer Review'''

This wiki has obviously been given a lot of time and effort and it shows. The text isn't too heavy and I've learnt a few things about DeGeorge Syndrome. Very thoroughly researched and overall, looks and feels very neat and concise. A few points to be made:

:*No need to define congenital disorder. I recommend just leaving it out entirely.

:*Some pictures still need to be captioned even after addressed by Mark Hill. Who is that person in the History section? Angelo DiGeorge? Which one is he?

:*The student drawn images are the let-down. They look very rushed and haven't been given enough effort. The student drawn images on the wiki is also small, so to read the accompanying text by expanding the image, breaks up the flow of reading the wiki. It also hasn't followed the referencing format.

:*BACS- on beads technology image is a pdf file. Either put a picture in the designated area or remove the reference.

:*Amniocentesis doesn't have an image.

:*You should refrain from using the words "mental retardation" as this could be deemed offensive. Use "intellectual disability" as that is a more common term now used in Australia. Also use "learning difficulty" or "developmental delay". We should also encourage the use of person-first language e.g., "a child with an intellectual disability" rather than "intellectually disabled child". This promotes the idea that a person comes before their disability.

:*References section needs attention. Some referencing are not present at all in some casees.

--[[User:Z3293267|z3293267]] 07:12, 29 September 2011 (EST)

'''Group 2 Peer Review'''

• Your overall structure and layout of the page is really good! It’s really neat and all the images and text seem to be in proportion.

• All your pictures, graphs and tables show that you have a good understanding of this abnormality.

• The introduction gives a really good summary of the disease, however I think you should introduce the disease first and then go onto
to explain ‘congenital disorders’.

• Epidemiology could probably be broken down into sections, to make it an easier read and more interesting.

• The aetiology section needs an image to break up a large amount of text also to make it more interesting and informative.

• Good use of subheadings in the pathogenesis, very relevant! Student drawn images are good, could they be a little neater?

• Diagnostics test is really nice and clear, however consistency with the colour of the tables would be good.

• Clinical manifestations section has really good information, I think it could be structured better though, for example; only have the table describing each sign and symptom and then have another sub-heading related abnormalities where you could include ‘Teratology of Fallot as an example...’ (Just an idea).

• Current future research is obviously researched thoroughly, breaking it down into relevant subheadings would really improve it though.

• Make sure you fix up your repeated references. But good work overall!

--[[User:Z3289829|z3289829]] 02:40, 29 September 2011 (EST)

*Intro: Great intro, the picture is excellent and grabs your attention. Perhaps don’t start with a definition of congenital disorders. You can put that in the glossary or mention it after you have initially began discussing the disease.

*History: Love the timeline, clear, easy to follow.

*Epidemiology: Very word heavy which is not necessary for this section. Dot pints or some sort of visual representation would make it more appealing.

*Etiolgy: “ mentioned previously it has a prevalence of 1/2000 to 1/4000” This part is not necessary. Image of the gene would look good in this section. You refer to the disease as DGS (which is perfectly fine) but repeatedly refer to it as DiGeorge syndrome in the previous section, which can get a little confusing. Either use its full name or just the abbreviation.

*Pathogenesis:“As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion” probably unnecessary.
Excellent image, perhaps make it a bit bigger so that you can refer to it whilst reading.

*Diagnosis: The formatting of the text against it’s visual representation is fantastic and love the use of colour – refreshing! The use of colour can be expanded to the rest of the page to make it more cohesive. There is a an image heading with no image under the “ Amniocentesis” heading. There is also an image missing in the BAC’s image column replaced with a link- should fix this.

*Clinical manifestations: Once again great use of colour, but VERY word heavy. It shows that you have done a lot of research but it’s a lot to take in, you can definitely make it more compact.

*Treatment: I quite like this section. It’s informative and is formatted in a way that won’t bore you. The sections which have big blocks of text could benefit from this format. You need to choose a different colour for the block highlights though because you can barely see it.

*Research: Thorough research, very informative but again too much text. If you feel it’s necessary to keep the text you can break it down with word highlights/ bolding or dot points.

*Text/image: Great ratio except a few sections where the text can be cut down a little bit.

*Overall, very thorough, loved the colour and formatting and the student drawn image. Excellent work.

--[[User:Z3290270|z3290270]] 02:37, 29 September 2011 (EST)

'''Peer Review for Group 2'''

'''Peer Review'''
* Many of the pictures do not have a legend/explanation associated with them. However, the hand-drawn picture is underscored by a legend.
* The introduction is rather abrupt; definition of "congenital disorder" could have been a simple hyperlink or a note in the glossary.
* Is the historical background necessary? In the section, the photo of the two people is not explained.
* Section on epidemiology seems to cross over significantly with clinical manifestations.
* Thorough referencing throughout. However, some of the references appear strangely in the references section (could be a vestige of that crash a few weeks earlier?)
* The table in clinical manifestations is strangely.....implied. Section on Tetralogy of Fallot can be cleaned up in terms of layout.
* Inclusion of current and future research is noted, and well set out/referenced.
* Glossary is thorough.
* Overall, a very thorough and broad exploration of the topic.
--[[User:Z3290689|z3290689]] 00:11, 29 September 2011 (EST)

*I don’t think it would be necessary to start the intro with clarifying what congenital diseases are. It would be better if it starts with, ‘Di George Syndrome is a …’ sentence.
*In the intro, fix this sentence as it needs punctuation, ‘As there is currently no treatment education is vital to the wellbeing of those affected, directly or indirectly by this condition’
*Nice picture of Angelo, and also the history is presented well as it makes easy to read and follow.
*Information presented in the epidemiology section is interesting but not organised properly so it flows. Please fix this up.
*Etiology has some technical jargon that is not explained or put in the glossary. Please do so
*Thumb picture of the area where 22q deletion occurred doesn’t show when viewing the page.
*The first line of the Pathogenesis section is, I believe, not necessary as the section just before it just mentioned that fact.
*Punctuation needed for ‘ ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud’
*Pathogenesis/physiology easy to read and has good drawn diagram
*The diagnostics section has good information of how the tool works, what it detects and an image refering to the tool. However Amniocentesis section has no image and yet has a column for it. Please fix this if there is no image for it. Also the Ultrasound section should include what DiGeorge patients would have on Ultrasound scans.
*It is good that the clinical Manifestations section is presented in that way in the table as it explains the abnormalities really well.
*The four images in the Tetralogy of Fallot section may make the reader seem that one of these problems may occur, whilst all four problems are present in the TOF heart.
*The treatment section has information in regards to symptoms. This be under another subheading altogether and not under the treatment section
*Current and Future Research section provides the reader with a good image of the current status of this disease in regards to research.
*References are not properly formatted as repetition in the referencing could be seen. Please fix this.
*Please balance the text to image ratio as the page is text heavy and can be hard to read unless it is complemented with more images.
*Other than that good page.

--[[User:Z3291317|Z3291317]] 23:46, 28 September 2011 (EST)

'''Group 2 peer evaluation'''
*The introduction is done quite well. It is succinct and brief. You have done a very good introduction to the topics that your page is about to explore. Unfortunately you did fail to introduce some of the headings that your page have, like the diagnostic section. Aside from this it is a good introduction overall.
*Historical background is done very well. It has enough detail to see the ongoing achievements on the disease.
*The epidemiology was excellent. You have covered the demography of the disease and properly cited some of the facts that you try to get across. Revision of some of the sentences may be needed because some sentences are not expressed properly. Also it would have been really nice if you could incorporate some of the data that was mentioned in a more summarized form, like a table, dot points, or something. It just makes reading easier and less likely to get lost in the words
*I really like how concise yet very informative your etiology section. What would make this section better than what it is at the moment is an image that would complement the information, and also a bit of an explanation about some of the terms that is in there, like “hemizygous”.
*The Pathogenesis section is very well done. It contains enough detail that we get an in-depth knowledge about the development of the disease, and the images that were used are very helpful. One thing that would improve it though is that if you can elaborate further on the function of the TBX1 gene and how affecting the expression of this gene results to DiGeorge.
*The Diagnostic test section I think is perfect. The way the test works was described, and at the same time they were all related back to how this aids in the detection of the disease. The layout of the information is also very engaging.
*Clinical manifestation is very nicely done. The information was very descriptive and informative. It is also presented very well. Just one thing though is that there is no clear separation between two clinical outcomes, so it tends to get confusing sometimes when someone is reading it. I guess adding more space between would be a good idea.
*Treatments section is done quite well. If you could add a video of some of these treatments or even just a link to a video of it that would really make this section perfect.
*The research section is also very good, especially your insight to future direction of research on this disease. I guess it wouldn’t hurt to drop some current research articles within this section, which shows the readers that the information that they have just read is up-to-date.
*Glossary is a good idea, not really a big fan of it but good idea anyway.
--[[User:Z3290841|z3290841]] 10:20, 29 September 2011 (EST)

'''Group 2'''

Introduction: Introduction is good. The pictures look great.

Historical background: I like the timeline. I think the picture needs a caption underneath explaining who the people are.

Epidemiology: Needs some pictures to break up the text.

Etiology: This section is quite difficult to understand. I think a lot of terms need explaining eg. hemizygous deletion, microdeletion and halpingoinsufficiency.

Pathophysiology: This section is much easier to understand and flows quite well. The pictures should be bigger though.

Diagnostic tests: great section! Good layout and easy to read. The symptoms picture could be a bit bigger and it would be good if there were pictures for the bottom two.

Clinical manifestations: Again, great section. The table could use some more pictures though to balance out all the text.

Treatment: Needs some more pictures.

Current and future research: This section is quite well explained and has a good level of detail.
--[[User:Z3291324|z3291324]] 23:18, 28 September 2011 (EST)

'''Group 2:'''

•I’m not sure if you need the definition and explanation of congenital disorders at the very beginning of the page. The third sentence beginning with DiGeorge syndrome would make more sense as the beginning of the introduction.

•I like the use of images in the introduction and at the beginning of the page, but they are not referred to in the text and do not include captions. Perhaps you should include a brief caption under each image explaining what the image is portraying and why it is relevant.

•Be careful with the wording of some things, particularly in the introduction, i think some parts need to be edited and reworded as they are a little confusing to read.

•The fact that the timetable in the history goes all the way up to 2011 is good and this section seems to be referenced well.

•The student drawn image of the heart defects do not include the correct template that is required for proper copyright information.

•Good use of tables to break up the text, although the different colours is a bit distracting, i would recommend choosing one colour and using that throughout the page.

•The referencing needs to be fixed up as many references appear multiple times in the reference list.

--[[User:Z3332183|z3332183]] 21:24, 28 September 2011 (EST)

'''Peer Assessment Group 2-DiGeorge Syndrome'''
*The introduction and history look good with great use of images which makes for an interesting start.
*There could be at least one other picture in 'Epidemiology' and 'Etiology', otherwise it just looks like a big block of text
*The 'Diagnostic Tests' look good-the image for BACS still need to be uploaded
*The student drawn images are colorful however doesn't have copyright information-just states who drew them
*Some sentences seem incomplete or doesn't seem to convey a message e.g. "Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists".
*'Current and Future Research' has a lot of information however is it possible to condense it and give a basic summary instead. I understand that you have tried to do your best but it is just a lot of information. You might also wnat to consider using sub headings.
*The references need a bit of attention-you have a lot of links there which need to be changed to proper references
--[[User:Z3308968|Tahmina Lata]] 21:13, 28 September 2011 (EST)

'''Group 2 Peer Assessment'''
*Good introduction. Like the use of the image to grab the reader's attention but it might be a good idea to include one or two sentences in the text explaining the characteristic appearance of the patients and give the image a title (just to link the image to text straightway at first glance without having to click on the image to understand it's significance).
*Not sure if you need to explain the term 'congenital' in the introduction. Might be better to start straight away on the actual syndrome.
*Great job on the "Historical background" section. Maybe have small title for the image of Angelo DiGeorge.
*Good explanations in the 'epidemiology' and 'etiology' sections but the text is a bit too heavy. Try breaking it up with an image.
*Good use of images, table and the general arrangement and layout of information in the 'Diagnostic test" section. (Small spelling error in section name). Try to include an image in the "Amniocentesis" section as well to complete the table.
*Needs to explain the link in the "BACS- on beads technology" section and why it has been inserted.
*Like the student drawings in the 'tetralogy of fallout' section and good explanations of what is happening. Small grammatical error in the title (on instead of an).
*Good job on the 'treatment' and 'current/future research' sections.
--[[User:Z3291622|Z3291622]] 16:17, 28 September 2011 (EST)

'''Group 2'''

*The whole page is very nicely formatted
*Introduction is clear and concise although would it be more efficient to start talking about DiGeorge straight away rather then define congenital abnormalities?
*Historical background is obviously well researched
*There needs to be an image in epidemiology and/or etiology to break up the text or present some of the information in a table
*The pathogenesis section flows nicely although a few words need to be added to the glossary
*Great table for diagnostic tests- this makes it easy to follow
*A few more pictures would be great for clinical manifestation and maybe this would be better in dot points?
*Student drawn images of tetralogy of fallot were excellent
*Subheadings are needed for Current/future research
*Good project overall, obviously a lot of effort has been put into this.

'''Group 2 - Peer assessment'''

*The introduction is easy to read and understand. Maybe one thing you could improve on is the organization of the paragraphs because it looks abit too choppy as of now.
*The history looks amazing and well researched AND well referenced! Makes me believe and trust your project even more. Furthermore the picture on the right just makes the section more appealing.
*Epidemiology - the information flows well and examples are also mentioned which is nice to see
*Etiology - The information is ok but maybe it could be better explained with explanation of the technical terms within your texts
*Pathogenesis/Pathophysiology - the student drawn images look amazing! And the organisation of information is good. Maybe a suggestion would be to hyperlink some of the terms in the text because there was alot of technical terms to be scrolling down and up for.
*Diagnostic Tests - The layout is very appealing and consistent with the rest of the page. The spelling of the heading is wrong!
*Maybe for the glossary it would be a good idea to include headings such as "A", "B" etc
*Fixing up double referencing would be a good idea aswell

--[[User:Z3330313|z3330313]] 19:36, 28 September 2011 (EST)

'''Peer Assessment Group2'''

*Epidemiology – hyperlink technical terms to glossary?
*The pathophysiology/pathogenesis sections (pharyngeal arches onwards) needs to be linked back to the syndrome. You list it in the “genes” section then describe the normal development, but it needs to be described to what happens in the syndrome/abnormal development.
*Don’t forget to add in the missing images in the diagnostic techniques
*You have several (excellent) summary tables – I think the format should be consistent in each, would make it look/flow better
*Typical symptoms: Newborn section can be condensed
*Current and future research could benefit by being broken up a bit – maybe use subheadings, colour or bold main points – it just is a big slab of text and looks daunting to read.
*References: some just have the PMID number and need to be fixed so it reads the whole reference (just for consistency)
--[[User:Z3332824|z3332824]] 23:18, 27 September 2011 (EST)

GROUP 2: DiGeorge Syndrome
*I don't know if the congenital disorder definition is needed in the intro, maybe you can included in the glossary instead
*The image in the intro could use a legend
*Info in the intro is comprehensive and informative
*History section has got good, succinct information and i like the fact that it goes up to 2011, however maybe you can consider putting the timeline in a table. Image could also have a legend
*Epidemiology has been researched relatively well, info is comprehensive and flows well, however, could be improved with a graph of some sort to accompany info with a visual
*Etiology contains very descriptive, informative info, could be improved with an image of the chromosome and the area of deletion
*It would be a good idea if the acronyms are included in the glossary
*It is evident that the Pathogenesis/Pathophysiology section has been very well researched, maybe the "genes involved in DiGeorge syndrome" section could be formatted in a table
*The use of a table in Diagnostic tests is succinct and informative. You should check for spelling mistakes (Dianostic Tests is spelt wrong), images to accompany these tests are useful, however, again a legend for each of these would be help
*Image missing in the Amniocentesis part of diagnosis
*I don't know if the image link for BACS- on beads technology is really helpful
*Clinical manifestations has clearly been researched extesively, however, this section is very overwhelming,too much text in my opinion. It would be easier to read if it was summarised more, a graph may be helpful
*Treatment section is comprehensive and summarised well
*I have found that incidence has been mentioned in quite a few sections, is this really necessary? Can it just be mentioned in epidemiology?
*Current and future has got some good info but it is quite lengthy and could be better to summerise it a bit more so u don't lose the reader
*The last two images need to be referenced properly, with the template and correct referencing

Overall:
*The whole project has been researched very well
*Some of the images could use legends to describe what they are about and you could also consider moving the images around a bit so there's variety and making some of them a little bigger so their features can be seen
*Maybe acronyms could be included in the glossary
*some sections could be reviewed and info could be condensed
*references need to be reviewed and correctly structured (some work on this is required)
*You could improve this project by also linking the glossary terms to the text to make it easier to access, also some graphs could be used

--[[User:Z3331556|z3331556]] 22:51, 27 September 2011 (EST)

'''Group 2: DiGeorge Syndrome'''
*initial browse through the webpage: well balanced use of text, image, colour and table format.
*introduction: well summarised and good use of image. It is interesting and provides a good overview to the syndrome. Minor adjustment: give one or two examples of symptoms rather than providing a list.
*Historical background: good use of timeline, and layout.
* Epidemiology & Etiology: needs to define terms in glossary such as velocardial syndrome.
*I appreciate the subheadings used in the pathogensis section... it breaks up the mass of information, creates flow and also shows understanding. Needs to define a few terms in glossary such as: hypoplasia, hypoparathyroidism, parturition etc.
*Diagnostic tests: well set out, I think the use of colour is aesthetically pleasing and adds to the overall presentation of the webpage.
*Clinical Manifestations: well set out and good use of images. Table could benefit from use of borders, just to clearly separate the rows where the information appears to overlap.
*Current&Future Research: could benefit from formatting of previous headings. That is, in a table to break up the information, or by using subheadings
--[[User:Z3332327|z3332327]] 15:42, 27 September 2011 (EST)

'''Peer Assessment group 2'''
*Introduction is clear cut and enters the topic with easy understanding though should incorporate the image more, where the image has no description of what its suppose to explain where symptoms would link to the image would help a lot.
*Timeline used correctly in displaying the increased understanding of the disorder, image used was does not have a description so don’t know who is the discover right or left and what is the image suppose to show.
*Etiology refers to a lot of studies or research which is not clearly explained how the research shows the causation of the disorder with various results showing different reasons for causation
*athogenesis clearly links image to the common deletion of gene with clear explanations of genetics component of Digeorge syndrome. Though would become more fluid with introduction of embryological effects instead of leading to pharyngeal defects.
*Embryological component didn’t expand the defects of the pharyngeal arches as well not much of the parathyroid which is major component of calcium levels also poorly linked to the image without any mention of the figure.
*Diagnostic tests require an introduction onto the topic and techniques, where heading directly states the techniques without any understanding of what these means.
*Clinical manifestations describes information clearly though the congenital heart defects images would work better below the information, so text and information with image below.
*Treatment has image relating to plastic surgery could have a description even though it’s a example of surgery.
*Current and future research should be more organised instead of paragraphs have dot points to know the difference between new research and current also images not place in correct manner but in between the glossary as well.
*Referencing has not been done correctly with only links, repeats and some are even blank.
*Glossary not linked to the term or bolded to note that it’s in the glossary so while reading its confusing if you have no pathology background.
z3332250 23:42, 26 September 2011 (EST)

Group 2 Peer Review

*Well structured page in terms of headings, good choice of topics covered
*Do not need to define congenital abnormality. If you want to define it perhaps add it to the glossary instead?
*Symptoms in introduction would probably be best in another section
*Great images. Some need to be made bigger in order to easily read the detail on it
*Most images are on the right side of the page. Could you move them around a bit to make it visually more appealing?
*Faint colour highlighting under treatment needs to be made darker or deleted
*Some duplication in referencing
*Well researched-great
*Overall, an informative and well presented page. Just some minor details which need to be adjusted to finalise page
--[[User:Z3308965|Fleur McGregor]] 16:55, 26 September 2011 (EST)

===Comments on Group Project 2===

Group 2

*By looking at your page it’s clear you’ve performed extensive research on DiGeorge Syndrome, well done on the effort
*Spelling needs to be attended to....’Diagnostic Tests’
*The image included in the introduction could use a legend. Maybe you could refer to it in the introduction, but to me it’s just a picture of 3 babies
*Nice work on the historical background, grammar could be attended to easily, just some minor things really. This timeline could be better formatted though, maybe in a table. The image included here doesn’t have a legend or some form of description. Just a picture of two old-timers shaking hands.
*Epidemiology is great although it might be useful to include an image of some sort if possible (I’ve got the same problem) as it’s just a block of text
*Etiology is good, very descriptive and evidence of a well researched sub-heading.
*Diagnostic Tests – clever heading, clever formatting and great information. The images included definitely need legends and descriptions
*Current and Future Research heading could be broken up with some sub-headings
*Glossary looks great

--[[User:Z3331469|z3331469]] 06:57, 29 September 2011 (EST)

'''Strengths:'''
*Good placement of sub-headings and headings.
*I like how the introduction gives an overview of the syndrome.
*All images have copyright statements.
'''Weaknesses:'''
*The epidemiology and etiology sections seem like really wordy, overwhelming to read. It is paragraphed but maybe the paragraphs could be more distinct.
*It would be good to link the words that is defined the glossary to the glossary.
*Some of the references are not formatted properly.
'''Specific corrections:'''
*It would be good if introduction immediately started with what is DiGeorge Syndrome instead of leading up with the definition/characteristic of congenital disorder. This definition can be shifted to the glossary
*Just curious, it will be interesting to hear how different the first sound of a DiGeorge baby differs from a normal one.
*”Dianostic Tests” is spelt incorrectly.
*Instead of the sub-heading “Based on symptoms”, it could be “Symptomatic diagnosis”.
*What is “clinodactyly” in the description of the image under “based on symptoms”?
*The link under images for BAC subheading could go under external links section?
*Maybe the table under “Tetralogy of Fallot...in DiGeorge Syndrome” could be vertical instead of horizontal? It will look neater.

--Z3389806 06:40, 26 September 2011 (EST)

'''Group 2'''

*Introduction: good content, but the symptoms do not really belong there.

*Very nice historical section, nice to read

*Epidemiology and etiology seem almost like one big section. Maybe separate the content a bit more (no repetitions), and break it done with subheadings.

*Pathogenesis: includes helpful explanations and information, good use of reasonable subheadings. The drawn images could have been done with more
accuracy.

*Diagnostic tests: very nice informative section, good use of images to visualize the content. I think the choice of colour for the table could be
better, maybe another shade of the pink (darker, red...) that has been used for clinical manifestations. The green disrupts the flow of the entire page.

*Clinical manifestations: very nice section, precise information, good structure, useful images.

*Treatment: lots of information in a nice form, but the image would look better on the right edge (like the ones in ” research” ). Good use of subheadings.

*Research: good content, but would be easier to follow if you would break it down with subheadings.

*Glossary: looks good, but explanations like “malformation: see dysmorphia” should be avoided. It would be better to define every term separately.
--[[User:Z3387190|Z3387190]] 11:34, 25 September 2011 (EST)

'''Group 2 Critique'''

#• The introduction needs to be re-written in proper English. Some of the sentences don’t make proper sense. Also, the introduction should focus primarily on DiGeorge’s Syndrome and not explain what a congenital abnormality is
#• Historical background was good
#• Epidemiology should not explain clinical features, such as the baby making a noise which is nasally in tone
#• Aetiology is ok
#• Pathogenesis is quite detailed, however genes should be explained a little more clearly
#• Diagnostic tests section was impressive
#• Clinical manifestations was good
#• Treatment was good
#• Future research was good
#• Glossary was good

Images were appropriately used. --[[User:Z3289991|Robert Klein]] 18:36, 24 September 2011 (EST)

Group 2

Hey Group 2, firstly, well done on putting in the effort to create this page, it really shows your dedication and cooperation as a team! Here are some points I thought you could improve on to take this page to that extra level

#The key points relating to the topic that your group allocated are clearly described.
#* Introduction: Good overview. Image would look better with a border or as a thumb
#* History: Image too large, again maybe a border?
#* Epidemiology: Need to define velocardiofacial syndrome in glossary, also break it down into subheadings, eg. Incidence, Sex, etc
#* Etiology: Maybe better if in a table
#* Pathogenesis: I liked how you broke it doen into relevant subheadings. However, on a slightly negative note, the DG Pathophysiology Diagram looks rushed; I think it would've looked better if it was neater and easier to read.
#* Diagnosis: I felt citing was done poorly in this section, eg. the last 4/5 sentences in the FISH technique was not referenced at all, but again, this is very easily fixed. But good to see you have put in the effort and time
#* Clinical: Image of normal and cleft palate, if based on a textbook, I think you still need permission to adapt it (not quite sure, please ask Mark)? Table with 'How it is caused' would be better by itself as pathophysiology. Tetralogy of Fallot needs to be fitted into this section more smoothly, at the moment, it makes this section look very cramped. Also, the image regarding Tetralogy needs the correct format for student drawn images (ie. 'I (student no.)....)
#* Research: Maybe break it down into subheadings
#The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
#* Good images used with a nice range of self drawn images. However, no where in the page is there any reference to the images within the text.
#Content is correctly cited and referenced.
#* I feel citation needs to be improved overall. Lots of the sections have missing citations, especially Diagnostic Tests. Also in the reference list, refs 33,40,47, 49 have nothing in it (is it meant to be like this?)
#The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
#* Nice drawings, though some could've done better with more effort
#Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
#* Nice range of references used
#Relates the topic and content of the Wiki entry to learning aims of embryology.
#Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
#Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
#The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
#* It's very clear to me that you guys have worked together well and there has been good team work going on here to create this page, so well done
#Develops and edits the wiki entries in accordance with the above guidelines

"What would improve this project...."

* I feel your page is too heavy with the text, although there's a lot of images as well, it just doesn't quite balance out with the text.
* Also felt the different colours used for the tables, although adding a splash of colour to your page, brought down the overall quality of the page. However, please keep in mind that others might really like this approach of table formatting, it's just that personally, I think you could benefit from keeping all table colours consistent.
* Sometimes you refer to DiGeorge Syndrome as DGS and also as DS. Small and easy to fix, adds consistency
* Please don't forget to add the {template} for student uploaded images
* Definitely needs more words in the Glossary, such as Meiosis, de novo, microarray

--[[User:Z3291643|z3291643]] 16:02, 24 September 2011 (EST)

'''DiGeorge Syndrome'''

*The page has a really nice setout, the introduction and history looks really good. It has a nice flow.
*There could be at least one other picture in 'Epidemiology' and 'Etiology', otherwise it just looks like a big block of text
*The second last paragraph in 'Epidemiology' would be better suited in 'Clinical Manifestations'
*There's a bit of repetition between 'Etiology' and 'Pathology', it could be better to combine these
*The 'Diagnostic Tests' look really good, fantastic table and images
*I love the ultrasound picture
*The table in 'Clinical Manifestations' is really great with lots of detail
*I understand it's difficult to find, but more images in 'Clinical Manifestations' to give a visual representation would be fantastic
*"Teratoogy of Fallot as ''an'' example...."
*"Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists" This doesn't make muhc sense, that was from the 'Treatment' section.
*You had a lot of good information in 'Current and Future Research', but I found myself getting lost in all the text. Maybe subheadings would help?
*Don't forget to fix up the references, we don't want to see webpages as a reference even if it leads you to the paper
*Overall your page looks very good, some minor formatting would be useful

* A very clear format has been used. The mixed use of dot points and paragraph form were used appropriately in most sections and made your web-page easy to read and follow
* Good use of self drawn images, however the large image of Angelo DiGeorge seemed slightly irrelevant and took up a large portion of your page. Your first two images should probably have small heading below the image, just to make them a bit more clear to the reader.
* A coherent history/timeline was used.
* You’re referencing needs to be tidied up; there are multiple entries from the same source that tends to clutter your reference section. Some references are incompletely, or have no linking information such as reference 49.
* Your current research section was good but perhaps could have been tabulated just for easier reading and to really draw out the main points.
* Your table for clinical manifestations could have been summarised otherwise it should maybe just be written in paragraph form.
* Your page definitely reflects the time and effort you have placed into the assignment. I really liked the range of formatting you used and the use of colour made your page easy to read and follow. Another great feature was the section based on the example of Tetralogy of fallot. It was interesting to read how other defects that we have discussed in class, linked in with your studied abnormality.
--[[User:Z3332629|z3332629]] 15:21, 22 September 2011 (EST)

'''Group 2'''
* Structure- headings, subheadings and tables make this a very readable page with a nice flow.
* It may be nice to have the colours of the tables continuous throughout the page. eg only yellow.
* Ensure all your pictures are correctly referenced, it would be a shame if Mark deleted them, as they add a lot to your page and aid in read ability.
* not to text heavy which is good!
* Intro well written an gives a good scope to the syndrome.
* Dianostic Tests: I like this section and that the images accompany the text.
* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome: Very interesting example, great pictures!! very well drawn. maybe you could put the pictures vertically down the page.
* Current and Future Research section it might be nice to add subheadings of what the research is.
* Good use of citing/ referencing it gives your page authority/ believability, just beware of the doubling in your reference list.
* It might nice to collate all the genetic info into one section.

*'''Introduction''': Good in general. Last paragraph needs a slight revision in sentence structure. "The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality" - significant in what way? As in they have a big impact? And also, poor quality of what? Life?
*'''Historical Background''' : Very detailed, which is nice. The layout isn't quite 100% consistent, which should be easily fixed. Some findings could do with further explanations to show how this lead to progress. Also, some terms should be linked to the glossary, or in some cases, a mention that subsequent paragraphs will provide more detail.
*'''Epidemiology''': Seems fine to me, though a figure would be nice to break up the text.
*'''Etiology''': Links to glossary needed. This part contains many technical terms that aren't explained. Also, is it known why this region is specially prone to rearrangements?
*'''Pathogenesis''': Seems to repeat what was said in etiology, but in more detail. Well written and explained.
*'''Diagnosis''': There's a typo in the title - Dianostic instead of Diagnostic. You might want to split your table into prenatal and postnatal, as otherwise it is a bit confusing to read "ultrasound" as a diagnostic tool. It does become obvious very quickly that it is prenatal, but just for clarity's sake, splitting the table could help, especially as you mix pre- and postnatal tools throughout the table. Also, just be careful about using capitals - in the beginning you say BACS, and later you say BACs. BACs is the plural of BAC, which is what Bacterial Artificial Chromosome stands for, not BACS. Your explanations in this part of the table are quite technical - you might want to explain more terms in the glossary at least.
*'''Clinical Manifestations''': Very thorough and detailed, which is good. I like the table, but including some more figures might help break up the long bits of text.
*'''Treatment''': Also quite thorough, well explained.
*'''Current and Future Research''': Very good and detailed, well explained. Maybe include headings for the different sections, so it's easier to see what each is talking about?
*'''Glossary''': More terms need explanations.
*'''References''': Seem fine in general, though there are a few links that probably should be cited differently. Also, some references link to emptiness?
*General: All the tables are slightly differently formatted, you might want to get that more uniform.

'''Group 2 Critique'''

*Do the symptoms need to be listed in the introduction, or is that repetitive since it’s also in the etiology portion?
*Historical Background- Overall this section looks good, but each bullet needs to be consistent. Ie:
-only the first few bullets have a colon after the date while the others don’t. I think either a colon or a – mark should be used after the date to show a better separation.
-some sentences don’t end with periods.
*The Etiology and Epidemiology sections have good content, but it looks rather wordy from an aesthetic viewpoint. A picture or some bullet points for separation might be helpful to solve this.
*For the image Chromosome22DGS.jpg, surely you didn’t know this layout from your own knowledge… Wouldn’t you have had to copy this image from another source, and wouldn’t that source also need to be cited as well?
*For terms that are in the glossary, it would be good to format the words in the wiki so that when you click on them it takes the reader directly to that term in the glossary.
*Several of the references aren’t formatted correctly, or are missing entirely.
*This might be a bit nit-picky, but for the references given throughout the wiki, there isn’t any consistency. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
--[[User:Z3391078|Ashley Smith]] 11:05, 27 September 2011 (EST)

'''Peer Assessment: Group Project 2'''
*The information in the introduction is good, however you may want to introduce the syndrome in the first sentence and then explain what congenital abnormalities are.
*The timeline is clearly set out, maybe decide whether you want to put a colon or not after the date to keep consistency.
*The diagnostic tests section has a good balance between being informative through pictures and text. It would be good to place an image for amniocentesis and also replace the link on BACS technology to either have an image and use the paper as an extra link or to replace the heading of 'image' to 'additional information' or some such title.
*Maybe an image could be inserted in the section on etiology or epidemiology. An graph to accompany some of the statistics might make the information more accessible.
*Under the information of the images you have uploaded, you need put <nowiki>{{Template:2011 Student Image}}</nowiki>.
*In the glossary writing "A" above the group of A words and so on and so forth for the rest of it, would make it easier for the reader to quickly find the desired word.
*Some of the references should have more information in them (references 1, 2, 3, 4, 5, 46, 47, 48, 49 and others).
*The references should not be duplicated and can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.

--[[User:Z3217345|z3217345]] 12:43, 27 September 2011 (EST)

'''Group 2:'''
* The introduction is very easy to read and is accompanied by a great image, although this image should include a legend. It would be beneficial to link the image with the symptoms mentioned in the intro and to only mention a couple of important symptoms instead of listing them all here and having to repeat yourself later on.
* Very extensive historical background. Very impressive and well referenced. Image needs to include a legend.
* Epidemiology needs to be proof read as there are a couple of little mistakes that lessen the value of what is a really well researched section; “Due to the fact that 22q11.2 deletions can also resulting in signs that...”, “It has been well documented that there individuals who...” and “which may be resultant form a learning dysfunction or heart disease.”
* Etiology is also done well and is very comprehensive, however there is a spelling mistake “interstital deletions of chromosome 22” so make sure you re-read this section too.
*An image either in epidemiology or etiology would help break up a huge chunk of text.
* Pathogenesis/Pathophysiology section is very strong with great student drawn images relevant to the text. Only suggestion is to hyperlink glossary terms since there are a lot of terms in this section which need to be explained further.
* Diagnostic Test section is done well with a well formatted table making it easy to read. Some images are missing as I’m sure you’re aware of and make sure to include <nowiki>“{{Template:2011 Student Image}}”</nowiki> for these images.
* Clinical manifestations; perhaps the table describing the symptoms could immediately proceed after “The most common signs and symptoms include:” instead of having the symptoms in dot points and repeated twice. The student drawn image may benefit from pointing out that A is at rest and B is during normal speech – just to clarify. I also noticed a spelling mistake “In more severs cases..” so just make sure you go over this section with a fine comb.
* Treatment also had a couple of little mistakes for example “and consult various specialists, from example a cardiologist”. A legend for the images here would improve this section.
*Current and future research is very extensive and well researched.
Hats off to you guys!

Peer Assessment

* interesting layout
* pictures were good examples
* maybe need a touch up with the referencing
* i liked it how it was worded in a way that could be understood for a wide audience however the structure and format could not be read so easily

--[[User:Z3060621|z3060621]] 20:37, 28 September 2011 (EST)

--z3290815 14:09, 28 September 2011 (EST)

'''Group 2'''

'''*The key points relating to the topic that your group allocated are clearly described.'''
Well described, but very hard to follow at points due to volume of text.

'''*The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'''
Tables include too much information. it should summarise the main points, for large chunks of text put it in the body of the wiki.

'''*Content is correctly cited and referenced.'''
Fix up some references - there is duplication and links provided in place of a reference as well as missing references. reference for Chest PA 1.jpeg, DiGeorge-Intra Operative XRay.jpg and FISH for DiGeorge Syndrome.jpg should be fixed. also include {{Template:2011 Student Image}} in all images.

'''*The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.'''
Good diagram explaining pathophysiology but it can be neaten up by doing the text on a program (paint would suffice).

'''*Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'''
Very high research volume put into the page but there is too much text going on. Try using some sub-headings to break up the information into easily digestible sections. It also allows for easy location of specific sections.

'''*Relates the topic and content of the Wiki entry to learning aims of embryology.'''
Good information on genetics but if possible say how the deletion occurs?

'''*Develops and edits the wiki entries in accordance with the above guidelines.
Apart from small things, the wiki has been edited well.

--z3329495 21:09, 28 September 2011 (EST)

==The final Pimp==

Hi guys, how is your week end? Thursday is the due date for our side and I think it's looking great already. I just read through it all and noticed the following.

1) I changed 1/4000 to 1/2000 to 1/4000 in the introduction (hope that's ok) this way we are all saying the same.

2) I think we should still change what Mark Hill suggested for the "Historical Background" section: date first and picture not within the text. I'm happy to do it, just thought I should check with you Sarah...

3) There are still some references that need to be fixed

4) Do you guys want to add some of the scientific words that you used to the glossary, otherwise that would be incomplete

and 5) Mark Hill wanted to help me with the tetrallogy of fallot picture but I think he forgot, so I'll ask him again after the lecture and than it's going to be a fancy scenic view picture.

So, let's do the final pimp: I wouldn't leave it until Wednesday because the system is probably going to crash on that day;)
Let me know if you need any help and let us know if you think something els should be changed/edited as well.--Anna Marx 16:40, 18 September 2011 (EST)

Hi Anna, yup, 1) sounds fine; we still have that issue with the ultrasound image and removing the text from the background don't we? I'll have a trawl through the references later and see what I can do, and for most of the scientific words I know the sections that I've done have their wording in there; everyone else just has to go through it a bit?

btw guys it looks fantastic :D --[[User:Z3288827|Leonard Tiong]] 10:51, 20 September 2011 (EST)

hey i changed up the history and put the tables in different colours so they dont look like they ar all the same thing if you know what i mean?? anyway... hope its ok :) --[[User:Z3288729|Sarah Jenkins]] 13:20, 21 September 2011 (EST)

Cool, looks good. I like the colours :) --Anna Marx 11:47, 22 September 2011 (EST)

==Question==

Hi Sarah, I have a question, do you think we can split the baby pictures that you used in you introduction. Sounds super lazy of me, I know. But my problem is, that I would like to put one in my section about facial abnormalities and I couldn't find one that shows these abnormalities well and that has copyright. I wanted to use the one that is in the epidemiology section but I think Leonard wants to keep it there??? Don't really know. Any way, if we would split yours, you could get one baby and I would use the other one. What do you think? --Anna Marx 22:01, 10 September 2011 (EST)

Hey Anna, I wouldnt have a problem doing that but it is one image within the journal and im not sure if we are allowed to manipulate the images? I will talk to Mark about it and if it is ok then i will cut it up for you and put one of them in your section :) Hope this helps. --[[User:Z3288729|Sarah Jenkins]] 08:54, 11 September 2011 (EST)

Hi anna, I SAID down there that you could use the image! :D '''Feel free to take it because I also think it would assist in that section'''. I'm just squabbling over the image filename with Mark because it's not descriptive. There's another one there that has a picture of another fellow whose facial abnormalities are quite apparent so I was thinking to use them as they've got a pretty strong contrast between the two of them. What do you think? I've also uploaded my drawings, they took ages and they look so crap :( But I've been scrolling through some of the other groups and we're in good shape guys! It looks really great :) I'll sort out my glossary terms tomorrow morning. Excellent work over the break guys. --[[User:Z3288827|Leonard Tiong]] 21:42, 11 September 2011 (EST)

==Update==

Hey, how are you holidays coming along? I just wanted to let you know four things;):

1. I am "done" with clinical manifestations. So you can have a look if you like it... I'll still upload at least three images of which two are drawings.

2. So we have got the drawings covered. I just have to scan them.

3. I'll still work on the treatment section tomorrow.

4. For the matching up of our individual sections, Sarah would you mind to change the typical symptoms in your introduction to the same ones I talked about in detail. I think it would look good. Anyway...It would be the following ones:
* Congenital heart defects
* Defects of the palate/velopharyngeal insufficiency
* Recurrent infections due to immunodeficiency
* Hypocalcaemia due to hypoparathyrodism
* Learning difficulties
* Abnormal facial features
Have a good brake guys, --Anna Marx 2--[[User:Z3288827|Leonard Tiong]] 10:45, 8 September 2011 (EST)0:22, 3 September 2011 (EST)

Hi, so I have done my treatment section as well including references and glossary. --Anna Marx 21:43, 6 September 2011 (EST)

Thanks Anna :) I will change it all up now. I know you are doing the drawings but the rest of us need to get some pictures up if possible? --[[User:Z3288729|Sarah Jenkins]] 08:55, 7 September 2011 (EST)

Hey guys, i have a few pictures to load up, so will get onto that..

Was also going to ask if anyone came across anything good under the future research heading? I have found a bit, struggling a little though, and i feel like there should be more.. Just wondering if anyone came across any interesting points/areas when doing your own research.. Also had the suggestion that maybe pathogenesis/etiology could fall under the same heading, as they are both very similar topics, and maybe I/we could write something up more focussing on the pathophysiology as another heading... I know Anna does talk about this a bit in her clinical manifestations, but thought there was room to potentially cover pathophysiology in a bit more detail under anther heading, and we could maybe reduce the detail in her table as a result, make it a little less large.. let me know what you think..

--[[User:Z3288196|Timothy Ellwood]] 09:21, 7 September 2011 (EST)

really good job with everything at the moment it looks really fantastic. tomorrow is my allocated day to get through this work, so I'll be sure to get a large chunk of my sections "done". Anna, excellent work done so far, it looks really fantastic. Umm tim, as for your struggles at the moment, I'll be sure to keep that in mind when I'm looking at my other papers; just having a look at the moment and I'll get a little more help for you tomorrow, if possible. looking great so far guys! --[[User:Z3288827|Leonard Tiong]] 14:23, 7 September 2011 (EST)

hey tim, another idea is to change the heading to 'current and future research' that way you can look into what is being down now and very recently. that will give you heaps :) --[[User:Z3288729|Sarah Jenkins]] 07:13, 8 September 2011 (EST)

ps. i used a wikipedia image so we cant put another one up now... hope this isnt a problem --[[User:Z3288729|Sarah Jenkins]] 07:14, 8 September 2011 (EST)

By the way Anna, I'll probably draw my image and upload it later this evening; I can't find any images that best match what I want without having to go through all of the copyright information, so I'll just draw it :D slowly trawling through my sections. Epidemiology might be a bit short (as there's not that much you can write on it) but the pathophysiology section should be quite lengthy (Hopefully :) ) --[[User:Z3288827|Leonard Tiong]] 10:45, 8 September 2011 (EST)

Slowly going through pathophysl now. by the way guys, '''Mark Hill has put something at the top of our page if you haven't already seen it. I think it would be best to implement the points that he has noted; they're relatively minor, if you guys haven't gotten round to doing it by say, tomorrow (?) then i'll see if I can change it :) '''
I'm finding this INCREDIBLY FRUSTRATING that I can't save the material but no one else seems to be online. :(

Hello! I just thought let you know that I did two drawings which I plan to put into the table under clinical manifestations. And I also have images on my computer, that also go into the table. I just have trouble uploading them (may be it's because I have a mac... not sure). But in case I don't manage I'm sure one of you could help me on Thursday. I'll also try to make the tables a bid lighter. --Anna Marx 17:15, 8 September 2011 (EST)

ALL RIGHT, so I have change my tables. I have tried to explain it in a way so that people with no science background should understand it. Some words I had to leave in because that is just what it's called... Any way I think it'll be even better once I have the pictures in as well. If you like to have some thing changed let me know. --Anna Marx 19:12, 8 September 2011 (EST)

Hi Anna, just asking what have you done in your drawings? I drew the chromosome and the area in which deletions were most common, it's not the greatest drawing but I leave it up; and, I was thinking of drawing the presenting symptoms of DiGeorge (there aren't that many anyway). What do you think? Let me know what you've gotten down :) --[[User:Z3288827|Leonard Tiong]] 23:06, 8 September 2011 (EST)

Hey guys I will fix up what is wrong with my bits tomorrow afternoon sorry. I have had other things to do this week as well. Mark's comments are valid and relatively simple to fix luckily. --[[User:Z3288729|Sarah Jenkins]] 00:55, 9 September 2011 (EST)

Hey guys. Looks like Dr Hill's criticism was relatively minor which is great. Should be easy for us to fix. As for the future research I have found a heap more stuff, seems as if alot of current research on this deletion is in relation to schizophrenia, but have found alot more stuff relating to Digeorge. Suggestions still welcome of course. Sarah your suggestion is fanatastic, more relevant as well. I will change that now. As for my last section and images I will get to that tonight hopefully, just have been working full time over the break..
--[[User:Z3288196|Timothy Ellwood]] 10:24, 9 September 2011 (EST)

Hi, I have changed my table even more - hope you like it. In the end we might have to match the colours but we cna do that together in the lab. How is doing epidemiology, I planned on using exact the picture for clinical section where I describe facial abnormalities. That was the best one I found - that other children looked so said. Any way, may be I can steal it or I try to find another one.
Tim, I also thought I suggest, if you still can's find enough you could look into more specific stuff. For example into research of how to improve cardiac surgery, treatment for immunodeficiency etc... there should be loads out there. Any way, we are doing great team! --Anna Marx 16:40, 9 September 2011 (EST)

Hey guys,

Yeah, just have to put in a couple of images to help break things up. I've been looking at the things that the other groups have produced from the previous years and it looks really great, I think our project is beginning to look somewhat like that (which I feel will do us good!). I'm still trawling through some of the references and images; as for the epidemiology section, I've written all that I can find on that... if you guys want to put anything else in there feel free too but I feel there's a lot of repetition throughout the literature and what I've written covers epidemiology quite well. Having looked at some of the other groups we've done a really great job, anna, feel free to upload those pictures so that we can all have a look :)--[[User:Z3288827|Leonard Tiong]] 22:09, 9 September 2011 (EST)

Hi yeah, I will on Monday. I am sorry that I can't do it earlier! --Anna Marx 21:42, 10 September 2011 (EST)

==week 6==

hey awseome work with the page but u have to put references on your work asap or we will get done for plagiarism --[[User:Z3288729|Sarah Jenkins]] 07:18, 23 August 2011 (EST)

Yep, I'm working on it now. Is tim still working on the project with us? He hasn't written anything for his sections yet.. --[[User:Z3288827|Leonard Tiong]] 08:50, 1 September 2011 (EST)

Hey guys. Yeh im working on my sections, havnt posted anything up at all coz have been sick for the last week or so, and then working all weekend. I plan to have the majority of mine done by tonight though, then will start the editing process overall later in the week i guess. Sorry to hold things up.
--[[User:Z3288196|Timothy Ellwood]] 08:57, 5 September 2011 (EST)

== Discussion==

Hey sorry I missed the lab class today, im having some family troubles but will be back in sydney on the weekend. If somebody could let me know what happened etc I would really appreciate it. Are we still doing Duchennes or did another group choose it too?

Hello,
I hope that you family gets better soon. So, we had to flip a coin with another group about Duchennes and unfortunately lost. We decided that we'll all think about what else we would find interesting until Sunday and post our suggestions here so that we can make a decision about it on Sunday or early this week. If I understand right, it would be the best if we find a disorder that is really caused during embryonic development. Hence Duchennes and Thalassamia for example are not the best ones any way.
Have a good week end guys.
--Anna Marx 18:51, 11 August 2011 (EST)

Thanks Anna, I will have a look at some now and see what I can find :) --[[User:Z3288729|Sarah Jenkins]] 15:20, 12 August 2011 (EST)

== New Ideas==

* Conjoined twins. It results from abnormalities in the original process of cell division.

http://www.ncbi.nlm.nih.gov/pubmed/15278382

* Spina Bifida is due to incomplete closing of the neural tube

http://www.ncbi.nlm.nih.gov/pubmed/19918803

http://www.ncbi.nlm.nih.gov/pubmed/21790891

* Cri Du chat syndrome

http://www.ncbi.nlm.nih.gov/pubmed/21112524

http://www.health.medicbd.com/wiki/Cri_du_chat

* Ectodermal dysplasia

http://www.health.medicbd.com/wiki/Ectodermal%20dysplasia

http://www.ncbi.nlm.nih.gov/pubmed/21814340

== Another Idea ==

Hi! I think there are so many interesting congenital diseases/abnormalities which we could choose. I have had a look around and I think that [[DiGeorge Syndrome]] would be a good topic! First, it is due to some abnormalities in the chromosome 22, hence there is a genetic component. Second, it occurs in 1 of 4000 people and there are lots of variations from person to person, hence there will be a lot of research and a lot of information that we can use. Third, a defect in the migration of neural crest cells is included, which means it happens during embryonic development. So, may be you can have a look into it and let me know what you think.
Have a good week end, Anna
--Anna Marx 15:03, 13 August 2011 (EST)

I had a quick look and this looks like a good one. I'm happy to do DiGeorge if everyone else is?? --[[User:Z3288729|Sarah Jenkins]] 10:40, 14 August 2011 (EST)

Ok, sounds good! What about the rest of the group? Do you guys like DiGeorge too? I am open for any other suggestion, however I would suggest, that we make our decision soon, so that we can start our research about it. So I'll open a little "Agree with you signature" box and wait what happens :) --Anna Marx 17:41, 14 August 2011 (EST)

== DiGeorge Syndrome ==

If you like to make DiGeorge Syndrome to our team project, sign below.

--Anna Marx 17:43, 14 August 2011 (EST)
--[[User:Z3288729|Sarah Jenkins]] 19:09, 15 August 2011 (EST)
--[[User:Z3288196|Timothy Ellwood]] 09:30, 16 August 2011 (EST)
--[[User:Z3288827|Leonard Tiong]] 00:21, 17 August 2011 (EST)

==Project Plan==

I think it is important to keep moving on with the project. We need to quickly agree on things and get the job done. From previous experience, getting the work done early is a benefit to everyone involved. The project needs to be broken down into subheadings. I have listed some below which need to be covered without doubt, and I am open to other ideas as well. If everyone could pick 2 that they are happy to take on it means that everyone will have a round about even job. I spoke to [[Anna]] Earlier and she said she was willing to do the drawings. Is that still ok? If so I think its fair that you only have to do one subheading of theory work.

* Introduction (Sarah)

* Historical background of the disease and its research (Sarah)

* Epidemiology (Leonard)

* Etiology (Tim)

* Pathogenesis (Leonard)

* Clinical manifestations (and explanations of these) (Anna)

* Treatment options if available (Anna)

* Diagnosis of the disease, pre and post natally (Sarah)

* Further research possibilities (Tim)

* Image (Anna)

I would prefer it if i could do the introduction, historical background and diagnosis. I am willing to do 3 because the introduction is a pretty easy one. If anyone has a problem with this let me know. I also think first in best dressed to picking topics. I only think its fair and if not, we can sort it out later.
--[[User:Z3288729|Sarah Jenkins]] 19:09, 15 August 2011 (EST)

Hi, thank you for the layout. I think it is a good start!
I an still happy to do the drawings. So let me know if you have specific wishes or if you have suggestions of what we/I need to draw. I can also do Clinical manifestations and treatment options, which would make it three as well. However I thought pathogenesis will be a big one because that would include all the genetics. May be it will be enough if one person on it's own. Otherwise etiology would go well with it, leaving epidemiology and further research for the last one;) Further research might be big too... However, I am open to adjust. --Anna Marx 21:03, 15 August 2011 (EST)

Hey guys, sorry I haven't been in touch, just been busy with some orchestra stuff outside of uni. The stuff so far sounds great, I'll get to work tomorrow getting some papers together and seeing what I can find out about the condition. I wouldn't mind doing the epidemiology and pathogenesis sections - Anna, I think he said we only had to submit one self-drawn picture but I wouldn't mind doing some either, since I draw everything for anatomy :D either way, let me know what you think! So far things sound really great, thanks for getting so much done and once again my apologies for not having chucked in my two cents earlier!
--[[User:Z3288827|Leonard Tiong]] 23:02, 15 August 2011 (EST)

Awesome, now that we are on the way there it should be easier to focus our reading. We also need to do a glossary, and i think its easier if we do it as we go. so when we come across words that need a definition (to non science people) just chuck it in the glossary. even if we define it later, having it there is easier than having to go through and pick them out later. :) thanks for being so enthusiastic. :) --[[User:Z3288729|Sarah Jenkins]] 07:13, 16 August 2011 (EST)

Hey guys, sorry for the late addition, busy with various other things as I'm sure most of you are! Im happy to take the two headings that are left over. Also it looks like some of the other headings might contain alot more work than the two I've got, i think the further research one could potentially contain alot but unsure at this stage.so i would be happy to share another one and help out if anyone would like?? It was suggested above that Pathogenesis and etiology could go well together.... Let me know. Glossary sounds like a great idea!

Also i thought it would be a good idea if before the lab on Thursday if we could each try to find say 2 articles that relate to the heading we have selected.. Similar to what Dr Hill asked us to do for last week but now we have our topics etc. it should help to get us up and running.
--[[User:Z3288196|Timothy Ellwood]] 09:29, 16 August 2011 (EST)

I have set up sections below for us to put any references we find. it makes it easy to find the ones we need, and if other people come across good references for a topic other than their own it allows us to share :)--[[User:Z3288729|Sarah Jenkins]] 15:22, 16 August 2011 (EST)

Hey tim, more then happy to switch doing etiology with you but I wouldn't mind doing both together either. We'd better tell Mark to change our title over to DiGeorge's syndrome, I'll get some papers up in the mean time but will be really busy until thursday! :(

Update - Hey guys, just found a rather general article on DiGeorge but thought it was interesting, will leave the link here, if you guys got a moment have a trawl through :) I don't know what I'm still doing up at this hour :\ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954737/?tool=pmcentrez I'll have a read of it tomorrow morning :)
--[[User:Z3288827|Leonard Tiong]] 23:55, 16 August 2011 (EST)

Assuming that was Leonard above? I dont mind at all, maybe we can talk about it on thursday and sort something out. In the meantime i guess ill try find whatever articles I can on both topics.

Also just thought i would point out this resource [http://www.nationwidechildrens.org/22q11-deletion-syndrome], as it says that DiGeorge Syndrome (DGS) falls under the the title of 22q11.2 Deletion Syndrome, which apparently includes a number of other very similar disorders such as Velocardiofacial Syndrome, Conotruncal Anomoly Syndrome, Autosomal Dominant Opitz G/BBB Syndrome, Cayler Cardiofacial Syndrome and Shprintzen Syndrome. Not sure if we wanted to include these in our research, but worth considering I think as there could be alot more research under one of these titles and allow us for a broader and more accurate picture of the disorder as a whole.

--[[User:Z3288196|Timothy Ellwood]] 15:21, 17 August 2011 (EST)

Good work guys, our project has taken shape already. I have now changed our project title, hence we should be safe and good to go! See you tomorrow in the lab --Anna Marx 20:19, 17 August 2011 (EST)

Things are looking really splendid guys, I'm starting my sections now but it doesn't seem like there's that much for me to write on. I'll try to see if i can spruce things up a little bit more. Referring to several textbooks (anyone got any suggestions?) for some of my basic info, and I'll find original sources later. But yeah, difficulties in trying to find specific information. Especially since there's so much overlap at the moment with the other different names. So far the four major ones that I got (I know you guys have included them) but four definite names involve (obviously) DiGeorge syndrome, Velocardiofacial Syndrome (VCFS), Conotrunchal anomalies facie syndrome (CTAF) Syndrome, and CATCH22. I don't think CATCH22 is a diagnostic name but rather a mnemonic that helps them remember the symptons of DiGeorge. Onto my writing! Just another thing that I'm well aware of, I haven't put many references into my work as of yet, still trying to find the best sources for the information. I've got a bunch of them written down and need to just go through them to make sure that I've the right sources from the right place but my laptops out of battery at the moment :( I'll try to get that done by tonight or tomorrow. :) --[[User:Z3288827|Leonard Tiong]] 18:25, 22 August 2011 (EST)

== Review Article ==
Hey guys, just found a review article that I thought was rather interesting, it's an animal model for Duchenne's muscular dystrophy[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022202/]. I also found a primary journal article that discusses drug delivery for the condition [http://www.jstage.jst.go.jp/article/bpb/34/5/712/_pdf]. I will print these articles for myself tonight and give them a quick read tomorrow and then paste a quick summary of the articles here just for you guys to consider :)

'''Review''' [http://www.ncbi.nlm.nih.gov/pubmed/21274260 Mammalian models of Duchenne Muscular Dystrophy: pathological characteristics and therapeutic applications.]

'''Primary''' [http://www.ncbi.nlm.nih.gov/pubmed/21681700 Detection of duchenne/becker muscular dystrophy carriers in a group of Iranian families by linkage analysis.]

--[[User:Z3288729|Sarah Jenkins]] 10:00, 6 August 2011 (EST)

'''Primary''' http://www.ncbi.nlm.nih.gov/pubmed/15991868 Diagnosis and management of Duchenne muscular dystrophy in a developing country over a 10-year period.

'''Review''' http://www.ncbi.nlm.nih.gov/pubmed/14526374 Advances in Duchenne muscular dystrophy gene therapy.

--Anna Marx 12:52, 8 August 2011 (EST)

----

'''Duchennes Muscular dystrophy'''

----
--[[User:Z3288827|z3288827]] 21:53, 8 August 2011 (EST)

== Review Article ==
Hey guys, just found a review article that I thought was rather interesting, it's an animal model for Duchenne's muscular dystrophy[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022202/]. I also found a primary journal article that discusses drug delivery for the condition [http://www.jstage.jst.go.jp/article/bpb/34/5/712/_pdf]. I will print these articles for myself tonight and give them a quick read tomorrow and then paste a quick summary of the articles here just for you guys to consider :)

== References ==
[1] Nakamura A., Takeda S.; Mammalian Models of Duchenne Muscular Dystrophy: Pathological Characteristics and Therapeutic Applications, J. Biomedicine and Biotechnology Vol. 2011, Article ID 184393

[2] Yukihara et al; Effective Drug Delivery System for Duchenne Muscular Dystrophy Using Hybrid Liposomes Including Gentamicin along with Reduced Toxicity, J. Biol. Pharm. Bull, Volume 34, No. 5 pp. 712-716

== Found References==

===Introduction===

[http://www.ncbi.nlm.nih.gov/books/NBK22179/ DiGeorge]

[http://emedicine.medscape.com/article/135711-overview DiGeorge Anomaly]

===Historical Background===

=== Epidemiology===

[http://emedicine.medscape.com/article/886526-overview#a0199 Epidemiology]

===Etiology===

A Genetic etiology for DiGeorge syndrome [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682598/]

Inactivation of TGF􏰀 signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome [http://genesdev.cshlp.org/content/19/5/530.full.pdf]

A deletion in chromosome 22 can cause digeorge syndrome [http://www.springerlink.com/content/r85p0r5q05rj6w88/]

DiGeorge syndrome phenotype in mice mutant for the T-box gene [http://webcourse.cs.technion.ac.il/234523/Winter2002-2003/hw/WCFiles/DiGeorge.pdf]

=== Pathogenesis===

[[http://www.ncbi.nlm.nih.gov/pubmed/20833244 Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: patterning, proliferation, and mitochondrial functions of 22q11 genes]]

[http://emedicine.medscape.com/article/886526-overview#a0104 Pathophysiology]

===Diagnosis===

[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=10600329&ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Diagnostic Criteria]

===Clinical===

{http://www.ncbi.nlm.nih.gov/pubmed/19665396 Seizures and EEG findings in an adult patient with DiGeorge syndrome: a case report and review of the literature.]

http://www.chw.org/display/PPF/DocID/23047/router.asp

===Treatment===

===Research===

This looks like an excellent resource, listing over 100 research papers on nearly every aspect of DiGeorge from the 70's to present. [http://omim.org/entry/188400]

Deciphering DiGeorge Syndrome: Big Advances In Understanding Microdeletions [http://www.sciencedaily.com/releases/2005/03/050308134838.htm]

== Images==

FISH carried out to detect DiGeorge syndrome. FISH is abbreviated as fluorescent in-situ hybridisation and is carried out to detect abnormalities whilst babies are still developing in the womb. --
[[Image:FISH_for_DiGeorge_Syndrome.jpg|400px|left|FISH to detect DiGeorge syndrome[1]]]
[[User:Z3288827|Leonard Tiong]] 00:17, 17 August 2011 (EST)

[[File:DiGeorge T cell receptor Diversity post thymus transplant.jpg|400px|left]]

--[[User:Z3288729|Sarah Jenkins]] 08:54, 18 August 2011 (EST)

Facial manifestations of patient with DiGeorge Syndrome

[[File:Facial manifestations of patient with DiGeorge Syndrome.jpg|left]]

--z3279511 21:18, 17 August 2011 (EST)

2011 Group Project 2

2011-09-30T10:14:53Z

Z3279511: /* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows in the following manner: Body-right atrium (RA) - right ventricle (RV) - Lung - left atrium (LA) - left ventricle - body. The separation of the chambers by the interventricular septum and the valves is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation. <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E). <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-09-30T10:07:10Z

Z3279511: /* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

== Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome ==

The images and descriptions below illustrate the each of the four features of tetralogy of fallot in isolation. In real life however, all four features occur simultaneously.
{|
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']]. Blood flows from the body into the right atrium, then into the right ventricle and is from there pumped into the Lung. The blood comes back from the lung into the left atrium, flows from there into the left ventricle and is then pumped back into the body. The separation of the chambers in function of the valves separation the chambers and great blood vessel is crucial for the function of the heart.
| valign="top"|''' Ventricular septal defects'''
If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung (see image B)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood (see image C) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
If the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation (see image D)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-09-30T09:49:13Z

Z3279511: /* Treatment */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

===Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome===

{|
| Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome |
|-
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
| valign="top"|''' Ventricular septal defects'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']] (see image A). If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung (see image B)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood (see image C) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
In the healthy heart, blood from the left ventricle flows into the aorta and from there into the systemic circulation (see image A). However if the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation (see image D)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Late-occurring features: Hypocalcaemia
* Late-occurring features: Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-09-30T09:44:31Z

Z3279511: Undo revision 73747 by Z3279511 (talk)

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

===Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome===

{|
| Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome |
|-
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
| valign="top"|''' Ventricular septal defects'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']] (see image A). If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung (see image B)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood (see image C) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
In the healthy heart, blood from the left ventricle flows into the aorta and from there into the systemic circulation (see image A). However if the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation (see image D)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Hypocalcaemia
* Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-09-30T09:39:35Z

Z3279511: /* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

===Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome===

{|
| Image
| The four features of teralogy of fallot
|-
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| valign="top"| '''The Normal heart'''
|-
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| valign="top"|''' Ventricular septal defects'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']] (see image A). If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung (see image B)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
|-
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood (see image C) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|-
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| valign="top"| '''"Overriding" aorta'''
In the healthy heart, blood from the left ventricle flows into the aorta and from there into the systemic circulation (see image A). However if the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation (see image D)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|-
| [[File:Heart Defect E.PNG | left | 150px]]
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Hypocalcaemia
* Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-09-30T09:26:33Z

Z3279511: /* Clinical Manifestations */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severe cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example of a congenital heart disease, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

===Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome===

{|
| Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome |
|-
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
| valign="top"|''' Ventricular septal defects'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']] (see image A). If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung (see image B)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood (see image C) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
In the healthy heart, blood from the left ventricle flows into the aorta and from there into the systemic circulation (see image A). However if the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation (see image D)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Hypocalcaemia
* Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-09-30T09:17:52Z

Z3279511: /* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severs cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

===Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome===

{|
| Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome |
|-
| [[File:Drawing Of A Normal Heart.PNG | left | 150px]]
| [[File:Ventricular Septal Defect.PNG | left | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | left |150px]]
| [[File:'Overriding' Aorta.PNG | left | 150px]]
| [[File:Heart Defect E.PNG | left | 150px]]
|-
| valign="top"| '''The Normal heart'''
| valign="top"|''' Ventricular septal defects'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']] (see image A). If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung (see image B)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood (see image C) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
In the healthy heart, blood from the left ventricle flows into the aorta and from there into the systemic circulation (see image A). However if the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation (see image D)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Hypocalcaemia
* Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-09-30T09:08:29Z

Z3279511: /* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severs cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

===Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome===

{|
| valign="right" [[File:Drawing Of A Normal Heart.PNG | 150px]]
| valign="right" [[File:Ventricular Septal Defect.PNG | 150px]]
| valign="right" [[File:Obstruction of Right Ventricular Heart Flow.PNG | 150px]]
| valign="right" [[File:'Overriding' Aorta.PNG | 150px]]
| valign="right" [[File:Heart Defect E.PNG | 150px]]
|-
| valign="top"| '''The Normal heart'''
| valign="top"|''' Ventricular septal defects'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']] (see image A). If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung (see image B)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood (see image C) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
In the healthy heart, blood from the left ventricle flows into the aorta and from there into the systemic circulation (see image A). However if the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation (see image D)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Hypocalcaemia
* Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

2011 Group Project 2

2011-09-30T09:03:21Z

Z3279511: /* Plastic Surgery */

{{2011ProjectsMH}}

== '''DiGeorge Syndrome''' ==

--[[User:S8600021|Mark Hill]] 10:54, 8 September 2011 (EST) There seems to be some good progress on the project.

* It would have been better to blank (black) the identifying information on this [[:File:Ultrasound_showing_facial_features.jpg|ultrasound]].
* Historical Background would look better with the dates in bold first and the picture not disrupting flow (put to right).
* None of your figures have any accompanying information or legends.
* The 2 tables contain a lot of information and are a little difficult to understand. Perhaps you should rethink how to structure this information.
* Currently very text heavy with little to break up the content.
* I see no student drawn figure.
* referencing needs fixing, but this is minor compared to other issues.

== Introduction==

[[File:DiGeorge Baby.jpg|right|200px|Facial Features of Infants with DiGeorge|thumb]]
DiGeorge [[#Glossary | '''syndrome''']] is a [[#Glossary | '''congenital''']] abnormality that is caused by the deletion of a part of [[#Glossary | '''chromosome''']] 22. The symptoms and severity of the condition is thought to be dependent upon what part of and how much of the chromosome is absent. <ref>http://www.ncbi.nlm.nih.gov/books/NBK22179/</ref>.

About 1/2000 to 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an [[#Glossary | '''autosomal dominant''']] fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The patients experience heart defects, [[#Glossary | '''immunodeficiency''']], learning difficulties and facial abnormalities. These facial abnormalities can be seen in the image seen to the right. <ref>http://emedicine.medscape.com/article/135711-overview</ref> DiGeorge is a serious syndrome affecting many of the body systems.

The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality of life and a shortened lifespan in general for the patient. As there is currently no treatment education is vital to the well-being of those affected, directly or indirectly by this condition. <ref>http://www.bbc.co.uk/health/physical_health/conditions/digeorge1.shtml</ref>

Current and future research is aimed at how to prevent and treat the condition, there is still a long way to go but some progress is being made.

==Historical Background==

* '''Mid 1960's''', Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrome after himself. The symptoms that he recognised were '''hypoparathyroidism''', underdeveloped thymus, conotruncal heart defects and a cleft lip/[[#Glossary | '''palate''']]. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

[[File: Angelo DiGeorge.png| right| 200px| Angelo DiGeorge (right) and Robert Shprintzen (left) | thumb]]

* '''1974''' Finley and others identified that the cardiac failure of infants suffering from DiGeorge could be related to abnormal development of structures derived from the pouches of the 3rd and 4th pouches in the pharangeal arches. <ref><pubmed>4854619</pubmed></ref>

* '''1975''' Lischner and Huff determined that there was a deficiency in [[#Glossary | '''T-cells''']] was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients . <ref><pubmed>1096976</pubmed></ref>

* '''1978''' Robert Shprintzen described patients with similar symptoms (cleft lip, heart defects, absent or underdeveloped thymus, '''hypocalcemia''' and named the group of symptoms as velo-cardio-facial syndrome. <ref>http://digital.library.pitt.edu/c/cleftpalate/pdf/e20986v15n1.11.pdf</ref>

*'''1978''' Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function. <ref><pubmed>1148386</pubmed></ref>

* '''1980s''' technology develops to identify that these patients have part of a [[#Glossary | '''chromosome''']] missing. <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

* '''1981''' De La Chapelle suspects that a chromosome deletion in '''22q11''' is responsible for DiGeorge syndrome <ref><pubmed>7250965</pubmed></ref>

* '''1982''' Ammann suspects that DiGeorge syndrome may be caused by alcoholism in the mother during pregnancy. There appears to be abnormalities between the two conditions such as facial features, cardiovascular, immune and neural symptoms. <ref><pubmed>6812410</pubmed></ref>

* '''1989''' Muller observes the clinical features and natural history of DiGeorge <ref><pubmed>3044796</pubmed></ref>

* '''1993''' Pueblitz notes a deficiency in thyroid C cells in Digeorge patients <ref><pubmed> 8372031 </pubmed></ref>

* '''1995''' Crifasi uses FISH as a definitive diagnosis of DiGeorge <ref><pubmed>7490915</pubmed></ref>

* '''1998''' Davidson diagnoses DiGeorge prenatally using '''echocardiography''' and [[#Glossary | '''amnocentesis''']]. This was the first reported case of prenatal diagnosis with no family history. <ref><pubmed> 9160392</pubmed></ref>

* '''1998''' Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome <ref><pubmed>9827824</pubmed></ref>

* '''2001''' Lee links heart defects to the chromosome deletion in DiGeorge syndrome <ref><pubmed>1488286</pubmed></ref>

* '''2001''' Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of [[#Glossary | '''Tetralogy of Fallot''']]. <ref><pubmed>11455393</pubmed></ref>

* '''2001''' Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome <ref><pubmed>11412027</pubmed></ref>

* '''2004''' Rice expresses that while thymic transplantation is effective in restoring some immune function in Digeorge patients, the multifaceted disease requires a more rounded approach to treatment <ref><pubmed>15547821</pubmed></ref>

* '''2005''' Yang notices dental anomalies associated with 22q11 gene deletions <ref><pubmed>16252847</pubmed></ref>

*''' 2007''' Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge <ref><pubmed>17164259</pubmed></ref>

* '''2011''' Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome <ref><pubmed>21721477</pubmed></ref>

==Epidemiology==

It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking the most frequent cause of genetic abnormality at birth, behind Down Syndrome <ref> <pubmed> 9733045 </pubmed> </ref>. Due to the fact that 22q11.2 deletions can also resulting in signs that are predictive of velocardiofacial syndrome as well, there is some confusion over the figures for epidemiology <ref> <pubmed> 8230155 </pubmed> </ref>. Due to these afore mentioned factors, it is therefore difficult to generate an exact figure for the epidemiology of DiGeorge syndrome; the 1 in 4000 live births is the minimum estimate of incidence <ref> http://www.sciencedirect.com/science/article/pii/S0140673607616018 </ref>. For example, the study by Goodship et al examined 170 infants, 4 of which had a ventricular septal defect. This study, performed by directly examining the infants themselves produced an estimate of 1 in 3900 births, which is quite similar to the predicted value of 1 in 4000<ref> <pubmed> 9875047 </pubmed> </ref>. Other epidemiological analyses of DiGeorge syndrome, such as the study performed by Devriendt et al, have referred to birth defect registries, which produces an average value of 1 in 6935. However, this incidence is specific to Belgium, and does not represent the true incidence of DiGeorge syndrome <ref> <pubmed> 9733045 </pubmed> </ref>.

The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with [[#Glossary | '''malformations''']]. The initial presentation of DiGeorge syndrome include [[#Glossary | '''hypocalcaemia''']], decreased T cell numbers, [[#Glossary |'''dysmorphic''']] features, renal abnormalities and possibly a cardiac defect<ref> <pubmed> 9875047 </pubmed> </ref>. Cardiac defects present in about 75% of patients<ref>http://omim.org/entry/188400</ref>. When the infant makes his/her first noises, if nasal in tone, then DiGeorge will be suspected. Other indications of DiGeorge syndrome are unusually high susceptibility to infection during the first six months of life, or abnormalities in facial features.

It has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DiGeorge syndrome until later in life, which may be resultant form a learning dysfunction or heart disease. DiGeorge syndrome frequently presents with cleft palate, as well as congenital heart defects<ref> <pubmed> 21846625 </pubmed> </ref>. As would be suspected, it appears that cardiac complications are the largest causes of mortality. Infants face constant recurrent infection as a secondary result of T-cell immunodeficiency, caused by the hypoplastic thymus.

There is no preference to either sex or race <ref> <pubmed> 20301696 </pubmed> </ref>. Depending on the severity of DiGeorge syndrome, it can be diagnosed at varying ages. Those that present with cardiac symptoms can be diagnosed at birth; others may present much later in life and be diagnosed with DiGeorge (up to 50 years of age).

==Etiology==

DiGeorge Syndrome (DGS) is a developmental field defect that is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11 <ref><pubmed> 2871720 </pubmed></ref>. This region is particularly susceptible to rearrangements that cause congenital anomaly disorders, namely; Cat-eye syndrome (tetrasomy), Der syndrome (trisomy) and VCFS (Velo-cardio-facial Syndrome)/DGS (Monosomy).

VCFS/DGS are the most common syndromes associated with 22q11 rearrangements, and as mentioned previously it has a prevalence of 1/2000 to 1/4000 <ref><pubmed> 11715041 </pubmed></ref>.

The micro deletion locus is comprised of approximately 30 genes <ref><pubmed> 21134246 </pubmed></ref>, with the TBX1 gene shown by mouse studies to be a major candidate DGS, as it is required for the correct development of the pharyngeal arches and pouches <ref><pubmed> 11971873 </pubmed></ref>. Comprehensive functional studies on animal models revealed that TBX1 is the only gene with haploinsufficiency that results in the occurrence of a [[#Glossary | '''phenotype''']] characteristic for the 22q11.2 deletion Syndrome <ref><pubmed> 11971873 </pubmed></ref>.

Some reported cases show [[#Glossary | '''autosomal dominant''']], autosomal recessive, X-linked and chromosomal modes of inheritance for DGS.
<ref><pubmed> 3146281 </pubmed></ref>. However more current research suggests that the majority of microdeletions are [[#Glossary | '''autosomal dominant''']]t, with 93% of these cases originating from a de novo deletion of 22q11.2 and with 7% inheriting the deletion from a parent <ref><pubmed> 20301696 </pubmed></ref>.

Cytogenetic studies indicate that about 15-20% of patients with DGS have chromosomal abnormalities, and that almost all of these cases are either unbalanced translocations with monosomy or interstital deletions of chromosome 22 <ref><pubmed> 1715550 </pubmed></ref>.

A recent study supported this by showing a 14.98% presence of microdeletions in 22q11.2 for a group of 87 children with DGS symptoms. This same study, by Wosniak Et Al 2010, showed that 90% of patients the microdeletion covered the region of 3 Mbp, encoding the full 30 genes <ref><pubmed> 21134246 </pubmed></ref>.

Whereas a microdeletion of 1.5 Mbp including 24 genes was been found in 8% of patients. A minimal DiGeorge critical region (MDGCR) is said to cover about 0.5 Mbp and several genes<ref> PMC9326327 </ref>. The remaining 2% included patients with other chromosomal aberrations <ref><pubmed> 21134246 </pubmed></ref>.

== Pathogenesis/Pathophysiology==

As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion.
[[File:Chromosome22DGS.jpg|thumb|right|The area 22q11.2 involved in microdeletion leading to DiGeorge Syndrome]]

DiGeorge is a result of a 2-3million base pair deletion from the long arm of chromosome 22. It seems that this particular region in chromosome 22 is particularly vulnerable to microdeletions, which usually occur during meiosis. These microdeletions also tend to be new microdeletions, hence DiGeorge can present in families that have no history of DiGeorge syndrome. However, DiGeorge can also be inherited in an [[#Glossary | '''autosomal dominant''']] manner <ref> <pubmed> 9733045 </pubmed> </ref>.

There are multiple genes responsible for similar function in the region, resulting in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. This means that all 22q11.2 microdeletion syndromes have very similar presentation, making the exact pathogenesis difficult to treat, and unfortunately DiGeorge syndrome is well known by several other names, including (but not limited to) Velocardiofacial syndrome (VCFS), Conotruncal anomalies facie (CTAF) syndrome, as well as CATCH-22 syndrome<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. The acronym of CATCH-22 also describes many signs of which DiGeorge syndrome presents with, including '''C'''ardiac defects, '''A'''bnormal facial features, '''T'''hymic [[#Glossary | '''hypoplasia''']], '''C'''left palate, and '''H'''ypocalcemia. Variants also include Burn’s proposition of '''Ca'''rdiac abnormality, '''T''' cell deficit, '''C'''lefting and '''H'''ypocalcemia.

=== Genes involved in DiGeorge syndrome ===

The specific gene that is critical in development DiGeorge syndrome when deleted is the ‘‘TBX1’’ gene<ref> <pubmed> 20301696 </pubmed> </ref>. The ‘‘TBX1’’ chromosomal section results in the failure of the third and fourth pharyngeal pouches to develop, resulting in several signs and symptoms which are present at birth. These include thymic hypoplasia, hypoparathyroidism, recurrent susceptibility to infection, as well as congenital cardiac abnormalities, craniofacial dysmorphology and learning dysfunctions<ref>http://www.sciencedirect.com/science/article/pii/S0140673607616018</ref>. These symptoms are also accompanied from hypocalcemia as a direct result of the hypoparathyroidism; however, this may resolve within the first year of life. ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud. This loss of ‘‘TBX1’’ results in the cardiac malformations that are observed. It is also important in the regulation of paired-like homodomain transcription factor 2 (PITX2), which is important for body closure, craniofacial development and asymmetry for heart development. This gene is also expressed in neural crest cells, which leads to the behavioral and cognitive disturbances commonly seen<ref> <pubmed> PMID 17950858 </pubmed> </ref>. The ‘‘Crkl’’ gene is also involved in the development of animal models for DiGeorge syndrome.

===Structures formed by the 3rd and 4th pharyngeal pouches===

Embryologically, the 3rd and 4th pharyngeal pouches are structures that are formed in between the pharyngeal arches during development. <ref> Schoenwolf et al, Larsen’s Human Embryology, Fourth Edition, Church Livingstone Elsevier Chapter 16, pp. 577-581</ref>

The thymus is primarily active during the perinatal period and is developed by the [[#Glossary | '''third pharyngeal pouch''']], where it provides an area for the development of regulatory T cells.
The [[#Glossary | '''parathyroid glands''']] are developed from both the third and fourth pouch.

===Pathophysiology of DiGeorge syndrome===

There are two main physiological points to discuss when considering the presentation that DiGeorge syndrome has. Apart from the morphological abnormalities, we can discuss the physiology of DiGeorge below.

[[File:DiGeorge_Pathophysiology_Diagram.jpg|thumb|right|Pathophysiology of DiGeorge syndrome]]

==== Hypocalcemia ====
Hypocalcemia is a result of the parathyroid hypoplasia. [[#Glossary | '''Parathyroid hormone''']] (PTH) is the main mechanism for controlling extracellular calcium and phosphate concentrations, and acts on the intestinal absorption, [[#Glossary | '''renal excretion''']] and exchange of calcium between bodily fluids and bones. The lack of growth of the parathyroid glands results in a lack of PTH resulting in the observed hypocalcemia<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 79, p. 985</ref>.

==== Decreased Immune Function ====
Hypoplasia of the thymus is also observed in the early stages of DiGeorge syndrome. The thymus is the organ located in the anterior mediastinum and is responsible for the development of T-lymphocytes in the embryo. It is crucial in the early development of the immune system as it is involved in the exposure of lymphocytes into thousands of different [[#Glossary | '''antigen''']]s, providing an early mechanism of immunity for the developing child. The second role of the thymus is to ensure that these lymphocytes that have been sensitized do not react to any antigens presented by the body’s own tissue, and ensures that they only recognize foreign substances. The thymus is primarily active before parturition and the first few months of life<ref>Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Elsevier Saunders publishing, Chapter 34, p. 440-441</ref>. Hence, we can see that if there is hypoplasia of the thymus gland in the developing embryo, the child will be more likely to get sick due to a weak immune system.

== Diagnostic Tests==

===Fluorescence in situ hybridisation (FISH)===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. <ref>http://www.springerlink.com/content/u3t2g73352t248ur/fulltext.pdf</ref> When viewed under fluorescent light, the labelled regions will be visible. This test allows for the determination of whether or not chromosomes or parts of chromosomes are present. This procedure differs from others in that the test does not have to take place during cell division. <ref> http://www.genome.gov/10000206</ref> FISH is a significant test used to confirm a DiGeorge diagnosis. Since the syndrome features a loss of part or all of chromosome 22, the probe will have nothing or little to attach to. This will present as limited fluorescence under the light and the diagnostician will determine whether or not the patient has DiGeorge. As with any testing, it is difficult to rely on one result to determine the condition. The patient must present with certain clinical features and then FISH is used to confirm the diagnosis.
| [[Image:FISH_for_DiGeorge_Syndrome.jpg|300px| FISH is able to detect missing regions of a chromosome| thumb]]
|}

=== Symptomatic diagnosis ===
{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| DiGeorge patients often have similar symptoms even though it is a condition that affects a number of the body systems. These similarities can be used as early tools in diagnosis. Practitioners would be looking for features such as the following:
* '''Hypoparathyroidism''' resulting in '''hypocalcaemia'''
* Poorly developed or missing thyroid presenting as immune system malfunctions
* Small heads
* Kidney function problems
* Heart defects
* Cleft lip/ palate <ref>http://www.chw.org/display/PPF/DocID/23047/router.asp</ref>

When considering a patient with a number of the traditional symptoms of DiGeorge, a practitioner would not rely solely on the clinical symptoms. It would be necessary to undergo further tests such as FISH to confirm the diagnosis. In addition, with modern technology and [[#Glossary | '''prenatal care''']] advancing, it is becoming less common for patients to present past infancy. Many cases are diagnosed within pregnancy or soon after birth due to the significance of the heart, thyroid and parathyroid.
| [[File:DiGeorge Facial Appearances.jpg|300px| Facial features of a DiGeorge patient| thumb]]
|}

===Ultrasound ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| An ultrasound is a '''prenatal care''' test to determine how the fetus is developing and whether or not any abnormalities may be present. The machine sends high frequency sound waves into the area being viewed. The sound waves reflect off of internal organs and the fetus into a hand held device that converts the information onto a monitor to visualize the sound information. Ultrasound is a non-invasive procedure. <ref>http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ultrasound_scan</ref>

Ultrasound is able to pick up any abnormalities with heart beats. If the heart has any abnormalities is will lead to further investigations to determine the nature of these. It can also be used to note any physical abnormalities such as a cleft palate or an abnormally small head. Like diagnosis based on clinical features, ultrasound is used as an early indication that something may be wrong with the fetus. It leads to further investigations.
| [[File:Ultrasound Demonstrating Facial Features.jpg|250px| right|Ultrasound technology is able to note any abnormal facial features| thumb]]
|}

=== Amniocentesis ===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
| [[#Glossary | '''Amniocentesis''']] is a medical procedure where the practitioner takes a sample of amniotic fluid in the early second trimester. The fluid is obtained by pressing a needle and syringe through the abdomen. Fetal cells are present in the amniotic fluid and as such genetic testing can be carried out.

Amniocentesis is performed around week 14 of the pregnancy. As DiGeorge syndrome presents with missing or incomplete chromosome 22, genetic testing is able to determine whether or not the child is affected. 95% of DiGeorge cases are diagnosed using amniocentesis. <ref>http://medical-dictionary.thefreedictionary.com/DiGeorge+syndrome</ref>
|}

===BACS- on beads technology===

{|
|-bgcolor="lightgreen"
| Technique
| Image
|-
|BACs on beads technology is a fast, cost effective alternative to FISH. 'BACs' stands for Bacterial Artificial Chromosomes. The DNA is treated with fluorescent markers and combined with the BACs beads. The beads are passed through a cytometer and they are analysed. The amount of fluorescence detected is used to determine whether or not there is an abnormality in the chromosomes.This technology is relatively new and at the moment is only used as a screening test. FISH is used to validate a result.

BACs is effective in picking up microdeletions. DiGeorge has microdeletions on the 22nd chromosome and as such is a good example of a syndrome that could be diagnosed with BACs technology. <ref>http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf</ref>
| The link below is a great explanation of BACs on beads technology. In addition, it compares the benefits of BACs against FISH

http://www.ngrl.org.uk/Wessex/downloads/tm10/TM10-S2-3%20Susan%20Gross.pdf
|}

==Clinical Manifestations==

A syndrome is a condition characterized by a group of symptoms, which either consistently occur together or vary amongst patients. While all DiGeorge cases are caused by deletion of genes on the same chromosome, clinical phenotypes and abnormalities are variable <ref>PMID 21049214</ref>. The deletion has potential to affect almost every body system. However, the body systems involved, the combination and the degree of severity vary widely, even amongst family members <ref><pubmed>9475599</pubmed></ref> <ref><pubmed>14736631</pubmed></ref>. The most common [[#Glossary | '''sign''']]s and [[#Glossary | '''symptom''']]s include:

* Congenital heart defects

* Defects of the palate/velopharyngeal insufficiency

* Recurrent infections due to immunodeficiency

* Hypocalcaemia due to hypoparathyrodism

* Learning difficulties

* Abnormal facial features

A combination of the features listed above represents a typical clinical picture of DiGeorge Syndrome <ref>PMID 21049214</ref>. Therefore these common signs and symptoms often lead to the diagnosis of DiGeorge Syndrome and will be described in more detail in the following table. It should be noted however, that up to 180 different features are associated with 22q11.2 deletions, often leading to delay or controversial diagnosis <ref><pubmed>16027702</pubmed></ref>.

{|
|-bgcolor="lightpink"
| Abnormality
| Clinical presentation
| How it is caused
|-
| valign="top"|'''Congenital heart defects'''
| valign="top"|Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality. In more severs cases, the abnormalities are detected during pregnancy or at birth, where the infant presents with shortness of breath. More often however, no symptoms will be noted during childhood until changes in the pulmonary vasculature become apparent. Then, typical symptoms are shortness of breath, purple-blue skin, loss of consciousness, heart murmur, and underdeveloped limbs and muscles. These changes can usually be prevented with surgery if detected early <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> <ref><pubmed>18636635</pubmed></ref>.
| valign="top"|Congenital heart defects are commonly due to faulty development from the 3rd to the 8th week of embryonic development. Cardiac development includes looping of the heart tube, segmentation and growth of the cardiac chambers, development of valves and the greater vessels. Some of the genes involved in cardiac development are located on chromosome 22 <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref> and in case of deletion can lead to various congenital heard disease. Some of the most common ones include patient [[#Glossary | '''ductus arteriosus''']], tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities <ref><pubmed> 18770859 </pubmed></ref>. To give one example, the tetralogy of Fallot will be described and illustrated in image below.
|-
| valign="top"|'''Defect of palate/velopharyngeal insufficiency''' [[Image:Normal and Cleft Palate.JPG|The anatomy of the normal palate in comparison to a cleft palate observed in DiGeorge syndrome|left|thumb|150px]]
| valign="top"|Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities when the upper lip is affected as well, a cleft palate presents with hypernasality (nasal speech), nasal air emission and in some cases with feeding difficulties <ref> PMID: 21861138</ref>. The from a cleft palate resulting speech difficulties will be discussed in the image on the left.
| valign="top"|The roof of the mouth, also called soft palate or velum, the [[#Glossary | '''posterior''']] pharyngeal wall and the [[#Glossary | '''lateral''']] pharyngeal walls are the structures that come together to close off the nose from the mouth during speech. Incompetence of the soft palate to reach the posterior pharyngeal wall is often associated with cleft palate. A cleft palate occur due to failure of fusion of the two palatine bones (the bone that form the roof of the mouth) during embryologic development and commonly occurs in DiGeorge syndrome <ref><pubmed>21738760</pubmed></ref>.
|-
| valign="top"|'''Recurrent infections due to immunodeficiency'''
| valign="top"|Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. it should be noted, that the variability amongst patients is high and that in most cases these problems cease before the first year of life. However some patients may have a persistent immunodeficiency and develop [[#Glossary | '''autoimmune diseases''']] such as juvenile [[#Glossary | '''rheumatoid arthritis''']] or [[#Glossary | '''graves disease''']] <ref>PMID 21049214</ref>.
| valign="top"|The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign [[#Glossary | '''antigen''']]s (bacteria, viruses etc.) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from [[#Glossary | '''haemapoietic stem cells''']] and undergo a selection process. In embryonic development the thymus develops from the third pharyngeal pouch, a structure at which abnormalities occur in the event of a 22q11.2 deletion. Hence patients with DiGeorge syndrome have failure in T-cell mediated response due to hypoplasticity or lack of the thymus and therefore difficulties in dealing with infections <ref><pubmed>19521511</pubmed></ref>.
[[#Glossary | '''Autoimmune diseases''']] are thought to be due to T-cell regulatory defects and impair of tolerance for the body's own tissue <ref><pubmed<21049214<pubmed/></ref>.
|-
| valign="top"|'''Hypocalcaemia due to hypoparathyrodism'''
| valign="top"|Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause [[#Glossary | '''seizures''']] in the fetus <ref><pubmed>21049214</pubmed></ref>. However symptoms may as well be absent until adulthood. Typical signs and symptoms of hypoparathyrodism are for example seizures, muscle cramps, tingling in finger, toes and lips, and pain in face, legs, and feet<ref><pubmed></pubmed>18956803</ref>.
| valign="top"|The superior parathyroid glands as well as the parafollicular cells are formed from arch four in embryologic development and the inferior parathyroid glands are formed from arch three. Developmental failure of these arches may lead to incompletion or absence of parathyroid glands in DiGeorge. The parathyroid gland normally produces parathyroid hormone, which functions by increasing calcium levels in the blood. However in the event of absence or insufficiency of the parathyroid glands calcium deposits in the bones to increased amounts and calcium levels in the blood are decreased, which can cause sever problems if left untreated <ref><pubmed>448529</pubmed></ref>.
|-
| valign="top"|'''Learning difficulties'''
| valign="top"|Nearly all individuals with 22q11.2 deletion syndrome have learning difficulties, which are commonly noticed in primary school age. These learning difficulties include difficulties in solving mathematical problems, word problems and understanding numerical quantities. The reading abilities of most patients however, is in the normal range <ref><pubmed>19213009</pubmed></ref>.
DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation<ref><pubmed>17845235</pubmed></ref>.
| valign="top"|While the exact reason for these learning difficulties remains unclear, studies show correlation between those and functional as well as structural abnormalities within the frontal and parietal lobes (front and side parts of the brain) <ref><pubmed>17928237</pubmed></ref>. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes <ref><pubmed>11339378</pubmed></ref>.
|-
| valign="top"|'''Abnormal facial features''' [[Image:DiGeorge_1.jpg|abnormal facial features observed in DiGeorge syndrome|left|150px]]
| valign="top"|To the common facial features of individuals with DiGeorge Syndrome belong <ref><pubmed>20573211</pubmed></ref>:
* broad nose
* squared shaped nose tip
* Small low set ears with squared upper parts
* hooded eyelids
* asymmetric facial appearance when crying
* small mouth
* pointed chin
| valign="top"|The abnormal facial features are, as all other symptoms, based on the genetic changes of the chromosome 22. While there are broad variations amongst patients, common facial features can be seen in the image on the left <ref><pubmed>20573211</pubmed></ref>.
|-
|}

===Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome===

{|
|-bgcolor="lightgrey"
| [[File:Drawing Of A Normal Heart.PNG | 150px]]
| [[File:Ventricular Septal Defect.PNG | 150px]]
| [[File:Obstruction of Right Ventricular Heart Flow.PNG | 150px]]
| [[File:'Overriding' Aorta.PNG | 150px]]
| [[File:Heart Defect E.PNG | 150px]]
|-
| valign="top"| '''The Normal heart'''
| valign="top"|''' Ventricular septal defects'''
The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the [[#Glossary | '''interventricular septum''']] (see image A). If the interventricular septum fails to fuse completely, deoxygenated blood can flow from the right ventricle to the left ventricle and therefore flow back into the systemic circulation without being oxygenated in the lung (see image B)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>
| valign="top"| ''' Obstruction of right ventricular outflow'''
Outgrowth of the heart muscle can cause narrowing of the right ventricular outflow to the lungs, which in turn leads to lack of blood flow to the lungs and lack of oxygenation of the blood (see image C) <ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''"Overriding" aorta'''
In the healthy heart, blood from the left ventricle flows into the aorta and from there into the systemic circulation (see image A). However if the aorta is abnormally located it connects to the left and also to the right ventricle, where it "overrides", hence blood from both left and right ventricle can flow straight into the systemic circulation (see image D)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
| valign="top"| '''Right ventricular hypertrophy'''
Due to the right ventricular outflow obstruction, more pressure is needed to pump blood into the pulmonary circulation. This causes the right ventricular muscle to grow larger than its usual size (compare image A with image E)<ref> Kumar, V., Abbas, A., Fausto, N., Mitchell, R. N. (2007). Robbins Basic Pathology. In Saunders Elsevier (Ed 8), Philadelphia. https://evolve.elsevier.com/productPages/s_1221.html</ref>.
|}

== Treatment==

There is no cure for DiGeorge syndrome. Once a gene has mutated in the embryo de novo or has been passed on from one of the parents, it is not reversible <ref>PMID 21049214</ref>. However many of the associated symptoms, such as congenital heart defects, velopharyngeal insufficiency or recurrent infections, can be treated. As mentioned in clinical manifestations, there is a high variability of symptoms, up to 180, and the severity of these <ref><pubmed>16027702</pubmed></ref>. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries <ref><pubmed>16027702</pubmed></ref> <ref><pubmed>15754359</pubmed></ref>.
Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists, from example a cardiologist for congenital heard defect, a plastic surgeon for a cleft palet or an immunologist for recurrent infections, in order to receive the best therapy available. Furthermore, some symptoms can be prevented or stopped from progression if detected early. Therefore, it is of importance to diagnose DiGeorge syndrome as early as possible <ref> PMID 21274400</ref>.
Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below <ref><pubmed>16027702</pubmed></ref><ref><pubmed>9350810</pubmed></ref>:
* Newborn: heart defects
* Newborn: cleft palate, cleft lip
* Newborn: seizures due to hypocalcaemia
* Newborn: other birth defects such as kidney abnormalities or feeding difficulties
* Late-occurring features: [[#Glossary | '''autoimmune''']] disorders (for example, juvenile rheumatoid arthritis or Grave's disease)
* Hypocalcaemia
* Psychiatric illness (for example, DiGeorge syndrome patients have a 20-30 fold higher risk of developing [[#Glossary | '''schizophrenia''']])
Once alerted, one of the diagnostic tests discussed above can bring clarity.

The treatment plan for DiGeorge syndrome will be both treating current symptoms and preventing symptoms. A range of conditions and associated medical specialties should be considered. Some important and common conditions will be discussed in more detail in the table below.

===Cardiology===

{|
|-bgcolor="lightblue"
| Therapy options for congenital heart diseases
|-
| The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both other abnormalities caused DiGeorge syndrome, such as a deprived immune system and hypocalcaemia, and the anatomy of the cardiac defects <ref><pubmed>18636635</pubmed></ref>. In order to achieve the best outcome timing is of importance <ref><pubmed>2811420</pubmed></ref>.
Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly <ref><pubmed>5696314</pubmed></ref>.
|}

===Plastic Surgery===

{|
|-bgcolor="lightblue"
| Therapy options for cleft palate
| Image
|-
| Plastic surgery in clef palate patients is performed to counteract the symptoms. Here, two opposing factors are of importance: first, the surgery should be performed relatively late, so that growth interruption of the palate is kept to a minimum. Second, the surgery should be performed relatively early in order to facilitate good speech acquisition. Hence there is the option of surgery in the first few moth of life, or a removable orthodontic plate can be used as transient palatine replacement to delay the surgery<ref><pubmed>11772163</pubmed></ref>. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality <ref><pubmed> 21740170</pubmed></ref>. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy <ref><pubmed>8884403</pubmed></ref>.
| [[File:Repaired Cleft Palate.PNG | Repaired cleft palate | thumb | 300 px]]
|}

===Immunology===

{|
|-bgcolor="lightblue"
| Therapy options for immunodeficiency
|-
|The immune problems in children with DiGeorge syndrome should be identified early, in order to take special precaution to prevent infections and to avoiding blood transfusions and life vaccines <ref>PMID 21049214</ref>. Part of the treatment plan would be to monitor T-cell numbers <ref><pubmed> 21485999</pubmed></ref>. A thymus transplant to restore T-cell production might be an option depending on the condition of the patient. However it is used as last resort due to risk of rejection and other adverse effects <ref><pubmed>17284531</pubmed></ref>.
|}

===Endocrinology===

{|
|-bgcolor="lightblue"
| Therapy options for hypocalcaemia
|-
| Hypocalcaemia is treated with calcium and vitamin D supplements. Calcium levels have to be monitored closely in order to prevent hypercalcaemic (too high blood calcium levels) or hypocalcaemic (too low blood calcium levels) emergencies and possible calcification of tissue in the kidney <ref><pubmed>20094706</pubmed></ref>.
|}

==Current and Future Research==

Advances in DNA analysis have been crucial to gaining an understanding of the nature of DiGeorge Syndrome. Recent developments involving the use of Multiplex Ligation-dependant Probe Amplification (MLPA) have allowed for the beginning of a true analysis of the incidence of 22q11.2 syndrome among newborns <ref><pubmed> 20075206 </pubmed></ref>. As mentioned earlier the syndrome has an approximated incidence of 1/2000 to 1/4000, however due to the highly variable phenotypes presented among patients it has been suggested that this figure may be underestimated. Hence future research directed at gaining a more accurate figure of the incidence is an important step in truly understanding the variability and prevalence of DiGeorge Syndrome among our population.

Other developments in microarray technology have allowed the very recent discovery of copy number abnormalities of distal chromosome 22q11.2 that are distinctly different from the better-studied deletions of the proximal region <ref><pubmed> 21671380 </pubmed></ref>. This 2011 study of the phenotypes presenting in patients with these copy number abnormalities has revealed a complicated picture of the variability in phenotype, which hinders meaningful genotype-phenotype correlations. However, future research aimed at decoding the complex variable phenotypes presenting with 22q11.2 deletion and hence allow a deeper understanding of this syndrome.

[[File:Chest PA 1.jpeg|200px|thumb|right| A preoperative chest PA showing a narrowed superior mediastinum suggesting thymic agenesis, apical herniation of the right lung and a resultant left sided buckling of the adjacent trachea air column]]

There has been a large amount of current research into the complex genetic and neural substrates that alter the normal embryological development of patients with 22q11.2DS. It is known that patients with 22q11.2DS have a great chance of having attention deficits and other psychiatric conditions such as schizophrenia <ref><pubmed> 17049567 </pubmed></ref>, however little is known about how abnormal brain function is manifested in neural circuits and neuroanatomical changes <ref><pubmed> 12349872 </pubmed></ref>. Hence future research aimed at revealing the intricate details at the neuronal level and the relation between brain structure and function and cognitive impairments in patients with 22q11.2DS will be a key step in allowing a predicted preventative treatment for young patients to minimize the expression of the phenotype <ref><pubmed> 2977984 </pubmed></ref>. Once structural variation of DNA and its implications in various types of brain dysfunction are properly explored and these prodromes are understood preventative treatments will be greatly enhanced and hence be much more effective for patients with 22q11.2DS.

As there is no known cure for DiGeorge, there is much focus on preventative treatment of the various phenotypic anomalies that present with this genetic disorder. Ongoing research into the various preventative and corrective procedures discussed above forms a particularly important component of DiGeorge research, as this is currently our only form of treating DiGeorge affected patients.

[[File:DiGeorge-Intra_Operative_XRay.jpg|200px|thumb|right|Intraoperative chest AP film showing newly developed streaky and patch opacities in both upper lung fields. ETT above the carina is also shown]]

Hypocalcaemia, as discussed above, often presents as an emergency in patients, where immediate supplements of calcium can reverse the symptoms very quickly <ref><pubmed> 2604478 </pubmed></ref>. Due to this fact, most of the evidence for treatment of hypocalcaemia comes from experience in clinical environments rather than controlled experiments in a laboratory setting. Hence the optimal treatment levels of both calcium and vitamin D supplements are unknown. It is known however, that the reduction of symptoms in more severe cases is improved when a larger dose of the calcium or vitamin D supplement is administered <ref><pubmed> 2413335 </pubmed></ref>. Future research directed at analyzing this relationship is needed to improve the effectiveness of this treatment, which in turn will improve the quality of life for patients affected by this disorder.

As discussed above, there are various surgical procedures that are commonly used to treat some of the phenotypic abnormalities presenting in 22q11.2 DS. It has recently been noted by researchers of a high incidence of aspiration pneumonia and Gastroesophageal reflux developing in the perioperative period for patients with 22q11.2 deletion. This is of course a major concern for the patient in regards to preventing normal and efficient recovery aswell as increasing the risks associated with these surgeries <ref><pubmed> 3121095 </pubmed></ref>. Although this research did not attain a concise understanding of the prevalence of these surgical complications, it was suggested that active prevention during surgeries on patients with 22q11.2 DS is necessary as a safeguard. Further research into the nature of these surgical complications would greatly increase the success rates of these often complicated medical procedures as well as reveal further the extremely wide range of clinical manifestations of DiGeorge Syndrome.

==Glossary==

'''Amniocentesis''' The sampling of amniotic fluid using a hollow needle inserted into the uterus, to screen for developmental abnormalities in a fetus

'''Antigen''' a substance or molecule which will trigger an immune response when introduced into the body

'''Arch of aorta''' first part of the aorta (major blood vessel from heart)

'''Autoimmune''' of or relating to disease caused by antibodies or lymphocytes produced against substances naturally present in the body (against oneself)

'''Autoimmune disease''' caused by mounting of an immune response including antibodies and/or lymphocytes against substances naturally present in the body

'''Autosomal Dominant''' is a method by which diseases can be passed down through families. It refers to a disease that only requires one copy of the abnormal gene to acquire the disease

'''Chromosome''' genetic material in each nucleus of each cell arranged and condensed strands. In humans there are 23 pairs of chromosomes of which 22 pairs make up autosomes and one pair the sex chromosomes

'''Cleft Palate''' refers to the condition in which the palate at the roof of the mouth fails to fuse, resulting in direct communication between the nasal and oral cavities

'''Congenital''' preset from birth

'''Ductus arteriosus''' duct from the pulmonary trunk (the blood vessel that pumps blood from the heart into the lung) to the aorta that closes after birth

'''Dysmorphia''' refers to the abnormal formation of parts of the body.

''Echocardiography''' The use of ultrasound waves to investigate the action of the heart

'''Graves disease''' symptoms due to too high loads of thyroid hormone, caused by an overactive [[#Glossary | '''thyroid gland''']]

'''Haemapoietic stem cells''' multipotent cells that give rise to all blood cells

'''Hypocalcaemia''' deficiency of calcium in the blood stream

'''Hypoparathyrodism''' diminished concentration of parthyroid hormone in blood, which causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasm

'''Hypoplasia''' refers to the decreased growth of specific cells/tissues in the body

'''Immunodeficiency''' insufficiency of the immune system to protect the body adequately from infection

'''Lateral''' anatomical expression meaning of, at towards, or from the side or sides

'''Malformation''' see dysmorphia

'''Palate''' the roof of the mouth, separating the cavities of the nose and the mouth in vertebraes

'''Parathyroid glands''' four glands that are located on the back of the thyroid gland and secrete parathyroid hormone

'''Parathyroid hormone''' regulates calcium levels in the body

'''Pharynx''' part of the throat situated directly behind oral and nasal cavity, connecting those to the oesophagus and larynx

'''Phenotype''' set of observable characteristics of an individual resulting from a certain genotype and environmental influences

'''Platelets''' round and flat fragments found in blood, involved in blood clotting

'''Posterior''' anatomical expression for further back in position or near the hind end of the body

'''Prenatal Care''' Health care given to pregnant women.

'''Renal''' of or relating to the kidneys

'''Rheumatoid arthritis''' a chronic disease causing inflammation in the joints resulting in painful deformity and immobility especially in the fingers, wrists, feet and ankles

'''Schizophrenia''' a long term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation. There are various different types and degree of these.

'''Seizure''' fit, very high neurological activity in the brain that causes wild thrashing movements

'''Sign''' an indication of a disease detected by a medical practitioner even if not apparent to the patient

'''Symptom''' a physical or mental feature that is regarded as indicating a condition of a disease, particularly features that are noted by the patient

'''Syndrome''' group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

'''T-cell''' a lymphocyte that is produced and matured in the thymus and plays an important role in immune response

'''Tetralogy of Fallot''' is a congenital heart defect

'''Third Pharyngeal pouch''' pocked-like structure next to the third pharyngeal arch, which develops into neck structures

'''Thyroid Gland''' large ductless gland in the neck that secrets hormones regulation growth and development through the rate of metabolism

'''Ventricular septum''' membranous and muscular wall that separates the left and right ventricle

==References==
<references/>

{{2011Projects}}

Talk:2011 Group Project 2

2011-09-29T11:40:33Z

Z3279511: /* The Final Fix up */

[[2011_Group_Project_2|'''Group 2''']]: [[User:z3279511]] | [[User:z3288196]] | [[User:z3288729]] | [[User:z3288827]]

{{2011GroupDiscussionMH}}

==The Final Fix up==

hey not sure what you guys think but what if we take the advice we got on our own sections and focus on fixing them up? I can go through and link the terms to the glossary if someone else wants to fix up the references?

Hi, sounds like a good idea! Will do my part over the week end. anna

Group 2 Critique:
*What Can I say, well researched, nicely sub headed.
*Historical Background shows amazing work. The only 2 things I noticed are the “ 22q11 is in purple” is that on purpose? And the second thing is the image has a source but no reference.
*Epidmiology and Etiology may need some images to balance the words. Also, some spacing between the paragraphs would make it more readable.
* Nice illustration via drawings in the Pathophysiology sections . well structured.
* This section is well established, it has colours and few paragraphs. You might want to consider the size of images probably into something bigger like (Based on symptoms, Ultrasound) and add one more photo in the last two sections (Amniocentesis, BACS- on beads technology)
* one of the best sections on this page is Clinical manifestations. Great work on the table. Perhaps more images along with the abnormality would make a more presentable table. Also, you may consider re-phrasing ( the sub-heading “ How it is caused”) into something with one word. Fabulous work on Heart Drawings.
* in the Section of “ Current and Future research”, allocation of each would be more organised.
The large number of references show how much you guys spent on the page. Some of the references may need to be formatted ( 1,2,3,4,5, etc) note: reference 33,40,47,49, are empty . Overall Great Job.
z3284061

'''Group 2'''

* Well researched and set out page
* An image is needed in either Epidemiology or Etiology would be good
* Diagnostic section tests section is good, however, images are needed for BAC and Amniocentesis
* Glossary is well set out, maybe links to the glossary would be helpful
* Subheadings might be useful in the Current/future research section
* some of the referencing will need to be fixed such as double references
--[[User:Z3292953|z3292953]] 11:11, 29 September 2011 (EST)

'''''DiGeorge Syndrome (Group 2) Peer Review:'''''

Introduction: Well introduced topic. Picture needs description at bottom. Seems to be referenced appropriately.

Historical Background: Extensive timeline which is good. Try to be a little bit more consistent with the colon – either place it after the date or not. Also, picture seems a bit random and needs to have a description at the bottom so that the reader knows what it encompasses.

Epidemiology: Could be a bit more spaced out to make it easier for the reader to read through.

Etiology: Good information and referencing. Try to include a picture in this section as it would help the reader visualize what you are conveying in words.

Pathogenesis/ Pathophysiology: This section is well done. Information is good and images are well-drawn and also contain a relevant description at the bottom. Well done!

Diagnostic Tests: Very extensive. Great use of images. Could you possible also find an image for amniocentesis and BACS? Some image references are not in the correct format and images in this section need to have a label at the bottom.

Clinical Manifestations: This section is well done as well. Possibly too much information which may overwhelm the reader though.

Treatment: Slight inconsistency with the formatting, but otherwise no major dramas. Also possibly more images needed in this section.

Current and Future Research: This section is quite interesting. Research is extensive and images are good – however, they lack correct referencing format and the student template in the information section.

Glossary: Extensive. Well done.

Overall, good job! --[[User:Z3290808|z3290808]] 10:40, 29 September 2011 (EST)

Group 2:

There seems to be a lot of references, almost an excessive amount.

A picture for epidemiology and aetiology would be good.

Diagnostic tests was done well

Clinical manifestations should include some info on what the normal structure and function of the heart.

There is a very large amount of written information and this is reflected in the reference section that takes up alot of space on the page. There are slabs of writing which makes it hard to read the page. It’s boring to see long slabs of writing. The long glossary reflects the long slabs of writing. It’ll be hard to read through. Its not that clear and concise.

z3332178 =]

'''Group 2:'''

*Intro: the first sentence is a little vague. Rather joining sentence 1 and 2 together and defining congenital disorder and explaining it at the same time would be better. I liked the pictures but the trio in that arrangement left the section looking a little unfinished.

*Historical background: image is not explained, a little confused as to why it is there.

*epidemiology: good section, good referencing

*etiology: its a little awkward in flow as you jump from talking about one study, and after one sentence talk about what another study said. Maybe work on building it into an actual paragraph instead of making them merely sentences.

*pathogenesis: the images would look better if they were larger so you get the vague image of it at a glance. Good section, flows nicely

*diagnosis: great section. Layout made it easy to read. Maybe increase the size of the image in the symptoms part, this was harder to see.

*clinical manifestation: good section. Maybe with the last set of images with the heart, leave a space or include a pink heading like you did for the table above it to indicate another table. This was hard to see

*treatment: good section. Maybe change the colour of the bit that you highlighted in that pale orange/skin colour thing. It’d be nice to have that stand out a little more so those headings can actually be seen and not seen as random words.

--[[User:Z3290558|z3290558]] 09:55, 29 September 2011 (EST)

'''Peer review'''
WOW!
This page looks fantastic. The editing is great. All of the information is presented neatly and concisely.
However, just look in "historical background" and make sure all of the lines are edited uniformly. Some have ":" some don't.
Obviously that is nothing major, I'm just nit-picking.
I think you may want to redraw your "pathology of Di George syndrome". It seems quite cluttered.

Overall: Excellent. There really isn't much to say about this page.

--[[User:Z3290618|Ziggy Harrison-Tikisci]] 10:29, 29 September 2011 (EST)

'''Group 2 peer review'''

Introduction: Please explain what the images is about.

Historical background: Please be careful that you type 'DiGeorge syndrome' throughout the section. For example, the point about the 1981 event has 'diGeorge syndrome'. There are also some spelling errors. Furthermore, a legend for the image would clarify.

Epidemiology: Breaking up the segments with images will make understanding the content easier for the reader.

Diagnositic test: Information on the ultrasound test, particularly the second paragraph, is repetitive. The layout is great and the images breaks up the text nicely. A legend for the image will be good. In particular, please clarify what is abnormal with the male face.

Treatment: Are 'Hypocalcaemia' and 'Psychiatric illness' a late occuring feature or an observable condition in newborns.

--[[User:Z3289301|z3289301]] 09:42, 29 September 2011 (EST)

'''Peer Review'''

:*The first three sentences about congenital disease is misplaced. This should be in your glossary, not in your very first sentences.

:*The common symptoms could be left out of the introduction and discussed in the appropriate section.

:*Written like an essay rather than a webpage. Language such as “for example” not necessary.

:*Clinical Diagnosis was well structured and good use of pictures.

:*Clinical Manifestations could be simplified slightly in the table.

:*Some references need to be adjusted rather than just a web address.

--[[User:Z3217043|z3217043]] 08:42, 29 September 2011 (EST)

'''Peer Review'''

This wiki has obviously been given a lot of time and effort and it shows. The text isn't too heavy and I've learnt a few things about DeGeorge Syndrome. Very thoroughly researched and overall, looks and feels very neat and concise. A few points to be made:

:*No need to define congenital disorder. I recommend just leaving it out entirely.

:*Some pictures still need to be captioned even after addressed by Mark Hill. Who is that person in the History section? Angelo DiGeorge? Which one is he?

:*The student drawn images are the let-down. They look very rushed and haven't been given enough effort. The student drawn images on the wiki is also small, so to read the accompanying text by expanding the image, breaks up the flow of reading the wiki. It also hasn't followed the referencing format.

:*BACS- on beads technology image is a pdf file. Either put a picture in the designated area or remove the reference.

:*Amniocentesis doesn't have an image.

:*You should refrain from using the words "mental retardation" as this could be deemed offensive. Use "intellectual disability" as that is a more common term now used in Australia. Also use "learning difficulty" or "developmental delay". We should also encourage the use of person-first language e.g., "a child with an intellectual disability" rather than "intellectually disabled child". This promotes the idea that a person comes before their disability.

:*References section needs attention. Some referencing are not present at all in some casees.

--[[User:Z3293267|z3293267]] 07:12, 29 September 2011 (EST)

'''Group 2 Peer Review'''

• Your overall structure and layout of the page is really good! It’s really neat and all the images and text seem to be in proportion.

• All your pictures, graphs and tables show that you have a good understanding of this abnormality.

• The introduction gives a really good summary of the disease, however I think you should introduce the disease first and then go onto
to explain ‘congenital disorders’.

• Epidemiology could probably be broken down into sections, to make it an easier read and more interesting.

• The aetiology section needs an image to break up a large amount of text also to make it more interesting and informative.

• Good use of subheadings in the pathogenesis, very relevant! Student drawn images are good, could they be a little neater?

• Diagnostics test is really nice and clear, however consistency with the colour of the tables would be good.

• Clinical manifestations section has really good information, I think it could be structured better though, for example; only have the table describing each sign and symptom and then have another sub-heading related abnormalities where you could include ‘Teratology of Fallot as an example...’ (Just an idea).

• Current future research is obviously researched thoroughly, breaking it down into relevant subheadings would really improve it though.

• Make sure you fix up your repeated references. But good work overall!

--[[User:Z3289829|z3289829]] 02:40, 29 September 2011 (EST)

*Intro: Great intro, the picture is excellent and grabs your attention. Perhaps don’t start with a definition of congenital disorders. You can put that in the glossary or mention it after you have initially began discussing the disease.

*History: Love the timeline, clear, easy to follow.

*Epidemiology: Very word heavy which is not necessary for this section. Dot pints or some sort of visual representation would make it more appealing.

*Etiolgy: “ mentioned previously it has a prevalence of 1/2000 to 1/4000” This part is not necessary. Image of the gene would look good in this section. You refer to the disease as DGS (which is perfectly fine) but repeatedly refer to it as DiGeorge syndrome in the previous section, which can get a little confusing. Either use its full name or just the abbreviation.

*Pathogenesis:“As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion” probably unnecessary.
Excellent image, perhaps make it a bit bigger so that you can refer to it whilst reading.

*Diagnosis: The formatting of the text against it’s visual representation is fantastic and love the use of colour – refreshing! The use of colour can be expanded to the rest of the page to make it more cohesive. There is a an image heading with no image under the “ Amniocentesis” heading. There is also an image missing in the BAC’s image column replaced with a link- should fix this.

*Clinical manifestations: Once again great use of colour, but VERY word heavy. It shows that you have done a lot of research but it’s a lot to take in, you can definitely make it more compact.

*Treatment: I quite like this section. It’s informative and is formatted in a way that won’t bore you. The sections which have big blocks of text could benefit from this format. You need to choose a different colour for the block highlights though because you can barely see it.

*Research: Thorough research, very informative but again too much text. If you feel it’s necessary to keep the text you can break it down with word highlights/ bolding or dot points.

*Text/image: Great ratio except a few sections where the text can be cut down a little bit.

*Overall, very thorough, loved the colour and formatting and the student drawn image. Excellent work.

--[[User:Z3290270|z3290270]] 02:37, 29 September 2011 (EST)

'''Peer Review for Group 2'''

'''Peer Review'''
* Many of the pictures do not have a legend/explanation associated with them. However, the hand-drawn picture is underscored by a legend.
* The introduction is rather abrupt; definition of "congenital disorder" could have been a simple hyperlink or a note in the glossary.
* Is the historical background necessary? In the section, the photo of the two people is not explained.
* Section on epidemiology seems to cross over significantly with clinical manifestations.
* Thorough referencing throughout. However, some of the references appear strangely in the references section (could be a vestige of that crash a few weeks earlier?)
* The table in clinical manifestations is strangely.....implied. Section on Tetralogy of Fallot can be cleaned up in terms of layout.
* Inclusion of current and future research is noted, and well set out/referenced.
* Glossary is thorough.
* Overall, a very thorough and broad exploration of the topic.
--[[User:Z3290689|z3290689]] 00:11, 29 September 2011 (EST)

*I don’t think it would be necessary to start the intro with clarifying what congenital diseases are. It would be better if it starts with, ‘Di George Syndrome is a …’ sentence.
*In the intro, fix this sentence as it needs punctuation, ‘As there is currently no treatment education is vital to the wellbeing of those affected, directly or indirectly by this condition’
*Nice picture of Angelo, and also the history is presented well as it makes easy to read and follow.
*Information presented in the epidemiology section is interesting but not organised properly so it flows. Please fix this up.
*Etiology has some technical jargon that is not explained or put in the glossary. Please do so
*Thumb picture of the area where 22q deletion occurred doesn’t show when viewing the page.
*The first line of the Pathogenesis section is, I believe, not necessary as the section just before it just mentioned that fact.
*Punctuation needed for ‘ ‘‘TBX1’’ is expressed in early development in the pharyngeal arches, pouches and otic vesicle; and in late development, in the vertebral column and tooth bud’
*Pathogenesis/physiology easy to read and has good drawn diagram
*The diagnostics section has good information of how the tool works, what it detects and an image refering to the tool. However Amniocentesis section has no image and yet has a column for it. Please fix this if there is no image for it. Also the Ultrasound section should include what DiGeorge patients would have on Ultrasound scans.
*It is good that the clinical Manifestations section is presented in that way in the table as it explains the abnormalities really well.
*The four images in the Tetralogy of Fallot section may make the reader seem that one of these problems may occur, whilst all four problems are present in the TOF heart.
*The treatment section has information in regards to symptoms. This be under another subheading altogether and not under the treatment section
*Current and Future Research section provides the reader with a good image of the current status of this disease in regards to research.
*References are not properly formatted as repetition in the referencing could be seen. Please fix this.
*Please balance the text to image ratio as the page is text heavy and can be hard to read unless it is complemented with more images.
*Other than that good page.

--[[User:Z3291317|Z3291317]] 23:46, 28 September 2011 (EST)

'''Group 2 peer evaluation'''
*The introduction is done quite well. It is succinct and brief. You have done a very good introduction to the topics that your page is about to explore. Unfortunately you did fail to introduce some of the headings that your page have, like the diagnostic section. Aside from this it is a good introduction overall.
*Historical background is done very well. It has enough detail to see the ongoing achievements on the disease.
*The epidemiology was excellent. You have covered the demography of the disease and properly cited some of the facts that you try to get across. Revision of some of the sentences may be needed because some sentences are not expressed properly. Also it would have been really nice if you could incorporate some of the data that was mentioned in a more summarized form, like a table, dot points, or something. It just makes reading easier and less likely to get lost in the words
*I really like how concise yet very informative your etiology section. What would make this section better than what it is at the moment is an image that would complement the information, and also a bit of an explanation about some of the terms that is in there, like “hemizygous”.
*The Pathogenesis section is very well done. It contains enough detail that we get an in-depth knowledge about the development of the disease, and the images that were used are very helpful. One thing that would improve it though is that if you can elaborate further on the function of the TBX1 gene and how affecting the expression of this gene results to DiGeorge.
*The Diagnostic test section I think is perfect. The way the test works was described, and at the same time they were all related back to how this aids in the detection of the disease. The layout of the information is also very engaging.
*Clinical manifestation is very nicely done. The information was very descriptive and informative. It is also presented very well. Just one thing though is that there is no clear separation between two clinical outcomes, so it tends to get confusing sometimes when someone is reading it. I guess adding more space between would be a good idea.
*Treatments section is done quite well. If you could add a video of some of these treatments or even just a link to a video of it that would really make this section perfect.
*The research section is also very good, especially your insight to future direction of research on this disease. I guess it wouldn’t hurt to drop some current research articles within this section, which shows the readers that the information that they have just read is up-to-date.
*Glossary is a good idea, not really a big fan of it but good idea anyway.
--[[User:Z3290841|z3290841]] 10:20, 29 September 2011 (EST)

'''Group 2'''

Introduction: Introduction is good. The pictures look great.

Historical background: I like the timeline. I think the picture needs a caption underneath explaining who the people are.

Epidemiology: Needs some pictures to break up the text.

Etiology: This section is quite difficult to understand. I think a lot of terms need explaining eg. hemizygous deletion, microdeletion and halpingoinsufficiency.

Pathophysiology: This section is much easier to understand and flows quite well. The pictures should be bigger though.

Diagnostic tests: great section! Good layout and easy to read. The symptoms picture could be a bit bigger and it would be good if there were pictures for the bottom two.

Clinical manifestations: Again, great section. The table could use some more pictures though to balance out all the text.

Treatment: Needs some more pictures.

Current and future research: This section is quite well explained and has a good level of detail.
--[[User:Z3291324|z3291324]] 23:18, 28 September 2011 (EST)

'''Group 2:'''

•I’m not sure if you need the definition and explanation of congenital disorders at the very beginning of the page. The third sentence beginning with DiGeorge syndrome would make more sense as the beginning of the introduction.

•I like the use of images in the introduction and at the beginning of the page, but they are not referred to in the text and do not include captions. Perhaps you should include a brief caption under each image explaining what the image is portraying and why it is relevant.

•Be careful with the wording of some things, particularly in the introduction, i think some parts need to be edited and reworded as they are a little confusing to read.

•The fact that the timetable in the history goes all the way up to 2011 is good and this section seems to be referenced well.

•The student drawn image of the heart defects do not include the correct template that is required for proper copyright information.

•Good use of tables to break up the text, although the different colours is a bit distracting, i would recommend choosing one colour and using that throughout the page.

•The referencing needs to be fixed up as many references appear multiple times in the reference list.

--[[User:Z3332183|z3332183]] 21:24, 28 September 2011 (EST)

'''Peer Assessment Group 2-DiGeorge Syndrome'''
*The introduction and history look good with great use of images which makes for an interesting start.
*There could be at least one other picture in 'Epidemiology' and 'Etiology', otherwise it just looks like a big block of text
*The 'Diagnostic Tests' look good-the image for BACS still need to be uploaded
*The student drawn images are colorful however doesn't have copyright information-just states who drew them
*Some sentences seem incomplete or doesn't seem to convey a message e.g. "Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists".
*'Current and Future Research' has a lot of information however is it possible to condense it and give a basic summary instead. I understand that you have tried to do your best but it is just a lot of information. You might also wnat to consider using sub headings.
*The references need a bit of attention-you have a lot of links there which need to be changed to proper references
--[[User:Z3308968|Tahmina Lata]] 21:13, 28 September 2011 (EST)

'''Group 2 Peer Assessment'''
*Good introduction. Like the use of the image to grab the reader's attention but it might be a good idea to include one or two sentences in the text explaining the characteristic appearance of the patients and give the image a title (just to link the image to text straightway at first glance without having to click on the image to understand it's significance).
*Not sure if you need to explain the term 'congenital' in the introduction. Might be better to start straight away on the actual syndrome.
*Great job on the "Historical background" section. Maybe have small title for the image of Angelo DiGeorge.
*Good explanations in the 'epidemiology' and 'etiology' sections but the text is a bit too heavy. Try breaking it up with an image.
*Good use of images, table and the general arrangement and layout of information in the 'Diagnostic test" section. (Small spelling error in section name). Try to include an image in the "Amniocentesis" section as well to complete the table.
*Needs to explain the link in the "BACS- on beads technology" section and why it has been inserted.
*Like the student drawings in the 'tetralogy of fallout' section and good explanations of what is happening. Small grammatical error in the title (on instead of an).
*Good job on the 'treatment' and 'current/future research' sections.
--[[User:Z3291622|Z3291622]] 16:17, 28 September 2011 (EST)

'''Group 2'''

*The whole page is very nicely formatted
*Introduction is clear and concise although would it be more efficient to start talking about DiGeorge straight away rather then define congenital abnormalities?
*Historical background is obviously well researched
*There needs to be an image in epidemiology and/or etiology to break up the text or present some of the information in a table
*The pathogenesis section flows nicely although a few words need to be added to the glossary
*Great table for diagnostic tests- this makes it easy to follow
*A few more pictures would be great for clinical manifestation and maybe this would be better in dot points?
*Student drawn images of tetralogy of fallot were excellent
*Subheadings are needed for Current/future research
*Good project overall, obviously a lot of effort has been put into this.

'''Group 2 - Peer assessment'''

*The introduction is easy to read and understand. Maybe one thing you could improve on is the organization of the paragraphs because it looks abit too choppy as of now.
*The history looks amazing and well researched AND well referenced! Makes me believe and trust your project even more. Furthermore the picture on the right just makes the section more appealing.
*Epidemiology - the information flows well and examples are also mentioned which is nice to see
*Etiology - The information is ok but maybe it could be better explained with explanation of the technical terms within your texts
*Pathogenesis/Pathophysiology - the student drawn images look amazing! And the organisation of information is good. Maybe a suggestion would be to hyperlink some of the terms in the text because there was alot of technical terms to be scrolling down and up for.
*Diagnostic Tests - The layout is very appealing and consistent with the rest of the page. The spelling of the heading is wrong!
*Maybe for the glossary it would be a good idea to include headings such as "A", "B" etc
*Fixing up double referencing would be a good idea aswell

--[[User:Z3330313|z3330313]] 19:36, 28 September 2011 (EST)

'''Peer Assessment Group2'''

*Epidemiology – hyperlink technical terms to glossary?
*The pathophysiology/pathogenesis sections (pharyngeal arches onwards) needs to be linked back to the syndrome. You list it in the “genes” section then describe the normal development, but it needs to be described to what happens in the syndrome/abnormal development.
*Don’t forget to add in the missing images in the diagnostic techniques
*You have several (excellent) summary tables – I think the format should be consistent in each, would make it look/flow better
*Typical symptoms: Newborn section can be condensed
*Current and future research could benefit by being broken up a bit – maybe use subheadings, colour or bold main points – it just is a big slab of text and looks daunting to read.
*References: some just have the PMID number and need to be fixed so it reads the whole reference (just for consistency)
--[[User:Z3332824|z3332824]] 23:18, 27 September 2011 (EST)

GROUP 2: DiGeorge Syndrome
*I don't know if the congenital disorder definition is needed in the intro, maybe you can included in the glossary instead
*The image in the intro could use a legend
*Info in the intro is comprehensive and informative
*History section has got good, succinct information and i like the fact that it goes up to 2011, however maybe you can consider putting the timeline in a table. Image could also have a legend
*Epidemiology has been researched relatively well, info is comprehensive and flows well, however, could be improved with a graph of some sort to accompany info with a visual
*Etiology contains very descriptive, informative info, could be improved with an image of the chromosome and the area of deletion
*It would be a good idea if the acronyms are included in the glossary
*It is evident that the Pathogenesis/Pathophysiology section has been very well researched, maybe the "genes involved in DiGeorge syndrome" section could be formatted in a table
*The use of a table in Diagnostic tests is succinct and informative. You should check for spelling mistakes (Dianostic Tests is spelt wrong), images to accompany these tests are useful, however, again a legend for each of these would be help
*Image missing in the Amniocentesis part of diagnosis
*I don't know if the image link for BACS- on beads technology is really helpful
*Clinical manifestations has clearly been researched extesively, however, this section is very overwhelming,too much text in my opinion. It would be easier to read if it was summarised more, a graph may be helpful
*Treatment section is comprehensive and summarised well
*I have found that incidence has been mentioned in quite a few sections, is this really necessary? Can it just be mentioned in epidemiology?
*Current and future has got some good info but it is quite lengthy and could be better to summerise it a bit more so u don't lose the reader
*The last two images need to be referenced properly, with the template and correct referencing

Overall:
*The whole project has been researched very well
*Some of the images could use legends to describe what they are about and you could also consider moving the images around a bit so there's variety and making some of them a little bigger so their features can be seen
*Maybe acronyms could be included in the glossary
*some sections could be reviewed and info could be condensed
*references need to be reviewed and correctly structured (some work on this is required)
*You could improve this project by also linking the glossary terms to the text to make it easier to access, also some graphs could be used

--[[User:Z3331556|z3331556]] 22:51, 27 September 2011 (EST)

'''Group 2: DiGeorge Syndrome'''
*initial browse through the webpage: well balanced use of text, image, colour and table format.
*introduction: well summarised and good use of image. It is interesting and provides a good overview to the syndrome. Minor adjustment: give one or two examples of symptoms rather than providing a list.
*Historical background: good use of timeline, and layout.
* Epidemiology & Etiology: needs to define terms in glossary such as velocardial syndrome.
*I appreciate the subheadings used in the pathogensis section... it breaks up the mass of information, creates flow and also shows understanding. Needs to define a few terms in glossary such as: hypoplasia, hypoparathyroidism, parturition etc.
*Diagnostic tests: well set out, I think the use of colour is aesthetically pleasing and adds to the overall presentation of the webpage.
*Clinical Manifestations: well set out and good use of images. Table could benefit from use of borders, just to clearly separate the rows where the information appears to overlap.
*Current&Future Research: could benefit from formatting of previous headings. That is, in a table to break up the information, or by using subheadings
--[[User:Z3332327|z3332327]] 15:42, 27 September 2011 (EST)

'''Peer Assessment group 2'''
*Introduction is clear cut and enters the topic with easy understanding though should incorporate the image more, where the image has no description of what its suppose to explain where symptoms would link to the image would help a lot.
*Timeline used correctly in displaying the increased understanding of the disorder, image used was does not have a description so don’t know who is the discover right or left and what is the image suppose to show.
*Etiology refers to a lot of studies or research which is not clearly explained how the research shows the causation of the disorder with various results showing different reasons for causation
*athogenesis clearly links image to the common deletion of gene with clear explanations of genetics component of Digeorge syndrome. Though would become more fluid with introduction of embryological effects instead of leading to pharyngeal defects.
*Embryological component didn’t expand the defects of the pharyngeal arches as well not much of the parathyroid which is major component of calcium levels also poorly linked to the image without any mention of the figure.
*Diagnostic tests require an introduction onto the topic and techniques, where heading directly states the techniques without any understanding of what these means.
*Clinical manifestations describes information clearly though the congenital heart defects images would work better below the information, so text and information with image below.
*Treatment has image relating to plastic surgery could have a description even though it’s a example of surgery.
*Current and future research should be more organised instead of paragraphs have dot points to know the difference between new research and current also images not place in correct manner but in between the glossary as well.
*Referencing has not been done correctly with only links, repeats and some are even blank.
*Glossary not linked to the term or bolded to note that it’s in the glossary so while reading its confusing if you have no pathology background.
z3332250 23:42, 26 September 2011 (EST)

Group 2 Peer Review

*Well structured page in terms of headings, good choice of topics covered
*Do not need to define congenital abnormality. If you want to define it perhaps add it to the glossary instead?
*Symptoms in introduction would probably be best in another section
*Great images. Some need to be made bigger in order to easily read the detail on it
*Most images are on the right side of the page. Could you move them around a bit to make it visually more appealing?
*Faint colour highlighting under treatment needs to be made darker or deleted
*Some duplication in referencing
*Well researched-great
*Overall, an informative and well presented page. Just some minor details which need to be adjusted to finalise page
--[[User:Z3308965|Fleur McGregor]] 16:55, 26 September 2011 (EST)

===Comments on Group Project 2===

Group 2

*By looking at your page it’s clear you’ve performed extensive research on DiGeorge Syndrome, well done on the effort
*Spelling needs to be attended to....’Diagnostic Tests’
*The image included in the introduction could use a legend. Maybe you could refer to it in the introduction, but to me it’s just a picture of 3 babies
*Nice work on the historical background, grammar could be attended to easily, just some minor things really. This timeline could be better formatted though, maybe in a table. The image included here doesn’t have a legend or some form of description. Just a picture of two old-timers shaking hands.
*Epidemiology is great although it might be useful to include an image of some sort if possible (I’ve got the same problem) as it’s just a block of text
*Etiology is good, very descriptive and evidence of a well researched sub-heading.
*Diagnostic Tests – clever heading, clever formatting and great information. The images included definitely need legends and descriptions
*Current and Future Research heading could be broken up with some sub-headings
*Glossary looks great

--[[User:Z3331469|z3331469]] 06:57, 29 September 2011 (EST)

'''Strengths:'''
*Good placement of sub-headings and headings.
*I like how the introduction gives an overview of the syndrome.
*All images have copyright statements.
'''Weaknesses:'''
*The epidemiology and etiology sections seem like really wordy, overwhelming to read. It is paragraphed but maybe the paragraphs could be more distinct.
*It would be good to link the words that is defined the glossary to the glossary.
*Some of the references are not formatted properly.
'''Specific corrections:'''
*It would be good if introduction immediately started with what is DiGeorge Syndrome instead of leading up with the definition/characteristic of congenital disorder. This definition can be shifted to the glossary
*Just curious, it will be interesting to hear how different the first sound of a DiGeorge baby differs from a normal one.
*”Dianostic Tests” is spelt incorrectly.
*Instead of the sub-heading “Based on symptoms”, it could be “Symptomatic diagnosis”.
*What is “clinodactyly” in the description of the image under “based on symptoms”?
*The link under images for BAC subheading could go under external links section?
*Maybe the table under “Tetralogy of Fallot...in DiGeorge Syndrome” could be vertical instead of horizontal? It will look neater.

--Z3389806 06:40, 26 September 2011 (EST)

'''Group 2'''

*Introduction: good content, but the symptoms do not really belong there.

*Very nice historical section, nice to read

*Epidemiology and etiology seem almost like one big section. Maybe separate the content a bit more (no repetitions), and break it done with subheadings.

*Pathogenesis: includes helpful explanations and information, good use of reasonable subheadings. The drawn images could have been done with more
accuracy.

*Diagnostic tests: very nice informative section, good use of images to visualize the content. I think the choice of colour for the table could be
better, maybe another shade of the pink (darker, red...) that has been used for clinical manifestations. The green disrupts the flow of the entire page.

*Clinical manifestations: very nice section, precise information, good structure, useful images.

*Treatment: lots of information in a nice form, but the image would look better on the right edge (like the ones in ” research” ). Good use of subheadings.

*Research: good content, but would be easier to follow if you would break it down with subheadings.

*Glossary: looks good, but explanations like “malformation: see dysmorphia” should be avoided. It would be better to define every term separately.
--[[User:Z3387190|Z3387190]] 11:34, 25 September 2011 (EST)

'''Group 2 Critique'''

#• The introduction needs to be re-written in proper English. Some of the sentences don’t make proper sense. Also, the introduction should focus primarily on DiGeorge’s Syndrome and not explain what a congenital abnormality is
#• Historical background was good
#• Epidemiology should not explain clinical features, such as the baby making a noise which is nasally in tone
#• Aetiology is ok
#• Pathogenesis is quite detailed, however genes should be explained a little more clearly
#• Diagnostic tests section was impressive
#• Clinical manifestations was good
#• Treatment was good
#• Future research was good
#• Glossary was good

Images were appropriately used. --[[User:Z3289991|Robert Klein]] 18:36, 24 September 2011 (EST)

Group 2

Hey Group 2, firstly, well done on putting in the effort to create this page, it really shows your dedication and cooperation as a team! Here are some points I thought you could improve on to take this page to that extra level

#The key points relating to the topic that your group allocated are clearly described.
#* Introduction: Good overview. Image would look better with a border or as a thumb
#* History: Image too large, again maybe a border?
#* Epidemiology: Need to define velocardiofacial syndrome in glossary, also break it down into subheadings, eg. Incidence, Sex, etc
#* Etiology: Maybe better if in a table
#* Pathogenesis: I liked how you broke it doen into relevant subheadings. However, on a slightly negative note, the DG Pathophysiology Diagram looks rushed; I think it would've looked better if it was neater and easier to read.
#* Diagnosis: I felt citing was done poorly in this section, eg. the last 4/5 sentences in the FISH technique was not referenced at all, but again, this is very easily fixed. But good to see you have put in the effort and time
#* Clinical: Image of normal and cleft palate, if based on a textbook, I think you still need permission to adapt it (not quite sure, please ask Mark)? Table with 'How it is caused' would be better by itself as pathophysiology. Tetralogy of Fallot needs to be fitted into this section more smoothly, at the moment, it makes this section look very cramped. Also, the image regarding Tetralogy needs the correct format for student drawn images (ie. 'I (student no.)....)
#* Research: Maybe break it down into subheadings
#The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
#* Good images used with a nice range of self drawn images. However, no where in the page is there any reference to the images within the text.
#Content is correctly cited and referenced.
#* I feel citation needs to be improved overall. Lots of the sections have missing citations, especially Diagnostic Tests. Also in the reference list, refs 33,40,47, 49 have nothing in it (is it meant to be like this?)
#The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
#* Nice drawings, though some could've done better with more effort
#Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
#* Nice range of references used
#Relates the topic and content of the Wiki entry to learning aims of embryology.
#Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
#Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
#The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
#* It's very clear to me that you guys have worked together well and there has been good team work going on here to create this page, so well done
#Develops and edits the wiki entries in accordance with the above guidelines

"What would improve this project...."

* I feel your page is too heavy with the text, although there's a lot of images as well, it just doesn't quite balance out with the text.
* Also felt the different colours used for the tables, although adding a splash of colour to your page, brought down the overall quality of the page. However, please keep in mind that others might really like this approach of table formatting, it's just that personally, I think you could benefit from keeping all table colours consistent.
* Sometimes you refer to DiGeorge Syndrome as DGS and also as DS. Small and easy to fix, adds consistency
* Please don't forget to add the {template} for student uploaded images
* Definitely needs more words in the Glossary, such as Meiosis, de novo, microarray

--[[User:Z3291643|z3291643]] 16:02, 24 September 2011 (EST)

'''DiGeorge Syndrome'''

*The page has a really nice setout, the introduction and history looks really good. It has a nice flow.
*There could be at least one other picture in 'Epidemiology' and 'Etiology', otherwise it just looks like a big block of text
*The second last paragraph in 'Epidemiology' would be better suited in 'Clinical Manifestations'
*There's a bit of repetition between 'Etiology' and 'Pathology', it could be better to combine these
*The 'Diagnostic Tests' look really good, fantastic table and images
*I love the ultrasound picture
*The table in 'Clinical Manifestations' is really great with lots of detail
*I understand it's difficult to find, but more images in 'Clinical Manifestations' to give a visual representation would be fantastic
*"Teratoogy of Fallot as ''an'' example...."
*"Once diagnosed, there is no single therapy plan. Opposite, each patient needs to be considered individually and consult various specialists" This doesn't make muhc sense, that was from the 'Treatment' section.
*You had a lot of good information in 'Current and Future Research', but I found myself getting lost in all the text. Maybe subheadings would help?
*Don't forget to fix up the references, we don't want to see webpages as a reference even if it leads you to the paper
*Overall your page looks very good, some minor formatting would be useful

* A very clear format has been used. The mixed use of dot points and paragraph form were used appropriately in most sections and made your web-page easy to read and follow
* Good use of self drawn images, however the large image of Angelo DiGeorge seemed slightly irrelevant and took up a large portion of your page. Your first two images should probably have small heading below the image, just to make them a bit more clear to the reader.
* A coherent history/timeline was used.
* You’re referencing needs to be tidied up; there are multiple entries from the same source that tends to clutter your reference section. Some references are incompletely, or have no linking information such as reference 49.
* Your current research section was good but perhaps could have been tabulated just for easier reading and to really draw out the main points.
* Your table for clinical manifestations could have been summarised otherwise it should maybe just be written in paragraph form.
* Your page definitely reflects the time and effort you have placed into the assignment. I really liked the range of formatting you used and the use of colour made your page easy to read and follow. Another great feature was the section based on the example of Tetralogy of fallot. It was interesting to read how other defects that we have discussed in class, linked in with your studied abnormality.
--[[User:Z3332629|z3332629]] 15:21, 22 September 2011 (EST)

'''Group 2'''
* Structure- headings, subheadings and tables make this a very readable page with a nice flow.
* It may be nice to have the colours of the tables continuous throughout the page. eg only yellow.
* Ensure all your pictures are correctly referenced, it would be a shame if Mark deleted them, as they add a lot to your page and aid in read ability.
* not to text heavy which is good!
* Intro well written an gives a good scope to the syndrome.
* Dianostic Tests: I like this section and that the images accompany the text.
* Tetralogy of fallot as on example of the congenital heart defects that can occur in DiGeorge syndrome: Very interesting example, great pictures!! very well drawn. maybe you could put the pictures vertically down the page.
* Current and Future Research section it might be nice to add subheadings of what the research is.
* Good use of citing/ referencing it gives your page authority/ believability, just beware of the doubling in your reference list.
* It might nice to collate all the genetic info into one section.

*'''Introduction''': Good in general. Last paragraph needs a slight revision in sentence structure. "The clinical manifestations of the chromosome 22 deletion are significant and can lead to poor quality" - significant in what way? As in they have a big impact? And also, poor quality of what? Life?
*'''Historical Background''' : Very detailed, which is nice. The layout isn't quite 100% consistent, which should be easily fixed. Some findings could do with further explanations to show how this lead to progress. Also, some terms should be linked to the glossary, or in some cases, a mention that subsequent paragraphs will provide more detail.
*'''Epidemiology''': Seems fine to me, though a figure would be nice to break up the text.
*'''Etiology''': Links to glossary needed. This part contains many technical terms that aren't explained. Also, is it known why this region is specially prone to rearrangements?
*'''Pathogenesis''': Seems to repeat what was said in etiology, but in more detail. Well written and explained.
*'''Diagnosis''': There's a typo in the title - Dianostic instead of Diagnostic. You might want to split your table into prenatal and postnatal, as otherwise it is a bit confusing to read "ultrasound" as a diagnostic tool. It does become obvious very quickly that it is prenatal, but just for clarity's sake, splitting the table could help, especially as you mix pre- and postnatal tools throughout the table. Also, just be careful about using capitals - in the beginning you say BACS, and later you say BACs. BACs is the plural of BAC, which is what Bacterial Artificial Chromosome stands for, not BACS. Your explanations in this part of the table are quite technical - you might want to explain more terms in the glossary at least.
*'''Clinical Manifestations''': Very thorough and detailed, which is good. I like the table, but including some more figures might help break up the long bits of text.
*'''Treatment''': Also quite thorough, well explained.
*'''Current and Future Research''': Very good and detailed, well explained. Maybe include headings for the different sections, so it's easier to see what each is talking about?
*'''Glossary''': More terms need explanations.
*'''References''': Seem fine in general, though there are a few links that probably should be cited differently. Also, some references link to emptiness?
*General: All the tables are slightly differently formatted, you might want to get that more uniform.

'''Group 2 Critique'''

*Do the symptoms need to be listed in the introduction, or is that repetitive since it’s also in the etiology portion?
*Historical Background- Overall this section looks good, but each bullet needs to be consistent. Ie:
-only the first few bullets have a colon after the date while the others don’t. I think either a colon or a – mark should be used after the date to show a better separation.
-some sentences don’t end with periods.
*The Etiology and Epidemiology sections have good content, but it looks rather wordy from an aesthetic viewpoint. A picture or some bullet points for separation might be helpful to solve this.
*For the image Chromosome22DGS.jpg, surely you didn’t know this layout from your own knowledge… Wouldn’t you have had to copy this image from another source, and wouldn’t that source also need to be cited as well?
*For terms that are in the glossary, it would be good to format the words in the wiki so that when you click on them it takes the reader directly to that term in the glossary.
*Several of the references aren’t formatted correctly, or are missing entirely.
*This might be a bit nit-picky, but for the references given throughout the wiki, there isn’t any consistency. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
--[[User:Z3391078|Ashley Smith]] 11:05, 27 September 2011 (EST)

'''Peer Assessment: Group Project 2'''
*The information in the introduction is good, however you may want to introduce the syndrome in the first sentence and then explain what congenital abnormalities are.
*The timeline is clearly set out, maybe decide whether you want to put a colon or not after the date to keep consistency.
*The diagnostic tests section has a good balance between being informative through pictures and text. It would be good to place an image for amniocentesis and also replace the link on BACS technology to either have an image and use the paper as an extra link or to replace the heading of 'image' to 'additional information' or some such title.
*Maybe an image could be inserted in the section on etiology or epidemiology. An graph to accompany some of the statistics might make the information more accessible.
*Under the information of the images you have uploaded, you need put <nowiki>{{Template:2011 Student Image}}</nowiki>.
*In the glossary writing "A" above the group of A words and so on and so forth for the rest of it, would make it easier for the reader to quickly find the desired word.
*Some of the references should have more information in them (references 1, 2, 3, 4, 5, 46, 47, 48, 49 and others).
*The references should not be duplicated and can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.

--[[User:Z3217345|z3217345]] 12:43, 27 September 2011 (EST)

'''Group 2:'''
* The introduction is very easy to read and is accompanied by a great image, although this image should include a legend. It would be beneficial to link the image with the symptoms mentioned in the intro and to only mention a couple of important symptoms instead of listing them all here and having to repeat yourself later on.
* Very extensive historical background. Very impressive and well referenced. Image needs to include a legend.
* Epidemiology needs to be proof read as there are a couple of little mistakes that lessen the value of what is a really well researched section; “Due to the fact that 22q11.2 deletions can also resulting in signs that...”, “It has been well documented that there individuals who...” and “which may be resultant form a learning dysfunction or heart disease.”
* Etiology is also done well and is very comprehensive, however there is a spelling mistake “interstital deletions of chromosome 22” so make sure you re-read this section too.
*An image either in epidemiology or etiology would help break up a huge chunk of text.
* Pathogenesis/Pathophysiology section is very strong with great student drawn images relevant to the text. Only suggestion is to hyperlink glossary terms since there are a lot of terms in this section which need to be explained further.
* Diagnostic Test section is done well with a well formatted table making it easy to read. Some images are missing as I’m sure you’re aware of and make sure to include <nowiki>“{{Template:2011 Student Image}}”</nowiki> for these images.
* Clinical manifestations; perhaps the table describing the symptoms could immediately proceed after “The most common signs and symptoms include:” instead of having the symptoms in dot points and repeated twice. The student drawn image may benefit from pointing out that A is at rest and B is during normal speech – just to clarify. I also noticed a spelling mistake “In more severs cases..” so just make sure you go over this section with a fine comb.
* Treatment also had a couple of little mistakes for example “and consult various specialists, from example a cardiologist”. A legend for the images here would improve this section.
*Current and future research is very extensive and well researched.
Hats off to you guys!

Peer Assessment

* interesting layout
* pictures were good examples
* maybe need a touch up with the referencing
* i liked it how it was worded in a way that could be understood for a wide audience however the structure and format could not be read so easily

--[[User:Z3060621|z3060621]] 20:37, 28 September 2011 (EST)

--z3290815 14:09, 28 September 2011 (EST)

'''Group 2'''

'''*The key points relating to the topic that your group allocated are clearly described.'''
Well described, but very hard to follow at points due to volume of text.

'''*The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'''
Tables include too much information. it should summarise the main points, for large chunks of text put it in the body of the wiki.

'''*Content is correctly cited and referenced.'''
Fix up some references - there is duplication and links provided in place of a reference as well as missing references. reference for Chest PA 1.jpeg, DiGeorge-Intra Operative XRay.jpg and FISH for DiGeorge Syndrome.jpg should be fixed. also include {{Template:2011 Student Image}} in all images.

'''*The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.'''
Good diagram explaining pathophysiology but it can be neaten up by doing the text on a program (paint would suffice).

'''*Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'''
Very high research volume put into the page but there is too much text going on. Try using some sub-headings to break up the information into easily digestible sections. It also allows for easy location of specific sections.

'''*Relates the topic and content of the Wiki entry to learning aims of embryology.'''
Good information on genetics but if possible say how the deletion occurs?

'''*Develops and edits the wiki entries in accordance with the above guidelines.
Apart from small things, the wiki has been edited well.

--z3329495 21:09, 28 September 2011 (EST)

==The final Pimp==

Hi guys, how is your week end? Thursday is the due date for our side and I think it's looking great already. I just read through it all and noticed the following.

1) I changed 1/4000 to 1/2000 to 1/4000 in the introduction (hope that's ok) this way we are all saying the same.

2) I think we should still change what Mark Hill suggested for the "Historical Background" section: date first and picture not within the text. I'm happy to do it, just thought I should check with you Sarah...

3) There are still some references that need to be fixed

4) Do you guys want to add some of the scientific words that you used to the glossary, otherwise that would be incomplete

and 5) Mark Hill wanted to help me with the tetrallogy of fallot picture but I think he forgot, so I'll ask him again after the lecture and than it's going to be a fancy scenic view picture.

So, let's do the final pimp: I wouldn't leave it until Wednesday because the system is probably going to crash on that day;)
Let me know if you need any help and let us know if you think something els should be changed/edited as well.--Anna Marx 16:40, 18 September 2011 (EST)

Hi Anna, yup, 1) sounds fine; we still have that issue with the ultrasound image and removing the text from the background don't we? I'll have a trawl through the references later and see what I can do, and for most of the scientific words I know the sections that I've done have their wording in there; everyone else just has to go through it a bit?

btw guys it looks fantastic :D --[[User:Z3288827|Leonard Tiong]] 10:51, 20 September 2011 (EST)

hey i changed up the history and put the tables in different colours so they dont look like they ar all the same thing if you know what i mean?? anyway... hope its ok :) --[[User:Z3288729|Sarah Jenkins]] 13:20, 21 September 2011 (EST)

Cool, looks good. I like the colours :) --Anna Marx 11:47, 22 September 2011 (EST)

==Question==

Hi Sarah, I have a question, do you think we can split the baby pictures that you used in you introduction. Sounds super lazy of me, I know. But my problem is, that I would like to put one in my section about facial abnormalities and I couldn't find one that shows these abnormalities well and that has copyright. I wanted to use the one that is in the epidemiology section but I think Leonard wants to keep it there??? Don't really know. Any way, if we would split yours, you could get one baby and I would use the other one. What do you think? --Anna Marx 22:01, 10 September 2011 (EST)

Hey Anna, I wouldnt have a problem doing that but it is one image within the journal and im not sure if we are allowed to manipulate the images? I will talk to Mark about it and if it is ok then i will cut it up for you and put one of them in your section :) Hope this helps. --[[User:Z3288729|Sarah Jenkins]] 08:54, 11 September 2011 (EST)

Hi anna, I SAID down there that you could use the image! :D '''Feel free to take it because I also think it would assist in that section'''. I'm just squabbling over the image filename with Mark because it's not descriptive. There's another one there that has a picture of another fellow whose facial abnormalities are quite apparent so I was thinking to use them as they've got a pretty strong contrast between the two of them. What do you think? I've also uploaded my drawings, they took ages and they look so crap :( But I've been scrolling through some of the other groups and we're in good shape guys! It looks really great :) I'll sort out my glossary terms tomorrow morning. Excellent work over the break guys. --[[User:Z3288827|Leonard Tiong]] 21:42, 11 September 2011 (EST)

==Update==

Hey, how are you holidays coming along? I just wanted to let you know four things;):

1. I am "done" with clinical manifestations. So you can have a look if you like it... I'll still upload at least three images of which two are drawings.

2. So we have got the drawings covered. I just have to scan them.

3. I'll still work on the treatment section tomorrow.

4. For the matching up of our individual sections, Sarah would you mind to change the typical symptoms in your introduction to the same ones I talked about in detail. I think it would look good. Anyway...It would be the following ones:
* Congenital heart defects
* Defects of the palate/velopharyngeal insufficiency
* Recurrent infections due to immunodeficiency
* Hypocalcaemia due to hypoparathyrodism
* Learning difficulties
* Abnormal facial features
Have a good brake guys, --Anna Marx 2--[[User:Z3288827|Leonard Tiong]] 10:45, 8 September 2011 (EST)0:22, 3 September 2011 (EST)

Hi, so I have done my treatment section as well including references and glossary. --Anna Marx 21:43, 6 September 2011 (EST)

Thanks Anna :) I will change it all up now. I know you are doing the drawings but the rest of us need to get some pictures up if possible? --[[User:Z3288729|Sarah Jenkins]] 08:55, 7 September 2011 (EST)

Hey guys, i have a few pictures to load up, so will get onto that..

Was also going to ask if anyone came across anything good under the future research heading? I have found a bit, struggling a little though, and i feel like there should be more.. Just wondering if anyone came across any interesting points/areas when doing your own research.. Also had the suggestion that maybe pathogenesis/etiology could fall under the same heading, as they are both very similar topics, and maybe I/we could write something up more focussing on the pathophysiology as another heading... I know Anna does talk about this a bit in her clinical manifestations, but thought there was room to potentially cover pathophysiology in a bit more detail under anther heading, and we could maybe reduce the detail in her table as a result, make it a little less large.. let me know what you think..

--[[User:Z3288196|Timothy Ellwood]] 09:21, 7 September 2011 (EST)

really good job with everything at the moment it looks really fantastic. tomorrow is my allocated day to get through this work, so I'll be sure to get a large chunk of my sections "done". Anna, excellent work done so far, it looks really fantastic. Umm tim, as for your struggles at the moment, I'll be sure to keep that in mind when I'm looking at my other papers; just having a look at the moment and I'll get a little more help for you tomorrow, if possible. looking great so far guys! --[[User:Z3288827|Leonard Tiong]] 14:23, 7 September 2011 (EST)

hey tim, another idea is to change the heading to 'current and future research' that way you can look into what is being down now and very recently. that will give you heaps :) --[[User:Z3288729|Sarah Jenkins]] 07:13, 8 September 2011 (EST)

ps. i used a wikipedia image so we cant put another one up now... hope this isnt a problem --[[User:Z3288729|Sarah Jenkins]] 07:14, 8 September 2011 (EST)

By the way Anna, I'll probably draw my image and upload it later this evening; I can't find any images that best match what I want without having to go through all of the copyright information, so I'll just draw it :D slowly trawling through my sections. Epidemiology might be a bit short (as there's not that much you can write on it) but the pathophysiology section should be quite lengthy (Hopefully :) ) --[[User:Z3288827|Leonard Tiong]] 10:45, 8 September 2011 (EST)

Slowly going through pathophysl now. by the way guys, '''Mark Hill has put something at the top of our page if you haven't already seen it. I think it would be best to implement the points that he has noted; they're relatively minor, if you guys haven't gotten round to doing it by say, tomorrow (?) then i'll see if I can change it :) '''
I'm finding this INCREDIBLY FRUSTRATING that I can't save the material but no one else seems to be online. :(

Hello! I just thought let you know that I did two drawings which I plan to put into the table under clinical manifestations. And I also have images on my computer, that also go into the table. I just have trouble uploading them (may be it's because I have a mac... not sure). But in case I don't manage I'm sure one of you could help me on Thursday. I'll also try to make the tables a bid lighter. --Anna Marx 17:15, 8 September 2011 (EST)

ALL RIGHT, so I have change my tables. I have tried to explain it in a way so that people with no science background should understand it. Some words I had to leave in because that is just what it's called... Any way I think it'll be even better once I have the pictures in as well. If you like to have some thing changed let me know. --Anna Marx 19:12, 8 September 2011 (EST)

Hi Anna, just asking what have you done in your drawings? I drew the chromosome and the area in which deletions were most common, it's not the greatest drawing but I leave it up; and, I was thinking of drawing the presenting symptoms of DiGeorge (there aren't that many anyway). What do you think? Let me know what you've gotten down :) --[[User:Z3288827|Leonard Tiong]] 23:06, 8 September 2011 (EST)

Hey guys I will fix up what is wrong with my bits tomorrow afternoon sorry. I have had other things to do this week as well. Mark's comments are valid and relatively simple to fix luckily. --[[User:Z3288729|Sarah Jenkins]] 00:55, 9 September 2011 (EST)

Hey guys. Looks like Dr Hill's criticism was relatively minor which is great. Should be easy for us to fix. As for the future research I have found a heap more stuff, seems as if alot of current research on this deletion is in relation to schizophrenia, but have found alot more stuff relating to Digeorge. Suggestions still welcome of course. Sarah your suggestion is fanatastic, more relevant as well. I will change that now. As for my last section and images I will get to that tonight hopefully, just have been working full time over the break..
--[[User:Z3288196|Timothy Ellwood]] 10:24, 9 September 2011 (EST)

Hi, I have changed my table even more - hope you like it. In the end we might have to match the colours but we cna do that together in the lab. How is doing epidemiology, I planned on using exact the picture for clinical section where I describe facial abnormalities. That was the best one I found - that other children looked so said. Any way, may be I can steal it or I try to find another one.
Tim, I also thought I suggest, if you still can's find enough you could look into more specific stuff. For example into research of how to improve cardiac surgery, treatment for immunodeficiency etc... there should be loads out there. Any way, we are doing great team! --Anna Marx 16:40, 9 September 2011 (EST)

Hey guys,

Yeah, just have to put in a couple of images to help break things up. I've been looking at the things that the other groups have produced from the previous years and it looks really great, I think our project is beginning to look somewhat like that (which I feel will do us good!). I'm still trawling through some of the references and images; as for the epidemiology section, I've written all that I can find on that... if you guys want to put anything else in there feel free too but I feel there's a lot of repetition throughout the literature and what I've written covers epidemiology quite well. Having looked at some of the other groups we've done a really great job, anna, feel free to upload those pictures so that we can all have a look :)--[[User:Z3288827|Leonard Tiong]] 22:09, 9 September 2011 (EST)

Hi yeah, I will on Monday. I am sorry that I can't do it earlier! --Anna Marx 21:42, 10 September 2011 (EST)

==week 6==

hey awseome work with the page but u have to put references on your work asap or we will get done for plagiarism --[[User:Z3288729|Sarah Jenkins]] 07:18, 23 August 2011 (EST)

Yep, I'm working on it now. Is tim still working on the project with us? He hasn't written anything for his sections yet.. --[[User:Z3288827|Leonard Tiong]] 08:50, 1 September 2011 (EST)

Hey guys. Yeh im working on my sections, havnt posted anything up at all coz have been sick for the last week or so, and then working all weekend. I plan to have the majority of mine done by tonight though, then will start the editing process overall later in the week i guess. Sorry to hold things up.
--[[User:Z3288196|Timothy Ellwood]] 08:57, 5 September 2011 (EST)

== Discussion==

Hey sorry I missed the lab class today, im having some family troubles but will be back in sydney on the weekend. If somebody could let me know what happened etc I would really appreciate it. Are we still doing Duchennes or did another group choose it too?

Hello,
I hope that you family gets better soon. So, we had to flip a coin with another group about Duchennes and unfortunately lost. We decided that we'll all think about what else we would find interesting until Sunday and post our suggestions here so that we can make a decision about it on Sunday or early this week. If I understand right, it would be the best if we find a disorder that is really caused during embryonic development. Hence Duchennes and Thalassamia for example are not the best ones any way.
Have a good week end guys.
--Anna Marx 18:51, 11 August 2011 (EST)

Thanks Anna, I will have a look at some now and see what I can find :) --[[User:Z3288729|Sarah Jenkins]] 15:20, 12 August 2011 (EST)

== New Ideas==

* Conjoined twins. It results from abnormalities in the original process of cell division.

http://www.ncbi.nlm.nih.gov/pubmed/15278382

* Spina Bifida is due to incomplete closing of the neural tube

http://www.ncbi.nlm.nih.gov/pubmed/19918803

http://www.ncbi.nlm.nih.gov/pubmed/21790891

* Cri Du chat syndrome

http://www.ncbi.nlm.nih.gov/pubmed/21112524

http://www.health.medicbd.com/wiki/Cri_du_chat

* Ectodermal dysplasia

http://www.health.medicbd.com/wiki/Ectodermal%20dysplasia

http://www.ncbi.nlm.nih.gov/pubmed/21814340

== Another Idea ==

Hi! I think there are so many interesting congenital diseases/abnormalities which we could choose. I have had a look around and I think that [[DiGeorge Syndrome]] would be a good topic! First, it is due to some abnormalities in the chromosome 22, hence there is a genetic component. Second, it occurs in 1 of 4000 people and there are lots of variations from person to person, hence there will be a lot of research and a lot of information that we can use. Third, a defect in the migration of neural crest cells is included, which means it happens during embryonic development. So, may be you can have a look into it and let me know what you think.
Have a good week end, Anna
--Anna Marx 15:03, 13 August 2011 (EST)

I had a quick look and this looks like a good one. I'm happy to do DiGeorge if everyone else is?? --[[User:Z3288729|Sarah Jenkins]] 10:40, 14 August 2011 (EST)

Ok, sounds good! What about the rest of the group? Do you guys like DiGeorge too? I am open for any other suggestion, however I would suggest, that we make our decision soon, so that we can start our research about it. So I'll open a little "Agree with you signature" box and wait what happens :) --Anna Marx 17:41, 14 August 2011 (EST)

== DiGeorge Syndrome ==

If you like to make DiGeorge Syndrome to our team project, sign below.

--Anna Marx 17:43, 14 August 2011 (EST)
--[[User:Z3288729|Sarah Jenkins]] 19:09, 15 August 2011 (EST)
--[[User:Z3288196|Timothy Ellwood]] 09:30, 16 August 2011 (EST)
--[[User:Z3288827|Leonard Tiong]] 00:21, 17 August 2011 (EST)

==Project Plan==

I think it is important to keep moving on with the project. We need to quickly agree on things and get the job done. From previous experience, getting the work done early is a benefit to everyone involved. The project needs to be broken down into subheadings. I have listed some below which need to be covered without doubt, and I am open to other ideas as well. If everyone could pick 2 that they are happy to take on it means that everyone will have a round about even job. I spoke to [[Anna]] Earlier and she said she was willing to do the drawings. Is that still ok? If so I think its fair that you only have to do one subheading of theory work.

* Introduction (Sarah)

* Historical background of the disease and its research (Sarah)

* Epidemiology (Leonard)

* Etiology (Tim)

* Pathogenesis (Leonard)

* Clinical manifestations (and explanations of these) (Anna)

* Treatment options if available (Anna)

* Diagnosis of the disease, pre and post natally (Sarah)

* Further research possibilities (Tim)

* Image (Anna)

I would prefer it if i could do the introduction, historical background and diagnosis. I am willing to do 3 because the introduction is a pretty easy one. If anyone has a problem with this let me know. I also think first in best dressed to picking topics. I only think its fair and if not, we can sort it out later.
--[[User:Z3288729|Sarah Jenkins]] 19:09, 15 August 2011 (EST)

Hi, thank you for the layout. I think it is a good start!
I an still happy to do the drawings. So let me know if you have specific wishes or if you have suggestions of what we/I need to draw. I can also do Clinical manifestations and treatment options, which would make it three as well. However I thought pathogenesis will be a big one because that would include all the genetics. May be it will be enough if one person on it's own. Otherwise etiology would go well with it, leaving epidemiology and further research for the last one;) Further research might be big too... However, I am open to adjust. --Anna Marx 21:03, 15 August 2011 (EST)

Hey guys, sorry I haven't been in touch, just been busy with some orchestra stuff outside of uni. The stuff so far sounds great, I'll get to work tomorrow getting some papers together and seeing what I can find out about the condition. I wouldn't mind doing the epidemiology and pathogenesis sections - Anna, I think he said we only had to submit one self-drawn picture but I wouldn't mind doing some either, since I draw everything for anatomy :D either way, let me know what you think! So far things sound really great, thanks for getting so much done and once again my apologies for not having chucked in my two cents earlier!
--[[User:Z3288827|Leonard Tiong]] 23:02, 15 August 2011 (EST)

Awesome, now that we are on the way there it should be easier to focus our reading. We also need to do a glossary, and i think its easier if we do it as we go. so when we come across words that need a definition (to non science people) just chuck it in the glossary. even if we define it later, having it there is easier than having to go through and pick them out later. :) thanks for being so enthusiastic. :) --[[User:Z3288729|Sarah Jenkins]] 07:13, 16 August 2011 (EST)

Hey guys, sorry for the late addition, busy with various other things as I'm sure most of you are! Im happy to take the two headings that are left over. Also it looks like some of the other headings might contain alot more work than the two I've got, i think the further research one could potentially contain alot but unsure at this stage.so i would be happy to share another one and help out if anyone would like?? It was suggested above that Pathogenesis and etiology could go well together.... Let me know. Glossary sounds like a great idea!

Also i thought it would be a good idea if before the lab on Thursday if we could each try to find say 2 articles that relate to the heading we have selected.. Similar to what Dr Hill asked us to do for last week but now we have our topics etc. it should help to get us up and running.
--[[User:Z3288196|Timothy Ellwood]] 09:29, 16 August 2011 (EST)

I have set up sections below for us to put any references we find. it makes it easy to find the ones we need, and if other people come across good references for a topic other than their own it allows us to share :)--[[User:Z3288729|Sarah Jenkins]] 15:22, 16 August 2011 (EST)

Hey tim, more then happy to switch doing etiology with you but I wouldn't mind doing both together either. We'd better tell Mark to change our title over to DiGeorge's syndrome, I'll get some papers up in the mean time but will be really busy until thursday! :(

Update - Hey guys, just found a rather general article on DiGeorge but thought it was interesting, will leave the link here, if you guys got a moment have a trawl through :) I don't know what I'm still doing up at this hour :\ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954737/?tool=pmcentrez I'll have a read of it tomorrow morning :)
--[[User:Z3288827|Leonard Tiong]] 23:55, 16 August 2011 (EST)

Assuming that was Leonard above? I dont mind at all, maybe we can talk about it on thursday and sort something out. In the meantime i guess ill try find whatever articles I can on both topics.

Also just thought i would point out this resource [http://www.nationwidechildrens.org/22q11-deletion-syndrome], as it says that DiGeorge Syndrome (DGS) falls under the the title of 22q11.2 Deletion Syndrome, which apparently includes a number of other very similar disorders such as Velocardiofacial Syndrome, Conotruncal Anomoly Syndrome, Autosomal Dominant Opitz G/BBB Syndrome, Cayler Cardiofacial Syndrome and Shprintzen Syndrome. Not sure if we wanted to include these in our research, but worth considering I think as there could be alot more research under one of these titles and allow us for a broader and more accurate picture of the disorder as a whole.

--[[User:Z3288196|Timothy Ellwood]] 15:21, 17 August 2011 (EST)

Good work guys, our project has taken shape already. I have now changed our project title, hence we should be safe and good to go! See you tomorrow in the lab --Anna Marx 20:19, 17 August 2011 (EST)

Things are looking really splendid guys, I'm starting my sections now but it doesn't seem like there's that much for me to write on. I'll try to see if i can spruce things up a little bit more. Referring to several textbooks (anyone got any suggestions?) for some of my basic info, and I'll find original sources later. But yeah, difficulties in trying to find specific information. Especially since there's so much overlap at the moment with the other different names. So far the four major ones that I got (I know you guys have included them) but four definite names involve (obviously) DiGeorge syndrome, Velocardiofacial Syndrome (VCFS), Conotrunchal anomalies facie syndrome (CTAF) Syndrome, and CATCH22. I don't think CATCH22 is a diagnostic name but rather a mnemonic that helps them remember the symptons of DiGeorge. Onto my writing! Just another thing that I'm well aware of, I haven't put many references into my work as of yet, still trying to find the best sources for the information. I've got a bunch of them written down and need to just go through them to make sure that I've the right sources from the right place but my laptops out of battery at the moment :( I'll try to get that done by tonight or tomorrow. :) --[[User:Z3288827|Leonard Tiong]] 18:25, 22 August 2011 (EST)

== Review Article ==
Hey guys, just found a review article that I thought was rather interesting, it's an animal model for Duchenne's muscular dystrophy[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022202/]. I also found a primary journal article that discusses drug delivery for the condition [http://www.jstage.jst.go.jp/article/bpb/34/5/712/_pdf]. I will print these articles for myself tonight and give them a quick read tomorrow and then paste a quick summary of the articles here just for you guys to consider :)

'''Review''' [http://www.ncbi.nlm.nih.gov/pubmed/21274260 Mammalian models of Duchenne Muscular Dystrophy: pathological characteristics and therapeutic applications.]

'''Primary''' [http://www.ncbi.nlm.nih.gov/pubmed/21681700 Detection of duchenne/becker muscular dystrophy carriers in a group of Iranian families by linkage analysis.]

--[[User:Z3288729|Sarah Jenkins]] 10:00, 6 August 2011 (EST)

'''Primary''' http://www.ncbi.nlm.nih.gov/pubmed/15991868 Diagnosis and management of Duchenne muscular dystrophy in a developing country over a 10-year period.

'''Review''' http://www.ncbi.nlm.nih.gov/pubmed/14526374 Advances in Duchenne muscular dystrophy gene therapy.

--Anna Marx 12:52, 8 August 2011 (EST)

----

'''Duchennes Muscular dystrophy'''

----
--[[User:Z3288827|z3288827]] 21:53, 8 August 2011 (EST)

== Review Article ==
Hey guys, just found a review article that I thought was rather interesting, it's an animal model for Duchenne's muscular dystrophy[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022202/]. I also found a primary journal article that discusses drug delivery for the condition [http://www.jstage.jst.go.jp/article/bpb/34/5/712/_pdf]. I will print these articles for myself tonight and give them a quick read tomorrow and then paste a quick summary of the articles here just for you guys to consider :)

== References ==
[1] Nakamura A., Takeda S.; Mammalian Models of Duchenne Muscular Dystrophy: Pathological Characteristics and Therapeutic Applications, J. Biomedicine and Biotechnology Vol. 2011, Article ID 184393

[2] Yukihara et al; Effective Drug Delivery System for Duchenne Muscular Dystrophy Using Hybrid Liposomes Including Gentamicin along with Reduced Toxicity, J. Biol. Pharm. Bull, Volume 34, No. 5 pp. 712-716

== Found References==

===Introduction===

[http://www.ncbi.nlm.nih.gov/books/NBK22179/ DiGeorge]

[http://emedicine.medscape.com/article/135711-overview DiGeorge Anomaly]

===Historical Background===

=== Epidemiology===

[http://emedicine.medscape.com/article/886526-overview#a0199 Epidemiology]

===Etiology===

A Genetic etiology for DiGeorge syndrome [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682598/]

Inactivation of TGF􏰀 signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome [http://genesdev.cshlp.org/content/19/5/530.full.pdf]

A deletion in chromosome 22 can cause digeorge syndrome [http://www.springerlink.com/content/r85p0r5q05rj6w88/]

DiGeorge syndrome phenotype in mice mutant for the T-box gene [http://webcourse.cs.technion.ac.il/234523/Winter2002-2003/hw/WCFiles/DiGeorge.pdf]

=== Pathogenesis===

[[http://www.ncbi.nlm.nih.gov/pubmed/20833244 Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: patterning, proliferation, and mitochondrial functions of 22q11 genes]]

[http://emedicine.medscape.com/article/886526-overview#a0104 Pathophysiology]

===Diagnosis===

[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=10600329&ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Diagnostic Criteria]

===Clinical===

{http://www.ncbi.nlm.nih.gov/pubmed/19665396 Seizures and EEG findings in an adult patient with DiGeorge syndrome: a case report and review of the literature.]

http://www.chw.org/display/PPF/DocID/23047/router.asp

===Treatment===

===Research===

This looks like an excellent resource, listing over 100 research papers on nearly every aspect of DiGeorge from the 70's to present. [http://omim.org/entry/188400]

Deciphering DiGeorge Syndrome: Big Advances In Understanding Microdeletions [http://www.sciencedaily.com/releases/2005/03/050308134838.htm]

== Images==

FISH carried out to detect DiGeorge syndrome. FISH is abbreviated as fluorescent in-situ hybridisation and is carried out to detect abnormalities whilst babies are still developing in the womb. --
[[Image:FISH_for_DiGeorge_Syndrome.jpg|400px|left|FISH to detect DiGeorge syndrome[1]]]
[[User:Z3288827|Leonard Tiong]] 00:17, 17 August 2011 (EST)

[[File:DiGeorge T cell receptor Diversity post thymus transplant.jpg|400px|left]]

--[[User:Z3288729|Sarah Jenkins]] 08:54, 18 August 2011 (EST)

Facial manifestations of patient with DiGeorge Syndrome

[[File:Facial manifestations of patient with DiGeorge Syndrome.jpg|left]]

--z3279511 21:18, 17 August 2011 (EST)

User:Z3279511

2011-09-28T07:19:10Z

Z3279511:

Talk:2011 Group Project 11

2011-09-28T07:17:05Z

Z3279511: /* Peer review of Group Project 11 */

'''Group 11:''' [[User:z3308965]] | [[User:z3292953]] | [[User:z3308968]] | [[User:z3272325]] | [[User:z3284061]]

{{2011GroupDiscussionMH}}

== Peer review of Group Project 11 ==
Please include your reviews below this section, and nowhere else in this discussion. This is to facilitate easy reference later. Thank you.

'''Group 11: Peer Assessment'''
* You have picked an interesting topic, surely you can write a more engaging introduction
* Some of you headings and subheadings need rearrangement
* The history section is good but takes a bid too much space. May be you can compress it a bid, make it a little shorter?
* Some of you information is double
* The neuroembryology and functional anatomy of craniofacial cleft is interesting and well written
* Good diagnostic section. An image would be nice
* Some more references in the treatment and associated problems section are needed
* You could put some more words into the glossary
* You have some "double referencing"
* Overall, you have an interesting page. Good work. You just need a little more formatting, referencing and fixing here and there.--z3279511 17:16, 28 September 2011 (EST)

'''Group 11'''

*Introduction: needs more contend

*History: the contend is ok, references are missing, include the timeline

*Diagnosis: well done

*Syndromes and anomalies: the contend looks fine, some parts are missing, the conditions would look better in a table

*Development:?

*Aetiology: looks fine, but are there references missing?

*What staging are you talking about?

*Types: well done

*Pathophysiology: unfinished, otherwise good, maybe add some subheadings for more structure

*Configuration: references missing, what is the third paragraph womb or external environment?

*Neuroembryology: well done, nice image

*Treatment: references missing, maybe add a detailed outline of the most frequent techniques

*Problems: references missing

*Research: add more contend

*Glossary: incomplete

*Rearrange the order of headings

*Some images lack a copyright notice

*Textbooks ?
--[[User:Z3387190|Z3387190]] 14:34, 28 September 2011 (EST)

'''Group 11'''

*Introduction is way too short and should include an image
*History would work better just in a timeline
*I think you should rearrange your headings from here on to make your project flow in a logical way
*Current/future research should be extended and explained
*Glossary needs to be extended
*I also can’t seem to find your student drawing
*Some sections repeat some information- go through this

===Comments on Group Project 11===
'''Strengths:'''
*Good use of tables especially under Diagnosis.
*Some of the images are quite good especially on the correcting process (surgery) for cleft palate.
'''Weaknesses:'''
*Placement of headings is not quite appropriate. It gives the page a disjointed feel to it.
*There is a lack of use of subheadings.
*The introduction did not give an overview of the condition.
'''Specific corrections:'''
*Timeline should be a subheading under History section
*Introduction should answer these questions: What is it characterised by? How does it appear on individuals with this condition? What causes it? etc. It will be good to include a picture/ cartoon of an individual with cleft palate and lip.
*Duplication of references should be avoided.
*Some of the references are not formatted correctly.
*For current and future research, it will be good to give a brief synopsis (2-3 sentences) of each point so that readers can get the gist of the direction of cleft palate and lip research that it is heading towards.
*For genetic configuration, it might be better to use subheadings to point out the 4 different types of environmental factors.
*Do include a student-drawn image.
*Some words that should be included in the glossary are Malocclusion, nodules etc.
*It would be better to make use of tables under treatment.

--Z3389806 11:50, 27 September 2011 (EST)

'''Group 11 Peer Assessment'''
*Introduction needs to be expanded a bit seems like the description of the incidence
*History needs together with the timeline which would benefit the section, where the timeline is done properly with the image of the founder though time line better together then separated
*Diagnosis is well done though images would benefit this section
*Syndromes and anomalies should be expanded a bit though good linkage of the images to the rare cases *Development should be changed to aetiology instead
*Pathophysiology needs more images though nice use of tables
*Genetic configuration needs references to back up the evidence otherwise is just statements
*Neurology greatly structured and well presented and has image to liven the section
*Treatment generally well structured though ex[and more on the surgical aspect as well problems associated with cleft palate
*Current and future research needs more information as well separation between the current and the future research.
*Glossary needs to be expanded further and linked either to section or bolded throughout the web page.
*References need a little tweaking with the removal of the repeats, also no other information in the sub heading textbooks
z3332250 00:01, 27 September 2011 (EST)

'''Group 11 Critique'''

#• Introduction is far too short and more work needs to be done
#• History is also very short and more information needs to be added
#• The timeline is quite good
#• Diagnosis is alright
#• Syndromes and anomalies associated with cleft is detailed. Good job!
#• Development is good. Maybe use more images
#• The other sections are good, up until current research. More work needs to be done here as there is not enough information
#• Glossary is too short
#• Is the gallery really needed if you have images illustrating your text?

--[[User:Z3289991|Robert Klein]] 16:38, 26 September 2011 (EST)

''Cleft Palate and Lip''

*Your introduction needs to be ''seriously'' expanded. What exactly is it? Defining features? Anything?
*'History' could be expanded on a bit, but the timeline looks good. Try to take the spaces out between each date of the timeline, at the moment it's a bit unneccesarily long
*'Diagnosis' would fit better towards the end of the page closer to treatment. It is a bit hard to understand before we've even had a proper description of the disorder and clinical symptoms
*Though the information in 'Diagnosis' is quite good, the table is also quite interesting
*'Syndromes and Anomalies Associated with Cleft', title should fixed up 'Associated Syndromes and Anomalies' sound better. It also needs to be finised!
*There's not even a single reference in 'Atiology'
*'Developmental Staging' are you refering to Carnegie stages? If so, say so.
*Reference!! And finish 'Pathophysiology'. You won't get the marks for just saying 'it will be done soon', think of the rest of your group
*There is not a ''single'' reference in 'Genetic Configuruation', so where then did you get your information? This section also needs images, and a bit of formating. There isn't much consistency in the use of captial letters for 'Cleft Lip'. Either use it or don't, "seems to be related to the cause of Cleft palate and cleft lip incidence" and throughout the page aswell
*For 'Treatment' and 'Complications' a table would be good. It is not very visually appealing as a long list. That way you can incorporate some more information as well.
*'Problems Associated with Cleft Palate' would be better positioned higher up in the page. How do you know what your treating if you don't even know the associated problems. Reference!
*'Current and Future Research' really needs to be expanded. There is no where near enough information here
*The page is coming along, but it really needs to be finished, there are far too many gaps, and no where near enough references. Try reading multiple papers before adding information.

'''Group 11'''
* Interesting topic with good use of pictures, you guys have a great topic with a lot of interesting areas to discuss.
* The headings could be reorganised for example diagnosis could come after explaining in detail what cleft lips are and how they are formed embryonically.
* The introduction should introduce the main topics that you will be discussing but only briefly like what cleft palate is.. the information in the intro would fit nicely in epidemiology. (maybe you could add this section in).
* History section is very interesting I liked the extra research.
* The time line takes up a lot of room maybe condense it into a table format.
* Development?? is this a section??
* maybe put the type of cleft lip/palate into a table with a pictures corresponding to the specific type.
* Make sure all acronyms are in the glossary.
* It would be nice if the colours of the tables were continuous throughout the page.
* Neuroembryology and functional anatomy of craniofacial clefts section is very well written and enjoyable to read.
* Treatment & Problems associated with Cleft Palate sections have no referencing. It would strengthen and give your page some authority if you cited where your information was from.
* A little summary for your future and current research would make this section a bit more interesting rather then just using dot points.
* Make sure your references aren't doubled.
* Ensure your pictures are referenced correctly.
* Furlow Z-plasty technique picture is positioned so that it interrupts the flow of reading maybe rethink the position of this picture.
* Variations of Cleft Lip or Palate picture is great and I think it could be more of a "key " picture on your page maybe centralise it?.
* No student drawing.
* Gallery seems a little irrelevant.
* More needs to be added into glossary eg. Otitis media

Group 11
* The introduction is no where near long enough and needs an image
* History needs to be expanded and dates made more obvious to the reader
* Timeline- should be combined with history. So that my previous point is not needed
* The order of your subheadings is a little confusing
* Some sections double up the information
* Current research needs to be completed, as do other sections
* The glossary needs to be expanded
* The project has started to take form but there is work to go to complete the information and format it into a more easily accessible piece of work.

*'''Introduction''': Too short. Also, how come there are no references? How about starting with a brief anatomical description?
*'''History''': No reference for the first paragraph? I like the idea of mentioning Plato, but could you then also expand a little bit more on his thoughts? Also, what was the explanation offered by Philippe Frederick Blandin?
*'''Timeline''': Looks good to me, though some terms should be explained in the glossary.
*'''Diagnosis''': I'm not sure I'd make this follow on immediately from the Timeline. I would put this section between Types of Cleft Palate/Lip & Pathophysiology, maybe? While you do talk about the technical difficulties just before the Cleft Soft Palate Detection part, but considering you start a new subsection, it's confusing to keep talking as if it was the same paragraph. Maybe say "the technical difficulties mentionned above" instead? An explanation in the glossary of what a cleft soft palate actually is, is definately needed! The Cleft Hard Palate section is very well done.
*'''Syndromes and Anomalies associated with cleft''': Looks fine.
*'''Development''': Under construction? or is there meant to be no text, and you're simply splitting this section into the two subsections? If yes, you might want to make that clearer.
*'''Aetiology''': This part is slightly technical and could do with some more detailed explanations. It doesn't feel like a coherent section.
*'''Developmental Staging''': Well explained.
*'''Types of Cleft Palate/Lip''': Looks fine. Though the "algorhythm for repair..." figure seems to be in a slightly random place..? How does it relate to this section (or the next)?
*'''Pathophysiology''': The cranio-facial development pathway is a very complex process. Since the several points of development at which “Clefting” might occur is based on the condition and the wide range of its phonotypical expression. Make this one sentence? You start talking about neural crest cells quite out of the blue. Has there been any mention of them before? It's quite confusing to have them added into the story without having previously told why. The first two paragraphs under the table lack references? This part repeats what has been partly said before, but adds more physiological detail to it. I'd find it more logical to combine the different aspects to give one, more complete picture.
*'''Genetic configuration''': Very poor language/sentence structure. Where are the references? Putting womb and external environment together does make sense, but you might want to explain in a sentence why.
*'''Neuroembryology and functional anatomy of craniofacial clefts''': Excellent explanation, though some terms should be explained in the glossary. Why are some words in bold? Again, this sort of repeats previous information, again with more detail from a different point of view, apparently unrelated to what's been told before, as this section doesn't follow the previous sections?
*'''Treatment''': Can you explain the different techniques a little bit more, instead of just having bullet points? The figures are really nice, but don't illustrate all of the techniques mentioned.
*'''Problems associated with Cleft Palate''': Mere list with bullet points isn't enough, more explanations needed.
*'''Current and Future Research''': Very poor. There must be more than 3 articles?
*'''Glossary''': Poor. Many more terms need explanations.
*'''References''': Need fixing. The same article appears lots of times in the list. Watch out with your german references... the fact that you misspell the german makes me wonder whether you could have actually read the papers? In case you're citing a reference cited within the reference you've read, there usually is a special way of doing it.
*General: Your sections are really random and don't follow logically from one another. There is a lot of repetition of similar content in multiple different places, which is confusing. It is hard to keep an overview. Nevertheless, some of the sections are well done.

'''Group 11 Assessment'''
*The introduction and history sections are not very long… Maybe try adding more information and some pictures.
*The timeline should be a subheading under the history portion. Also, rather than doing a bulleted list, how about trying to format the information into a chart? This would be more aesthetically appealing.
*For the diagnosis section, the charts look great. Referencing is completed well also. Only thing I’d suggest is to possibly add a picture.
*For the references given throughout the wiki, there isn’t any consistency in how the [#] is given. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*There are several sentences throughout the wiki page which are missing punctuation at the ends of the sentences.
*The first portion of Aetiology doesn’t have any referencing…
*“Normal Palate Shelf…” jpg needs a sentence below it briefly describing it still.
*The Genetic Configuration section has absolutely no referencing. Neither does the Treatment section or Problems section. Where did all this information come from?
*Treatment and Problems would also flow better if they were placed into a chart format. Pictures could also be added.
*The Glossary seems a bit short. Are you sure there are no other words that would be helpful if they were defined? It would also flow better if it were bullet listed.
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
*A lot of the information is repetitive as well, and things should be formatted to flow better. Also work on the referencing issues and making the overall page more aesthetically appealing.
--[[User:Z3391078|Z3391078]] 17:26, 27 September 2011 (EST)

'''Peer Assessment: Group Project 11'''
*The introduction could definitely be expanded upon. Maybe include a short description of what cleft palate is.
*The timeline is great - clear and informative.
*The treatment, problems with cleft palate and genetic configuration sections are good. It might be good to move the picture in the treatment section to the right so it doesn't disturb the flow of the text. Also these sections need to have referencing added, for reliability purposes and such as if the reader wanted to know more about the findings that 'a number of drugs might be participating in creating this birth defect'.
*Syndromes and Anomalies associated with cleft section is great and as noted there needs to be some additional text added.
*The current and future research section could be expanded. Maybe find relevant articles, summarise their findings and see what direction is necessary to head in.
*In the glossary writing "C" above the group of C words and so on and so forth for the rest of it, would make it easier for the reader to quickly find the desired word.
*Under the information on all the images you have uploaded, you need to add <nowiki>{{Template:2011 Student Image}}</nowiki>.
*Some of the references are duplicated. They can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.
*Overall the project has a large amount of information and is put together reasonably well.
--[[User:Z3217345|z3217345]] 11:09, 28 September 2011 (EST)

==Discussion==

hey guys- keep abreast of the reviews coming in. some of them have valid points. it would be prudent to keep working on our relevant sections (without uploading it and altering the content of the wiki of course). hope you're all having a good weekend. i should be uploading the timeline later today. --[[User:Z3272325|Rahul Mohan]] 17:55, 25 September 2011 (EST)

uploaded another heading 'associated anomalies' --[[User:Z3308968|Tahmina Lata]] 10:58, 22 September 2011 (EST)

{|border="1px" cellspacing="1" align="center" cellpadding="3"

! Type !! Comment !! Picture!
|-
|'''Unilateral Cleft Lip'''
|This type of cleft refers to cleft of the lip that have only occurred on one side of the lip.
|[[File:.jpg|centre]]
|-
|'''Unilateral Cleft Palate'''
|This type of cleft refers to a cleft of the soft palate that occurs on one side of the palate. The cleft starts medially and extends laterally.
|[[File:.jpg|centre]]
|-
|'''Unilateral cleft lip with a cleft hard palate '''
|This refers to a cleft that has extended through the lip and into the hard palate. This cleft is on only one side of the lip and palate.
|[[File:.jpg|200px|centre]]
|-
|'''Unilateral cleft lip with cleft hard and soft palate'''
|This type of cleft refers to a cleft that extends through the lip, hard palate and into the soft palate. It also occurs on only one side.
|[[File:.jpg|centre]]
|-
|'''Bilateral cleft palate '''
|This refers to a cleft of the soft palate which occurs on both sides of the palate and appears as a opening medially.
|[[File:.jpg|300px|centre]]
|-
|'''Bilateral cleft lip'''
|This refers to a cleft of the lip that has occurred on both sides of the lip. There are many variations of this.
|[[File:.jpg|300px|centre]]
|-
|'''Bilateral cleft lip with cleft hard palate'''
|This refers to a cleft of the lip and hard palate that occurs on both sides.
|[[File:.jpg|300px|centre]]
|-
|'''Bilateral cleft lip with cleft hard and soft palate'''
|This refers to a cleft that has occurred on both sides of the lip and extended into both the hard and soft palates resulting in an medial opening of the soft palate.
|[[File:.jpg|300px|centre]]
|-
|}

hey guys heres the table so far. I'm having a bit of trouble uploading the photos and finding sources for the info in the middle but I'm working on it
--[[User:Z3292953|Elizabeth Wren]] 10:36, 22 September 2011 (EST)

Hey guys, just letting you know whats on the page under aetiology and treatment has not been finalised. I will need to upload images and tables. --[[User:Z3308965|Fleur McGregor]] 09:55, 22 September 2011 (EST)

Team, Found some amazing radiology images but they are under copyright. Would like to brainstorm with you all to se how we can request access. http://radiology.rsna.org/content/217/1/236.long
--[[User:Z3308968|Tahmina Lata]] 00:15, 22 September 2011 (EST)

Hey Rahul, I am still working on the resolution of the image, I am considering rediesigining the orginial design and increasing the font size. Will update on it soon.
I also have uploaded another brief subsection 'Problems associated with Cleft Palate'-hope it is useful.
--[[User:Z3308968|Tahmina Lata]] 23:56, 21 September 2011 (EST)

Hey Guys,

I have just uploaded the Draft section Genetic Configuration... It is under review since I'm doing this with Rahul. the final version will be integrated later on. --[[User:Z3284061|z3284061]] 21:37, 21 September 2011 (EST)

Hey Rahul,

I think we should go with the Articles we have, because this is our project, yes we can have a look at the other textbooks. But in the end, remember, this is designed by us as a group!
and the mdconsult website does not work! --[[User:Z3284061|z3284061]] 20:53, 21 September 2011 (EST)

Hey Meedo, pursuant to our conversation- here are the 2 links that seem to conflict. 
http://embryology.med.unsw.edu.au/Notes/face2.htm 
http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-3706-4..50012-8&isbn=978-1-4160-3706-4&uniqId=282776049-2#4-u1.0-B978-1-4160-3706-4..50012-8 

and I've spotted an error in reference 40 and 41. The chapter referred to is chapter 9, not 10. The necessary changes have been made. Timeline should be up soon.

--[[User:Z3272325|Rahul Mohan]] 17:53, 21 September 2011 (EST)

Hey Rahul, I got that info from the text book but I'd probably go by what Dr Hill has.
Beth --[[User:Z3292953|z3292953]] 12:20, 21 September 2011 (EST)

guys- i have a problem. in development so far- i'm trying to work on the time line for cleft lip/palate development. it so turns out that there's conflicting information everywhere. on one hand- we have (google turned this up for me) <http://embryology.med.unsw.edu.au/Notes/face2.htm> which is by Dr Hill- in which its stated that "Cleft lip and palate develop between the 4th and 8th week of gestation". On the other hand- we have what's already written up for the section under dev- which has it stated that cleft lip happens from/between carnegie stage 16 and 18- and cleft palate erin week 6 to 10 (which equates roughly to carnegie stage 15 onwards. if we follow what Dr HIll's said- that would amount to stages 10-around 21. so which do we follow?

--[[User:Z3272325|Rahul Mohan]] 23:45, 20 September 2011 (EST)

Hey Tahmina- the resolution could be slightly better. have you tried saving the document as a pdf file? with maximum resolution or something? I'm not entirely certain- but i'm fairly sure it can be done. mm. on another note, guys- here're a few resources that you could check out for your relevant sections if you haven't already:

http://www.organizedwisdom.com/Cleft_Palate (scroll down to the journals section)
http://www.jci.org/articles/view/22154/version/1 (particularly helpful for genetic---Meedo)
http://dev.biologists.org/content/103/Supplement/41.full.pdf (helpful for development- what i'm working on right now. the last bit on genes might be useful to meedo as well.)

--[[User:Z3272325|Rahul Mohan]] 23:00, 20 September 2011 (EST)

[[File:Figure Shows How the CNS is divided to supply different structures.jpg|800px|right|thumb|Figure Shows How the CNS is divided to supply different structures]]
Guys I am parking this image here for the time being as the resolution has not come out that well and I would like some feedback from you to see if we should add this to the page.

--[[User:Z3308968|Tahmina Lata]] 20:33, 20 September 2011 (EST)

Ravichandra KS, Vijayaprasad KE, Vasa AA, Suzan S.

J Indian Soc Pedod Prev Dent. 2010 Oct-Dec;28(4):311-4.

PMID: 21273723 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/15479962
--[[User:Z3308965|Fleur McGregor]] 12:15, 15 September 2011 (EST)

Permission to post figure:
https://s100.copyright.com/CustomerAdmin/PLF.jsp?lID=2011090_1316046741757
picture: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086810/bin/nihms284150f2.jpg

I have also included a hand drawn hierarchical table as I could not format such table in wiki. hope it is not looking too poorly done. --[[User:Z3308968|Tahmina Lata]] 23:30, 14 September 2011 (EST)

Hi Everyone,

I have tried to stretch as much as possible and uploaded my final versions of my headings. --[[User:Z3308968|Tahmina Lata]] 23:28, 14 September 2011 (EST)

Hello People,

I have uploaded my section which is just a DRAFT. References are not all completed, and my photos are to be uploaded soon with drawings.
--[[User:Z3284061|Maqdad Al Saif]] 20:35, 14 September 2011 (EST)

Guys,

As we have 5 people in our group we must have more content than other groups so I am adding a third heading 'Neuroembryology and functional anatomy of craniofacial cleft.' We really need to work hard on this as the page so far is not looking the best. I hope that someone will come up with an impressive table.

--[[User:Z3308968|Tahmina Lata]] 23:03, 8 September 2011 (EST)

Hi Guys,

I will be writing about 'Diagnosis of prenatal cleft lip and palate' for my second heading. --[[User:Z3308968|Tahmina Lata]] 22:44, 6 September 2011 (EST)

Here are some more useful links with photos in them.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562450/?tool=pubmed

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC420504/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825074/?tool=pubmed

http://www.ncbi.nlm.nih.gov/pubmed/19884685

http://www.ncbi.nlm.nih.gov/pubmed/20694165

--[[User:Z3308968|Tahmina Lata]] 22:46, 6 September 2011 (EST)

Hello Everyone,

I have uploaded the timeline here and under the heading- 'History' I am just going to include some interesting historical facts but after researching the other heading- 'Developmental Process' it seems to coincide with developmental staging and so it might not be a good idea to have that as a broad heading. Please let me know if you have any ideas on another heading or I will come up with a different heading and research that. Let me know what you think--[[User:Z3308968|Tahmina Lata]] 22:55, 5 September 2011 EST)

Hey Guys,

Great Work finding the articles :) I noticed in the second article of Tahmina, you can use the pictures to make the content more interesting. The same goes for Fleur, the last 2 articles have great information and pictures.

let's try updating the page before the end of the weekend

Cheers Guys... --[[User:Z3284061|Maqdad Al Saif]] 16:57, 5 September 2011 (EST)

Here are the articles I am studying at this stage:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825059/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825068/?tool=pubmed

--[[User:Z3308968|Tahmina Lata]] 21:18, 4 September 2011 (EST)

hey guys,

I've found some pictures which we can either use in the gallery or on the front page.

about my work, it will be all updated during the break but I will share with you what I'm doing. Meedo

--[[User:Z3284061|z3284061]] 11:29, 1 September 2011 (EST)

I also found these useful

http://www.cincinnatichildrens.org/assets/0/78/1067/1395/1883/1a654a12-a1b6-42cb-8a6b-9b270e322f4c.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2312243/pdf/annrcse00255-0003.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825076/

--[[User:Z3308965|Fleur McGregor]] 10:41, 1 September 2011 (EST)

Hey guys here some references I found that were kinda useful

Plast Reconstr Surg. 2011 Feb;127(2):812-21.The spectrum of median craniofacial dysplasia.Allam KA, Wan DC, Kawamoto HK, Bradley JP, Sedano HO, Saied S. PMID: 21285785

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011 Aug;112(2):249-57. Epub 2011 Jun 12.Comparison between multislice and cone-beam computerized tomography in the volumetric assessment of cleft palate.Albuquerque MA, Gaia BF, Cavalcanti MG. PMID: 21664153

Nat Rev Genet. 2011 Mar;12(3):167-78.Cleft lip and palate: understanding genetic and environmental influences.Dixon MJ, Marazita ML, Beaty TH, Murray JC. PMID:21331089

I also found the Larsons textbook had some stuff on cleft palate and lip.

Beth --[[User:Z3292953|z3292953]] 10:20, 1 September 2011 (EST)

Hey fellas, I reckon we could have inserted a brief discussion of the etymology of the word in the introduction. I don't reckon its big enough to warrant a heading of its own. Thus, I've gone ahead and taken the liberty to remove that heading from the page. Also included an "aetiology" section under development of disease- since its looking at causation of disease. Changed current research into Current and Future Research- to increase the scope of that heading.

--[[User:Z3272325|Rahul Mohan]] 12:48, 25 August 2011 (EST)

I am doing history and developmental process.

--[[User:Z3308968|Tahmina Lata]] 10:06, 25 August 2011 (EST)

Hey Guys,

There has been some changes in our page in terms of Subheading order.

Hey Rahul, I'd be happy to share the Genetic Configuration with you... and your comments have been taken into consideration.

--[[User:Z3284061|z3284061]] 11:43, 25 August 2011 (EST)

Thankyou z3284061 for the heads up on what to do.

I've put myself down as finding current research and associated figures. However- pertaining to the latter- this would involve finding figures and diagrams relevant to our research I suppose? I'm definitely not good at art- and as for the diagrams and pics- that would be dependent more on the content we come up with. Also, as a sub-section- isn't it weird to lump all animations and figures under one subsection- isolating it away from the rest of the topic? Thus being the case, I propose that we individually keep a look out for relevant animations under our own sub-heading and I would help out anyone doing a large topic. z3284061 has indicated that that genetic configuration is a large sub heading- so I'll be happy to help with that.

See you in a couple of hours, fellas.

--[[User:Z3272325|z3272325]] 04:18, 25 August 2011 (EST)

Hey Guys,

I think after we discussed last time, I'll be doing Pathophysiology and Genetic Configuration.Hmm, I just think it will be kinda big especially for Genetic Configuration :) if you guys find anything related to it, pleaase don't hesitate to post it in the discussion.

The only one who might not have been allocated to do something specific is z3272325- I think you are meant to do The Animations and figures + Current Associated research :)

Let's Start updating the page whenever we have information :)

Cheers --[[User:Z3284061|z3284061]] 23:11, 24 August 2011 (EST)

For the groupo project I will be researching Developmental Staging and Abnormaility Classification.

--[[User:Z3292953|z3292953]] 11:21, 24 August 2011 (EST)

I am researching the following sub headings: surgical timeline and etimiology. If you all post what you are researching we can forward any information we find regarding your sub heading. --[[User:Z3308965|Fleur McGregor]] 12:16, 23 August 2011 (EST)

Here's the image I've found. --[[User:Z3284061|Maqdad Al Saif]] 13:10, 18 August 2011 (EST)

[[File:Cleft lip.jpg]]

completely forgot I was meant to add a picture here as well. My apologies. And the group discussion's picking up- shall be more productive henceforth. here's a pic for cleft palate.

[[Image:In vitro fetal palate explant culture.jpg|frame|alt=Alt|In vitro fetal palate explant culture<ref><pubmed>PMC2841638</pubmed></ref>|center]]

'''References'''
<references/>
Wow!! That is sad Meedo! I didnt know you were in hospital!
Yes I think the condition is cleft lip and palate however I am working on the classifications of cleft lip as they can be disjoint at many different sites of the lip.
--[[User:Z3308968|Tahmina Lata]] 10:11, 18 August 2011 (EST)

Fantasitc Work Tahmina!!!! I can See a flow coming up!!!
and z3292953 - Great Photos!!!! Please save the references somewhere Safe :D

As for me, I haven't been able to attend classes since Thursday. I was at the hospital, extremely dysfunctional.

Anyways, I can say that we should finilize the topic to This one... I prefer not to change because it's week 5 now. It will be wise if we dig deeper in the topic and we shall get better information. I will start my search from tomorrow and sorry for the delay. I HAVE ONLY ONE QUESTION IS CLEFT PALATE and LIP KNOWN as the WHOLE condition???
--[[User:Z3284061|z3284061]] 23:46, 17 August 2011 (EST)

History

The earliest known history of cleft lip is based on a combination of religion, superstition, invention and charlatanism. While Greeks were indifferent of their existence, Spartans and Romans would kill the children with this condition as they were considered to harbour evil spirits.

Between (1295- 1351) the first to note the congenital origin of the cleft was made by Jean Yperman. He also classified the various forms of the condition and laid down the principles for their treatment.

Between (1537-1619) Fabricius ab Aquapendente first suggested the embryological basis of cleft lip.

This is how I started the history, please comment if you think anything needs changing. I will continue the list on and the references at the end.

--[[User:Z3308968|Tahmina Lata]] 20:00, 16 August 2011 (EST)

[[File:File-Cleft palate in newborn mice.jpg]]
<ref><pubmed>2924885</pubmed></ref>

--[[User:Z3292953|z3292953]] 12:08, 16 August 2011 (EST)

Hi Guys, I have started working on pathophysiology & history and modified some of the headings to include ones that were more relevant for Cleft palate and Lip.

--[[User:Z3308968|Tahmina Lata]] 21:51, 15 August 2011 (EST)

[[File:Mice mutants exhibit cleft palate and umbilical hernia.jpg|frame|alt=Alt|Mice mutants exhibit cleft palate and umbilical hernia<ref><pubmed>PMC2841638</pubmed></ref>|center]]

Mice mutants exhibit cleft palate and umbilical hernia

--[[User:Z3308968|Tahmina Lata]] 19:16, 15 August 2011 (EST)

So after careful consideration we have come to realise that Cleft Palate/Lip will be a more relevant topic to create a page about.
Some of you guys left last week when we registered this topic with Dr Hill. Please post here if you are still unsure of the topic. At this stage we are all reseraching different things on the topic so we can discuss about it this week.

--[[User:Z3308968|Tahmina Lata]] 16:44, 15 August 2011 (EST)

There appears to be no group discussion here on possible project topics?? --[[User:S8600021|Mark Hill]] 23:55, 7 August 2011 (EST)

We have decided to research each subheading listed on the Group Project page and then share all the information found next week. We will then be able to determine a clearer structure to the page based on what literature is available.

--[[User:Z3308968|Tahmina Lata]] 12:34, 11 August 2011 (EST)

'''Review Article'''
"Cystic fibrosis: pathogenesis and future treatment strategies"-This review summarizes our current understanding of the pathophysiology and treatment of cystic fibrosis lung disease<ref><pubmed>19393104</pubmed></ref>

'''Research Article'''
"Nasal endoscopic evaluation of children and adolescents with cystic fibrosis"-The questionnaire, clinical examination and especially nasal endoscopy performed as part of this research lead to a detailed assessment of the nasal characteristics of children and adolescents with cystic fibrosis. <ref><pubmed>20209279</pubmed></ref>

--[[User:Z3308968|Tahmina Lata]] 23:13, 10 August 2011 (EST)

Hi Guys,

I've modified the page with the required subheadings, we can change them later but it's important to get our heads around the foundations.

If have have anything to add, please do so. if you have any questions, post it here and we will try and help. --[[User:Z3284061|z3284061]] 22:52, 10 August 2011 (EST)

Novel concepts in evaluating antimicrobial therapy for bacterial lung infections in patients with cystic fibrosis.Rogers GB, Hoffman LR, Döring G. J Cyst Fibros.2011 Jul 18. [Epub ahead of print]

Vitamin D receptor agonists inhibit pro-inflammatory cytokine production from the respiratory epithelium in cystic fibrosis.McNally P, Coughlan C, Bergsson G, Doyle M, Taggart C, Adorini L, Uskokovic MR, El-Nazir B, Murphy P, Greally P, Greene CM, McElvaney NG.J Cyst Fibros. 2011 Jul 22.

--[[User:Z3292953|z3292953]] 15:59, 9 August 2011 (EST)

Hey Guys:

How are we going in the research process? Well, In case anyone wants to change the topic Tomorrow will be the last day we get to change! That’s if everyone agrees to do so.

For the time being, we are working on Cystic Fibrosis. I’ve found some interesting articles regarding the treatment.
The first one is a research while the other 2 are both Reviews.

I’ve Moved the articles of z3292953 to the discussion Page :)

Looking forward to create a great wiki page. --[[User:Z3284061|z3284061]] 22:34, 10 August 2011 (EST)

1. ''Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation ''

[http://www.nejm.org/doi/pdf/10.1056/NEJMoa0909825 Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation]

2. ''Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis''

'''Abstract'''

Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is caused by biofilm-growing mucoid strains. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy, and they can be treated by chronic suppressive therapy. New results from one small trial suggest that addition of oral ciprofloxacin to inhaled tobramycin may reduce lung inflammation. Clinical trials with new formulations of old antibiotics for inhalation therapy (aztreonam lysine) against chronic P. aeruginosa infection improved patient-reported outcome, lung function, time to acute exacerbations and sputum density of P. aeruginosa. Other drugs such as quinolones are currently under investigation for inhalation therapy. A trial of the use of anti-Pseudomonas antibiotics for long-term prophylaxis showed no effect in patients who were not already infected. Use of azithromycin to treat CF patients without P. aeruginosa infection did not improve lung function. Here I review the recent advances in the treatment of P. aeruginosa lung infections with a focus on inhalation treatments targeted at prophylaxis and chronic suppressive therapy.
<ref><pubmed>21463524</pubmed></ref>

3. ''Changes in strategies for optimal antibacterial therapy in cystic fibrosis.''

'''Abstract'''

Aggressive antibiotic therapy of bacterial airway infection is one of the main reasons for the dramatic increase in life expectancy over the last few decades. Staphylococcus aureus and Haemophilus influenzae are the predominant pathogens in younger patients, but the choice of antibiotic therapy against these pathogens remains highly controversial. There is general agreement that patients with pulmonary exacerbations should be treated and many cystic fibrosis (CF) centres will also try to eradicate bacteria in the absence of symptoms. Prophylactic antibiotic therapy, with anti-staphylococcal medications started at the time of diagnosis, is advocated by some groups but its positive effect remains unproven. In fact, recent studies have suggested that continuous prophylactic treatment with anti-staphylococcal antibiotics may increase the risk of early colonisation with Pseudomonas aeruginosa. P. aeruginosa is the main pathogen in older children with CF. While chronic airway infection with mucoid P. aeruginosa is considered irreversible, both the combination of oral ciprofloxacin with inhaled colistin and inhaled tobramycin alone has been used successfully in the early phase of colonisation. In patients chronically infected with P. aeruginosa, standard treatment of pulmonary exacerbations consists of intravenous combination therapy for 2-3 weeks. Controversy exists whether this treatment should be performed routinely every 3 months or only in the presence of a pulmonary exacerbation. Inhaled antibiotics such as tobramycin have been shown to improve lung function and reduce sputum density of P. aeruginosa, but both the optimal dose and the duration of therapy are unclear at the present time
<ref><pubmed>11165111</pubmed></ref>

Review:
Inhaled bronchodilators for cystic fibrosis. Halfhide C, Evans HJ, Couriel J. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD003428. DOI: 10.1002/14651858.CD003428.pub2 from http://www2.cochrane.org/reviews/en/ab003428.html

Research Article:
Identification of airborne dissemination of epidemic multiresistant strains of Pseudomonas aeruginosa at a CF centre during a cross infection outbreak. Jones AM, Govan JR, Doherty CJ, Dodd ME. Isalska BJ, Stanbridge TN, Webb AK. Thorax 58(6), 525-527.
from http://www.ncbi.nlm.nih.gov/pubmed/12775867
--[[User:Z3272325|Rahul Mohan]] 10:58, 11 August 2011 (EST)

==References==
<references/>

==Peer Assessments==
* I would suggest expanding on the current and future research section, maybe add in links to current research institutes or research papers.
* Perhaps add an image in for problems associated with cleft palate, just to add some dynamics and colour to the page.
* Perhaps tabulate the treatment section just so that the information is clearer
* Placing words in bold, although it was just a little touch, helped to highlight the main points you were trying to get across which was good.
* Good incorporation of tables and different formatting styles
* Your introduction was clear, simple and straight to the point.
* You’re referencing needs to be tidied up; there are multiple entries from the same source that tends to clutter your reference section.
* Your timeline was extremely spaced out, I would suggest deleting the space between your dot points just so that it reads easier.
--[[User:Z3332629|z3332629]] 15:31, 22 September 2011 (EST)

Talk:2011 Group Project 10

2011-09-28T07:15:55Z

Z3279511: /* Peer Review */

[[2011_Group_Project_10|'''Group 10''']]: [[User:z3332327]] | [[User:z3332629]] | [[User:z3332824]] | [[User:z3330313]]

{{2011GroupDiscussionMH}}

==Peer Review==

'''Group 10: Peer Assessment'''
* Your page is relatively short overall and could use some more pictures, especially in the first few sections.
* You have forgotten to put a title on you page
* The introduction is good
* You have got quite a bid of text in the history section, may be you can make a bid lighter with a time line?
* Epidemiology is nice to read and relevant
* Signs and symptoms belong into the clinical manifestation section
* Diagnostics could be more in detail
* The green and blue in the table is a bid too much colour all on a sudden. May be you can have some more colour overall or do the table in just one colour?
* It would be great to have more terms in the glossary
* I would put the diagnosis section right after pathogenesis
* Overall you have got good information on your page. May be you can work on the overall structure and some references. --z3279511 17:15, 28 September 2011 (EST)

'''Group 10'''

*Introduction: well done

*History: lots of information, some parts have no references, subheadings and a time line would be advantageous

*Epidemiology: good contend

*Aetiology: the contend seems fine, but more structure would be good

*Pathogenesis: looks good

*Signs and symptoms: that’s more like a list that a section, maybe combine it with manifestations

*Manifestations: well done, except for smooth muscle- seems incomplete?

*Diagnosis: you could add more information and details

*Treatment: the heading seems inappropriate, separate treatment and research, the contend could be more explained

*Glossary: is incomplete

*More images would be nice
--[[User:Z3387190|Z3387190]] 14:28, 28 September 2011 (EST)

'''Group 10'''

*Very poor image/text ratio – you need more images to break up the text
*Good intro
*History would work better in a timeline- you also mention nothing after the 1800s, more recent findings need to be included
*An image would be nice for pathogenesis to help the reader follow
*Not sure why you have made signs and symptoms a different heading to clinical manifestation- these could be combined
*Diagnosis is very brief and needs to be extended
*Glossary needs to be added to
*Maybe add a current research heading

===Comments on Group Project 10===
'''Strengths:'''
*The flow of the page is smooth with appropriate placement of the various headings.
*Clinical manifestation section looks really decent without appearing too verbose but yet sufficient information is given.
*The last image has correct referencing and the copyright statement is also included.
'''Weaknesses:'''
*Some of the references are not formatted properly. There are also a couple of duplications under References.
*Glossary is not complete.
*The formatting for the overall page is not as consistent as it can be.
'''Specific corrections:'''
*Maybe it would be better to have a heading for the genetic condition just on its own and not put it with the introduction heading.
* Maybe future treatments can come under a new heading “future research”?
*It will be good to elaborate more on current treatments.
*Diagnosis can be more detailed.
*Include a timeline under history to summarise that section.
*The copyright statement that allows wikiusers to use the student image after 6 months is not included.

--Z3389806 07:04, 27 September 2011 (EST)

'''Group 10 Peer assessment'''
*Heading order needs to re-arranged and done properly with diagnosis above before signs and symptoms.
*Introduction done sort of well needs to integrate image as an example of the myofibres.
*History rather bulky with too much text and no image, image of the founder would be fine. Also no time line present of DM needs to be added
*Epidemiology seems rather empty, images would benefit this section also more stats, further expansion of sub headings would also do well for this section
*Genetics aetiology needs to be expanded where seems to be cramped, though usage of image needs to be noted
*Pathogenesis needs images and further information
*Signs and symptoms needs to be expanded and image of some signs or tables
*Clinical manifestation done well with image and further sub-headings
*Diagnosis requires more attention with further methods of detection of DM
*Treatment is well done with the usage of the table
*Glossary needs to further expanded also linked to the pages so easy to follow the page
*References are not complete with links and repeats of the references
z3332250 23:59, 26 September 2011 (EST)

'''Group 10 Critique'''

#• The introduction was very good. Good use of images to give it a little decoration!
#• History is good
#• Epidemiology is good, however if possible try and make it longer/ include more information
#• The Genetics section is a bit too short. Add more information. Good hand drawn image!
#• Pathogenesis is a little short. Needs more information
#• Signs and Symptoms is good
#• Clinical manifestations is ok
#• Diagnosis, treatment and glossary are all well written. These sections should not require any change

--[[User:Z3289991|Robert Klein]] 16:27, 26 September 2011 (EST)

Group 10 ''Duchenne Muscular Dystrophy''
*The first paragraph of the introduction has no reference.
*The paragraphs in history are quite long, often with grammar mistakes, incorrect punctuations and many of the ideas within a sentence separated by a ''-''. For example the second last paragraph within history.
*The history is too verbose, a timeline with bullet points will look better
*Aetiology is quite concise and informative however gramatical errors are a distraction. For example ''There a multiple forms of dystrophin''. It might be a good idea to proofread the page.
*Well done with the student drawn image
*'Pathogenesis' is again well written however an image might have given it a balance between the text in the section and the pictures or tables
*The future therapies table is a little confusing, you might want to add more columns and define the therapy, and then discuss what the challenges and findings are and at the end column finish off with what the implication might be if the research is to be completed successfully. At the moment you have discussed all that in one big paragraph and the way the descriptions start, it sounds like there is no background to the description, just a little abrupt.
*The glossary is very short and you should include terms like de novo mutation.
*The existing definitions are unclear and incomplete

''Duchenne Muscular Dystrophy''

*Make sure you add a proper heading for the page, so it doesn't just start with 'Introduction'
*The 'Introduction' is a good start to the page, very easy to read and understand
*'History' is a bit difficult to read, try to make is sequential order, or at least '''bold''' the dates
*In 'History' we don't really want a story, but key dates in the history of the discovery of the disorder. Surely something has happened in the past 150 years?
*Good work with 'Pathogenesis', it is a good description of the development of the disorder
*Can we see an image relating to the signs and symptoms?
*'Clinical Manifestations' is a good thorough description, though I don't understand what going on with the last section 'Smooth Muscle' with the random '''&&&'''. It is also a whole lot more general than the preceeding sections. Is it finished?
*Could you give a bit more detail in 'Diagnosis'. It would be good to explain each method a bit more and explain why they are relevant.
*Can you expand on the table a bit? ie P188, what exactly is it used for? How does it treat it? How effective is it? When is it administered etc
*No current research section? This could be a good conclusion to the page - the 'Stem Cell Transplant' section from 'Treatments' would fit better here
*The glossary needs to be finished and expanded on
*Overall the page is not bad, but more images are needed and some clarification on topics

Group 10-
* Need more images to break up the text
* The introduction was really easy to read and had relevant information in it
* History should be in bullet point form to make it easier to access or at least have the dates in BOLD
* Does the history include dates after the 1800s? or did all research stop then?
* Epidemiology was good. Had all the relevant info
* Pathogenesis would benefit an image or a diagram
* Signs and symptoms could be put with clinical manifestations.
* What is the point of the ‘&&&’? in clinical manifestations and complications?
* Diagnosis could be expanded upon to explain how and why these methods work
* Treatment could also be expanded on. A list of drugs doesn’t explain much
* There is not current/future research section
* This is a good start to the project but more research needs to be done

'''Group 10'''
* The structure and use of headings and subheadings is good, make sure you title your page.
* Good info very informative and it gives a good overview to DMD.
* HIstory has a lot of text could you use a timeline here?
* i think a picture of the pathogenesis would improve this section.
* Has your group look at the CNS and cognitive function of DMD boys its a controversial area as many people have different attitudes towards this but Dr Stewart Head a UNSW lecture actually studies DMD and is very informative in the area and recently published a article in the journal Brain.
* The CNS is highly affected by the lack of dystrophin as well as GABA receptors. I think this area is very import to consider as it highly affects the boys at school.
* Could you add some pictures to your page or break it up with the use of more tables as it a lot of text in comparison to pictures and tables.
* Make sure your reference list is not doubled.
* Ensure all your pictures are referenced properly.
* Student image is present.
* This is a good start.

'''Group 10 Assessment'''
*The history is a bit wordy… Maybe consider consolidating the information into a table format for ease of reading. Could also use a picture to add to it.
*The Epidemiology section could also use a picture and maybe some more information, if possible.
*Point vs Frameshift mutation jpg: Good drawing, but in the last portion of the picture the product is labeled as a ‘tunicated protein product.’ Isn’t it supposed to be a ‘truncated’ product?
*The Signs and Symptoms section could use some formatting; it just looks rather dull currently. Maybe a chart or add in a picture?
*Smooth muscle section: Why are there random &&&’s?
*The top portion of the Treatment section could use some more referencing… Good chart though! Only thing I’d suggest for it is to add some pictures if possible?
*Glossary term list is rather short… Are you sure there’s nothing else that needs defining for clarification for the reader?
*It would be a good idea also to have the glossary terms linked with the words in the wiki page, so that the reader can easily get access to the word in the glossary.
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
*For the references given throughout the wiki, there isn’t any consistency in how the [#] is given. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*Overall, good information is included, just work on referencing things and the overall structure and you should be good!
--[[User:Z3391078|Z3391078]] 17:00, 27 September 2011 (EST)

'''Peer Assessment: Group Project 10'''
*I think the section heading of introduction accompanied by the question what is muscular dystrophy, works really well.
*It might be good to include an image in the history section to break up the text, such as of someone prominently involved with the disease findings.
*The information in clinical manifestations and complications is well written. There needs to be some fix to the formatting under the smooth muscle heading where some '&'s have been repeated.
*The current and future prospects section is great. You have summarised what
*Some of the definitions of words in the glossary need to be completed e.g. atrophy and protease.
*Under the information in some of the images such as the fisrt one, you still need to add <nowiki>{{Template:2011 Student Image}}</nowiki>.
*Some of the references are duplicated. They can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.
*An additional section of external links might provide information for those wanting to know more.
--[[User:Z3217345|z3217345]] 10:50, 28 September 2011 (EST)

==Discussion==

'''GROUP 10!'''

'''To make everything easier to follow, we have agreed to write any updates, info, discussion etc at the BOTTOM of this page, it will just stop us having to keep going up and down and wasting time trying to find the information we want.'''

----

Hey Everyone,

So Mark went through each group today during the lab and the webpages and discussed where we should be up to. By next week, he expects the subheadings & some content to be up and running. He also recommended that we should have some more research going on in our discussion page. E.g. Research articles links, interesting sites etc.

Topics have been allocated so please begin your research and typing up some content. We can further divide our headings if necessary, take a look at some other groups, they have some pretty good ideas. Mark will be checking this next week during our lab. He'll be coming around to each of us.

So hopefully see you all next week !

--[[User:Z3332327|z3332327]] 12:53, 25 August 2011 (EST)

==Subheadings for assignment==

Intro what is DMD

History/timeline

Genetic component

Why is it an abnormality - Symptoms effect

Diagnosis, future/current prospect (treatments?)

2 case studies

Glossary of terms

====Post online any preferences you may have in terms of the topics you wish to research and by Sunday we will allocate sub topics====
--[[User:Z3332629|z3332629]] 13:09, 18 August 2011 (EST)

Okay hey guys just to get the discussion going, umm I don't mind doing the first 2 on the list. And the "Why is it an abnormality - Symptoms effect" sounds pretty interesting as well.
What are your preferences?? :)

--[[User:Z3330313|z3330313]] 14:55, 23 August 2011 (EST)

Hey Everyone, Im happy to do the diagnosis/current/future prospects point and a case study.

--z3332327 15:36, 23 August 2011 (EST)

Hello,
I would like to do the 'why is it an abnormality - symptoms effect' and then it will be easy to incorporate that with a case study. So I guess that leaves Ashleigh to do the genetic component mostly, but we will ALL help out with that :D
How does this sound?

--[[User:Z3332824]] 10:22, 25 August 2011 (EST)

Duchenne Muscular Dystrophy - recessive X-linked form of muscular dystrophy, which results in muscle degeneration, difficulty walking, breathing, and death. It is caused by a mutation of the dystrophin gene at locus Xp21.

Osteogenesis Imperfecta - caused by defect in the gene that produces type 1 collagen, an important building block of bone. Most cases of OI are inherited from a parent, although some cases are the result of new genetic mutations. A person with OI has a 50% chance of passing on the gene and the disease to their children.

Congenital Adrenal Hyperplasia - refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands (steroidogenesis).

DiGeorge Syndrome - congenital immunodeficiency. Di George syndrome is an inherited condition that lies at the more severe end of a spectrum of syndromes (also known as CATCH22 or 22q11.2 deletion syndrome) that occur when a part of the DNA on chromosome 22 is missing. Several different genes are lost, resulting in a collection of different features, including problems with the immune system, congenital heart defects and abnormalities of the parathyroid glands.
[[User:Z3332327|z3332327]] 22:28, 7 August 2011 (EST)

Review Article: Targeting RNA to treat neuromuscular disease. Muntoni, F & Wood, M.J.A. (2011) Nature Reviews Drug Discovery 10, 621-637.
http://www.nature.com.wwwproxy0.library.unsw.edu.au/nrd/journal/v10/n8/full/nrd3459.html

Research Article: Ahmad N, Welch I, Grange R, Hadway J, Dhanvantari S, Hill D, Lee TY, Hoffman LM. Use of imaging biomarkers to assess perfusion and glucose metabolism in the skeletal muscle of dystrophic mice. BMC Musculoskelet Disord.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141608/pdf/1471-2474-12-127.pdf

z3332327 23:11, 10 August 2011 (EST)
______________________________________________________________________________________________________________________________________________

'''Friedreich Ataxia –''' Is caused by defect/mutation of the gene FXN, the disorder is recessive. It is an inherited disease that causes nervous system damage and impaired muscle coordination (ataxia) through spinal cord, peripheral nerve and cerebellum degeneration.

'''Lesch-Nyhan Syndrome –''' Rare inherited disorder where there is a deficiency of the enzyme: hypoxanthine-guanine phosphoribosyl transferase (HPRT). This is caused by mutations of the HPRT gene located on the x-chromosome. This disorder is an x-linked recession disease, it causes kidney probems (building up of uric acid in all body fluids) and moderate mental retardation.

'''Farber's Disease –''' Is an inherited autosomal recessive lysosomal storage disease. The gene responsible making the enzyme ceramidase is mutated. This enzyme breaks down fatty material in the body’s cell. [not recommended to do, limited disease]

'''Mucopolysaccharidoses –''' Inherited metabolic disease where a defective or missing enzyme cause large amounts of complex sugar molecules to accumulate in harmful amounts in the bodies cells and tissues. They can’t break down these glycosaminoglycans into smaller chains. It ends up causing progressive cellular damage which affects appearance, physical abilities, organ and system functioning, and, in most cases, mental development.

--[[User:Z3330313|z3330313]] 23:43, 7 August 2011 (EST)

{{2011ProjectsMH}}
Hey group 10 members!
I've quickly done some research on the top 4 listed disorders.
All of them had loads of info!!
Let me know what you think and lets say by monday we should pick a topic?

Angelman syndrome
- rare neuro-genetic disorder
- characterised by severe intellectual disability, speech impediment, sleep disturbance, unstable jerky gait, seizures and usually a happy demeanour
- occurs about one in 20,000 births
- Severe intellectual disability and developmental delay
- Profound speech impairment
- Movement for balance disorder

Turner’s syndrome
- affects about 1 in every 2,500 girls
- usually short in height
- born with only one X chromosome or they are missing part of one X chromosome
- prevents the ovaries from developing properly
- kidney problems, high blood pressure, heart problems, overweight, hearing difficulties, diabetes, and thyroid problems

Williams Syndrome
- rare genetic disorder characterized by mild to moderate mental retardation or learning difficulties, a distinctive facial appearance, and a unique personality that combines over-friendliness and high levels of empathy with anxiety.
- Common problem: cardiovascular disease caused by narrowed arteries
- A random genetic mutation (deletion of a small piece of chromosome 7), rather than inheritance, most often causes the disorder
- 50 percent chance of passing it on if they decide to have children

Cystic Fibrosis
- Cystic fibrosis (CF) is a recessive genetic disease of the mucus and sweat glands, which affects the entire body.
- affects mostly your lungs, pancreas, liver, intestines, sinuses and sex organs
- makes it easy for bacteria to grow
- Difficulty breathing
- multitude of other symptoms, including sinus infections, poor growth, diarrhea, and infertility result from the effects of CF on other parts of the body

--[[User:Z3332629|z3332629]] 14:10, 4 August 2011 (EST)

Sorry i accidently posted it on the actual project page lol

--[[User:Z3332629|Ashleigh Pontifex]] 13:31, 10 August 2011 (EST)
Review article: Functional characteristics of dystrophic skeletal muscle: insights from animal models.
Jon F. Watchko1, Terrence L. O'Day1, and Eric P. Hoffman2
http://jap.physiology.org/content/93/2/407.long

Research article: The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype
Elena Kudryashova1, Arie Struyk2,†, Ekaterina Mokhonova1, Stephen C. Cannon2 and Melissa J. Spencer1,*
http://hmg.oxfordjournals.org/content/early/2011/07/28/hmg.ddr311.long
--[[User:Z3332629|Ashleigh Pontifex]] 13:31, 10 August 2011 (EST)

----
Hello!
So my four diseases:

'''1. Fragile X Retardation:''' males mostly, the code CGG is repeated on a fragile area of the X chromosome. The more repeats, the more problems. See http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002633/ for more details on symptoms etc.

'''2. Klinefelter Syndrome:''' extra X chromosome in males - XXY. Abnormal body proportions, infertility, less hair, big boobs, problems with their genitals (poor things). http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001420/

'''3. Triple X:''' I think this is a trisomy and should be avoided? It is having XXX in females.

'''4. Thalassemia:''' blood disorder in which you have abnormal haemoglobin. Results lead to excessive destruction of RBC which leads to anaemia. Inherited from BOTH parents. Bone deformities in face, fatigue, growth failure, jaundice. See http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001613/

Personally, out of my four I think either Fragile X or Thalassemia will be the most interesting. Angelman Syndrome and Duchenne Muscular Dystrophy also sound cool. I think we should avoid all ones that are really specific biochem disorders (or to that effect)- something like Mucopolysaccharidoses - because we might get bogged down in the details and have to spend ages figuring out what its actually doing.

What is everyone else's thoughts?
See you tomorrow,
Rhiannon.

I think we should do Duchenne Muscular Dystrophy.
--[[User:Z3332629|Ashleigh Pontifex]] 11:03, 11 August 2011 (EST)

I agree !
Lisa Xiao 11:04, 11 August 2011 (EST)

Yes that sounds good, lets do it :)
--[[User:Z3330313|Joanna Pak]] 11:38, 11 August 2011 (EST)

Yep, I'm all for it. I'm glad we can bags it before everyone else :D
Rhiannon

--[[User:Z3332824|Rhiannon Bice]] 11:40, 11 August 2011 (EST)

== Useful Links ==

[http://www.genome.gov/19518854]National Human Genome Research Institute: Fact Sheet on Duchennes

'''Treatment'''

No known cure. However treatment aims to manage symptoms to maximize the quality of life.
Treatments includes:
- Physical Therapy: in order to maintain muscle strength and function. (Inactivity leads to weakened muscles and can worsen the condition)
- Orthopedic appliances such as braces and wheelchairs are available to improve mobility
- Aggressive management of dilated cardiomyopathy with anti-congestive medications
- The medication prednisone — a steroid — is given to improve the strength and function of individuals with DMD (However there are side affects associated with this medication)

'''Future Prospects'''
- Gene Therapy

[http://www.nlm.nih.gov/medlineplus/ency/article/000705.htm]Medline Plus: Encyclopedia

--z3332327 15:48, 16 August 2011 (EST)

Hey guys, I couldn't copy a picture relating to Duchenne, so i just got a random one :)
Rhiannon.

[[File:Patterns of zona pellucida deposition and ZPC-ubiquitin colocalization in porcine ocyte-cumulus complexes isolated from small antral follicles.JPG]]

Patterns of zona pellucida deposition and ZPC-ubiquitin colocalization in porcine ocyte-cumulus complexes isolated from small antral follicles.
<ref><pubmed>21383844</pubmed></ref>

<references/>

[[File:Flow of participants.JPG]]

File: Flow of Participants
--Lisa Xiao 12:43, 18 August 2011 (EST)

[[File:1532-429X-13-20-1.jpg]]

--[[User:Z3330313|z3330313]] 12:51, 18 August 2011 (EST)

Hey girls its Ashleigh, sorry I've been quite sick over the last week.
How about me copy and paste the headings again and write our names next to our bit and we can leave suggests as to what can fit into that heading etc? Ps did I miss anything from last weeks lab??

--[[User:Z3332629|Ashleigh Pontifex]] 19:38, 30 August 2011 (EST)

== Official discussion ==

''Subheadings for assignment''

Intro what is DMD

History/timeline

Genetic component

Why is it an abnormality - Symptoms effect

Diagnosis, future/current prospect (treatments?)

2 case studies

Glossary of terms

====Post online any preferences you may have in terms of the topics you wish to research and by Sunday we will allocate sub topics====
--[[User:Z3332629|z3332629]] 13:09, 18 August 2011 (EST)

Just found an awesome website!

http://emedicine.medscape.com/article/1173204-overview

Check it out when you can, it has info on history & treatment as well as some really good images.

[[File:Point vs frameshift mutations.jpg|500px|]]

Whoever is doing future direction of treatment etc., check out this article on PubMed

Cardiomyopathy of Duchenne muscular dystrophy: current understanding and future directions.

http://www.ncbi.nlm.nih.gov/pubmed/21674516?tool=MedlinePlus

Abstract

Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and occurs in 1 in 3500 male births. Improved survival due to improvements in clinical care of the musculoskeletal and respiratory systems has led to an increased incidence of cardiomyopathy. Cardiac-related deaths are now seen in approximately 20% of DMD patients. Our current understanding of DMD cardiomyopathy has increased significantly over the past 10 years, but further research is required to improve cardiac treatment and outcomes in DMD. This review provides a summary of the current literature and discussion of potential new therapies for DMD cardiomyopathy.

Copyright © 2011 Wiley Periodicals, Inc.

--[[User:Z3332629|Ashleigh Pontifex]] 20:00, 30 August 2011 (EST)

Some quick points from:
http://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy

- Mutations in the DMD gene causes DMD

- The DMD gene provides instructions for making a protein called dystrophin that helps stabilize and protect muscle fibers and may play a role in chemical signaling within cells.

- Mutations alter the structure or function of dystrophin, or prevent any functional dystrophin from being produced.

- Muscle cells without this protein become damaged as muscles repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies.

- This condition is inherited in an X-linked recessive pattern.

- Males are affected by X-linked recessive disorders much more frequently than females.

- Fathers cannot pass X-linked traits to their sons.

- Females who carry a DMD gene mutation also have an increased risk of developing heart abnormalities including dilated cardiomyopathy.

Hey guys
I found this slide show on DMD, quite easy to understand because all u have to do is listen!
So its http://hstalks.com.wwwproxy0.library.unsw.edu.au/main/citation_info.php?c=252
Oh and I'm not 100% sure on how to reference properly so bear with me if I make a mistake on the group page. And I'm going to try and borrow some books DMD to see if there's more of an indepth history of the disorder.
If u guys feel your part is too big, let me know because I'm willing to help out!!

(http://www.whonamedit.com/doctor.cfm/950.html)
--[[User:Z3330313|Joanna Pak]] 02:10, 1 September 2011 (EST)

I've been doing a bit of research and found some good papers.

Rodino-Klapac LR, Chicoine LG, Kaspar BK, Mendell JR. Gene therapy for duchenne muscular dystrophy: expectations and challenges. Arch Neurol. Sep 2007;64(9):1236-41

Bogdanovich S, Perkins KJ, Krag TO. Therapeutics for Duchenne muscular dystrophy: current approaches and future directions. J Mol Med. Feb 2004;82(2):102-15

Cossu G, Sampaolesi M. New therapies for Duchenne muscular dystrophy: challenges, prospects and clinical trials. Trends Mol Med. Dec 2007;13(12):520-6

AND the a copy of original book by Gower (one of the first to describe the disease etc) is at the library! Its called ' A manual of Diseases of the Nervous System'. Pages 378-393. I will be checking that out tonight or tomorrow.
-Rhi.

Treatment:
http://emedicine.medscape.com/article/1173204-overview -- Useful link

Inflammation is implicated in the pathogenesis of the dystrophinopathies despite the fact that most biopsies in patients with Duchenne muscular dystrophy do not show inflammatory cells. Corticosteroids have been used for more than 40 years with some success to treat patients with Duchenne muscular dystrophy. The central role of inflammation in the pathogenesis of the dystrophinopathies is suggested by the fact that use of corticosteroids, such as prednisone, results in prolongation of ambulation, maintenance of strength and function, and delay in the development of scoliosis. The side effects are well-known and do temper many clinicians enthusiasm to recommend its use in small children, patients with behavior or learning issues, or any patient for chronic use. A detailed understanding of the mechanism of action for corticosteroids on the body is still a large mystery.

To date, corticosteroids are the only medication that has demonstrated a modest benefit in modifying the course of the disease.[5] Clinical improvement is seen as early as 1 month after starting treatment and lasts as long as 3 years. Children who discontinue corticosteroids for various reasons soon revert to natural downward progression of the disease. It is hypothesized that prednisone reduces tissue inflammation, suppresses cytotoxic cells, improves calcium homeostasis, and stimulates myoblasts.

--[[User:Z3332327|Lisa Xiao]] 16:45, 31 August 2011 (EST)

----

== '''Clarification on components of the assignment''' ==

*If we find papers/books/info relating to another section that isn't ours, clearly write the name of the person it goes to and link/mention it e.g. Lisa: xyz
(this will just make it really easy to find)

*When we have the majority of the info up, we can meet and format the page, as well as edit it to make it flow.

*Keep checking this page for updates! Make this the main communication method between us, so keep an eye on it :D

*We also agreed that any updates will be here at the bottom of the page, just makes the flow easier. So keep updates down here!!

Sections:

Jo: intro/history/epidemiology

Ashleigh: genetic component/aetiology/pathogenesis (close work with Rhiannon)

Rhiannon: signs and symptoms/clinical manifestations/pathogenesis/CASE STUDY 1 (close work with Ashleigh)

Lisa: Diagnosis/treatment/futher research and directions/CASE STUDY 2

*Also, do we want to write anything about Becker's syndrome (the milder version of DMD?) Maybe we could do a comparison table if we can be bothered?
--[[User:Z3332824|Rhiannon Bice]] 13:02, 1 September 2011 (EST)

Hey guys, during my own research I've come across a lot of resources that each of you could use. They are only suggestions, but a few look really good!! I just thought I'd put them here to help us all along instead of you starting from scratch. I've spent most of today researching so its a bit of a waste if I don't pass it on :)

*'''Ashleigh'''- you may find details these sites helpful: http://www.nature.com/nature/journal/v333/n6172/abs/333466a0.html; http://www.unsworks.unsw.edu.au/primo_library/libweb/action/dlDisplay.do?vid=UNSWORKS&docId=unsworks_8295; http://docentes.cs.urjc.es/~odeluis/Docencia/ABP/Articulos/davies.pdf

*'''Lisa:''' http://www.sciencedirect.com/science/article/pii/0959437X9180033I. There is also a book at the library called "''Myoblast Transfer Therapy"'' written by the Muscular Dystrophy Association that you may find useful. It can be found at the library at Level 8, Main Library (MB 617.4730592/1). Also, I used a lot information found in the paper at {http://onlinelibrary.wiley.com/doi/10.1002/mus.22097/full}, so this may be a good starting point for treatment, especially about problems relating to the cardiac/respiratory systems. They also give some good info on the treatments available. Basically, you will get a lot out of that paper! If you can't download it properly, buzz me your email and I'll send it to you.

*'''Jo:''' Book called ''The history of a genetic disease : Duchenne muscular dystrophy or Meryon's disease'' Level 8, Main Library (MB 616.748/6). I think also when we all have our info about the actual disease written it will be heaps easier to write the introduction.

*YO! '''Found a LECTURE''' from a guy in America about it: http://hstalks.com/main/browse_talk_view.php?t=72&s=72&s_id=33&c=252. You can download the lecture slides too and use them (of course, we have to reference it properly as well). I think you found this before Jo? Anyway, check it out!!!

*I have found a tonne of papers as well, so if everyone puts up their emails I can send it to you all. Even if you get one good sentence to use out of the whole paper then thats great!

-Chamberlain, J. (2007), "Duchenne Muscular Dystrophy", in Dunn, B. (ed.), Protein Epidemiology: Diseases at the Level of Protein Structure and Function, The Biomedical & Life Sciences Collection, London (online at http://hstalks.com/bio)

Ashleigh's writing - maybe use?: Normal functioning of Dystrophin verses impaired functioning

Dystrophin is part of a group of proteins found in skeletal and cardiac muscle that work to protect and strengthen muscles fibers as they contract and relax upon movement. Dystrophin also functions in connecting muscle cell’s with other proteins and molecules in order to send and receive chemical signals amongst cells and to anchor muscle fibers. <ref>U.S. National Library of Medicine (2011). “Duchenne and Becker muscular dystrophy”. Author unknown, Genetics Home Reference. Accessed via http://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy </ref>

Skeletal and cardiac muscle cells of Duchennes patients have no functional dystrophin present and therefore the muscle fibers become extensively damaged as they contract and relax with use. Overtime, these damaged cells weaken and eventually die resulting in multiple health implications. <ref>U.S. National Library of Medicine (2011). “Duchenne and Becker muscular dystrophy”. Author unknown, Genetics Home Reference. Accessed via http://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy </ref>

---Rhiannon.

Talk:2011 Group Project 9

2011-09-28T07:15:05Z

Z3279511: /* Peer Review */

[[2011_Group_Project_9|'''Group 9''']]: [[User:z3331469]] | [[User:z3331556]] | [[User:z3332178]] | [[User:z3332183]]

{{2011GroupDiscussionMH}}

==Peer Review==

'''Group 9: Peer assessment'''
* The introduction is good
* The history section is informative but may be could be kept a little shorter
* The start of the page is quite text heavy, may be you can brake it up with a picture
* Rearrange you page, so that you have the epidemiology section right after the history section
* Genetic and aetiology sections are well done
* There are no references in the Phenotype section
* May be the detail in the foundations is a little over the top. Why not put a simple link to their web side instead?
* The research section could be a little more detailed
* It would be good to put more of the terms used into your glossary
* Overall the page is interesting to read. A few more images would be nice. --z3279511 17:15, 28 September 2011 (EST)

'''Group 9'''

*You don’t have a very good image/text ratio. More images are needed to break up the text.
*Good information in your introduction although you need an image
*Maybe try and condense your history just into a timeline?
*Genetic factors and etiology and diagnosis are good and have a nice flow
*I think the section epidemiology should closer to the beginning of your project- also not sure why management and treatment are mentioned here.
*Phenotypes should be organised better
*Good table for associated medical conditions
*A few of your headings should be reformatted
*Specialised facilities and supportive associations seems a little unnecessary
*Glossary is incomplete

'''Group 9'''

*Introduction: contend is fine

*History: could be a bit shortened, otherwise good

*Genetic and Etiology: well done

*Diagnosis: looks good

*Epidemiology: treatment doesn’t belong there (own section?), the contend is good

*Phenotype: references missing

*Cardiac conditions: well done, but what’s with other conditions?

*Genitourinary Conditions: the contend is good, but the structure could be clearer, a table for the grading system would be nice

*Endocrine: missing references, otherwise good section

*Other associated conditions: looks fine

*Cognitive, behavioural Phenotype: references missing?

*Structural diff. in the brain: is there really only one resource? Lack of structure and subheadings

*Special Facilities: I don’t think it is necessary to list the addresses of the foundations, and write down all their aims. The online link is enough.

*Research: could have more detailed information

*Glossary: incomplete

*The phenotype sections should be put together
--[[User:Z3387190|Z3387190]] 23:20, 27 September 2011 (EST)

===Comments on Group Project 9===
'''Strengths:'''
*Good use of subheadings. It gives the page a structured feel to it.
*For most part of the references, it is good with the initiative to prevent duplication of references.
* I really like the “Specialised Facilities and Supportive Associations” section. Parents who just found out about their child’s condition would probably want to know more and seek help and this would be good for them.
'''Weaknesses:'''
*The history section looks really overwhelming.
*The glossary section is poorly done, with missing definitions for some words. There are other words that should be included in the glossary but was not.
*The image of the typical facial feature of an individual with WS looks similar to the one shown during lecture by Dr Palmer. It would be good to acknowledge what the image drawn was based on.
'''Specific corrections:'''
*It will be good to include an image in either the introduction or history section. At least it will be able to grab some attention.
*Reference 23 is missing its source.
*It will be good to elaborate more on some of the research studies being done to give the readers a feel of the direction in which the research for Williams Syn is gearing towards.

--Z3389806 06:45, 27 September 2011 (EST)

'''Group 9 Peer Assessment'''
*Introduction has clear explanation of the topic though image would liven the section up
*History is very informative though have no images, image of the founder would suit this area. While the time line done properly and looks good but bullet points would make look better
*Genetic factors should incorporate the image used “fig 2”, although the use of the table is well made explaining the cases of genetic transmission.
*Diagnosis introduction done well though image “fig 3” not mentioned in the text which should also be integrated into the text.
*Epidemiology should be first before the diagnosis and treatment would be better as its own heading and below near the end.
*Headings needs to be more organised and some more images which are linked to the text otherwise very bulky with text
*Current research/ future research done well and separated with sub headings
*Glossary need to be expanded as most terms not understood without a dictionary
*Reference 23 and 2 needs to be fixed otherwise all done well
z3332250 23:57, 26 September 2011 (EST)

'''Group 9 Critique'''

#• Introduction is ok. Maybe add a picture or two to make the introduction look a little bit more interesting
#• History is pretty good. Nice work on the timeline!
#• The table in the section on genetic factors is appropriate. Good job!
#• Diagnosis is good
#• Epidemiology should be after introduction, not diagnosis, but otherwise ok
#• The overall project is quite good, however diagnosis should be at the end and not one of the first sections
#• Also, is it necessary to put in information about support groups? Something to think about
#• Glossary is unfinished
#• The current research and developments section should have more information in it. Two lines of information is not enough detail

--[[User:Z3289991|Robert Klein]] 16:16, 26 September 2011 (EST)

Peer Assessment Group 9 '''Williams-Beuren Syndrome'''

*The introduction could use a simple image of the chromosome 7q11.23 just to make the introduction look a bit more interesting
*History is too detailed and in a few instances a repetition of the timeline
*An image in the timeline section will make it a bit more interesting
*The section 'Genetic factors and Etiology' is a great balance of image, table and text. Interesting information presented simply and clearly
*Interesting image of the deleted gene location
*Under Epidemiology you could also talk about prevalence of the condition in certain regions of the world etc. It looks like a one sentence section.
*The management section looks like it is part of epidemiology. You might want to reformat this to make it look like it is a topic by itself.
* Too many one sentence paragraphs under 'Treatment'. It might be a good idea to organise the thoughts and bunch them into small paragraphs. Half a line in a paragraph doesn't look great, surely these single lines can relate to another paragraph.
*The heading 'other problems' don't sound descriptive enough, you might want to call it, 'Associated Abnormalities'.
*Please add 'Genitourinary Conditions' in addition to a heap of other unexplained terms in the glossary
*I like the addition of Figure 6. It is an interesting observation.
*The addition of support groups in Australia and other places is a useful section.
*Overall the page has been well researched, just find a balance between texts, images and tables and it will be an informative page to refer back to.

'''Williams-Beuren Syndrome'''

*'Introduction' is good, but need an image to open up the page
*Can you try to compile all that text in 'History' into the timeline? Otherwise it's a bit much and a bit repetitive; an image couldn't hurt either
*Good work with 'Genetics', easy to read and interesting
*Diagnosis might fit better below the signs and symptoms, ie after we know enough about the syndrome to fully appreciate the diagnosis
*'Treatment' doesn't really fit in 'Epidemiology', again this would be better towards the end of the page
*Nice table for 'Phenotype of Williams Syndrome', very clear and informative
*Your subtitles are a little confusing, you might want to try incorporating all the condions ie cardiac and genitinary into one section
*Though the information within these sections is very good
*You seem to be missing a ''lot'' of images, it's difficult to read when it's just blocks of text
*For 'Cognitive, Behavioural and Neurological Phenotype' you need more references. You should back up what your saying with at least 2 references; though there seems to be a lot of interesting information here
*'Structural Differences in Brain' - only 1 reference for all that information? That doesn't seem very reliable
*I like the topic 'Specialised Facilities and Supportive Associations', really interesting choice. Very good
*For 'Current Research', instead of just an article reference, make a brief summary of the paper and describe why it is significant? Otherwise this section is a bit pointless.
*The glossary can't hurt to be expanded..... and finished.
*Overall, the page looks good, clearly a lot of research has gone into it. Just focus on making it more visually appealing, and work on those references

Group 9-
* Glossary is incomplete
* There are very few images on the page to break up the text
* Introduction needs an image. Other than that the information is good
* History- not sure if you need the text AND the list of dates. Maybe you could combine it all into one
* Genetic factors and etiology- really good. Easy to understand and visually appealing
* Diagnosis is also easy to take in
* Epidemiology should be up the top before diagnosis
* Also you need to sort out your subheadings. Management and treatment are not part of epidemiology
* More information is needed on the actually epidemiology
* Phenotype should come before treatment so we know why the treatments are necessary
* Also- cardiac, endocrine and genitourinary conditions are part of the phenotype. Maybe consider including these in the table
* The whole phenotype section is confusing sorry. It is ALL phenotype but you have put it in different sections. Not really sure why you have done this. It needs to be formatted better.
* The information is all there it just isn’t organised properly
* Do you need this? ‘Specialised Facilities and Supportive Associations
* You have done a great job of researching and the information is all there its just really confusing sorry. You need to find a way of organizing it so that it is more accessible to the reader.

'''Group 9'''
* The structure and use of headings and subheadings is good but i think you need to rethink the order of your headings eg epidemiology should be closer to the beginning.
* Intro informative. maybe you could bullet point the phenotypic characteristics, just make it easier to read. could you add a picture in this section?
* Nice history, could you maybe put your timeline into a table.
* good use of the table in genetics and aetiology and nice to see the accompanying picture referenced.
* I feel treatment should be its own heading and not a subheading.
* Phenotype of Williams Syndrome- a nice easy to read section breaking up the text. Could you add anymore pictures here?
* Genitourinary Conditions is very text heavy could you add in some pictures here or tabulate some of the information, just to keep the page flowing nicely.
* The endocrine section should be renamed, as it does not really explain to the reader what your going to talk about.
* Other Associated Medical Conditions- is a nice section good use of the table.
* Cognitive, Behavioural and Neurological Phenotype section is very text heavy it needs to be broken up either by pictures or a table. but it seems like a lot of effort has been put into the research in this section.
* Im not sure whether this section is necessary for our assessment Specialised Facilities and Supportive Associations??
* Current research and developments should be above the preceding section and a summary of the information would be nice instead of dot points.

'''Group 9 Assessment'''
*Great job of linking the same resource to the same reference number in the reference section!
*The introduction and history are very thorough, but what’s missing are pictures to help it look more appealing.
*The timeline- the information it good, but it might look better in a table format.
*The genetic factors chart is good, but the last row doesn’t have any referencing…
*The diagnosis section definitely needs more referencing for all of the information.
*Epidemiology- This section could also really use some pictures to add to the section.
*The phenotype chart also needs all of the information referenced… It might also be helpful to have more pictures, at least one for each subgroup within the chart.
*The Genitourinary Conditions section is rather wordy… Pictures could definitely be helpful here as well as more bullet lists or possibly another chart to simplify the info.
*The complete list of problems and associated medical conditions is rather lengthy… It might be a good idea to simplify all of this information as much as possible and simply compile it ALL together into one chart….
*The whole “Cognitive, Behavioral and Neurological Phenotype” as well as the “Structural Differences in the Brain” sections definitely need more referencing.
*Are support groups really necessary to be included for this project?
*Current research could also a picture or two.
*Not all the words are defined in the glossary, and it might look better if a bullet list were used here. Also, it would be nice to have the glossary words linked to the actual words in the wiki page for easy reference.
*Overall, not bad. Just work on fixing the overall flow and referencing and you will be fine!
--[[User:Z3391078|Z3391078]] 16:35, 27 September 2011 (EST)

'''Peer Assessment: Group Project 9'''
*The introduction and history of the disease are informative and it is good to have both the detailed historical information in addition to the timeline.
*It might be good to have an image at the beginning of the page to break up the text, such as of someone prominently involved with the disease findings (John C.P. Williams or Alois J Beuren).
*The diagnostic section only has one reference which detracts from the reliability of the section and makes the reader wonder where the information was sourced from. It is also good to place it in as if the reader desires to know more about the subject, they are able to look at where certain parts came from.
*The phenotype section is really clear and well formatted, however there are no references in this section.
*In general there needs to be more images/figures/graphs to help the ease of reading. For example in sections: Genitourinary Conditions, Other Associated Medical Conditions and Cognitive, Behavioural and Neurological Phenotype.
*The section on specialised facilities and supportive associations is an additional section that really adds to the page.
*There needs to be a picture drawn by a student.
*Some of the definitions of words in the glossary need to be completed.
--[[User:Z3217345|z3217345]] 10:16, 28 September 2011 (EST)

*'''Intro''': More info about the syndrome itself needed. Add a picture if you can? The text alone is a bit dry.
*'''History''': ... 1952 is really not early. I'd call it a rather new syndrome if that's when it was discovered..? Otherwise, lots of info and references, which is good.
*'''Genetic factors and Etiology''': Looks good.
*'''Diagnosis''': Seems fine.
*'''Epidemiology''': Not sure it makes sense to have management and treatment under epidemiology? Content seems fine, though is very text-heavy, maybe find a figure to break it up?
*'''Phenotype''': I like the table. Gives an easy overview.
*'''Cardiac Conditions''': Good content. I assume the "other problems" section is still under construction?
*'''Genitourinary Conditions''': Content seems fine, but it's very text heavy, this really needs to be broken up somehow. Possibly use a table, or include more figures.
*'''Endocrine''': Endocrine what? Conditions? That title is a bit odd. Otherwise, looks good. How come the thyroid section doesn't have a reference?
*'''Other Associated Medical Conditions''': Good content, I like the table.
*'''Cognitive, Behavioural and Neurological Phenotype''': Very impressive amount of (really interesting) information, which however currently mainly consists of text. Some more figures will help break that down a bit. (Watch out with the spatial cognition part - the title is spelled correctly, but within the text it's all "spacial".) Otherwise, very well done!
*'''Structural Differences in the Brain''': Not quite sure it makes sense to have this section here - put it before the cognitive phenotype section, instead after? Content is very good.
*'''Specialised Facilities and Supportive Associations''': Interesting idea. Not quite sure it's needed cause I think we're supposed to focus on the science, but at the same time I don't see why not include it. Though your formatting makes it a very long section - I'd keep it more brief.
*'''Current research and developments''': A little bit too brief. You could expand a little bit more on what is being done. The links are good, but maybe give a few more examples of recent papers and reviews.
*'''Glossary''': Poor. MANY more terms need explanations.
*'''References''': Looks fine in general, though the link might need fixing, and also one reference leads to emptiness?
*General: From the conditions sections onwards I'm not quite sure the sections and different titles you have chosen make sense, it seems a bit confusing. Maybe rethink that and try and come up with a more clear structure? Also, you need to make your structuring and how you split up a section into subsections more uniform.
Overall though, you cover an impressive spectrum of information. Well done!

==Discussion==

hahaha everyone is commenting on the lack of images. yes guys, we know but there are little to no copyright free images out there.

--[[User:Z3331469|z3331469]] 14:36, 27 September 2011 (EST)

Hey, i've got no problem with that, i think it's a fair idea

--[[User:Z3331469|z3331469]] 19:06, 18 September 2011 (EST)

Hey guys ive been thinking that epidemiology isn't really in the right spot.... management and treatment should really go after all the descriptions of the abnormalities and incidence shoukd go at the beginning... so what i'm thinking is that we should split up the subheading and add incidence to the intro and have management and treatment as one heading towards the end...??? what do u guys suggest?

--[[User:Z3331556|z3331556]] 23:20, 17 September 2011 (EST)

Hey guys i found this really good article that deals with embryology in WS!! but i don't know where the info fits in...can u please have a quick glance over it and see where you think some of the info can go??? i just don't wanna mess up your parts by adding random info...

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629217/?tool=pubmed

--[[User:Z3331556|z3331556]] 17:36, 14 September 2011 (EST)

Yay!!! Yeah thats fine...were just gonna fix our ones up...coz we have another assignment to do tonight...so you n nobby can edit all u want tonight! Ohh and yeah sure...just post up the info you have for the timeline n then ill put it into a table!!

Hey, yeh no worries, im going to be working on it for the rest of the day now that my exams are over....i ll try get as much of it done ASAP. Oh and after i finish typing up the timeline, would one of u guys format it in a table for me??? i seriously tried to do it but I got a bit confused lol
Oh btw great job on the drawings!!! :)

--[[User:Z3331556|z3331556]] 13:54, 14 September 2011 (EST)

Hey sister 1 can you work on cardiac? I'll do other associated instead of sister 3.

--[[User:Z3332178|Z3332178]] 10:42, 14 September 2011 (EST)

and also, i just came across this page which is on the unsw embryo page....
http://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:Williams_Syndrome#Australia_-_Support_Groups

it lists some recent papers and current research, including one of steve palmer's papers.

--[[User:Z3331469|z3331469]] 08:31, 14 September 2011 (EST)

hey guys, yes moving epidemiology up is a great idea!!!!

--[[User:Z3331469|z3331469]] 07:25, 14 September 2011 (EST)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288273/ '''article for the visuospatial construction i.e. not able to draw house, bicycle etc, think this can be for our case studies...'''

yes i think that's a good idea, i was just about to mention that, shall i move it?? I fixed up a bit of the intro, is it ok? Btw I sware i thought i was on another page when i hit save cause all these tables and images came up, then i realised it was laticia and felicia's AWSOME WORK :), it looks really good!!! just thought i should mention that... I've spent hours trying to find images and most of the articles i've found have really good ones but we cant use them!! ahhh it's soo frustrating

--[[User:Z3331556|z3331556]] 23:58, 11 September 2011 (EST)

Also, in Marks feedback he said that epidemology should be linked earlier to diagnosis, so shall we just move it up and have it straight after diagnosis before the physical characteristics?
--[[User:Z3332183|z3332183]] 23:14, 11 September 2011 (EST)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129970/?tool=pubmed Hey guys...heres another open access article that we can use pics from!!!

--[[User:Z3332183|z3332183]] 22:48, 11 September 2011 (EST)

i think we can all use this article http://www.ncbi.nlm.nih.gov/books/NBK1249/ --[[User:Z3331556|z3331556]] 22:06, 11 September 2011 (EST)

http://www.nejm.org.wwwproxy0.library.unsw.edu.au/doi/full/10.1056/NEJMra0903074#t=article '''pretty good recent article :) but i don't know if we can use the pics, can someone double check...'''

--[[User:Z3331556|z3331556]] 21:46, 11 September 2011 (EST)

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1511580/?tool=pubmed] Clinical and molecular cytogenetic (FISH) diagnosis of Williams syndrome.

--[[User:Z3332183|z3332183]] 13:34, 7 September 2011 (EST)

Hey guys found this AWESOME article we can get pics off =D Leftward Lateralization of Auditory Cortex Underlies Holistic Sound Perception in Williams Syndrome PMID: 20808792 (forgot how to ref so this'll do for now)

--[[User:Z3332178|z3332178]] 22:51, 8 September 2011 (EST)

Hey! Yeah it think its better if they just go under the same heading because they go together and its impossible to separate them anyway...so yeah 'Genetic Factors and Etiology' should be fine...and we can add in any subheadings if we need em later... :D

--[[User:Z3332183|z3332183]] 19:54, 3 September 2011 (EST)

Hey guys i just changed the etiology, genetic factors/ cause headings, before we had genetic factors and etiology as separate headings with cause as a subheading below genetic factors and it didn't really make sense... so is it ok if we just have the heading 'Genetic Factors and Etiology'???

--[[User:Z3331556|z3331556]] 15:44, 3 September 2011 (EST)

Hey guys i just emailed Dr. Steve Palmer, will hope for a quick reply. Apparently he's taking the next lecture or something when we get back, but by then it will be too late, so it's best if we can arrange a meeting. Who wants to come with me to see him..........................................................................................=/

--[[User:Z3331469|z3331469]] 17:16, 1 September 2011 (EST)

Here's an article for diagnosis and management of the disease

[http://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.30139/abstract;jsessionid=E69D4793044A7511E77F50CA141F0825.d02t04?systemMessage=Wiley+Online+Library+will+be+disrupted+3+Sep+from+10-12+BST+for+monthly+maintenance]

Hey that's heaps good, we'll compare timetables tomorrow during the lab or something, this page is coming alongggggggggggg!

--[[User:Z3331469|z3331469]] 16:00, 31 August 2011 (EST)

Happy sister 1, you are awesome! I'll do Coronary artery stenosis, Pulmonary valve stenosis, Atrial septal defect, Ventricular septal defect if you didnt already start on any... I'm doin my williams research now so hopefully, i'll have my bit up tonight! *crosses fingers* I'm so sick of readin articles... =P Is there a time we can all go meet up with the WS proff?

--[[User:Z3332178|Z3332178]] 20:37, 30 August 2011 (EST)

Hey i found out who the researcher of WS at uni is, it's Dr Steve Palmer, here's his email s.palmer@unsw.edu.au, on the course outline it says that we have to make an appointment if we want to see him. We should try get together sometime this week or next week so we can go see him and ask about his current research???

--[[User:Z3331556|z3331556]] 18:51, 27 August 2011 (EST)

So i finally figured out how to reference on this thing, thought you guys might need help.... if you look on the main project page I've started to put some info up, so if you click on the edit button (on the side of each heading) the info and references come up, just copy and paste the ref name....blah blah part after your info BUT REPLACE THE PMID NUMBER WITH THE ONE YOU NEED FOR YOUR ARTICLE. When u save, the reference is automatically made in the reference heading at the bottom of the pages

Hope this makes sense lol

--[[User:Z3331556|z3331556]] 17:17, 27 August 2011 (EST)

Hey guys i've posted up some links to articles that may help in your research, they're on the reference list below. Oh and Felicia i think we should further split up the cardiovascular heading so we can research specific types and make them subheadings??? The OMIM clinical synopsis web page [http://omim.org/clinicalSynopsis/194050] has these as abnormalities associated with the heart:

Supravalvular aortic stenosis

Valvular aortic stenosis

Bicuspid aortic valve

Mitral valve prolapse

Mitral regurgitation

Coronary artery stenosis

Pulmonary valve stenosis

Atrial septal defect

Ventricular septal defect

which ones do you want to search???

--[[User:Z3331556|z3331556]] 15:22, 27 August 2011 (EST)

“The behavioral phenotype of Williams syndrome: A recognizable pattern of neurodevelopment” by Colleen A. Morris
The review article concludes that a person with William syndrome share distinct cognitive and behavioural features. The phenotype of a typical patient will be due to the deleted genes of chromosome 7 q11.23.[http://onlinelibrary.wiley.com.wwwproxy0.library.unsw.edu.au/doi/10.1002/ajmg.c.30286/full]

“Impaired geometric reorientation caused by genetic defect” by Laura Lakusta, Banchiamlack Dessalegn, and Barbara Landau
By testing participants in a plain or single blue walled chamber, the study was able to show that William syndrome patients show a failure to reconstruct and use geometric representations of the chamber o find hidden objecs.[http://www.ncbi.nlm.nih.gov.wwwproxy0.library.unsw.edu.au/pmc/articles/PMC2840366/?tool=pmcentrez]
--z3332178 22:42, 9 August 2011 (EST)

http://omim.org/entry/194050

Review Article: Research Review: Williams syndrome: a critical review of the cognitive, behavioral, and neuroanatomical phenotype. [http://www.ncbi.nlm.nih.gov/pubmed/18489677]

Research Article: Elevated Ambulatory Blood Pressure in 20 Subjects With Williams Syndrome[http://userwww.service.emory.edu/~erein/research/broder-et-al.pdf]

--[[User:Z3331469|z3331469]] 21:35, 10 August 2011 (EST)

--[[User:Z3331469|z3331469]] 13:19, 4 August 2011 (EST)

The genomic basis of the Williams - Beuren syndrome
C Schubert. Cellular and Molecular Life Sciences. Basel: Apr 2009. Vol. 66, Iss. 7; p. 1178
[http://proquest.umi.com/pqdweb?index=0&did=1892633801&SrchMode=1&sid=2&Fmt=6&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1312428336&clientId=25620]

--[[User:Z3332183|Z3332183]] 13:28, 4 August 2011 (EST)

J Hum Genet. 2009 Apr;54(4):193-8. Epub 2009 Mar 13.
William's syndrome: gene expression is related to parental origin and regional coordinate control.
Collette JC, Chen XN, Mills DL, Galaburda AM, Reiss AL, Bellugi U, Korenberg JR.
Source

Division of Neurogenetics, Cedars-Sinai Medical Center and Departments of Human Genetics and Pediatrics, UCLA, Los Angeles, CA, USA.

'''Abstract'''

William's syndrome (WS) features a spectrum of neurocognitive and behavioral abnormalities due to a rare 1.5 MB deletion that includes about 24-28 genes on chromosome band 7q11.23. Study of the expression of these genes from the single normal copy provides an opportunity to elucidate the genetic and epigenetic controls on these genes as well as their roles in both WS and normal brain development and function. We used quantitative RT-PCR to determine the transcriptional level of 14 WS gene markers in a cohort of 77 persons with WS and 48 normal controls. Results reported here: (1) show that the expression of the genes deleted in WS is decreased in some but not all cases, (2) demonstrate that the parental origin of the deletion contributes to the level of expression of GTF2I independently of age and gender and (3) indicate that the correlation of expression between GTF2I and some other genes in the WS region differs in WS subjects and normal controls, which in turn points toward a regulatory role for this gene. Interspecies comparisons suggest GTF2I may play a key role in normal brain development.

PMID:19282872[http://www.ncbi.nlm.nih.gov/pubmed/19282872] '''hey guys this is one of the articles i found but i've tried getting the whole article to read but sirius doesn't seem to have this particular volume '''

--[[User:Z3331556|z3331556]] 18:09, 6 August 2011 (EST)

''Review Article:The genomic basis of the Williams – Beuren syndrome''
•Williams syndrome is a genomic disorder with symptoms including mental retardation, visuospatial impairment & overfriendliness.

•It is caused due to a hemizygous contiguous gene deletion with regards to chromosome 7q11.23.

•This review article deals with the genomic assembly of the region involved in Williams syndrome as well as the chromosomal mechanisms such as deletions and duplications and the consequences of these.

Reference:
Schubert, C. The genomic basis of the Williams – Beuren syndrome. Cell, Mol. Life Sci. 66:1178-1197, 2009 [http://www.springerlink.com.wwwproxy0.library.unsw.edu.au/content/r41l072283g5222u/fulltext.pdf]

''Research Article: Functional, structural and metabolic abnormalities of the hippocampl formation in Williams syndrome''
•In this study, neuroimaging (PET and fMRI) was used to investigate the hippocampal structure, function and metabolic integrity of 12 people with Williams syndrome compared to 12 healthy controls.

•N-acetul aspartate can be seen as a marker for synaptic activity and measures of this were reduced in those with Williams syndrome

•Although regular hippocampal size was maintained in both groups, slight changes in the shape were present.

•Through the results of the investigation, it was suggested that the neurocognitive abnormalities seen in Williams syndrome may be partly due to hippocampal dysfunction.

Reference:
Meyer-Lindenberg A., et al. Functional, structural and metabolic abnormalities of the hippocampal formation in Williams syndrome. J Clin Invest. 115(7):1888-95, 2005 [http://www.ncbi.nlm.nih.gov.wwwproxy0.library.unsw.edu.au/pubmed/15951840/]

--[[User:Z3332183|z3332183]] 23:02, 9 August 2011 (EST)

'''ARTICLE'''

PLoS One. 2010 Apr 21;5(4):e10292.
Intelligence in Williams Syndrome is related to STX1A, which encodes a component of the presynaptic SNARE complex.
Gao MC, Bellugi U, Dai L, Mills DL, Sobel EM, Lange K, Korenberg JR.
Source

Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.

'''Abstract'''
Although genetics is the most significant known determinant of human intelligence, specific gene contributions remain largely unknown. To accelerate understanding in this area, we have taken a new approach by studying the relationship between quantitative gene expression and intelligence in a cohort of 65 patients with Williams Syndrome (WS), a neurodevelopmental disorder caused by a 1.5 Mb deletion on chromosome 7q11.23. We find that variation in the transcript levels of the brain gene STX1A correlates significantly with intelligence in WS patients measured by principal component analysis (PCA) of standardized WAIS-R subtests, r = 0.40 (Pearson correlation, Bonferroni corrected p-value = 0.007), accounting for 15.6% of the cognitive variation. These results suggest that syntaxin 1A, a neuronal regulator of presynaptic vesicle release, may play a role in WS and be a component of the cellular pathway determining human intelligence.

PMID:20422020 [http://www.ncbi.nlm.nih.gov/pubmed/20422020]

* Williams Syndrome presents with a distinct pattern of intellectual disabilities that differ from normal on subtests of the WAIS-R (Wechsler Adult Intelligence Scale-Revised). Found that relative to their overall performance, WS subjects tended to do well in tests of vocabulary (Vocabulary) and abstract reasoning (Similarities, Picture Arrangement), and poorly in tests of numeracy (Arithmetic), visual-spatial (Digit Symbol, Block Design, Object Assembly), and memory (Digit Span)

* Gene expression in the tissue of interest (brain) is not possible so quantitated gene expression in lymphoblastoid (LB) cell lines

* STX1A is best known as an important component of the presynaptic SNARE complex involved in priming of synaptic vesicles for release.

* Data indicate that peripheral STX1A expression levels measured in lymphoblastoid cell lines strictly grown, is related to an emergent property of the CNS, intelligence.

'''here's the actual article''' [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010292]

'''REVIEW ARTICLE'''

Arch Pediatr. 2009 Mar;16(3):273-82. Epub 2008 Dec 18.
[Williams-Beuren syndrome: a multidisciplinary approach].
[Article in French]
Lacroix A, Pezet M, Capel A, Bonnet D, Hennequin M, Jacob MP, Bricca G, Couet D, Faury G, Bernicot J, Gilbert-Dussardier B.
Source

Laboratoire langage, mémoire et développement cognitif, CNRS, UMR 6215, 99, avenue du Recteur-Pineau, 86000 Poitiers, France. agnes.lacroix@uhb.fr

'''Abstract'''
Williams-Beuren syndrome (WBS) (OMIM# 194050) is a rare, most often sporadic, genetic disease caused by a chromosomal microdeletion at locus 7q11.23 involving 28 genes. Among these, the elastin gene codes for the essential component of the arterial extracellular matrix. Developmental disorders usually associate an atypical face, cardiovascular malformations (most often supravalvular aortic stenosis and/or pulmonary artery stenosis) and a unique neuropsychological profile. This profile is defined by moderate mental retardation, relatively well-preserved language skills, visuospatial deficits and hypersociability. Other less known or rarer features, such as neonatal hypercalcemia, nutrition problems in infancy, ophthalmological anomalies, hypothyroidism, growth retardation, joint disturbances, dental anomalies and hypertension arising in adolescence or adulthood, should be treated. The aim of this paper is to summarize the major points of WBS regarding: (i) the different genes involved in the deletion and their function, especially the elastin gene and recent reports of rare forms of partial WBS or of an opposite syndrome stemming from a microduplication of the 7q11.23 locus, (ii) the clinical features in children and adults with a focus on cardiovascular injury, and (iii) the specific neuropsychological profile of people with WBS through its characteristics, the brain structures involved, and learning.

PMID:19097873 [http://www.ncbi.nlm.nih.gov/pubmed/19097873]

--[[User:Z3331556|z3331556]] 19:40, 10 August 2011 (EST)

'''Here's the image i showed you guys'''

[[File:Distribution of quantitative transcription of genes deleted in WS.png|Distribution of quantitative transcription of genes deleted in WS]]

--[[User:Z3331556|z3331556]] 12:23, 12 August 2011 (EST)

[[File:Auditory Cortex Location - Comparison Between Control Subject and WS Subject.jpg|300px]]

--[[User:Z3331469|z3331469]] 17:33, 16 August 2011 (EST)

The frequency of SD cells for RB1 and SNRPN in WS and control individuals.

[[File:The frequency of SD cells for RB1 and SNRPN in WS and control individuals.jpg|The frequency of SD cells for RB1 and SNRPN in WS and control individuals|400px]]

--[[User:Z3332178|z3332178]] 23:22, 16 August 2011 (EST)

I've found a good case study for WS, maybe we could have a case study sub-heading?? [http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1754.1993.tb03023.x/abstract]

--[[User:Z3331556|z3331556]] 13:38, 17 August 2011 (EST)

==Suggestions for areas of research==
I thought I could get the ball rolling, let me know if you want to add or remove anything.

===INTRODUCTION===
(z3331556)
-What is William’s Syndrome?

===History of the disease===
(z3331556)
-How it was discovered
-Who discovered it?
-Timeline of how knowledge developed

===Etiology===
(z3332183)
- Cause
- Susceptibility of the patient

===Diagnosis===
(z3332183)
-How it’s detected (tests/examinations)
-How soon it can be detected?

===Genetic Factors===
-deletions
(all)

===Physical Characteristics===
-Facial characteristics etc.
(z3332178)

===Associated medical conditions===
-Cardiac abnormalities (z3331556),(z3332178)

-Renal abnormalities (z3331469)

-other (hoarse voice, inguinal hernia, orthopaedic problems, hypercalcaemia etc.)
(z3332183)

===Cognitive, Behavioural and Neurological Problems===
(z3332178)

===Epidemiology===
-Incidence, distribution, and control of disease
(z3331469)

===Management/treatment===
-Treatment of individual symptoms, avoid taking increased levels of calcium and Vitamin D
(z3331469)

===Specialized Facilities/ supportive associations===
-Williams Syndrome Foundation (UK), Williams Syndrome Association
(all)

===Case studies===

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288273/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862007/

===Interesting facts===
(all)

===Current research and developments===
(all)

==References==

http://www.cddh.monash.org/assets/williams-synd.pdf

--[[User:Z3331556|z3331556]] 18:09, 17 August 2011 (EST)

http://books.google.com.au/books?id=qvKaSNg0pUcC&pg=PA158&lpg=PA158&dq=Williams+and+Barrett-Boyes&source=bl&ots=0SIpaamHuh&sig=4ouDsgFvt8XBbuwKPThFGWX9b4Y&hl=en&ei=8F5MTurlGuuNmQWA6eCyAg&sa=X&oi=book_result&ct=result&resnum=7&ved=0CEMQ6AEwBg#v=onepage&q=Williams%20and%20Barrett-Boyes&f=false

--[[User:Z3331556|z3331556]] 13:09, 18 August 2011 (EST)

Williams Syndrome Foundation, accessed 22 August 2011, http://www.williams-syndrome.org.uk/

Williams Syndrome Association, accessed 22 August 2011, http://williams-syndrome.org/

--[[User:Z3331469|z3331469]] 13:12, 22 August 2011 (EST)

http://omim.org/clinicalSynopsis/194050 '''this is a clinical synopsis that is a good starting point for medical and physical abnormalities, it basically lists all complications associated with WS. I think we can use these as subheadings???'''

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1728781/pdf/v080p00205.pdf '''This is a source for cardiac abnormalities'''

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946897/?tool=pmcentrez

http://www.nature.com/ejhg/journal/v18/n1/full/ejhg2009108a.html

'''These last two are basically introductory info on WS and they have info for the Genetics heading'''

--[[User:Z3331556|z3331556]] 15:44, 27 August 2011 (EST)

http://books.google.com.au/books?id=9E9q5112WBgC&pg=PA151&lpg=PA151&dq=hallux+valgus+in+williams+syndrome&source=bl&ots=LdaFmjSds_&sig=QW_9bjbIgo44rXQrwKTh2TF5hSo&hl=en&ei=__teTu2oNMjEmAXCx80B&sa=X&oi=book_result&ct=result&resnum=4&sqi=2&ved=0CCwQ6AEwAw#v=onepage&q&f=false

--[[User:Z3331556|z3331556]] 13:38, 1 September 2011 (EST)

http://www.ncbi.nlm.nih.gov/books/NBK1249/ '''another good source'''

--[[User:Z3331556|z3331556]] 14:39, 3 September 2011 (EST)

==Peer Assessments==
* Intro was good, it was brief and straight to the point
* The beginning paragraphs of the history could be more summarised especially considering that you have a timeline beneath
* Your use of a table for the genetics’ component was great. It was easy to read and concise. It was a different approach but it worked well.
* More information could have been added to the treatment section such as comparisons between key methods/strategies, the pros and cons
* The phenotype section was well set out although I believe it should have been placed up after the genetics section so that the information flows more consistently
* The layout of the implications section was slightly unclear. Maybe here you could have large heading for implications, followed by a list (dot point) of the implications occurred then have in paragraph form a description of each. Having headings such as: Other problems and other associated medical conditions tended to drag on this segment.
* The inclusion of the supportive associations was a nice little touch!
* Great use of referencing
--[[User:Z3332629|z3332629]] 15:30, 22 September 2011 (EST)

Talk:2011 Group Project 8

2011-09-28T07:13:45Z

Z3279511: /* Peer Review */

[[2011_Group_Project_8|'''Group 8''']]: [[User:z3294943]] | [[User:z3389343]] | [[User:z3329495]] | [[User:z3332250]]

{{2011GroupDiscussionMH}}

==Peer Review==

'''Group 8: Peer Assessment'''
* Overall you page is well structured, has relevant content and is written nicely. It also fits nicely together, good group work.
* May be you could put a picture of a person with this disorder in?
* Structure and content of the introduction and history is good. What happened between 1907 and 1988?
* Good use of subheadings in the epidemiology section
* You aetiology section is informative and nicely balanced
* "The fraxtaxin gene on chromosome 9": can you get a better contrast for that image?
* The aetiology, neuropathology, clinical presentations and diagnosis sections are all well written, interesting and have the right amount of text and images
* The current research section looks rather unfinished in comparison to the rest. May be you can put the information into a few paragraphs instead of bullet points.
* The current research section is interesting, just lacks dates
* Glossary, References and External links are fine --z3279511 17:13, 28 September 2011 (EST)

''' Group 8 peer review'''
* Introduction and History are well presented, and structured well. It's quite easy to read. The history section could perhaps have a little bit more substance, and your findings end around 1996; does this mean that there has been nothing done since 1996? What is the situation now? It's also slightly lacking in the time period between 1907-1988; surely some significant discoveries would have been made in this period.
* Epidemiology is well structured and covers all aspects of epidemiology. Perhaps a graph or table will structure the information slightly better, but otherwise, good.
* '''Protect your student-drawn image''' with the copyright statement, unless you're happy to let it go around! The subheadings in the aetiology section are appropriate and the bold words make it easy to read. The images help break up text and this section is very well outlined.
* Perhaps a little more could be written on the pathogenesis section? After all, this is the section where you can take the time to discuss the disease process and how it manifests itself into the form which presents with the condition in the clinic. Therefore, just a little bit more? Try explaining how it affects normal physiology (since patho- (disease) -physiology (normal function)); how disease state alters normal function.
* Excellent Neuropathology section with imaging and referencing all well outlined. The previously mentioned point about the pathophysiology section has to just refer to the neuropathology section to see how it is done!
* Clinical presentation is well set out with the tables used to break up the information. Diagrams and tables in the diagnosis section still require linking to the videos? Perhaps get an image snapshot of the video and link through there.
* Treatment section would be better with a diagram, otherwise it is adequate
* Current research doesn't really give me any dates as to the information, but otherwise is set out well.
* Reference section is extensive and well done - consider putting the glossary before the reference section to make it more accessible.
--[[User:Z3288827|Leonard Tiong]] 12:51, 28 September 2011 (EST)

'''Group 8'''

*Good introduction
*I find it hard to believe that you have only found 5 significant findings to put in your timeline, it should also more recent findings
*Good epidemiology
*There is a lot of information in etiology- although the subheadings are good try and think of a way to break up the text
(For further detail on the mechanisms of replication slippage, see Viguera et al (2001) is unnecessary
*Postnatal diagnosis table also seems a little unnecessary
*Treatment needs an image
*Current research should be explained
*Not sure why you put your glossary under your references but this should be the other way around so the reader can easily access the glossary

'''Group 8'''

*The index should be on the left side

*Introduction: contend is fine, but could be a little more general

*History: is there mo important milestone after 1996?

*Epidemiology: the first two subheadings could have more contend, the others are well done

*Aetiology: well done, good structure and contend, but the chromosome image could have been done with more effort

*Pathogenesis: looks good

*Neuropathology: well done, very nice drawings

*Clinical Presentation: good contend, but more subheadings to break up the text would look better

*Diagnosis: very well done

*Treatment: well done

*Research: should be more detailed contend

*The Glossary should be placed before the references
--[[User:Z3387190|Z3387190]] 22:37, 27 September 2011 (EST)

===Comments on Group Project===
'''Strengths:'''
*Smooth flow to the page due to good placements of headings, subheadings and subsubheadings.
*The referencing is well-done with correct formatting and there seemed to be no duplication.
*The external links section is good.
'''Weaknesses:'''
*There are some inconsistencies in formatting.
*Some of the images do not come with descriptions and copyright statements allowing wikiusers to use images, especially for student drawn ones.
'''Specific corrections:'''
*Maybe include “frataxin” in the glossary?
*Reference 38 is missing.
*The image on the frataxin gene is a bit faint, maybe it would be better to make the outline darker?

--Z3389806 06:25, 27 September 2011 (EST)

'''Group 8 Critique'''

#• Epidemiologic figures should not be included in the introduction. Also, neither should pathogenesis. Maybe just explain very simply what the condition is and explain the genes in the pathogenesis. The introduction should be organised a little better.
#• The history is rather short. You need to explain in a little more detail how the disease was discovered, and don’t mention pathogenesis or gene function.
#• The epidemiology is ok
#• Aetiology is fine. Good use of images to support your points
#• Pathogenesis should include the sentences on genes found in the introduction
#• Neuropathology is good, but you need to explain the image of the cross section of the spinal cord
#• Clinical presentation is quite good
#• Diagnosis is very good. Your tables in this section are excellent. Good use of images
#• Treatment and Current Research is very good.
#• Glossary is fine

--[[User:Z3289991|Robert Klein]] 16:05, 26 September 2011 (EST)

'''Peer Assessment Group 8-Friedreich's Ataxia'''

*I am sure you will fix the big gap at the beginning of the page where the contents are supposed to be
*While the introducton is good with relevant information, the paragraph is too long.Maybe consider breaking it into two paragraphs.
*The history section is repititive of the actual timeline. All the information under history could be summarized to incorporate in the timeline.
*The timeline needs further information of what has happened since 1996
*I like how you have the different sections within 'Epidemiology' highlighted. Only improvement you could make is maybe expand on 'Distribution,' 'Populations,' and 'Gender'.
*'Aetiology' has a good balance of interesting information, referencing and pictures.
* The image 'The frataxin gene on chromosome 9' has very poor resolution and missing the copyright information. The description could be a bit more detailed too
*The image 'Cross Section of the Spinal Cord' is missing a description.
*There are a number of student drawn images which is relevant to the section and makes the page look quite original
*The table under 'Diagnosis' is well done and informative
*The 'Current Research Section' will look better as paragraphs rather than bullet points.

'''Friedreich's Ataxia'''

*Where did the contents go?
*Try splitting the introduction up into a few paragraphs as opposed to just the one
*Is there ''nothing'' else to put in history? What you've got is good, but i'm interested in seeing a bit more
*'Atiology' looks good, there seems to be quite a bit of work gone into it. But how are there no references for 'Inheritance'
*Split your paragraphs up a bit more in 'Neuropathy', at the moment it is quite difficult to read
*Can you try to include all of the signs and symptoms into a table? It's a bit difficult to read when you list the in text; though the table already present looks really good
*Diagnosis looks fantastic, very nicely set out and lots of interesting information
*Try to get a picture for either 'Diagnosis' or 'Treatment'. The bottom half of the page looks a bit bare
*Can you expand 'Current Research' a bit, explain what and how they do the research etc
*No glossary?
*The page looks quite good, you've clearly got a lot of information there, just need to make it a bit easier to read
*'Glossary' will fit better before the references

Group 8
* Glossary under the references? This needs to be moved up so people can actually find it
* Good introduction. Gives the background and information that is needed
* History is very short. I believe there is more research after 1996 and what you have supplied is very limited
* Epidemiology is great. I like how you divided it up in sections! Easy to read and gauge the spectrum of the condition
* ‘(For further detail on the mechanisms of replication slippage, see Viguera et al (2001)’ This is not necessary
* etiology is very detailed! Maybe think of ways to break up the text for the reader. The subheadings are great but there is just A LOT to get through
* the diagnosis is great
* postnatal diagnosis- I don’t really understand why you need the table here
* treatment could do with an image. Other than that its really good information
* current research should not be a list. It should shed light on what is to come and the significance of current research- not just a list of papers published recently

'''Group 8 Assessment'''
*Kind of random, but I noticed all the pictures are formatted the same exact way and on the right hand side. It might be good to switch some of them around just so it looks more appealing and not cluttered.
*Great job of linking the same resource to the same reference number in the reference section.
*Good job of condensing down the timeline into a few major incidents. Maybe consider compiling them into a chart?
*The diagnostic tests chart was impeccable! Superb job on it. My only concern are the videos and whether or not they need better referencing.
*Only parts I saw that needed more referencing were: the Cerebellum and the symptoms chart.
*This is the best referencing job I have noticed thus far. Great job!!!
Only real negative comment is that it looks kind of jumbled and very wordy. Maybe separating things out into charts and bullet points would help to fix this problem…
*Glossary would also probably look a bit more organized if it were a bullet list. Also, do the definitions need to have references also?
*Might be a good idea to also have the glossary terms linked with the words in the wiki page, so that the reader can easily get access to the word in the glossary. Good job at least bolding them though!
*Great job guys! Just a few formatting things and some referencing and you should be good to go.
--[[User:Z3391078|Z3391078]] 16:14, 27 September 2011 (EST)

'''Peer Assessment: Group Project 8'''
*The contents would be improved by being placed on the left hand side of the page.
*Introduction and history are clear and concise.
*The information on etiology could be put in a table to increase the viewer's ease of reading.
*The sections on aetiology, neuropathology, clinical presentations and diagnosis are well written, formatted and have a good balance between images and text.
*The hand drawn images are clear and add to the text.
*In current research more of a summary of the papers and their findings would make the section more informative, as it is unknown what some of the papers are even about: "New advances in the treatment of Friedreich ataxia: promisses and pitfalls." What are these 'promises' and 'pitfalls'?
*The glossary and external links sections could be moved higher up, prior to the references as the references denote the end of the page.
*Overall this project provides a large amount of knowledge for the reader on Friedreich ataxia. It is obviously well researched and thoughtfully formatted.
--[[User:Z3217345|z3217345]] 09:56, 28 September 2011 (EST)

==Discussion==

--[[User:S8600021|Mark Hill]] 18:28, 11 August 2011 (EST) Your group left the lab today without notifying me of your selected group topic.

Sorry, we were the group that hadn't quite made up their mind yet, as you said we should have a think but decide within the next few days, we thought we didn't have to make a decision on the spot. Sorry, we will make our choice soon.
--[[User:Z3389343|z3389343]] 18:40, 11 August 2011 (EST)

Hi guys!
I agree with Elina we should just contact each other via this discussion page.
I have checked out some topics and I think Duchenne Muscular Dystrophy and Angelman's syndrome look very interesting.
They have many components associated like cognitive and skeletal disabilities..
Anyway let me know what you think or if you guys have looked into any topics yourselves.
I also think we should meet next week if we all have a break in between the lecture and lab would you guys like to meet then?
--z3294943 11:47, 6 August 2011 (EST)

Sorry I couldn't write at the bottom of page I'm on my iPhone. I think we need to choose some with both anatomical changes as well as neurological and I think duchenne MD and angelman's fit those categories. They are also both genetic so let's look into both as another group maybe interested in either topic. So let's come to the lab with the two journal article required and have our first choice ready and decide during the break. How does that sound?

--Karmen Magi 07:32, 8 August 2011 (EST)

(Shifted Elina's contribution to discussion page. --[[User:Z3329495|Z3329495]] 22:45, 7 August 2011 (EST))
Hey all,

I had a look at the list and thought I'd start making some suggestions. I am a neuroscience student, so my interest lies in anomalies that are related to the nervous system, but I won't insist on doing something about that if noone else wants to!

Here are the ones that so far seem most appealing to me:
* Holoprosencephaly: the forebrain of the developing embryo fails to fold into two hemispheres. Caused by Hox genes failing to activate along the midline of the developing brain. (I've done uni stuff on Hox genes before, so I know where to start looking for material.)
* Angelman's Syndrome: neurogenetic disorder with a variety of clinical features. characterised by a loss of a region of chromosome 15. this loss can be the result of varying genetic problems, including gender-related epigenetic imprinting, which makes me think that the genetics behind this Syndrome are very interesting (but I totally understand if that's just me).
* Fragile X syndrome: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002633/ again, I find the genetics behind this very interesting.

Then here's a list of the ones I [[wouldn't]] recommend doing:
* DiGeorge's Syndrome, Farber's Disease, Anencephaly, as there seems to be very little known about that (correct me if I'm wrong!)
* Turner's & Klinefelter Syndromes, Cystic Fibrosis - I'm just not particularly interested in them/sick of them (sorry)

And here are some I had a look at and feel neutral about:
* Williams Syndrome, Duchenne Muscular Dystrophy, Osteogenesis Imperfecta, Friedreich's Ataxia, Lesch-Nyhan Syndrome.

As you see, I didn't go through the whole list.

Let me know what you think :)

--[[User:Z3389343|Elina Jacobs]] 18:43, 7 August 2011 (EST)

Hi guys,

Duchenne Muscular Dystrophy sounds quite interesting to me - the anatomical changes (musculoskeletal) would be something i'm more comfortable in as i haven't done any physl, neuro or genetics course. as i'm an anatomy major i think i can contribute more with physical changes - as for molecular problems i'm not very strong with that.
Meeting up before the practical on Thursday sounds like a good time to meet up.
--[[User:Z3329495|Z3329495]] 22:45, 7 August 2011 (EST)

Hey All

looks like I'm last to contribute though, even so i did some searching for journals and reasearch papers and there is a fair bit on Duchenne Muscular Dystrophy though i am sorry i wasn't able to find a abnormality myself as it was my Mums birthday on the weekend so was busy planning that so i will find one by the next lab. Also im free the gap before the lab so if we are meeting after the lecture then I'm available.

--z3332250 22:29, 8 August 2011 (EST)

----
Articles
*Review article [http://www.ncbi.nlm.nih.gov.wwwproxy0.library.unsw.edu.au/pubmed/11834588 PMID:11834588]
*Research article[http://www.ncbi.nlm.nih.gov.wwwproxy0.library.unsw.edu.au/pubmed/20139167 PMID:20139167]
--z3294943 19:28, 8 August 2011 (EST)

There are at least two other groups that are looking at Duchenne Muscular Dystrophy, so I think it's good if we keep Angelman's Syndrome as our consideration as well. I think that still has enough anatomical features to it, and as I've done some molecular biology & genetics, I'd be happy to be the one focusing on that aspect. I'll try and find research and review articles on that today, so we can compare on thursday!
--[[User:Z3389343|z3389343]] 11:15, 9 August 2011 (EST)

Sure thing, so we're looking up articles on angelman's syndrome then?

Review article: http://jmg.bmj.com/content/40/2/87.short
Research article: http://jmg.bmj.com/content/38/12/834.abstract

--[[User:Z3329495|Z3329495]] 11:45, 9 August 2011 (EST)

----

Hi,

I choose to do a congenial abnormality more related to anatomy abnormality of the cleft and cleft pallets.

Articles:
* Review Article [http://www.ncbi.nlm.nih.gov/pubmed/21358192 PMID: 21358192]
*Research Article [http://http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124302/?tool=pubmed PMCID: PMC3124302]

--Ryan Tran 12:39, 9 August 2011 (EST)
----

Here are two more about Angelman Syndrome:

* Review: http://www.ncbi.nlm.nih.gov/pubmed/15668046
* Research: http://www.ncbi.nlm.nih.gov/pubmed/8958335

--[[User:Z3389343|z3389343]] 21:09, 9 August 2011 (EST)
----
hey, the second link seems to be broken?
--Z3329495 22:25, 10 August 2011 (EST)

----
Hi everyone,
I think we need to choose exactly what we are doing for the assessment before the week end.
I checked out holoprosenchephaly i think it is really neuro based and from what i have read ryan and i would like to do something more anatomical..
maybe we could try and decide on something that has all the components we are interested in and by the end of the weekend have made a decision.

I thought maybe Friedreich Ataxia kind of embodies all aspects we are interested in..
It is a defect of the nervous system which lead to muscular problems, special sensory organ problems, diabetes, heart problems and the genetics are well understood..
from what i see there is quite a lot of info on it..
so can we please come to a decision soon.. I think it will be easy to section think disease up eg history, embryonic development, the abnormality and when/where.how it occurs, the genetic component, neurological problems, skeletal muscle degeneration, structural/anatomical problems in the heart optic and auditory, diagnosis, treatment and what may happen in the future.
let me know what you think or if you have any other disease with similar categories so everyone in the group is happy with our choice.
--z3294943 17:37, 11 August 2011 (EST)

Jup I'm happy with that, as I've kinda mentioned already above, it's one of the topics that I'm not fuzzed about either way. If the others agree, I'm happy to go ahead. And thinking about it, it will probably be easier than deciding on a particular case of holoprosencephaly that will make everyone happy.
--[[User:Z3389343|z3389343]] 18:40, 11 August 2011 (EST)

Hey everyone this link from omim might give us better understanding of Friedreich Ataxia..[http://omim.org/entry/229300?search=Friedreich%20Ataxia&highlight=ataxia%20friedreich%20ataxias%20friedreichs]
If you guys have any other suggestions please let me know soon. As I would like to get start on categorising the aspects of the disease we choose and dividing them among the group.. have a good weekend! z3294943

----

read the link provided - looks good to me! seems pretty interesting in that you only get onset in late childhood to early teens. I'll be happy to do Friedreich ataxia.
--z3329495 22:20, 13 August 2011 (EST)

Ok great so have we decided on Friereich Ataxia?? DId you all want to meet in the computer room before the next lab in the break we have on thursday. Sorry i missed it last time but i thought we were meeting in the comp room and by the time i went to the lec room you were all gone :( I think we should discuss the aspects we want to research maybe we could all come with a few ideas that we each find interesting for thursday? What do you guys think? --Karmen Magi 11:09, 14 August 2011 (EST)

I came across Rubinstein-Taybi syndrome and thought that seemed quite interesting so I thought I'd suggest it: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002229/. Though if we're all happy with Friedreich's Ataxia let's go ahead with that. Aren't we missing somebody's opinion still?
--[[User:Z3389343|z3389343]] 15:02, 14 August 2011 (EST)

----
[[File:Oxidative Stress Response in Friedreich Ataxia.jpg|thumb|Oxidative Stress Response in Friedreich Ataxia]]
--Karmen Magi 11:43, 14 August 2011 (EST)

---

i think that's everyone? So we're settled on Friedreich's Ataxia?
--[[User:Z3329495|z3329495]] 10:17, 15 August 2011 (EST)
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[[File:Gene expression responses of Friedreich's ataxia.jpg|thumb|Gene expression responses of Friedreich's ataxia]]

Im ok with with Friedreich Ataxia it looks interesting I got nothing wrong with it.

--z3332250 23:48, 15 August 2011 (EST)

[[File:Pathogenesis of Friedreich Ataxia.jpg|thumb|Pathogenesis of Friedreich Ataxia]]

--[[User:Z3329495|Amanda Tan]] 11:30, 16 August 2011 (EST)

----
Ok great so i think we have finally decided! Are we still ok to meet between the lecture and lab this thursday? I think we should started working out what aspects of the disease we are interested in and what should be included on the wed page..
Could we all come with some ideas like pathogensis etc
let me know if you guys want to meet.. if so i think the computer room would be best. --Karmen Magi 20:20, 16 August 2011 (EST)

Yes that sounds good to me. And meeting in the computer room is fine, provided it is free, which I assume as it seemed to be last week? --[[User:Z3389343|z3389343]] 22:10, 16 August 2011 (EST)

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[[File:Frataxin mRNA levels and histone modifications on chromatin in the first intron of the frataxin gene in KIKI and WT mice.png|thumb|Frataxin mRNA levels and histone modifications in KIKI and WT mice]]

Suggested Outline:

#Background:
##History
##Epidemiology
#Genetics:
##Inheritance
##genetic expression (pre- and postnatally)
#Pathogenesis:
##first genetics aspect
##lead into physiology
#Pathophysiology & Clinical Symptoms - link them together
#Clinical aspect - split it into symptoms and complications
#Diagnosis (in table)
#Treatment (include genetic sreening)
#Current Research
#Glossary

*Amanda: pathpart of cardio & musculature, pathpart of pathogenesis, diagnosis
*Elina: Genetics, molecular & cellular parts of neurophysio aspect, current research
*Karmen: Neurophysiology aspect, background
*Ryan: Treatment, physiopart of pathogenesis, physiopart of cardio and musculature
everyone: make drawing, decide at the end which one we think is best, find video of possible

----

Karmen, i think this might be of interest to you. It includes historical information on Friedreich's ataxia: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062632/?tool=pmcentrez Friedreich’s ataxia: Pathology, pathogenesis, and molecular genetics]

Elina, this might be of use to you? [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373517/?tool=pmcentrez HDAC Inhibitors Correct Frataxin Deficiency in a Friedreich Ataxia Mouse Model] I tried reading through it but too much vital information about genetics just went right over my head. It looks promising in terms of research into treatment. Also: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859089/?tool=pmcentrez The Structure and Function of Frataxin] Possibly useful in genetics component when describing frataxin?

Novel treatment: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694693/?tool=pmcentrez Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARγ pathway as a therapeutic target in Friedreich’s ataxia]

--Z3329495 19:31, 19 August 2011 (EST)

Hi all, i'm having trouble locating information on the muscular effects of Friedreich's Ataxia. I've found much more information on the cardiac aspect of Friedreich's Ataxia but if anyone has found anything even mentioning muscular effects please let me know! all the papers i've located only mentions it in one or two lines.

--Z3329495 19:03, 22 August 2011 (EST)
Antioxidant treatment:
http://www.ncbi.nlm.nih.gov/pubmed/15824263

Prenatal detection of Friedreich: http://onlinelibrary.wiley.com/doi/10.1002/ajmg.1320340327/abstract

Pathology and pathogenesis of sensory neuropathy in Friedreich's ataxia.
http://www.ncbi.nlm.nih.gov/pubmed/20339857
The dorsal root ganglion in Friedreich's ataxia.
http://www.ncbi.nlm.nih.gov/pubmed/19727777
--z3294943 10:32, 25 August 2011 (EST)

Mitochondrial impairment of human muscle in Friedreich ataxia in vivo: http://www.sciencedirect.com/science/article/pii/S0960896600001085

Elina, if you could find this article it'd be a great help - A preliminary study of dynamic muscle function in hereditary ataxia.: http://www.ncbi.nlm.nih.gov/pubmed/7214252

--[[User:Z3389343|z3389343]] 17:23, 25 August 2011 (EST) so I can get access to this journal via Edinburgh Uni, but for some strange reason, there is no full text..? it's really weird. sorry :/

I found some things as well on Signs and a bit on heart:

'''[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC484058/?tool=pmcentrez Chest pain during exercise as first manifestation of Friedreich's ataxia.]'''<ref><pubmed>484058</pubmed></ref>

'''[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC482403/?tool=pmcentrez Left ventricular function in Friedreich's ataxia. An echocardiographic study.]'''<ref><pubmed>482403</pubmed></ref>

'''[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277199/?tool=pmcentrez Coronary disease, cardioneuropathy, and conduction system abnormalities in the cardiomyopathy of Friedreich's ataxia.]'''<ref><pubmed>1277199</pubmed></ref>

'''[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894724/?tool=pmcentrez Friedreich's Ataxia as a Cause of Premature Coronary Artery Disease]'''<ref><pubmed>1894724</pubmed></ref>

<references/>
----
Ryan Tran 10:55, 25 August 2011 (EST)
----

Carnitine therapy and muscular biopsies
http://jcn.sagepub.com/content/17/6/453.full.pdf+html
http://www.ncbi.nlm.nih.gov/pubmed/12174969
--z3294943 10:59, 25 August 2011 (EST)

Cognitive impairment in spinocerebellar degeneration. it could be interesting to talk about cognitive elements of FRDA
http://www.ncbi.nlm.nih.gov/pubmed/19295212

[[File:Chelator and vehicle effect on hematological indices.png|thumb|Chelator and vehicle effect on hematological indices. This is of note for using Chelator as a treatment option for FA (in particular cardiomyopathy).]]

For the glossary, i think we should bold the words we've put in the glossary for easy reference. what do you guys think? i've done two words in that style so see if you think it'll be a good idea to do.
--Amanda Tan 16:32, 25 August 2011 (EST)

For the current research: http://www.future-science.com/doi/abs/10.4155/cli.11.93?journalCode=cli
--[[User:Z3389343|z3389343]] 22:18, 25 August 2011 (EST)

Also, I think there will be different genetic factors that will have influences on the severity of the syndrome, I'll mention that in my genetics bit but won't go into detail about what the actual pathophysiology is, I'll just introduce it and then somehow mention that the pathophysiology will be dealt with in subsequent sections. Does that sound alright?
Here's an example: http://www.ncbi.nlm.nih.gov/pubmed/11269509
Also, if you find there's a genetic component mentionned, just let me know about that article and I'll make sure I cover the genetic explanation, so you can just mention that for details on the genetics, refer to the genetics section. Do you think that makes sense?

I think you could just add it into the pathophysiology part since you already read it? Right now i've just been reading all articles related to cardio and adding them into the relevant sections. Not that you should do other sections, but i think if you come across something relevant to another section it'd be easier if you just added it in rather than have the person doing that section read it all again to add it in?

Hey elina this might be helpful in understanding the frataxin gene. http://www.springerlink.com.wwwproxy0.library.unsw.edu.au/content/237n26h5wj083865/
-z3294943

Prenatal diagnosis FRDA http://www.ncbi.nlm.nih.gov.wwwproxy0.library.unsw.edu.au/pubmed/9742572
-z3294943

what is the intron-1 of the frataxin gene? the paper "The GAA repeat expansion in intron 1 of the frataxin gene is related to the severity of cardiac manifestation in patients with Friedreich’s ataxia" mentions it as an important part for ventricular hypertophy in relating GAA repeats in the intron-1 of the frataxin gene.

[http://www.ncbi.nlm.nih.gov/pubmed/21055653 Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment.] can someone please help me find this article? the UNSW database seems to have it but it won't allow me access to the full article even after opening it from Sirius.

explanation of an intron:

I guess you know how the coding bit of a gene is transcribed from DNA to mRNA (messenger RNA), which then gets translated into protein? basically, the preliminary RNA transcript you get is hardly ever translated into protein as such, there are a few modifications that happen first. one of these is that parts of the mRNA get cut out - this is called splicing. the bits that are cut out and not used for the translation are called introns. why exactly this mutation that sits in the intron, hence the part that is cut out, has such a big effect is quite interesting; haven't had the time to read thoroughly through the papers yet to find out why exactly that has an effect. but does this explanation help so far?
so intron-1 would be the first bit that is cut out of the mRNA molecule you get from the frataxin gene.

Hey guys!
here are some ways of diagnosis/characterising the progression of FRDA

* electromyogram (EMG), which measures the electrical activity of muscle cells,
* nerve conduction studies, which measure the speed with which nerves transmit impulses,
* electrocardiogram (ECG), which gives a graphic presentation of the electrical activity or beat pattern of the heart,
* echocardiogram, which records the position and motion of the heart muscle,
* blood tests to check for elevated glucose levels and vitamin E levels, and
* magnetic resonance imaging (MRI) or computed tomography (CT) scans, tests which provide brain and spinal cord images that are useful for ruling out other neurological conditions.
and i have been seeing this come up alot for treatment [http://www.ncbi.nlm.nih.gov/pubmed/21392622]
<ref name="PMID 21392622"><pubmed> 21392622</pubmed></ref>
--z3294943 19:39, 29 August 2011 (EST)

guys, you scare me with the amount of info you've already put up, but it's looking good! I really don't want to be lagging behind but I'm really stressing out with what I need to do this week, I'll try to put some stuff up but it won't be much. I promiss I'll work intensively on it the week it's due, cause before that I just won't have much time. sorry!
I do have a couple more genetics related references, they're on my own student page at the mo as I didn't wanna keep adding them randomly into the discussion, but thought it would be better to just put them here once I have a reasonable pool together that I've gone through and checked for relevance.

A possible teratogen? Taurine.. http://www.ncbi.nlm.nih.gov/pubmed?term=friedreich%20ataxia/embryology&cmd=correctspelling

Hi guys just with in text referencing eg... Tsou ''et al'', (2011) <ref name="PMID21652007"><pubmed>21652007</pubmed></ref>
lets just do the last name of first author et al and date + ref after!

Hey Ryan, could you do the table up (about the stuff carmen mentioned today) in diagnosis?

Hi guys! hope your enjoying you time off! I came across this book on pubmed it has PMID [http://www.ncbi.nlm.nih.gov/pubmed/20301458] i think we all should have a look it has alot of info!! hope you find it helpful! --z3294943 11:10, 5 August 2011 (EST)

Looks great! thanks! it'll help with the treatment section! --z3329495 22:09, 5 September 2011 (EST)

----

I've edited the treatment section but the person who filled in information on antioxidants please go through it and rewrite some of it. I didn't know all the information so i was hesitant to edit anything. Also include a sentence or two explaining why antioxidant treatment will work.
--z3329495 18:03, 8 September 2011 (EST)

----

Our references are missing?! i just noticed it! i fixed up some strange references, but it didn't fix it! if it doesn't reappear by next week we should talk to Mark.

--z3329495 19:51, 8 September 2011 (EST)

----
Hi guys,
Are we able to meet on the wednesday of next week?? I think we really need to go over this project.
We also need to add in more picture. So please if you find anything related to your subject please add it in. I am having trouble finding any picture that i am able to reuse so im having to draw alot of mine. so even if you cant find something please add a drawing or video.
just to reiterate what sections everyone is meant to be working on:

*Amanda: pathpart of cardio & musculature, pathpart of pathogenesis, diagnosis
*Elina: Genetics, molecular & cellular parts of neurophysio aspect, current research
*Karmen: Neurophysiology aspect, background, history
*Ryan: Treatment, physiopart of pathogenesis, physiopart of cardio and musculature
everyone: make drawing, decide at the end which one we think is best, find video of possible

Amanda are you doing diagnosis?? I think there is a few other ways that can be used like MRI/ECG. It might be interesting to add these in with pictures??
What do you think?
And Ryan I thought maybe we could add in some treatment option for the deformities like scoliosis? Ie surgery.. Is there anything to aid with pes cavus?
Have patient been able to survive heart transplantations? as this is the main cause of death would it help if they received a transplant?
I have also read some info about 5-hydroxytryptophan being used as an option of treatment.
Anyway let me know what you guys think?
--z3294943, 9 September, 2011 (EST)

Hi, yes i'm working on the table of stuff for diagnosis - its on my student page since i'm not done with it yet i didn't want to post it on the main page. Wednesday of next week is fine for me.

--z3329495 22:41, 9 September 2011 (EST)

Well for treatment i could only find clinical tested treatments for mainly cardiac related, but i think its a good idea for treatment for scoliosis. One more question has anyone done a hand drawing yet?.

----Ryan Tran 10:44, 10 September 2011 (EST)

I've put up the scoliosis one for the drawn image. also, there is new research into a different kind of iron chelation drug called deferiprone http://www.ncbi.nlm.nih.gov/pubmed/21791473 I've used a bit of this in the diagnosis for MRI (since this paper used MRI technology) but i think it'd worthwhile to put it into the current research.
--z3329495 14:18, 10 September 2011 (EST)

Is Elina working on prenatal diagnosis? I've included prenatal and genetic testing in the table i'm working on but i have no information on either. I'm just about finished with the table so i'll just post it on the main page to see how it looks like and what you guys think of it.
--z3329495 17:26, 10 September 2011 (EST)

----

What time we all meeting on Wednesday? and where?

Ryan Tran 23:42, 12 September 2011 (EST)

Hi guys,
unfortunately I am unable to come tomorrow i have some family issues. sorry!
but i think that thurs will be ok just for final lay out decisions. We need more pics.. so maybe we could all find 2/3 each i think think that would brighten up the page!!
If you guys still want to meet tomorrow you can.
z3294943

Hi guys, yes I (Elina) am working on prenatal diagnosis - do you want me to simply do it in the same kind of table format, and not have a subsequent section about it beneath? I think the table looks good, and I'd probably just be repeating myself.
--[[User:Z3389343|Elina Jacobs]] 19:14, 13 September 2011 (EST)

Hey Elina, could you just post a link to that paper with the muscular info here? I can get something knocked out as soon as.
--z3329495 13:26, 16 September 2011 (EST)

Hi guys, I heard today that monday maybe the last day we can upload something for the peer review. So if you have anything else you would like to add please get it done before then just incase!
I hope everyone has a great weekend! --Karmen Magi 20:16, 16 September 2011 (EST)

Amanda, here's the reference I was telling you about: Massimo Pandolfo Friedreich ataxia. Handb Clin Neurol: 2011, 103();275-94 PMID:21827895
It's a 20 pages review on what is known about FRDA so far, hopefully you'll find some useful stuff about the muscular aspect in it!

Ryan: here's the genetics treatment article I was talking about: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001958
let me know if you're struggling with the genetic "jargon" and I'll help you out.

--[[User:Z3389343|z3389343]] 11:44, 17 September 2011 (EST)

Hey Elina, there isn't anything much on the muscular system in that review but i found a paper which i cannot get access to on the UNSW database. If you could access it through your university it would help me a ton! [http://www.ncbi.nlm.nih.gov/pubmed/7634585 | Natural history of muscle weakness in Friedreich's Ataxia and its relation to loss of ambulation.]

Oh no, sorry about that! Also, your link doesn't work for me :/

Should work now - must be because i didn't put a space somewhere...

Sorry, but I can't get access to it either...

==Peer Assessments==
* Epidemiology was a bit brief and perhaps could be expanded on or supported with statistics from multiple nations etc.
* Aetiology section was really detailed and had a great span of information. Your image of the Friedreich’s pedigree could perhaps be slightly bigger on the page because I missed it the first time viewing your page.
* The neuropathology section was extremely ‘full’. The amount of text in heavy paragraphs may be off putting to some readers. A suggestion would be to break it down with the inclusion of tables and maybe dot-pointing the information that can be summarised.
* Maybe include a glossary so you can accommodate for all readers.
* It was good to see that you grouped your references :)
--[[User:Z3332629|z3332629]] 15:29, 22 September 2011 (EST)

Talk:2011 Group Project 7

2011-09-28T07:12:36Z

Z3279511: /* Peer review */

[[2011_Group_Project_7|'''Group 7''']]: [[User:z3291622]] | [[User:z3291643]] | [[User:z3387190]] | [[User:z3293267]]

{{2011GroupDiscussionMH}}

==Peer review==

'''Group 7: Peer Assessment'''
* The introduction is brief and informative and makes me want to read the rest.
* May be you can add an image in the introduction or history or both to make it even more engaging
* You history section is nicely to ready and captures my interest.
* While it is good to come straight to the point, your epidemiology section is really short
* The pathogenesis section is very informative and very good especially for people who are really looking to understand the disorder. May be a few subheadings on the way, just to make this text heavy section a little lighter.
* Diagnostic techniques would be nice in a table
* You still got some "double referencing", we have the same problem;)
* You glossary in comparison to most other projects seams to be relatively complex. Great
* The student images are well done!
* You have got a lot of information and I find it quite interesting. It seems a little text heavy overall. --z3279511 17:12, 28 September 2011 (EST)

'''Group 7 Peer Review'''
* Introduction is pretty short, and there is no image in the intro nor the history section. It makes it difficult to read. However, the information is quite adequate; perhaps mention the incidence in the introduction?
* History section is well presented, perhaps have an image or two around here. It'll help out :)
* Epidemiology section seems to just have the figures copied and pasted from these two presented papers. Can you explain the reasons as to why the current population is unknown? Surely there will be papers presented on these findings? Are there contributing factors to epidemiology and incidence; for example, why is the incidence so much higher in Denmark and Sweden; and are two countries directly comparable to '''Western Australia''', as opposed to the whole of Australia? There seems to be almost no thought placed in this section.
* Aetiology is sketchy, but will do. Is there more that can be said under this section?
* Pathogenesis section is well described and many of the terms are present in the glossary. There is a nice balance of diagrams and test images, and good referencing throughout these sections. Once again, a pet hate is the presence of the images on the left hand side of the page which breaks up the margin that is traced by the eye when reading the page, making it unnecessarily difficult to read the information. Also make sure that there is enough space left at the bottom of your section so that the signs and symptoms section isn't axed by the image.
* Signs and Symptoms is well described, and the use of the images also makes things much easier to observe. The subsections make it easier to observe as well. There are a few typos here and there; re-read your project and I'm sure you'll find them ;) Perhaps consider making complications an extension of the signs and symptoms section; it is too short to be a section by itself.
* Diagnosis is well presented - try using bold text for headings as it's simply easier to read. Once again, left-aligned images are a pet hate. Consider the related diseases section as a sub-section of diagnosis.
* Treatment and Management: Once again, absorb the next two sections and make them subsections. The information becomes a bit sketchy once we reach this stage of the project again.
* The current and future research would do well to link to some articles that have been published quite recently.
* Glossary has a nice layout and there are still some small issues in the referencing section that need to be addressed.
* Overall the project starts and finishes quite sketchily, but the detail in the middle of the project is impressive. Try to balance the entire project and ensure that each section has an even weighting. There is also a distinct lack of images in sections other than the pathogenesis section, and more information (let alone detail) needs to be added many sections. Images! Keep at it guys! :)
--[[User:Z3288827|Leonard Tiong]] 11:13, 28 September 2011 (EST)

'''Group 7'''

*Firstly, you don’t have a very good image/text ratio
*Introduction would grab my attention a little more with an image
*Try combining the text that you have for history in the timeline
*Epidemiology is not very extensive. You need to give more of a worldwide overview- also try and find information regarding Australia as a whole rather than just WA
*Obviously a lot of research has been put into pathogenesis- although there is a lot of information presented at once, try to break this up using bullet points etc
*Why have you included ‘Adapted from Smith JC, et al. Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet 2003;40:87-95 Adapted from Williams CA, et al Angelman syndrome: consensus for diagnostic criteria. J Med Genet 1995;56:237–8 ‘ in the text? This should be in your references
*Differential diagnosis and related diseases should be combined
*Genetic counselling has not been explained so makes little sense
*Current and future research should have subheadings

===Comments on Group Project 7===
'''Strengths:'''
*The history section was very well done. The block of text above the timeline provided just enough information and captured my interest. The timeline provided adequate summary of the major milestones in research of Angelman Syndrome.
*The glossary section seems decent.
*The student images are really good, especially the mechanism illustrations.
'''Weaknesses:'''
*Lack of use of subheadings. More subheadings can be used to break some of the sections up. It would not look so overwhelming then.
*Format of the overall page is not the best as it can be.
*There is some duplication in references.
'''Specific corrections:'''
*Just curious, why are males more predisposed to early developmental delay?
*It would be good to make the format of the stats under epidemiology consistent. Either fraction or ratio (I prefer ratio :D).
*Maybe for some of the tables, it will look better with an outline border so it is easier to see when the text in the table ends and when text in paragraphs starts.
*Use more subheadings e.g. Under Signs & Symptoms, the subheadings would be “Behavioural Characteristics”, “Communication Skills”, “Clinical & External Characteristics”, etc.
*Section under genetic counselling should come with an explanation or a paragraph of text. It will be good to elaborate further than just a table.

--Z3389806 05:53, 27 September 2011 (EST)

'''Group 7 assessment'''
*Introduction well established and clear though image can’t hurt
*History of angelmans would be lighten up with the image of the founder
*Epidemiology could be expanded a little more and even a map would make this section lively
*Aetiology description of the classes could have a paragraph explaining the table relating to the cause of angelmans
* Pathogenesis was a bit confusing with mostly genetic terms that were not found in the glossary. Otherwise structure is proper and well integrated with images
*Signs and symptoms table is confusing were addition of dot points in the table would be helpful
*Complications heading seems rather odd to be placed separately form the signs and symptoms, would be better added as a subheading.
*Diagnosis could introduce the diagnosis types in small paragraph, type are clearly expanded though image of the child could be made smaller
*Related diseases would be better in the symptoms with the complications as another sub heading instead of small niece headings
*Genetic council would be suited under the prognosis as chances of risks
*Research should be sub divided in to current and future research
*Referencing needs to remove repeats and link needs to be manually referenced. Glossary needs the addition of some genetic terms and method of indicating the glossary words to the web page.
z3332250 23:55, 26 September 2011 (EST)

'''Group 7 Critique'''

#• Introduction is good
#• History is really good. I like how you explain your table and introduce it
#• Epidemiology is too short. More statistics need to be included
#• Aetiology is ok
#• Pathogenesis is complicated. Maybe explain what the genes are and their function
#• Pathophysiology has the same problems as pathogenesis
#• The remaining sections are done pretty well. I wouldn’t really change anything
#• Great use of images throughout the project

--[[User:Z3289991|Robert Klein]] 08:54, 25 September 2011 (EST)

'''Angelman Syndrome'''

*You need to add an image in 'Introduction' or 'History', something to get the reader interested
*You kind of repeat yourself in 'History'. Try putting more information into the timeline, as opposed to the text.
*Epidemiology' looks a bit bare, is there a graph you can add or something? Also a bit more information can't hurt
*Pathogenesis is HUGE, looks like you've put a lot of work into it. But, it needs to be broken up a bit. Also, shrink that first image down, it's a bit out of place. Maybe try to use proper subheadings to break it up, not just bold. Are you able to make a table out of 'Animal Models'? Ie type (mice), advantages, disadvantages, diagram (if present).
*In 'Signs and Symptoms', you don't need the "Adapted from" you can just reference that. Or at least move it out of the table. I got confused and thought they were meant to be some of the symptoms
*But you've got some good information in the rest of the section, nicely arranged with the images
*Try shrinking the flow chart in 'Diagnosis', also reference it. It you made it yourself, say so
*Nice table for 'Treatments'
*Can you give a bit of an introduction to the table in 'Genetic Counselling', don't just jump straight into it
*Make sure you reference that first paragraph in 'Current Research', you can't just make statements without justifying them with articles
*Quite a good project, just need some more images and a bit of formatting

Group 7-
* Very text heavy!
* The introduction would benefit from an image
* You can probably put all of the history into the table. Having text then summarised in a table is a bit redundant
* Epidemiology is a little bland sorry. Table? Graph? Image? There is also not that much information there. And only including western Australia? I think you could find data for Australia as a whole
* There is A LOT of text in pathogenesis. It is good but could be improved by breaking it up a bit. Maybe bullet points?
* Animal models should be a new subheading
* ‘pathophysiology’ subheading is not needed. The information in it could be included in pathogenesis
‘Adapted from Smith JC, et al. Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet 2003;40:87-95
Adapted from Williams CA, et al Angelman syndrome: consensus for diagnostic criteria. J Med Genet 1995;56:237–8’
doesn’t need to be here. Just reference it normally. If this is your student drawn image I’m not sure it is enough. Making a table isn’t an “image”.
* Other than that I like the signs and symptoms section. Although I believe that the table is a little out of place
* Diagnosis section could be better formatted
* Differential diagnosis and related diseases would work well together under one subheading
* Referencing such as under the table in treatment is wrong. It isn’t done like this. You format it like everything else you reference. There is no place for the actual reference in the text. There should be a link for the reference in the reference section
* What is the genetic counselling section? It makes no sense and needs to be explained.
* Your project has obviously made progress but you need to look over it and make sure that things are formatted so that they are easily accessed, referenced properly and everything is in the right order.

'''Group 7'''
* Good use of headings, maybe you could add sub headings into beak up the text and make the page easy to follow.
* Intro section- maybe you could dot point the clinical features to make it easier to read.
* Some of your intro and history dates dont correlate but this might be a typing mistake? 1956 and 1965??
* Nice use of time line.
* The epidemiology looks a little bare. Is there anymore info that could be added.
* In the aetiology table make sure all your stats are referenced.
* UBE3A Ubiquitylation Pathway picture is extremely large, maybe you could resize this.
* I like the addition of animal models. With an amazing picture!
* Sings and symptoms section is very well put together structurally- good use of subheadings, pictures and tables.
* Are there anymore complication you could add for AS?
* Maybe you could tabulate your diagnosis section. I like the flow chart!
* Could have a common heading Related syndromes and differential diagnosis then use subheadings to split them up.
* Genetic Counselling unsure of what this section is and what the table relates to?
* I like that you colour scheme/tables are continuous through out the page.
* Just make sure you reference list isn't doubled for some references.
* make sure all acronyms are added to the glossary.
* Nice student illustrations.

'''Group 7 Assessment'''
*History section has almost no referencing at all. The information here definitely needs to be referenced. Pictures would also be helpful here.
*There is not nearly enough information in the Epidemiology section… This definitely needs some major work done on it. More information and pictures are needed.
*The student drawing for Chromosome 15 looks good, but where did you get this information from? Surely there’s a source you found the information from as to how to draw this figure. Shouldn’t you include that as well?
*The Aetiology section could also use more work as far as amount of information goes. Think about what else is important that you could add to this part. Also, more of the information in the chart should be cited, unless the whole chart is cited from one article, which should be shown.
*GREAT information given in the pathogenesis and Pathophysiology sections. Very well organized with superb supporting pictures and diagrams.
*The signs and symptoms chart seems a bit confusing… maybe because it’s too close to the information given below it, so they seem to run together. It would be helpful to space this out more. Also, not all the information given in the chart is referenced…
*Angelman Syndrome jpg needs correct referencing and also a descriptive sentence summarizing the information.
*Postnatal diagnosis needs referencing as well.
*The glossary would look more appealing if it used bullet points.
*It would be a good idea also to have the glossary terms linked with the words in the wiki page, so that the reader can easily get access to the word in the glossary.
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
*Overall some sections of this wiki are rather good and near completion, but others need some major work still. Once the changes are made I'm sure it'll be a great page!
--[[User:Z3391078|Z3391078]] 16:02, 27 September 2011 (EST)

*'''Introduction''': brief and to the point.
*'''History''': Very well explained, but references have been forgotten? Also, you mention two dates in the summary table, 1980 & 1982, that you don't seem to explain previously.
*'''Epidemiology''': Looks a little bit bare. If there simply is not much information about it, I wouldn't split it in three sections with each only containing a sentence, but rather write one short paragraph.
*'''Aetiology''': I assume the UBE3A gene lies within the 15q11.2-q13 region? You might want to specify that. Also, some terms should be linked to the glossary.
*'''Pathogenesis''': Watch out with your terminology - you say "its function is vague" - its function most likely isn't vague, but it is only vaguely known. Subtle, but important difference. Why do you mention LTP? Is LTP affected in AS? Otherwise, impressive detail in the mechanisms, well explained.
Not quite sure it makes sense to have the "animal models" subheading under pathogenesis. Maybe have a separate section, entitled, animal models used in the study of AS?
I'd also suggest having pathophysiology as a brief, but separate section from pathogenesis, and not have it as a subsection.
*'''Signs and Symptoms''': Not quite sure what the table is for? Having a table combined with text with subheadings seems a bit odd. The text is well explained. (Just correct obesity, not obeseness.)
*'''Complications''': A bit brief and out of the blue. How does it link in with the rest? Maybe include in under another section instead of have it as its own.
*'''Diagnosis''': Prenatal diagnosis looks good, very detailed. Just watch out with the chorionic villus sampling, not chronic villus sampling ;)
Postnatal: Revise your first sentence, doesn't quite make sense. Also, it seems a bit brief, maybe add a bit more detail?
Differential Looks fine.
*'''Related Diseases''': Might make sense to combine this with differential diagnosis? Also, considering pretty much exactly the same region is affected in PWS as in AS, you might want to explain more how this still leads to two separate syndromes.
*'''Treatment & Management''': Needs a bit more detail.
*'''Prognosis''': The information provided seems a bit random, thus needs a bit more explanations and how it relates to everything else.
*'''Genetic counseling''': No explanations provided, simple table. How are people supposed to understand this?
*'''Current and Future Research''': Fine.
*'''Glossary''': (Your definition of an allele is not quite right.) Otherwise looks good, though some more terms need explanations.
*'''References''': The links probably need fixing, and some papers appear several times in the list.

'''Peer Assessment: Group Project 7'''
*The history section is interesting and accessible but has very little referencing which detracts from its reliability.
*In the epidemiology section, a small table could be inserted for the demographic to make it easier to read.
*The aetiology section is clear and well balanced.
*The section on pathogenesis is really detailed and well written.
*Maybe you could include more information on how the different diagnostic techniques are conducted.
*The picture in the diagnosis section needs to be fixed so that it is displayed properly. Also the information with the pictures you uploaded in the diagnosis section need to include <nowiki>{{Template:2011 Student Image}}</nowiki>.
*In the glossary writing "A" above the group of A words and so on and so forth for the rest of it, would make it easier for the reader to quickly find the desired word.
*Some of the references are duplicated. They can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.
*Overall this group project is very thorough, giving good detail and adding appropriate additional sections which add to the clarity of the page and assist the reader in understanding more e.g. the external links, related diseases and complications.
--[[User:Z3217345|z3217345]] 09:39, 28 September 2011 (EST)

----
HELP. I made a flow chart for prenatal diagnosis but it is saved as pdf file. Does anyone know if I can upload a pdf file as an image? I'm too scared to do it in case it mucks up something. --[[User:Z3291622|N Fernando]] 21:51, 18 September 2011 (EST)

----
Hey guys, I've deleted the incidence and gender section from the introduction, caus it is outlayed in the epidemiology section anyway, and we would have had different statements.--[[User:Z3387190|Theodora Retzl]] 19:27, 18 September 2011 (EST)

Hey. I can't find the original article written by H, Angelman but I found a review on that original article published in 2008. It has the same title as the original angelman article. Here's the link:
http://onlinelibrary.wiley.com.wwwproxy0.library.unsw.edu.au/doi/10.1111/j.1469-8749.2008.03035.x/pdf
Can I use this?
It's more of a commentary of the original paper than a review.
--[[User:Z3291622|N Fernando]] 11:03, 18 September 2011 (EST)

----

Hey, maybe from now and til peer assessment day, we could work on the glossary? It's really hard to find a suitable image for intro and history. Nimeshi, have you managed to find the original article of Dr Harry's? We should probably ask Dr Hill first if getting a snapshot of the article isn't violating the copyright of the article. --[[User:Z3291643|Sang Lee]] 23:17, 17 September 2011 (EST)

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Hey guys, I know the history section is lengthy, don't worry I will shorten it. Julia, is this what you meant? I used information from both the sources. --[[User:Z3291622|N Fernando]] 12:47, 12 September 2011 (EST)

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Also, do you guys reckon we should put an image of Harry Angelman in the history section? --[[User:Z3291622|N Fernando]] 22:07, 11 September 2011 (EST)

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Hey, Julia, Yes I'll look through the articles and fix up the diagnosis part.
--[[User:Z3291622|N Fernando]] 20:22, 11 September 2011 (EST)

----

Hey, Julia, thx for the link. I put up some contant to my section and shifted the AS- PWS image there. I have also added some information to the pheno-genotyp correlation part, and the glossary. It would probably be good to focus on getting the page content we have so far and the sub- headings in order and work on what we have so far, rather than to add new content. Maybe delete the epidemiology section, as there is not enough specific information available that would make senece there (and is in the introduction anyway), what do you think? --[[User:Z3387190|Theodora Retzl]] 19:49, 11 September 2011 (EST)

Hey, Nimeshi, http://onlinelibrary.wiley.com.wwwproxy0.library.unsw.edu.au/doi/10.1002/ajmg.c.30278/pdf , http://www.angelman.org/stay-informed/facts-about-angelman-syndrome---7th-edition/harry-angelman-and-the-history-of-as/ , its good for history (like about Ellen Magenis, etc). Maybe we could have a paragraph giving a brief history then a timeline? --[[User:Z3291643|Sang Lee]] 17:28, 10 September 2011 (EST)

----

Forgot something, Nimeshi, do you think you could take the liberty of breaking down the diagnosis into pre and postnatal, just cos I remember reading about diagnosis and lots of papers have broken them down like so. I also think it won't hurt to have a picture of EEG or graph of AS patients, showing pheno-geno correlations, etc. I also think it'd be good to have more text accompanying the table for Treatment and Management, I knoe there's no treatment as such for AS, so maybe we should write that? Thanks
--[[User:Z3291643|Sang Lee]] 14:06, 8 September 2011 (EST)

----

Hey, I've added some more info to my section, but need to reupload the image cos I've made a spelling mistake, what do you guys think? Please feel free to make suggestions to refine the image. Also, Theodora, do you think the image of the PWS and AS patients would be better positioned in the signs and symptoms section instead of the intro? I think the intro image could be more general, like a photo of Dr Angelman,etc.. Also, is PWS one of the differential diagnoses of AS? I don't think I put it up there with the other diseases, if so, could the person who added it in also put in the reference for that? This is for Theodora and Nimeshi, PMID 12566516, I think we should lay out the symptoms table like they did here and have a spider diagram style for diagnosis. Just remember to acknowledge them by saying 'Adapted from...', at the bottom of table, etc. Thanks
--[[User:Z3291643|Sang Lee]] 13:46, 8 September 2011 (EST)

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Just posted up the pictures. If you're not satisfied about the chromosome 15 pic, just let me know and I can change it up for you.

--[[User:Z3293267|Eugene Chan]] 12:06, 3 September 2011 (EST)
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Hey guys just a quick note, we should refrain from using the words "mental retardation" as this could be deemed offensive. Use "intellectual disability" as that is a more common term now used in Australia. Also use "learning difficulty" or "developmental delay". We should also encourage the use of person-first language e.g., "a child with an intellectual disability" rather than "intellectually disabled child". This promotes the idea that a person comes before their disability.

Sorry to be very specific here, but if this is going to be a public-access website we should use the appropriate terminology.

Thanks
--[[User:Z3293267|Eugene Chan]] 10:41, 3 September 2011 (EST)
----

Yeah, sure thing. Nimeshi,I've put your timeline into a table, I've given up on trying to do a graphical timeline.
*PMID 12566516, I found this to be really good for Clinical features of AS (Theodora), I really liked the table formatting. It's relevant for Differential diagnosis, genetic counselling and phenotype/genotype correlation. It's also got a section on Management as well for Eugene.
*PMID 20445456, for signs and symptoms, geno/pheno correlation, diagnostic testing methods+prenatal diagnosis, treatment and management
*PMID 15668046, genetic diagnostic testing and clinical features (again in a table format according to frequency)
Also, I think we could also add Phenotype/genotype correlation and Animal models as subsections, what do you guys think?
--[[User:Z3291643|Sang Lee]] 23:12, 1 September 2011 (EST)

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Hey, I think it makes more sense to compare the symptoms in adults and children in a table, rather than to draw a timeline. There are no research articles really focusing on the symptoms in every age of the patients, and the changes from year to year.--[[User:Z3387190|Theodora Retzl]] 21:13, 1 September 2011 (EST)

----

Hey, I've just typed in some of the information I've collected so far. I'll definitely be writing a lot more on aetiology and pathogenesis, but I thought it won't hurt to contribute to other subsections as well. I'll add the references and glossary words bit later today. Please feel free to make

==Peer Assessments==
* Your pathogenesis section was good, it was thorough and went into significant depth. The use of animal models and the support of recent studies was also a positive aspect
* The photo of the ub pathway should be smaller or be placed as a thumb nail as it isn’t something that directly contributes to your defect
* It is a shame that there is such a large gap in your Aetiology section, but i do realise that this is slightly out of your control due to wiki formatting issues.
* I personally found the signs and symptoms section to be slightly confusing in format. Perhaps placing this info into a table would make it more concise.
* Treatment and management section had lots of detail and highlighted a few different methods which gave a good insight of the current technologies and strategies out there in the market.
--[[User:Z3332629|z3332629]] 15:27, 22 September 2011 (EST)

Talk:2011 Group Project 6

2011-09-28T07:11:38Z

Z3279511: /* Peer Review */

[[2011_Group_Project_6|'''Group 6''']]: [[User:z3290841]] | [[User:z3291317]] | [[User:z3291324]] | [[User:z3291423]]

{{2011GroupDiscussionMH}}

==Peer Review==

'''Group 6: Peer Assessment'''
* It would be good to see more images
* The introduction would be more engaging if it had an image
* The history section is informative however would be nicer in a chronologic fashion. May be a table?
* The extra surgical history makes it clear that surgery plays an important role. Good
* Signs and Symptoms and genetic abnormalities are good overall. Many of the terms need to be added to the glossary though and it might be better to put aetiology first.
* It's a quite big and text heavy table in your diagnostic section. May be you can make it shorter, put pictures in

* I found quite a few words that should be in the glossary
* There is no title for your reference section and it looks like you should have more references for the amount of text that you have written
* Overall your page is very informative, good content. You need more images, appropriate referencing and a more complex glossary. --z3279511 17:11, 28 September 2011 (EST)

'''Group 6 Peer Review'''
* Good introduction, although an image straight up would be nice!
* History is presented well, although a table format at the end that summarises everything you have said would be nice. Also, does the history stop around the 1950's? It seems like there has been nothing done on it until 1970/1980? Hence, the table format would be nice if it appears that I've missed information.
* Epidemiology section is really quite short. Is there nothing more that can be said on it? Does it have preference to specific race?
* Signs and symptoms - from the way that the page is formatted it appears that you've gone down onto the level 4 headings with 4 ='s paraphrasing each heading. Try to use 3 or so just to make sur e the headings are larger and each subsection can be identified.
* The genetics/aetiology section should be explained better; whilst this is aimed at academics, it is almost impossible to understand the information pertaining to the genetics section.
* The pathophysiology and abnormalities section is well explained, and the diagram is excellent to show exactly where the problem lies. A well done section, and a well-selected image for the blood flow patterns.
* Diagnostic tests: Still need to insert those images on the right hand side column! Also, ensure that the referencing is done in the correct format - this section still needs work.
* Treatment/Management section is done well, with a good balance between text and table.
* Current and Future research: Perhaps more dates? The formatting here also needs to be fixed up, and try to have dates on the papers that you are quoting from (although I understand it's difficult without the references in place)
* The glossary section needs more terms added to it! Especially from the genetics/aetiology section which is already terribly difficult to understand.
* Referencing section is quite short - but understandably the whole project feels like the referencing just needs to be finished.
* Overall a nice-looking project with a lot of promise. The spacing and format of the project makes it easy to read - perhaps more images and the use of some tables might also assist in the presentation of this project.
--[[User:Z3288827|Leonard Tiong]] 10:49, 28 September 2011 (EST)

'''Group 6'''

*My first impression is that this project is lacking images. There is way too much text in comparison to images.
*An image would nicely complement the introduction
*I feel that history would work better in a timeline
*Epidemiology needs a table/graph
*Good links in signs/symptoms although another image would be nice
*Genetics needs to be explained a little better
*Student drawn images were great- obviously a lot of effort has been put into these
*Diagnostic test table needs an image and needs to be referenced properly
*Again, an image is needed for prognosis
*Glossary needs to be extended
*Overall a good project but you need to fix a few things

'''Group 6'''

*Introduction: the contend is ok, but the structure could be clearer

*History: too text heavy, a timeline would be nice

*Epidemiology: more content would be good

*Symptoms: the picture could be more general

*Genetics/ Aetiology: the structure could be better, maybe use some more subheadings, and put the gene profile in tables

*Pathophysiology: you need references

*Diagnostic tests: why does it say “insert images”, that should be fixed

*Treatment/ management: looks like there are some references missing? Deleate “Want to learn about more surgery and treatment methods?”, the contend is good, types of shunt would look better as a table

*Prognosis: references missing? good use of subheadings,

*Glossary: incomplete
--[[User:Z3387190|Z3387190]] 21:52, 27 September 2011 (EST)

'''Group 6 peer assessment'''
*Introduction is clear though lack images where a image of example of a blue baby would suffice
*History begins clearly though becomes about surgical history instead of the disease, where time line is not even present of how understanding of this disease improved.
*Epidemiology should be expanded either the genetics of the disease, in general have more information of the causes, incidence and distribution of the disease.
*Signs and symptoms poorly structured and requires more images also doesn’t have an introduction to the signs and symptoms. Although the extra links to comparison of the heart is useful and nicely used.
*Pathophysiology should add supplementary information to back up all the information.
*Diagnosis please add the images, while there is the content though no image following also first box has “insert text” very confusing.
*Treatment/management indicate the separation of surgery and other treatment types in the introduction which is lacking otherwise all is A ok
*Glossary needs to be referenced to other sections of the web page also expanded as most language used is unknown without a dictionary.
*Referencing needs to be fixed as links is not proper referencing also the repeats need to be removed
z3332250 23:53, 26 September 2011 (EST)

===Comments on Group Project 6===
'''Strengths:'''
*The flow between sections and sub-sections is good with appropriate placements of headings and sub-headings.
*Some of the references have good use of multiple referencing so as to avoid duplication.
*The external links under signs and symptoms is very apt and will interest readers.
'''Weaknesses:'''
*Almost half of the references are not properly formatted.
*Some of the words that should be in the glossary are not under that section e.g. Velocardiofacial, Conotruncal, Hypothyroidism, nengoitrous, embryotoxon.
*Punctuation in some sections can be better.
'''Specific corrections:'''
*”muattional” under 22q11.21 sub-heading is spelt incorrectly.
*”cyamnosis” under signs and symptoms is spelt incorrectly.
*”enlargenemt" under clubbing is spelt incorrectly.
*Insert a timeline under history to provide a summary.
*It might be better to have genetics section before signs and symptoms.
*Under Treatment/Management, it will be good to put “medical therapy”, “palliative procedures” and “surgery” as sub-headings.

--Z3389806 08:03, 26 September 2011 (EST)

'''Group 6 Critique'''

#• Introduction is ok, however it needs to be structured a lot better than what it is
#• History is interesting
#• Epidemiology needs a lot more detail. A few lines is not good enough
#• Signs and Symptoms is ok
#• Genetics needs to be explained a lot more clearly than what it is
#• Abnormalities is ok
#• Diagnostic tests table is impressive
#• Treatment/management section is very good
#• Prognosis and future directions section is great
#• Glossary is incomplete. Check the first term and fix this

--[[User:Z3289991|Robert Klein]] 19:05, 24 September 2011 (EST)

'''Tetralogy of Fallot'''

*An image in the 'Introduction' to introduce the topic would not go astray
*"...Infants turning blue when crying..." middle of sentence, no capital is required. What is tet spells?
*History might work better as a timeline, otherwise at least '''bold''' the dates so I know whats going on
*Surgical history has been covered through most of 'Contemporary History', there's not a whole lot of point having two subheadings here
*The 'Epidemiology' is a bit sparce? Are there no other stats to add to this section?
*There is a lot of good in information in 'Genetics', but I think you need something to break it up, you've got the images of the chromosomes (which are very good), but can you find other images? Maybe put some of the information into a table?
*The 'Abnormalities' section looks really good. The information is clear, succinct, with good illustrative images
*Though in number 4 under 'abnormalities' can you give a quick definition on what hypertrophy actually is?
*Diagnosis is poor, it isn't referenced and clearly isn't finished ("insert text here"). This does not flow on from the rest of the page at all. It looks a bit dry with no colour or images
*There are minimal references in 'Treatment', surely you didn't all that information out of only a few papers?
*I like the table in 'Treatment'
*Can you make the subheadings in 'Treatment' as actually subheadings as opposed to just bold?
*It's coming along, but you need more images! It starts off well, but there aren't many toward the end.
*Make sure you finish the project off!

Group 6-
* No way near enough images. As I scrolled through there was HEAPS of text and only a few images, all of which are on the right hand side. It would be better if they were scattered around
* An image in the introduction would be helpful
* What are ‘tet spells’? mentioned in the introduction (described later but when seen in the introduction it looks like a typo)
* History would work better as a list of dates rather than paragraphs. I do like the section at the top with the quote though
* Epidemiology needs an image- perhaps a table or a graph.
* Signs and symptoms could do with another image to visualise the clinical manifestations
* I really liked the audio clips but the first one didn’t work on my computer? I couldn’t hear anything. Not sure if it was just me
* I think you can come up with a better way of formatting the genetics section. Maybe a table? The information is good it just looks a bit funny
* The pathogenesis doesn’t actually say HOW is happens in infants. Is this a condition formed during embryonic development or after?
* The diagnosis section is far from complete. This needs to be corrected
* Diagnosis section is also not referenced properly
* Why is there a reference at the bottom of the diagnosis section?
* As funny as this was: ‘Want to learn about more surgery and treatment methods? Check here!’…. maybe not appropriate sorry. It should be a little more formal. If you want the reader’s attention- try colour.
* Prognosis- image needed please. Maybe a graph?
* The glossary also needs to be extended
* The references need to be tidied up- there are also not many?
* You need to reference your images properly. ‘normal fetal blood flow and tetralogy of fallot’ is an example. You have but the copyright but not the reference. The web address is not a reference
* You are clearly on your way with the project but more work is required. You need to FINISH the content and format it a little better with more images.

''Group 6 Assessment'''
*First, I’d like to note good job on using a reference more than once in the correct way instead of referencing the same thing multiple times. At least this is done in the first few sections. First time I’ve seen this done correctly!
*The introduction, however, has no references whatsoever. Where did this information come from?
*It might also be good to add a simple picture in the introduction section so it looks more appealing.
*Good information included in the history section. It might look better if this were laid out in a bullet format though.
*The epidemiology section looks rather bland. Not only is there not a picture, but there also isn’t very much information included. Think about what else you could include here or what you could go into depth about.
*The signs and symptoms section has good information, but it might be a good idea to represent this information in a better format, possibly in a chart, with pictures of each symptom included in the chart.
*Finger-clubbing.jpg also needs a detailed description still.
*Good organization and format under the Genetics section.
*Under the pathyphysiology and Abnormalities section there are no references made. Where did this information come from? Diagnostic Tests and Treatment also needs more referencing.
*Pictures still haven’t been inserted into the Diagnostic Tests chart.
*More referencing is needed for the Prognosis section. Also, does the glossary terms need to be referenced?
*It would be a good idea also to have the glossary terms linked with the words in the wiki page, so that the reader can easily get access to the word in the glossary. References 7-14 are the same reference. Fix these so they are under one single reference number.
*For the references given throughout the wiki, there isn’t any consistency in how the [#] is given. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*Overall, there is a substantial amount of information given within this page, which is good. I like the basic format of everything and most of the pictures which are included. Just work on weaving everything together better and referencing things correctly. Good job!

--[[User:Z3391078|Z3391078]] 15:32, 27 September 2011 (EST)

'''Group 6'''
* Nice overall structure and good use of headings and subheading. It gives the page a nice flow.
* INtroduction is nice and straight to the point and gives the reader a good overview of your topic.
* I like the historical section with interesting subheadings used, maybe you could add a timeline just to simplify the info.
* Signs and symptoms nicely arranged. could you add some more pictures here?
* Pathophysiology and Abnormalities section need to have the references accompanying the information. Just so the read can identify where all the info is from.
* The diagnostic tests table would be nice with some colour and when the images are it will look complete. It's a little text heavy for a table maybe try bullet points. also the referencing system has changed in this table? and a little unsure of the reference at the bottom of the section?
* Treatment/Management section is nicely arranged.. could you add another picture here just to compensate for the amount of text. the table really brightens up the page!
* Future directions section is nicely summarised and I like the tone of voice used here. just make sure the referencing is correct as it is a little confusing and interrupts the flow of the section.
* Maybe the use of similar tables and colour scheme will increase the continuity of the page.
* Make sure your references are not doubled in the list.
* Ensure all of your pictures are correctly referenced.
* Make sure all acronyms and scientific wording is in the glossary.

*'''Intro''': What's a tet spell?
*'''History''': Very good in general. Not sure it makes sense to split it into 2 parts, with surgical being separate? I think it would work just as well combining the two.
*'''Edidemiology''': Looks fine
*'''Signs and Symptoms''': Otherwise good, but considering you have a whole subsection entitled clubbing, I'd suggest explaining what it is right there, and not just in the glossary.
*'''Genetics/Aetiology''': Love the detail and depth, though the more technical terms should be explained in the glossary. Tiny comment: "there is only a single copy of the gene in one allele" - I know what you're trying to say, only one allele is functioning, but saying it like this kinda means, this allele only has one copy of the gene, whereas usually there are multiple copies of a gene in one allele, which is, as far as I know, not the case (that would just be contradictory, as an allele is a copy/varient of a gene).
*'''Pathophysiology and Abnormalities''': Very good, nice use of figures.
*'''Diagnostic Tests''': Not sure I like the table. It is just a hell of a lot of text... in a table. It doesn't really help give an overview, maybe just have subheadings, with (once you have an image) a picture on the side? Also, referencing needs fixing.
*'''Treatment/Management''': Very good, nice amount of detail. Again not sure a table is required. Also, the colour is a bit in your face, but that might just be me. I like the links at the end.
*'''Prognosis''': Content seems fine. A bit odd there's only one reference?
*'''Future directions''': Otherwise seems fine, though referencing needs fixing.
*'''Glossary''': A bit poor. More technical terms need to be explained.
*General: The last few sections lack some figures, it is just a lot of text. The content in general (as in of the whole project) was really good, so well done!

'''Peer Assessment: Group Project 6'''
*The introduction and the section on pathophysiology and abnormalities have no references. This needs to be rectified.
*The introduction and some of the history section have short paragraphs that are only one sentence long and would be improved, both for formatting and information purposes, by incorporating them into the rest of the information.
*Inserting a small timeline in the history section would make the sequence of events more accessible to the reader.
*Some sentences are too long such as, 'Children with TOF don’t grow at the rate of normal children as whilst breastfeeding in infancy, the babies would get tired quicker and during the growth of the infant, normal functionability of the heart and oxygen saturated blood is needed for proper growth'. This sentence could be broken up and also improved by a greater explanation of why the process of growth is abnormal in TOF.
*Maybe explain more about what 'clubbing' is.
*In the diagnostic tests section the images need to be inserted and needs to be properly referenced. The information is good but as noted one section is totally void of text.
*The section on prognoses needs proper referencing.
*The section on future directions is well written, however the referencing needs to be adapted to the wiki format.
*Under the information in some of the images you have uploaded such as in the portait of A. Fallot, you still need to add <nowiki>{{Template:2011 Student Image}}</nowiki>.
*The project is informative, however formatting and referencing are issues that need to be addressed.
--[[User:Z3217345|z3217345]] 22:23, 27 September 2011 (EST)

Test:

{| style="color:black; background-color:#ffffcc;" width="85%" cellpadding="10%" cellpadding="15%" cellspacing="0" border="1"
| colspan="2" | '''Diagnosis'''
|}

--[[User:Z3291423|z3291423]] 11:57, 22 September 2011 (EST)

Hey Jaz, thanks for letting me know...my english can fail me at times.....lol...fixed it up... regards--[[User:Z3291317|Z3291317]] 18:49, 18 September 2011 (EST)

Hey guys! i just realised that the caption of helen taussig and ballot say portraight....not PORTRAIT!?!! i tried to change it but it don't really know how..anyone have any ideas to this?! :S thanks --[[User:Z3291423|z3291423]] 00:06, 17 September 2011 (EST)

Table Test! --[[User:Z3291423|z3291423]] 22:16, 16 September 2011 (EST)
{|
|-bgcolor="# 99FFFF"
| '''Type of Shunt'''
| '''Description'''
| '''Reasons for it not being used'''
| '''Image'''
|-
| Pott’s Shunt
| This shunt is a connection that is established between the lower part of the Aorta (on the left side of chest) to the left branch of the Pulmonary artery.
| The shunt has a tendency to increase the pulmonary blood flow and it is also very hard to close when complete repair is undertaken
| Insert image
|-
| Waterston Shunt
| This shunt was placed between the back of the Aorta, to the right branch of the pulmonary.
| This shunt’s use is more suited to those with pulmonary artery stenosis and also the procedure is quite difficult to perform.
| Insert Image
|-
| Glenn Shunt
| The Super Vena Cava is anastomosed via a shunt to the right pulmonary artery.
| This procedure is very complicated and difficult to perform, also complete repair becomes a laborious task.
| Insert image
|}

Table test (fingers crossed!) --[[User:Z3291324|Jacqueline Ellero]] 10:49, 15 September 2011 (EST)

==TOF diagnostic techniques==

{|border="1px" cellspacing="1" align="center" cellpadding="5" style="background:seashell"

|+ This table describes different diagnostic tests for TOF
! Diagnostic technique !! How the procedure works !! Presentation in TOF patient !! Image

|-
|Physical examination
|TOF is often diagnosed during fetal life by echocardiography (Apitz, Webb, & Redington, 2009). If TOF is not detected during fetal life, certain signs and symptoms at birth may alert the need for further investigation. These signs and symptoms include mild to moderate cyanosis, which worsens when the baby cries, difficulty feeding and difficulty gaining weight. However, TOF often goes undiagnosed until adult life. Most adult patients will appear normal, however, some may present with cyanosis and clubbing of the fingers. The jugular venous pressure is usually normally (raised jugular venous pressure often indicates right ventricular failure). If the aorta is pushed to the right (so it is continuous with both the left and right ventricle), a lift below the right sternoclavicular joint may be noted. (Somerville, 1993)

|Insert text here
|Insert physical examination image
|-
|Heart murmurs
|Heart murmurs are sounds caused by the turbulent flow of blood. They are heard using a stethoscope. They are often the result of problems including valvular stenosis (narrowing of valves), valvular regurgitation (leakage of valves due to incomplete closure) or defects in the heart wall allowing blood to flow in unusual directions.
|Examination of the heart of a patient with TOF may reveal a loud second heart sound (produced by the closure of the pulmonary valve). A harsh systolic ejection murmur may be heard and a palpable thrill may be felt along the left sternal border. These sounds occur because the pulmonary outflow tract is obstructed. Although this murmur is often present, sometimes it may be short or difficult to hear and is often missed on physical examination. A pansystolic (occurring throughout the whole of systole) murmur may also be heard. This type of murmur occurs due to the ventricular septal defect between the left and right ventricles. The increased pressure in the left ventricle forces blood back into the right ventricle, causing a murmur, which lasts the whole of systole (contraction phase). http://ccjm.org/content/77/11/821.full
|Insert heart murmur image
|-
|Electrocardiogram
|Once TOF is suspected, electrocardiogram and chest radiographs are performed. Electrocardiography is used to assess the electrical activity of the heart. The electrical activity is detected by electrodes, which are placed on the skin of the patient and recorded by an external device.
|The electrocardiogram is extremely important in detecting a right bundle branch block (a block in the electrical conducting system of the heart), which is common in patients with TOF. An electrocardiogram will also reveal a heart that is deviated slightly to the right and an enlarged right ventricle due to the ventricular hypertrophy.(Somerville, 1993)
|Insert electrocardiogram image here
|-
|Chest radiograph
|A chest radiograph (or chest x-ray) uses ionising radiation to develop an image of the patient’s chest. It is used to diagnoses many conditions including the thorax and structures within the thoracic cavity including the heart, lungs and major blood vessels entering and leaving the heart. Chest radiographs are often used to screen for certain diseases but further tests are required for a definitive diagnosis.
|In a patient with TOF, a chest radiograph will demonstrate a prominent right ventricular shadow, giving the heart a boot-like appearance, which is typical of patients with TOF. The right ventricular hypertrophy causes the apex of the right ventricle to rise on top of the relatively unfilled left ventricle, giving the heart its boot-shaped appearance on examination. (Bailliard & Anderson, 2009) The radiograph will also show a right-sided aorta in approximately one-quarter of patients. (Somerville, 1993)
|Insert CXR image here
|-
|Echocardiogram
|An echocardiogram (also called a cardiac ultrasound) is performed to confirm the above findings. Echocardiography uses ultrasound to produce two-dimensional (and now also three-dimensional) images of the heart. It assesses cardiac tissue, valve function, the velocity of blood flow and any abnormal communications within the heart.
|The echocardiogram identifies important abnormalities of the heart including obstruction of the pulmonary outflow tract, the size of the pulmonary arteries, the degree of aortic override and the size of the defect in the interventricular septum. (Bailliard & Anderson, 2009)
|Insert echo image here
|-
|Magnetic resonance imaging
|Magnetic resonance imaging (MRI) is evolving as the most important technique for evaluating the size and functioning of the right ventricle. An MRI machine uses a magnetic field to produce a detailed image of the scanned area of the body. It is especially useful in viewing soft tissues as it provides greater contrast than techniques such as x-ray.
|MRI’s are important in assessing pulmonary valve competence and the severity of regurgitation (the amount of blood that flows back into the right ventricle due to the incomplete closure of the pulmonary valves) in patients with TOF. It can measure the volume and mass of the right and left ventricles and can assess the degree of pulmonary outflow tract obstruction. Finally, MRIs are important in measuring the degree of ventricular septal defect. (Somerville, 1993)
|Insert MRI image here
|-
|}

Hey peeps just put a intro just as a draft...tell me what you guys think of it. Edit it as you may wish.... And Jaq, if you describe briefly how each test works it would be good, regards --[[User:Z3291317|Z3291317]] 23:16, 14 September 2011 (EST)

hey jaz, ive fixed up the diagnosis, but feel free to add anything! or let me know if you think i should add anything. --[[User:Z3291324|z3291324]] 10:06, 14 September 2011 (EST) should i describe each diagnostic test!!??--[[User:Z3291324|z3291324]] 10:07, 14 September 2011 (EST)

Hey Guys! just added a very few changes, links etc to treatment. I've begun to add make a bit of notes on diagnosis that could just add a bit of detail to the diagnosis section. just wondered if any of you guys know what particular section of the ECG indicates...Left Ventricular Hypertrophy etc maybe ill call up a cardiologist :P nonetheless ill add references and some things to diagnosis tmrw night. regards, --[[User:Z3291423|z3291423]] 00:15, 14 September 2011 (EST)

Hey jaq. no particular order, the referencing system in the wiki automatically arranges it according to the order it is found in the text. In text referencing is NEEDED, lol. Type in the text title into Pubmed and when the article is found, the pmid code will be found at the bottom of the abstract for that article. if you cant figure out how to reference, put in the pubmed ids as intext citations then ill fix it for you...Make pathophys a bit more simpler, but do not compromise the anatomical words, i.e. write the anatomical word, then write in brackets what it means, eg. ''...anterolaterally (at the top away from the midline)'' is just an example (a crap one to lol). Also did you find any new info for diagnostic tests? and Rom, why did you remove info from the 22q section???? regards --[[User:Z3291317|Z3291317]] 22:02, 13 September 2011 (EST)

hey guys, quick question about the referencing. are they in any particular order? or should i just add mine to the end of the list? and do we need to do in-text referencing?? and how do you find the pmid code? also, any suggestions on how i should improve pathophys? ie make it more anatomical based or reword it so its simpler? thanks --[[User:Z3291324|z3291324]] 21:30, 13 September 2011 (EST)

Hey Rom, looking good thus far. if you need help with referencing even after trying so much i can help you during the 1 hour we have afta the lecture tomorrow to go through and help you fix em up... its a bit tricky but can get a handle of it... --[[User:Z3291317|Z3291317]] 20:37, 12 September 2011 (EST)

Hey guys sorry for the delay, but I'm slowly uploading all my stuff up. I'm just a bit confused about how I do the reference tag thing, as you can see there is a massive red thing on our reference list. I tried copying how you guys did it but I failed at it. I'll be posting some more in the next couple of hours, I just need to get a hang of this coding thing gah!
--[[User:Z3290841|z3290841]] 19:36, 12 September 2011 (EST)

hey rommel, we really need to see your part of the project and get your suggestions on parts we have done because its due on thursday --[[User:Z3291324|z3291324]] 19:16, 12 September 2011 (EST)

Hey Peeps, Just reconstucted the referencing so they are done exactly as it should be... Also just uploaded a pic of Mr fallot Himself without any copyright restrictions ( aha ow ye ow ye, took me long before i found it lol). I left the intext references jac and jaz put in their sections for future reference. Thats about it for now... Jaz i hope u liked the pics i showed you, and i hope rom is going well in his section... See yous soon... Regards --[[User:Z3291317|Z3291317]] 17:36, 11 September 2011 (EST)

update: uploaded the drawn images, took ages but its finally done :) and I've just finished the future directions :) so it should be fine to edit and look over in the next couple of days!
regards --[[User:Z3291423|z3291423]] 13:16, 11 September 2011 (EST)

looking good jaz. thanks for the articles fru. ive had a quick look at them but will need to fix it up after work this arvo! --[[User:Z3291324|z3291324]] 11:59, 11 September 2011 (EST)

Hey Jac, ive got 2 articles that i will send to your email, both talk about Cardiac Magnetic Resonance, one some detail about electrocardiography. Also, Jaz i have an article that has a section based on 'Future Innovations' for TOF, have a read and i reckon it will help out with the future directions part... i will send these articles to your emails so look at them when yous can... and rom, you breathing my friend?... regards --[[User:Z3291317|Z3291317]] 01:29, 11 September 2011 (EST)

hey guys, just reworded diagnosis so it makes sense. can anyone suggest any good articles to read for diagnosis? im having trouble accessing a lot of articles (they keep asking for passwords) and a lot of the articles dont discuss diagnosis in much detail at all. help is much appreciated!! thanks :) --[[User:Z3291324|z3291324]] 21:12, 10 September 2011 (EST)

hey rom, this might be helpful for genetics. not sure what youve got already though http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747103/
--[[User:Z3291324|z3291324]] 20:50, 10 September 2011 (EST)

also what should i do about the symptoms-pathophys overlap. should i alter the pathophys so its more anatomical like in the below article??--[[User:Z3291324|z3291324]] 20:10, 10 September 2011 (EST)

On to it now fru. thanks for the article. should i reword pathophys too so its easier to read/understand?--[[User:Z3291324|z3291324]] 20:08, 10 September 2011 (EST)

Hey Fru: in regards to the below comments, im working on future directions now :) also i read through the history section and it seems a lot more better :) just one mistake is the
"durng such operations there need". Ill have my edited prognosis and futures up by tonight! :) ohh and the heart! regards --[[User:Z3291423|z3291423]] 11:03, 10 September 2011 (EST)

Hey Jac i was reading the article: Review - Tetralogy of Fallot by Frederique Bailliard and Robert H Anderson ( im sure you have this one) and theres a section absed on " Anatomical variants of Tetralogy of Fallot, and associated anomalies". i believe if you could also include this section into the Pathophysiology section it would be great! Furthermore would you please do the things Mark said in regards to your sections it would be good, especially the diagnostic tests part :). Also to everyone we need to get Future Directions and especially Genetics up ASAP! thus respective people have them completed asap. --[[User:Z3291317|Z3291317]] 22:49, 9 September 2011 (EST)

Hey jaz, the prognosis sounds pretty good. maybe expand/explain how the hypoxic spells, brain abscesses etc cause death. i think in general we could expand upon most sections. off to work now guys but ill fix up my couple of sections tonight/tomorrow morn! --[[User:Z3291324|z3291324]] 08:30, 9 September 2011 (EST)

Thanks Fru! I will definitely crack onto those suggestions, I'm going to first email the owner of the children's hospital video on youtube to get permission for using the video, and then ill put it up in my section.
ALSO, I've nearly done the picture! I've got an outline and as your reading this, i should have it coloured, labelled and ready for upload! :D

have a great weekend guys!

Reagards
--[[User:Z3291423|z3291423]] 23:29, 8 September 2011 (EST)

Hey jaz just read your prognosis section. You made it well, however,i picked up 2 things you could do and it woould be good if you do them: 1. The causes of death after no surgery has done; if you can explain how these 'causes of death' occur due to TOF, it will portray the role TOF has in these problems. 2. You should talk about any complications that could arise in both patients that dont have corrected TOF and the ones who do have the surgery (i.e. any conditions that could develop after having the surgery or not, not just the death of the patient if they dont correct their heart). Other than that great work! :) --[[User:Z3291317|Z3291317]] 23:17, 8 September 2011 (EST)

Ye Jaz, thanks for the pic. Aswell ive attached a reviewed file of the treatment section on an email i sent to you. Maybe the youtube cideo based on the TOF fix up can now be put under this section as an embedded video... --[[User:Z3291317|Z3291317]] 22:19, 8 September 2011 (EST)

hey jaz, the treatment section is much better, much easier to read. thanks for the heart pic! im pretty sure my section is he one that is too "verbose" so anyone feel free to fix it up--[[User:Z3291324|z3291324]] 19:47, 8 September 2011 (EST)

Hey Guys! sorry prognosis took me a bit longer to do, but It will be up by tonight :) and ill upload the heart pic as well :) which took forever to make!
regards --[[User:Z3291423|z3291423]] 16:05, 8 September 2011 (EST)

hey guys just put up some diagnosis, let me know if you want me to add anything to it. furkan, glossary looks good! rommel, how are you going with the genetics do you need any help? and jaz are you able to post up the prognosis? once they are all up we should go through and edit them all together and fix up the wording. --[[User:Z3291324|z3291324]] 15:50, 8 September 2011 (EST)

Hey peoples...im going to start constucting the glossary wordbank as i read the entire document. Please add words yous think i missed out on... Also i found a pic of Mr Fallot but i think theres copyright rights on it. i think i gotta clear it somehow...--[[User:Z3291317|Z3291317]] 19:19, 7 September 2011 (EST)

hey jaz, i think the treamtment section is alright. maybe reword the first bit into sentences (i think it was the bit on how severe the cyanosis is) so its a bit clearer. but otherwise good :) what do you think about pathophys?--[[User:Z3291324|z3291324]] 12:40, 7 September 2011 (EST)

hey guys, i cant tell if this pic has copyright or not. can someone please have a look for me? http://www.nhlbi.nih.gov/health/health-topics/topics/tof/ thanks!--[[User:Z3291324|z3291324]] 09:49, 6 September 2011 (EST)
--> REPLY: I looked at the pic and looks great. however, i couldnt see if it was copyright or not. HOWEVER, it is found on a public government website, and from what i remember Mark said we can use these materials. To make sure just please check it with him aswell. Also, im going to format your pathophysioligy section now so it looks prettier :)--[[User:Z3291317|Z3291317]] 19:19, 7 September 2011 (EST)

Hey guys, i Just finished the Treatment part, I've got palliative in this heading to still complete but Its very brief so i thought id get cracking on getting that drawing done and also the prognosis will be up by tomorrow! also check this out! http://www.nemours.org/content/dam/nemours/www/filebox/service/medical/cardiology/defect/tof.swf
--[[User:Z3291423|z3291423]] 23:57, 5 September 2011 (EST)
-->REPLY: Cool animation. Would we use an external link to this animation due to copyright restrictions?--[[User:Z3291317|Z3291317]] 19:19, 7 September 2011 (EST)

Hey Peepz

I just finished the sections of History, Signs and symptoms and Epidemiology

just please check these sections, especially the epidemiology one, do yous want it more detailed or is it enough?

z3291324 your section seems alright so far, show us your edited version so we can fully critic it then.

p.s. the post below my one i dont really understand itl who is speking to who and what are yous refering to? lol

Regards --[[User:Z3291317|Z3291317]] 23:44, 4 September 2011 (EST)

j: the article on future treatment directions sounds good. i might add some of the info in to the pathophysiology section because it links in well with the pulmonary stenosis and right ventricular hypertrophy. --[[User:Z3291324|z3291324]] 13:47, 2 September 2011 (EST)
I think this article makes some good points which could be added into the treatment section (eg discuss treatment/surgery after birth and also follow up treatments in adulthood- pulmonary valve replacement etc due to valvular incompetence and regurgitation because of the growing heart)

=pathophysiology=
hey guys. ive written some basic notes (UNEDITED) for pathophysiology. Just want to get an idea of how much detail i should go into before i start adding links to journal articles etc. can someone please have a quick look through and give me an idea of how much more detail is needed. thanks :)

The four features of tetralogy of fallot are pulmonary stenosis, overriding aorta, ventricular spetal defect and right ventricular hypertrophy. These features result from the anterosuperior displacement of the infundibular septum. The severity of symtpoms is determined by the extent of right ventricular outflow obstruction. 
'''Pulmonary stenosis'''
(Symptoms include cyanosis, right ventricular hypertrophy, hepatomegaly and peripheral oedema (of the legs). More mild symptoms include sudden fainting and dizziness from exercise. ) 
Valvular or infundibular stenosis (narrowing of the outflow tract of the right ventricle). Obstructs the outflow of blood from the right ventricle reducing pulmonary flow. If the pulmonary stenosis is mild, a left to right shunt (with no cyanosis) will form, due to the higher pressure in the left ventricle. However, significant pulmonary stenosis can raise right ventricular pressure above the left ventricular pressure and cause a right to left shunt (cyanosis etc). The pathophysiology of pulmonary stenosis usually worsens with age because the pulmonary orifice stays the same size despite an increase in the size of the heart. 
'''Overriding aorta'''
The aortic valve has a biventricular connection. Instead of being positioned over the left ventricle, the aortic valve is located above the interventricular spetal defect allowing blood from both the right and left ventricles to pass through the aortic valve. The degree to which the overriding aorta is continuous with the right ventricle determines the severity of symptoms. Because the right ventricle receieves deoxygenated blood from the systemic circulation, the percent oxygenation of bloood entering the aorta and hence back into the systemic circulation is decreased. 
'''Ventricular septal defect'''
The interventricular septum dividing the left and right ventricles is incomplete at its superior, membranous end. During ventricular contraction, blood from the left ventricle passes into the right ventricle and then re-enters the pulmonary circulation. Leakage of blood from the left to right ventricle raises the right ventricular volume and pressure resulting in pulmonary hypertension. (Shortness of breath, dizziness and fainting) If the right ventricular pressure exceeds that of the left, the left to right shunt is reversed and the patient will experience cyanosis and deoxygenated blood is by-passing the lungs and entring the systemic circulation. (also breathlessness, poor feeding and failure to thrive in infancy.) 
'''Rigth ventricular hypertrophy'''
Compensatory response to pulmonary stenosis ...to be contined.

--[[User:Z3291324|z3291324]] 13:38, 2 September 2011 (EST)

=link to pathology textbook=

hey guys, this is the link to tetralogy of fallot in robbins pathology
--[[User:Z3291324|z3291324]] 13:05, 2 September 2011 (EST)

=More genetics and Surgery=

Hey Peeps, i forund another article in regards to Genetics as it does an genotype-phenotype anaylis os TOF Patients. Have a read and see if it can help in the assignment subsection. if you cant get the full article tell me and ill give you the pdf of it.

Article: PMID: 19948535

And Regards to surgery and its prognosis post-operation i found these articles that may be helpful for 3291423. Again if yous cant find the pdf tell me and i'll send yous the pdf articles of these.

Articles: PMID: 20091166 ; PMID: 21769263 ; PMID: 21566339 (hey 3291423 this is the article i showed you in the lab and you wanted it from me)

Anyways peeps i hope all the assignments are coming along well

Regards --[[User:Z3291317|Z3291317]] 19:03, 1 September 2011 (EST)

REPLY: Thanks z3291317, I had a look through the files and am using them now for summarising :) also, can you send through the picture of what you want the abnormal TOF heart to look like and ill get cracking on it to produce/draw it :)

regards --[[User:Z3291423|z3291423]] 22:15, 1 September 2011 (EST)

=Genetics=
Hey guys, found some articles relating to genetics and the deletion of the 22q11 gene. take a look :)
--[[User:Z3291423|z3291423]] 21:09, 27 August 2011 (EST)

AS Bassett, EWC Chow and J Husted et al., Clinical features of 78 adults with 22q11 deletion syndrome, Am J Med Genet 138 (2005), pp. 307–313. http://pediatrics.aappublications.org.wwwproxy0.library.unsw.edu.au/content/112/1/101

http://www.sciencedirect.com.wwwproxy0.library.unsw.edu.au/science?_ob=MiamiImageURL&_imagekey=B6T18-3V8RDDJ-11-1&_cdi=4884&_user=37161&_pii=S0735109798002599&_check=y&_origin=&_coverDate=08%2F31%2F1998&view=c&wchp=dGLbVlW-zSkWz&md5=0a4f32c3b75ebff2513309081ac0468f&ie=/sdarticle.pdf

http://pediatrics.aappublications.org.wwwproxy0.library.unsw.edu.au/content/112/1/101

=Treatment and future directions info/readings=

Hey guys, found this really amazing article about treatments and their repercussions http://www.ccjm.org/content/77/11/821.long#abstract-3
--[[User:Z3291423|z3291423]] 21:09, 27 August 2011 (EST)

=Online lab 4 info=
I my friends , colleagues and countrymen am going to be undertaking the research of the subsection Genetics/Aetiology in the topics that have been discussed. --[[User:Z3290841|z3290841]] 10:18, 25 August 2011 (EST)

Im going to be researching Treatment/Management, Prognosis & Future directions. - z3291423

regards, --[[User:Z3291423|z3291423]] 23:30, 24 August 2011 (EST)

Thanks for typing them up. I'm going to research Pathophysiology and abnormalities and diagnostic tests.
--[[User:Z3291324|z3291324]] 15:40, 24 August 2011 (EST)

Hey Group 6

From the Meeting on Tuesday after the Embryo lecture, we had concluded that we are going to divide the group project of TOF into the following sub-sections (if i am not mistaken):

* Introduction
* History
* Epidemiology
* Signs and Symptoms
* Genetics/Aetiology
* Pathopgysiology and Abnormalities
* Diagnostic Tests
* Treatment/Management
* Prognosis
* Future Directions
* Glossary
* References

From these subsections, I (z3291317) will research the History, Epidemiology and Signs & Symptoms subsections of the group Project.

Just wanted to put forward my part for the group project :)

Regards --[[User:Z3291317|Z3291317]] 15:01, 24 August 2011 (EST)

=Resources=
Hey Group 6

When i was looking around for info in regards to TOF, i found some videos on youtube made by an american hospital which we could use on our page in the "more info" section. Check them out and tell me what yous think...

- http://www.youtube.com/watch?v=ACRfFkxow7w
- http://www.youtube.com/watch?v=jgLC2QABcxo

So what you guys think? --[[User:Z3291317|Z3291317]] 22:54, 21 August 2011 (EST)

COMMENT: great stuff! that really is a great tool, maybe we can incorporate that in as a link, or something to really explain it! without all the mumbo jumbo :) --[[User:Z3291423|z3291423]] 22:22, 22 August 2011 (EST)

=Articles=

Found really good article detailing some clinical aspects http://journals.cambridge.org.wwwproxy0.library.unsw.edu.au/action/displayAbstract?fromPage=online&aid=331031 its called: The clinical anatomy of tetralogy of Fallot, http://www.sciencedirect.com.wwwproxy0.library.unsw.edu.au/science/article/pii/S0140673609606577 - Tetraology of ballot by christian apitz, just google scholar it via unsw or use the link I've given you :) --[[User:Z3291423|z3291423]] 19:10, 20 August 2011 (EST)

=Images=
Hey guys, this is an image of tetralogy of fallot with pulmonary atresia

[[File: Tetralogy of Fallot with pulmonary atresia.jpg]]
--[[User:Z3291324|z3291324]] 22:07, 17 August 2011 (EST)

Hey guys, just found this still frame showing large ventricular septal defect, aortic override, and right ventricular hypertrophy which are all very common to patients with ToF
[[File:Some common effects for patients with Tetralogy of Fallot.jpg]]
--[[User:Z3291423|z3291423]] 21:43, 17 August 2011 (EST)

Hey guys this is my image of our disease, it is just outlining some of the basic changes that happens to the heart, mainly the right ventricle.

[[File:Right ventricle of heart with Tetralogy of Fallot.jpg]]

--[[User:Z3290841|z3290841]] 13:42, 17 August 2011 (EST)

----

Hey Group 6, its z3291317

I just wanted to make it clear that we add all new entries into our discussion page at the top of the page and not at the bottom of it. Thats how we are told to edit this discussion page.

Anyways this is my Image for Lab 3 Question 2:

[[File:Normal fetal blood flow and Tetralogy of Fallot.jpg]]

I hope it would be beneficial for our page...

--[[User:Z3291317|Z3291317]] 12:05, 17 August 2011 (EST)

--[[User:Z3291317|Z3291317]] 17:00, 7 August 2011 (EST)
Hey Group 6

i just done some research on a possible group project subject. It is quite detailed and interesting (to me) disease to write on.What do you guys think? Here is the review and research article for it:

The Disease:'''Tetralogy of Fallot'''

Review Article:

Orphanet J Rare Dis. 2009 Jan 13;4:2.

'''''Tetralogy of Fallot.'''''

Bailliard F, Anderson RH.

North Carolina Children's Heart Center, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. frederique_bailliard@med.unc.edu

Link: <ref><pubmed>19144126</pubmed></ref>

Description: This paper gives an overview about the disease, how it happens, and clinical manifestations.

Research Article:

J Med Genet. 2010 May;47(5):321-31. Epub 2009 Nov 30.

'''''Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot.'''''

Rauch R, Hofbeck M, Zweier C, Koch A, Zink S, Trautmann U, Hoyer J, Kaulitz R, Singer H, Rauch A.

Institute of Medical Genetics, Schorenstrasse 16, CH-8603 Zurich-Schwerzenbach, Switzerland. anita.rauch@medgen.uzh.ch

Link: <ref><pubmed>19948535</pubmed></ref>

Description: A study was done to see the prevalent phenotype for Tetralogy of fallot, and it was found that the 22q11.2 deletion was the most common type in Tetralogy of Fallot.

'''''References:'''''

<references/>

--[[User:Z3291317|Z3291317]] 17:00, 7 August 2011 (EST)

----

--[[User:Z3290841|z3290841]] 09:36, 8 August 2011 (EST)

Hey Guys,

I did research on Cystic fibrosis and these are the 2 articles that I found that explains a lot about the disease, and the genetic research on it.

Review Article:

'''Cystic Fibrosis: Seminar'''

Description: This is basically outlining the pathophysiology of the disease, disease manifestation,current treatments diagnostic tool.

Ratjen F & Doring G.(2003).Cystic Fibrosis: Seminar.''The Lancet'', 361, 681-9. Retrieved from http://www.sciencedirect.com/science/article/pii/S0140673603125676

Research Article:

'''Gene expression profile study in CFTR mutated bronchial cell lines'''

Description: This article provides information about the severity of gene expression in relation of the extent or type of mutation.

Gambardella S, Biancolella M, D'Apice M, Amati F, Sangiuolo F, Farcomenti A, Chillemi G, Bueno S, Desideri A & Novelli G.(2006).Gene expression profile study in CFTR mutated bronchial cell lines.''Clinical and Experimental Medicine '', 6, 157-65. Retrieved from http://proquest.umi.com/pqdlink?Ver=1&Exp=08-05-2016&FMT=7&DID=1187181501&RQT=309&cfc=1

--[[User:Z3290841|z3290841]] 09:36, 8 August 2011 (EST)

--[[User:Z3291324|z3291324]] 20:48, 10 August 2011 (EST)

Hey guys, I like the disease that Furkan found (tetralogy of fallot)! What does everyone think?

These are the two articles I found. The review article gives a pretty good description of the disease, symptoms, treatment and complications etc. The research article looks at some of the genetic causes.

Goldmuntz, E., Geiger, E., & Benson, D. W. (2001). NKX2.5 mutations in patients with tetralogy of fallot. Circulation, 104(21), 2565-2568.

Apitz, C., Webb, G. D., & Redington, A. N. (2009). Tetralogy of Fallot. Lancet, 374(9699), 1462-1471.

Hey kiddes just done some research! check it out, its about Hypoplastic left heart syndrome

Review article:

2001 May-Jun;21(3):705-17.
'''Hypoplastic left heart syndrome.'''
Bardo DM, Frankel DG, Applegate KE, Murphy DJ, Saneto RP.

Link: [http://www.ncbi.nlm.nih.gov/pubmed/11353117]

Research:

2011 Aug 1;108(3):421-7. Epub 2011 May 31.
'''Prenatal diagnosis of hypoplastic left heart syndrome in current era.'''
Kipps AK, Feuille C, Azakie A, Hoffman JI, Tabbutt S, Brook MM, Moon-Grady AJ.
Link: [http://www.ncbi.nlm.nih.gov/pubmed/21624547]

References
<references/>
1. Bardo DM, Frankel DG, Applegate KE, Murphy DJ, Saneto RP ""Hypoplastic left heart syndrome.""Radiographics. 2001 May-Jun;21(3):705-17 <ref><pubmed>11353117</pubmed></ref>

2. Kipps AK, Feuille C, Azakie A, Hoffman JI, Tabbutt S, Brook MM, Moon-Grady AJ ""Prenatal diagnosis of hypoplastic left heart syndrome in current era."" Am J Cardiol. 2011 Aug 1;108(3):421-7. Epub 2011 May 31 <ref><pubmed>21624547</pubmed></ref>

==Peer Assessments==
* I would suggest placing the history section into a timeline or table format just so that significant dates are more clear and emphasised.
* The gene profile section was great. It was in detail, it was coherent and the inclusion of gene images enhanced my understanding of this particular section.
* Maybe for the “how the procedure works” section of the diagnostics table could have been summarised into a flow diagram or through images, rather than having a chunk of text. This could make it more straight forward to the reader.
* Your website was generally well-written and to the point. You varied your formatting regularly which made your page entertaining.
* My last suggestion would to only use the image of the shunt once and finding a different image as the repetitiveness of this is slightly disengaging
--[[User:Z3332629|z3332629]] 15:26, 22 September 2011 (EST)

Talk:2011 Group Project 5

2011-09-28T07:10:09Z

Z3279511: /* Peer Assessments */

[[2011_Group_Project_5|'''Group 5''']]: [[User:z3290618]] | [[User:z3290689]] | [[User:z3290808]] | [[User:z3290815]]

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=='''PEER REVIEW COMMENTS'''==
Be nice?

==Peer Assessments==

'''Group 5: Peer Assessment'''
* Your page looks a bid 80's with all the different pinks in your table. Not a bad thing, however may be just one colour per table would be enough
* The introduction is too brief and written a little careless and lacks referencing.
* The history table is good in the way that it's chronologic and easy to read but you could write a bid more about the relevance of these events.
* Your drawing needs some copyright information and if the writing would have more contrast it would come more into account.
* The aetiology section is informative overall but some long sentences could be separated and more explanatory. Put the pictures on the same side may be to give it a bid more shape.
* The development of the disease section and signs and symptoms section read well and there is good use of subheadings.
* Is there some current research you could talk about?
* Your glossary and your references clearly need some editing and fixing up
* Overall your page seems to be written a bid careless but there are bids of interesting information in there. --z3279511 17:10, 28 September 2011 (EST)

'''Peer Assessment #5'''
*Intro looks funny with a pic on each side of the text – reconsider this formatting. Maybe both on one side and one under the other?
*Intro 1st para is very detailed for an intro- perhaps explain it more, or in more general terms. The detail will come later
*The intro sentence in history would be better in the intro.
*You keep referring to the FMR1 gene, but I have no idea what this is or how it is relevant. Please explain it somewhere! Maybe have a short para just on it and explain about it.
*In signs and symptoms, are ‘emotional characteristics’ and ‘language and speech’ meant to be their own subheadings, or subheadings of ‘intellectual development’?
*Diagnosis section is not complete, needs a lot more info and explanation of the techniques, how they work, why they are used/relevant. – Modified PCR section is too wordy.
*Treatment table is good, can you stretch it so it takes up the whole box instead of being centered? Would look better
*Recent research – surely there is more you can discuss/other areas?
*I’m sure everyone else has mentioned it, but the glossary needs work. Really, just define lots of the ‘big’ words, as you can’t assume everyone knows what they all mean.
--[[User:Z3332824|z3332824]] 11:59, 28 September 2011 (EST)

''' Group 5 Peer Assessment'''
* First student figure has no explanation as to what it's all about, and is a pretty simple diagram. What does it contain? Where is your copyright information? The same can be said with the second student-drawn figure. Make sure this is fixed!
* The introduction section appears to be pretty short. Try to keep away from using the brackets and just enter your information in a continuous format.
* The headings and subheadings work quite well. However, the lack of images in the signs and symptoms section make this difficult to read; it seems like a large block of text without anything to assist in the breakup of the page (making it difficult to read and easy for us to lose attention).
* Subheadings are used quite well. The treatment section is well presented in table format, but once again, any images to help break things up?
* The recent and future research section doesn't seem to be completed. Is there anything that can be done for the future of the disease? Is it related to any other disease processes? The glossary also seems short and isn't in alphabetic order. Please add all the terms to the glossary to ensure that there is completeness of the project! There are many terms that are difficult to understand, so slot them in here.
* There just needs to be more work done overall to ensure that the project flows smoothly and all the smaller details are accounted for. At the moment there is still a large part of the project that feels quite sketchy and requires more work.
--[[User:Z3288827|Leonard Tiong]] 10:33, 28 September 2011 (EST)

Group 5: Fragile X
*Introduction: Maybe a bit too concise, some of the content that should be in the intro is missing. Maybe this should be redone with references! Also, it doesn’t draw the reader’s attention unfortunately.
*History: Simple table, but a small explanation regarding the significance of the discoveries would be very helpful.
*Epidemiology: Nice picture, had to tilt my head a little. The “Screening/Population testing” seems like a whole new section itself. Might have to look into that?
*Etiology: This section was very well managed.
*Development: I like the subheadings, maybe an image to help add some visuals, but not required.
*Signs and Symptoms: This again, was well done, though detailed, the mass text was slightly disorientating, another image perhaps?
*Diagnosis: Looks incomplete, more info required, probably another sub-heading would do.
*Treatment: Best section in this webpage. Detailed and neatly laid out.
*Glossary: Some explanations and a few more words added here would do the trick!
*Overall: The basic fundamentals are there, some more info here, and a few tweaks there is all that is needed! Keep it up.
--[[User:Z3332327|Lisa Xiao]] 01:25, 28 September 2011 (EST)

'''Group 5'''

*Introduction should be explained a little better and also referenced
*Hand drawn image needs the correct referencing/copyright info
*Good use of subheadings in epidemiology
*Etiology is a little hard to follow
*Development of disease needs an image to break up the text
*Signs and symptoms is very text heavy- try to change it up a bit i.e. use of dot points
*Good use of table in treatment
*Glossary needs to be extended
*Overall, this has potential to be a good project with a few adjustments

'''Group 5'''

*Introduction: too much detail, give an overview. Only one of the images would be enough.

*History: well done

*Epidemiology: screening / population testing should be a separate section, very good image

*Etiology: well done,

*Development and Symptoms: both sections are clear and easy to follow, good use of subheadings

*Diagnosis: seems incomplete

*Treatment: very detailed

*Research: I would add some other examples. If you want to outline only autism, maybe change the heading.

*Glossary: there is a lot missing

*Make sure to include the copyright notice in all images
--[[User:Z3387190|Z3387190]] 21:31, 27 September 2011 (EST)

'''Group Peer assessment'''
*Introduction images placement may work better on one side or below the information though current placement is confusing affecting text as well.
*History requires more elaboration as well at least indication of the founder in the introduction of the history even an image of the founder would benefit this section, although the timeline is nicely done.
*Development and disease would be better as a sub heading under eitology as development of the disease links with the causation of the disease.
*Glossary needs work done as most terms are genetic related and those without a genetic background will find difficulty understanding the web page.
*Referencing only needs to adjust the links, links need to be sited properly manually.
z3332250 23:50, 26 September 2011 (EST)

Group 5 Peer Review

*Introduction does not entice the reader to read the rest of the page. Maybe less scientific language in the introduction?
*Table under history is well presented and visually appealing
*“Postnatally” and “postpubescent” need to have “development” added to the subheadings
*Well referenced
*The consistent colour scheme throughout is a nice touch
*Another image under signs and symptoms would make this section look more balanced
*Diagnosis seems brief-add information or perhaps merge with another subheading
*Glossary needs to be expanded
*Logical, clear and organised structure
*Overall, a good page. The bulk of it is there. If each section just changed some minor things, this page would improve greatly.
--[[User:Z3308965|Fleur McGregor]] 19:38, 26 September 2011 (EST)

===Comments on Group Project 5===
'''Strengths:'''
*The use of same reference for different part of the page is good.
*The treatment section is put together.
*Images are appropriate and useful.
'''Weaknesses:'''
*Formatting is not as best as it could be.
*For some sections, punctuation is a slight problem.
*The flow under the epidemiology section doesn’t seem quite right. Seems to give a disjointed feel.
*The section under Diagnosis could be further elaborated.
'''Specific corrections:'''
*Maybe testing and counselling can go under a new heading, “Management”.
*The subheadings “Post Natally” & “Postpubescent” could be changed to “Post Natal Development” & “Post Pubescent Development” instead to give it a uniform formatting.
*Some of the words in the page should be in the glossary section e.g. tactile defensiveness and face encoding.
*Improve format for some of the references.
*Include explanations and the copyright statements on student images allowing for re-use for wikiusers.

--Z3389806 07:34, 26 September 2011 (EST)

'''Group 5 Critique'''

#• Introduction should not contain clinical manifestations. It should introduce the topic as a whole. This section needs to be re-written
#• The history section is ok. The timeline could be explained a little better to give a clearer view of what the history of the disease is to the reader
#• Epidemiology should not contain the advantages and disadvantages of population testing. This should be another section in itself
#• Aetiology was fine
#• Development of the disease was ok
#• Signs and Symptoms was good
#• Diagnosis needs to be more detailed than what it is
#• Treatment and recent research is impressive
#• Glossary needs more terms added to it. It is too short, however that will be fixed when you add more explanations to the other sections and define the terms here.

--[[User:Z3289991|Robert Klein]] 18:57, 24 September 2011 (EST)

'''Fragile X Syndrome'''

*You need a bit more in your introduction. Introduce the basics before jumping straight into the methylation of specific genes etc. Try to describe what CGC triplet is, what methylation is, on what chromosome is FMR1 gene on? You need to spell some of this stuff out to begin with
*The table in 'History' looks good, there is a nice outline of dates there
*Nice diagram in 'Epidemiology', it's a really good illustration
*'Etiology' can you do a brief explanation of what "amplification" implies
*There is a lot of good information in 'Signs and Symptoms', but it's lost in a block of text. It would be good if you broke it up with some images of clinical symptoms or something
*How do the diagnostic tests work? Why are they used? What are the benefits and diadvantages of them? This section needs to be filled out a bit
*Clearly a lot of work has gone into 'Treatment'
*'Recent Research' is structured nicely, makes it a lot easier to read
*There's more than 8 words that require a definition
*There's clearly a lot of good information in the project, but there is a lot of detail and it needs to be broken up a bit. Though, overall it is not a bad project

* I liked your page as it had a simple and easy-to-follow lay out
* Some of the images could have been made larger on your actual page just so that it adds dynamics to your page
* I was left wanting to know more about the diagnosis, this section was quite brief
* I personally found your treatment table hard to read because there was so much information. Personally I believe that maybe dot-point form could have been used to get your main points across.
* Perhaps expand upon your glossary as there were some words that weren’t in there that maybe should have been.
--[[User:Z3332629|z3332629]] 15:25, 22 September 2011 (EST)

'''Group 5 Assessment'''
*The Fragile X Chromosme. Jpg needs both an explanation and referencing.
*There is no referencing in the Introduction section. Where did you get this information from?
*History- Good idea to setup using a chart to organize the data. First time I’ve seen that.
*Fragile X Inheritance jpg looks great!!! Way to incorporate the data into a figure. However, it does still need citing.
*Not all the information in the Screening/Test Population is cited. Where is this information referenced from?
*The Development of Disease portion could use a figure or two to make it more appeasing to look at.
*Some of the information under Signs and Symptoms is also not cited. Where was this information drawn from?
*Good chart under the treatment section. However, maybe try a bullet list on the right hand column to help set the ideas apart from each other?
*The glossary link seems a little short… Are you sure there aren’t any more words which would be helpful to define for the audience?
*For the references given throughout the wiki, there isn’t any consistency in how the [#] is given. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
*Overall, good work! Just work on the referencing and some of the visual aspects.
--[[User:Z3391078|Z3391078]] 15:09, 27 September 2011 (EST)

Group 5
* Straight into it hey- a little bit more of an “introduction” might help sorry. The first line kind of scared me. Yes it is relevant information but I think you need to almost ‘warm the reader up’ if you know what I mean. When reading anything I don’t think jumping straight into the nuts and bolts of how it works benefits anyone. I think you should start with what it is and why it is important that the reader learns about your topic
* The history section is brief and I don’t actually understand the relevance of the discoveries. While putting the information in a table shows that you know how to format it to look pretty, it is not the most effective way of showing
* Your hand drawn images still need to be referenced and copyright put on them
* Reading through I am overwhelmed by the content. This may be due to a lack of proper introduction or early explanation. I feel like the information isn’t as accessible as it could be
* Development of the disease would work well in a table I think
* Maybe put the clinical manifestations into dot points? I just feel like everything is a bulk of text and it would be better if you broke it up a little
* An image in diagnosis would help
* Treatment works well in a table
* Glossary could be extended
* You are on the right tract it is just a very heavy project. The content is all there but I found it really hard to get through.

'''Group 5'''
* Great structure with headings and subheadings, very easy to follow and read.
* Nice succinct intro. good over view of the disease. - Maybe you could dot point phenotypic abnormalities
* Some areas a little text heavy, additional pictures would fix this problem. for example some more pictures in signs and symptoms.
* Good simple history, well researched. easy to follow.
* Maybe Screening/Population testing could be its own heading.
* Great section on development of disease! I like the format very interesting relevant information! well done!
* Treatment section well put together but a little text heavy- try condensing info or bullet points.
* Make sure all the pictures are referenced properly.
* Nice to see your references grouped.
* NIce student drawn picture.
* Make sure all your acronyms/ scientific lingo is in the glossary.
* I liked that you has a continuous colour scheme for your tables. It makes your page look very neat.
* The bottom of the page is a little text heavy.

*'''Introduction''': Concise and to the point.
*'''History''': 1977... revise this sentence, I don't quite understand it. Generally, the explanations about the different discoveries could be longer and explain more how this lead to progress with regards to FXS.
*'''Epidemiology''': All of the sudden you talk about "other populations" - which was the population you were initially referring to? Also, when you bullet-point the studies about the different populations, it would be good including a reference to each study.
*'''Screening/Population testing''': Looks fine.
*'''Etiology''': Generally well explained, though your last paragraph remains rather technical. You also sometimes use very long sentences - try to break those down, that'll make it easier to follow the argument. None of your terms seem to be explained in the glossary, and I doubt that anyone who hasn't done somewhat advanced genetics will understand the stuff relating to the RICS complex, the dicer enzyme and mRNA and miRNA regulation. Otherwise, nice depth and detail.
*'''Development''': Well explained, good use of subheadings.
*'''Signs and Symptoms''': Also well explained, good use of subheadings.
*'''Diagnosis''': Too short. What about non-genetic diagnosis?
*'''Treatment''': You jump in with mGluR5 treatment without having previously mentioned that this is affected by the syndrome. Mention it somewhere earlier, so it makes more sense that it needs to be treated?
*'''Recent Research''': The autism related bit is well explained, but is there no current research looking at other aspects of the disease?
*'''Glossary''': Too short, more terms need to be explained.
*'''References''': The links probably need fixing. Also, a few articles seem to appear a couple of times in the list, but in general it looks fine.
*General: I feel like you mainly focus on the behavioural/cognitive aspects of the disease. Is there nothing more physiologicall to it? Otherwise, well organised, but maybe include a few more figures, as most of the page appears to be text?

'''Peer Assessment: Group Project 5'''
*The introduction has no references.
*More pictures in the sections on development, signs and symptoms and diagnosis would help to make the written work easier to follow. Examples of pictures that could be added are images of neural crest development put in the development section or images of diagnostic techniques in the section on diagnosis.
*The section on treatment is clear and informative.
*The different diagnostic procedures could be explained more, such as how they are each conducted.
*Instead of having the uncommon words highlighted in bold, maybe you could link the words to their definition down in the glossary section.
*Some of the references are duplicated. They can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.
*In conclusion, this project is both accessible to people who have no great scientific knowledge, but also delves into quite specific knowledge. A good balance.
--[[User:Z3217345|z3217345]] 21:59, 27 September 2011 (EST)

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{{2011GroupDiscussionMH}}

=='''Discussion'''==

Collins SC, Coffee B, Benke PJ, Berry-Kravis E, Gilbert F, et al. (2010) Array-Based FMR1 Sequencing and Deletion Analysis in Patients with a Fragile X Syndrome–Like Phenotype. PLoS ONE 5(3): e9476. doi:10.1371/journal.pone.0009476

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Nice work Sandra! I will keep looking and i see you changed your table to pink too haha --[[User:Z3290815|Tara Lofthouse]] 20:54, 18 September 2011 (EST)

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Hey guys, i have just edited our group page and put up 3 pictures! Please try to find more before Monday (especially under development of the disease and signs and symptoms as these parts are so dense with writing and thus need pictures to break it up a little bit)! Cheers, --[[User:Z3290808|Sandra Issa]] 00:24, 18 September 2011 (EST)

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Here:

http://3.bp.blogspot.com/-88xXtruHpyo/TlaALBe6CaI/AAAAAAAABx8/ZMdZULFKEns/s1600/happy%2Bcamper.jpg

{|
|-
| Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD)
| The prevalence of ADHD symptoms in individuals with FXS is much higher than that of other individuals with either genetic conditions or non-specific intellectual disability. Stimulants have been shown to improve ADHD symptoms in FXS patients. These drugs are distributed in addition to individualized therapies and behavioural intervention.
Some associated problems of using stimulants when treating symptoms of ADHD in younger children (such as 5 years of age and under) is that they may induce irritability and other behavioural problems. In this case, administration of non-stimulant medications may be more beneficial. Such alternative medications include adrenergic receptor agonists, such as clonidine and guanfacine.
Clonidine has shown to be helpful for children with ADHD who have sleep disturbances (a asymptom often present in FXS patients). Guanfacine can also improve ADHD symptoms, such as “including hyperactivity and frustration intolerance, as well as hyperarousal.”
|-
| Treatment of Mood Instability and Aggression
| Antipsychotic drugs, such as Risperidone and Aripiprazole, are proven to be helpful in treating mood instability, aggression, perseverative behaviours and irritability in patients with FXS.
Risperidone was the most popular and clinically effective antipsychotic drug in the past for treatment of aggression and mood instability in patients of FXS. “The typical risperidone dose range for children with FXS is 1 to 2.5 mg/day.”
Aripiprazole was the second most popular atypical antipsychotic agent for targeting multiple behaviour difficulties in patients with FXS. “Typically, low doses of aripiprazole (2.5–5.0 mg for adolescents and even lower doses for younger children) work best for patients with FXS.”

|}

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Hey guys, yep i will be there at 10 count me in! --[[User:Z3290808|z3290808]] 09:42, 15 September 2011 (EST)

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It looks like it is going to be late nights all round. We should try and pump out an intro in that time tomorrow as well as at least one image? --[[User:Z3290815|Tara Lofthouse]] 18:52, 14 September 2011 (EST)

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Okay, Tomorrow at 10am it is. I'll finish my stuff off tonight (it looks like being a late night :P).
I'm assuming that it doesn't have to be perfect by tomorrow. It just needs to look alright, so that people can give us feedback before we finish it, yeah?
Also, Boris, Interview is on the 27th. I was just visiting a friend. I'll tell you how it goes though, when it does happen. --[[User:Z3290618|Ziggy Harrison-Tikisci]] 17:43, 14 September 2011 (EST)
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I can make it at 10am on Thursday as well --[[User:Z3290815|Tara Lofthouse]] 12:08, 14 September 2011 (EST)

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Ooo, interview? How'd it go?
I don't have time to meet up today (Wednesday), but I can see you guys in the lab at 10 tomorrow, before the class.
--[[User:Z3290689|Boris Zolotarev]] 10:39, 14 September 2011 (EST)--[[User:Z3290689|Boris Zolotarev]] 10:39, 14 September 2011 (EST)

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Hey Guys, Sorry I've been in Melbourne for the week, so haven't done any work. Getting on it now. Going to do all my referencing, editing etc.
Wanted to ask if there is a time when we can get together, go through it all and make it pretty. Did we just want to do this before our lab on thursday, or if you guys have some time on wednesday afternoon?
Furthermore, how harsh is the criticism/feedback? Doesn't mince his words, does he? --[[User:Z3290618|Ziggy Harrison-Tikisci]] 12:51, 12 September 2011 (EST)

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Hey Boris yes i am experiencing the same problem. I cannot see the references and the reference list looks like a bunch of arrows facing superiorly. I got a bit worried but then checked the other groups and they had the same issue. I'm not sure what we can do? Let me know. ---[[User:Z3290808|Sandra Issa]] 09:49, 9 September 2011 (EST)

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WHAT HAPPENED TO OUR REFERENCES. Can you guys do me a favour and tell me if you can see them? I was trying to put in an image just then and when I did the save it came up with references wiped. I tried undoing my last edit to no avail. There are still 30 something references, there's just nothing IN them. When I finished my word edit earlier today I actually saved the ENTIRE script as a word document; when I tried to rewrite EVERYTHING with that same (working) script it still came up with stuffed up references.

Let me know if you guys see the same problem. If you do, I'll have to get in contact with Mark Hill to fix the script.
--[[User:Z3290689|Boris Zolotarev]] 23:31, 8 September 2011 (EST)

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I hate how the times shown on the editing thing are totally out of whack....can I post anything up at the moment? ><
--[[User:Z3290689|Boris Zolotarev]] 23:27, 7 September 2011 (EST)

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Hey guys, i have just added the diagnosis part of our page and have also finished the treatment. Let me know if you think the treatment is too long? Or if you want to make any changes to the "Recent Research" part of our page.

Also, i will add in more references for this part very soon. I have put in a general reference (review article) but will make sure i include all references used very soon.

Have a good night, --[[User:Z3290808|Sandra Issa]] 21:16, 7 September 2011 (EST)

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Suggestion: rename '''Development of disease''' to '''Progression of disease'''. Also, I should have a heap up later tonight, I'm compiling it all in a separate document at the moment.

--[[User:Z3290689|Boris Zolotarev]] 15:39, 7 September 2011 (EST)

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Hey guys, just letting you know that i have found a great article which addresses many current 'treatments' for FXS. Also, i have found another article which summarises the current methods of diagnosing FXS. I will add this information (what i think is most relevant from the articles) onto our group page under the headings "treatment" and "diagnosis" '''very soon'''. Please feel free to add in anything that you believe i have not addressed under these headings. Also, i will try to edit our page as a whole soon so that it looks more uniform in appearance. Over the next couple of days we should all read each of the sections and try to add in additional information that someone else may have missed. Also, a reminder to keep an eye out for relevant pictures that have unrestricted access to add onto our page!
Cheers,
--[[User:Z3290808|Sandra Issa]] 12:32, 5 September 2011 (EST)

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Hey, I'm doing a whole bunch now. I'll properly reference it all later, but I'm getting a lot of it off the american National Institute of Health. They've got references for all of it. So when I have more time, I'll go through those references, add them, and edit the information. So, what I put on the group page will just be an overview. Also, you people should go to bed earlier :)
http://www.nichd.nih.gov/publications/pubs/fragileX/sub6.cfm
--[[User:Z3290618|z3290618]] 09:49, 1 September 2011 (EST)

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z3290808: I don't know why it wouldn't let you save, i wasn't editing at that time. Try again and if it doesn't work maybe paste your work here with your references and one of us can put it onto the project page for you?

Boris: At least something is up :) My section needs a lot more editing and a lot more cross checking with other references as well.. Any progress is good progress at the moment
--[[User:Z3290815|Tara Lofthouse]] 03:35, 1 September 2011 (EST)

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Heya, I took a stab at my section but I'm a bit dead at the moment '''(points to timestamp)'''. I'll try get some more done tomorrow between the lecture and lab.

On the plus side, I added another 6 or 7 references to our thingy ^^

--[[User:Z3290689|Boris Zolotarev]] 01:28, 1 September 2011 (EST)

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Guys it's not letting me save what i have written onto the group page! Is anyone currently on and trying to edit at this same time?
--[[User:Z3290808|z3290808]] 22:41, 31 August 2011 (EST)

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Yo Boris, You do Etiology, I'll do signs and symptoms. We can work towards the middle.
That leaves history and epidemiology to Tara and Recent research to Sandra. And then we can all refine it/make an intro.
We can at least do that to start with.
Also: can everyone contribute to the glossary. If you find any terms that people (eg. me) wont understand, please keep them.--[[User:Z3290618|Ziggy Harrison-Tikisci]] 10:10, 25 August 2011 (EST)

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The only reason why we need to put our names down now is to satisfy the weekly individual assessment but of course we can change things. Just put your name down for epidemiology or whatever was left over and we'll discuss it tomorrow. Maybe if we could get to the lab 10-15min earlier because we never get enough time at the end of the lab?

--[[User:Z3290815|Tara Lofthouse]] 19:50, 24 August 2011 (EST)

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Just skimmed through this (damn I left it late >< ), should I nominate something now or should we discuss it tomorrow?
Also, what do you guys think of having some sort of realtime chat method? Facebook or something of the sort...
--[[User:Z3290689|Boris Zolotarev]] 19:17, 24 August 2011 (EST)

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Yeah i know but the ones i put my name down for are really not that lengthy. We definitely need to have a chat tomorrow.
--[[User:Z3290815|Tara Lofthouse]] 17:45, 24 August 2011 (EST)

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Hey guys, you haven't left much for Boris and i to do lol .. I don't mind doing the recent research part - focussing on autism and fragile x.. but then i don't know what Boris would do? I will sign my name for now but i think we will have to change it around a little to better make the work load equally spread.

Cheers, --[[User:Z3290808|Sandra Issa]] 16:17, 24 August 2011 (EST)

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I've taken it all on board and changed it. I'm fine for you to do whatever you want but doing both the genetic component and the signs and symptoms might be a lot of work. As long as everything is spread evenly i don't mind :)

--[[User:Z3290815|Tara Lofthouse]] 16:35, 23 August 2011 (EST)

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Hey, I was wondering if anyone minds if I do 'Genetic contribution'. Also, is it okay if I follow the timeline of the disease? I will start with the chromosome, saying what the defect causes at a molecular level, and then when it first presents, and how it affects the development etc up until how it presents in the adult. Which means I'd probably do "Signs and symptoms (clinical Presentation)" as well.
ALSO, we need to do a brief history of the disorder. So, below I've just tweaked the layout Tara and Sandra put up: let me know what you think

* Introduction
* History of Disease
* Epidemiology
* Etiology
** Genetic contribution
* Development of Disease
** Fetal Development
** At birth
** In Adult
*** Signs and symptoms
* Recent research
** Fragile X and Autism
** Diagnosis
** Treatment
--[[User:Z3290618|z3290618]] 15:18, 23 August 2011 (EST)

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Yeah, i think it makes sense how you've got it Sandra. However like Boris said maybe instead of having the heading "Autism and Fragile X Syndrome" maybe we could have recent research/current studies or something along those lines and include it there along with diagnosis and treatment? Do you think that etiology is too similar to genetic contribution?

ALSO!!!
What headings would you like to research? I set up a "Who's doing what?" heading on this page to sign your name next to.

--[[User:Z3290815|Tara Lofthouse]] 12:39, 23 August 2011 (EST)

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Hey guys, i have come up with a couple of headings that we can use:

* Introduction (short summary)
* Epidemiology
* Signs and Symptoms (Clinical Presentation)
* Etiology
* Genetic Contribution
* Autism and Fragile X syndrome
* Diagnosis?
* Treatment?
* References

Tara i also like the format that you have included below.. i basically have made something similar but in different order based on what i think should come first perhaps? The ones with a question mark beside them are ones that i am unsure if we should include or not. Let me know what you think!
Cheers,
--[[User:Z3290808|Sandra Issa]] 12:03, 23 August 2011 (EST)

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Hahaha of course it's your place to say so.. good suggestion, i'll fix it up now and if we want to change it again than that's no problem. I just thought i'd put something up to get started and we can go from there. What i've done is no where near completed.
--[[User:Z3290815|Tara Lofthouse]] 18:52, 22 August 2011 (EST)

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(I know it's not my place to say so before I've submitted my own suggestion but) I think I'd put "Autism and Fragile X Syndrome" within the "recent research" subtopic. I'll put up a suggestion by tomorrow evening, if not earlier.
--[[User:Z3290689|Boris Zolotarev]] 09:27, 22 August 2011 (EST)

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'''Hello everyone,''' what do you think about using the following headings for our project? Are there ones that you think we could omit or ones that you would like to add? We also need to decide on who is doing what.
* Signs and symptoms
* Diagnosis
* Genetics
* Etiology
* Epidemiology
* Treatment
* Recent research
** Autism and Fragile X Syndrome
* References

--[[User:Z3290815|Tara Lofthouse]] 16:26, 21 August 2011 (EST)

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[http://embryology.med.unsw.edu.au/embryology/index.php?title=2011_Lab_2_-_Group_Project Group project] --[[User:Z3290618|Ziggy Harrison-Tikisci]] 12:58, 4 August 2011 (EST)

[http://www.ncbi.nlm.nih.gov/omim OMIM]--[[User:Z3290618|Ziggy Harrison-Tikisci]] 12:59, 4 August 2011 (EST)

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Here's another interesting topic.

[http://en.wikipedia.org/wiki/Apert_syndrome Apert Syndrome aka acrocephalosyndactyly] --[[User:Z3290689|z3290689]] 11:38, 11 August 2011 (EST)

=='''Congenital Hypomyelinating Neuropathy'''==

What do you guys think you of this topic [http://omim.org/entry/605253 Congenital Hypomyelinating Neuropathy]?

There are quite a few articles on it:

Clinical Phenotypes of Different MPZ (P0) Mutations May Include Charcot–Marie–Tooth Type 1B, Dejerine–Sottas, and Congenital Hypomyelination.

Analysis of congenital hypomyelinating Egr2 Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination.

P0 Glycoprotein Overexpression Causes Congenital Hypomyelination of Peripheral Nerves.

Congenital hypomyelinating neuropathy, central dysmyelination, and Waardenburg–Hirschsprung disease: Phenotypes linked by SOX10 mutation.

A lot of them overlap with their findings and the focus of their studies, so it seems to be a pretty thorough topic.

--[[User:Z3290689|Boris Zolotarev]] 21:03, 7 August 2011 (EST)

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I’m all for doing '''Congenital Hypomyelinating Neuropathy''' as our topic.

Here are some articles I have found:

'''Research Articles:'''

[http://neuro.cjb.net/content/29/8/2312.full.pdf+html Congenital Hypomyelinating Neuropathy with Lethal Conduction Failure in Mice Carrying the Egr2 I268N Mutation]

* Describes the engineering and characterisation of a mouse carrying the I268N mutation in Egr2.

* The proper formation of myelin by Schwann cells requires a series of transcription factors including SOX10, SCIP/Oct6, Egr2, and Nab1/Nab2.

* A loss of these transcription factors disrupts the myelination process, as does persistent overexpression.

* This was observed in patients with recessively inherited Charcot–Marie–Tooth (CMT) disease type 4E, which is predicted to alter the ability of Egr2 to interact with the Nab transcriptional coregulatory proteins.

* Charcot–Marie–Tooth disease (CMT) is a common inherited disorder of peripheral nerves characterized by progressive sensory loss and weakness beginning in the feet and legs, and later progressing to the hands

* Mice homozygous for Egr2I268N developed a congenital hypomyelinating neuropathy similar to human counterparts.

* Egr2I268N is expressed at normal levels in developing nerve but is unable to interact with Nab proteins or to properly activate transcription of target genes critical for proper peripheral myelin development.

* Egr2I268N/I268N mutant mice maintain normal weight and have only mild tremor until 2 weeks after birth, at which point they rapidly develop worsening weakness and uniformly die within several days. Nerve electrophysiology revealed conduction block, and neuromuscular junctions showed marked

[http://jnnp.bmj.com/content/48/12/1269.full.pdf Congenital hypomyelinating neuropathy]

* Describes the symptoms of two patients with congenital hypomyelinating neuropathy

* Hypotonia = low muscle tone (amount of tension or resistance to movement in a muscle)

* Areflexia = absence of neurologic reflexes such as the knee jerk

* Distal muscle weakness

* Atrophy = wasting of a part of the body

* Exceedingly slow nerve conduction velocities

* Usually leading to early death or severe disability.

* It contains great images of the histology of the condition as well as the actual patients

* It contains a detailed recount of sural nerve biopsies of the patients

* It compares the symptoms of congenital hypomyelinating neuropathy in Trembler mice as they are very similar to human symptoms

'''Review Article:'''

[http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TBD-3W37BMX-C-1&_cdi=5140&_user=1975841&_pii=S0887899498001386&_origin=&_coverDate=03%2F31%2F1999&_sk=999799996&view=c&wchp=dGLzVzb-zSkWA&md5=d2e9e64dfc821d71ec81675f01932b8a&ie=/sdarticle.pdf Congenital hypomyelinating neuropathy: two patients with long-term follow-up]

* Review of previously reported cases of congenital hypomyelinating neuropathy (CHN) aswell as two unrelated females with CHN

* The first patient is now 9 years old and has showed continual improvement of motor function even though her follow up nerve conduction velocities remained unchanged

* The second patient is now 5 years old and has also showed continual motor function improvement since her first visit even though her follow up nerve conduction velocities also remained unchanged

--[[User:Z3290815|Tara Lofthouse]] 12:22, 9 August 2011 (EST)

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=='''Fragile X Syndrome'''==

==='''Articles'''===

Hey guys,
I had a look at Congenital Hypomyelinating Neuropathy and to be honest i did not find it very appealing. I found the disorder "Fragile X Syndrome" to be very interesting! Can you guys please check out the following link on [http://www.fragilex.org/html/cause.htm/ Fragile X Syndrome] and let me know if the disease also interests you!? I found the information on it is quite extensive and the disease is well known. If you do not want to base our project on this syndrome, i am sure we can decide on one we can all enjoy studying! :)

Here are some interesting articles that i have found on '''Fragile X Syndrome''':

* '''Review Article''': Fragile X syndrome: from gene discovery to therapy <ref><pubmed>21196228</pubmed></ref>

- This review focuses on the molecular and biochemical pathways shown to be relevant in the Fragile X Syndrome. It describes that a mutation in the FMR-1 gene was found to lead to Fragile X Syndrome due to excessive repeats of the trinucleotide sequence CGG which is known to inactivate the FMR-1 gene, making the X chromosome fragile and prone to breakage. This review article also demonstrates the many vital functions of the FMR-1 gene such as its role in RNA transport and stability, thus absence of the protein transcribed and translated from this gene is thought to affect brain development and thus leads to signs of mental retardation.

* '''Research Article:''' DNA methylation represses FMR-1 transcription in fragile X syndrome <ref><pubmed>1301913</pubmed></ref>

- This research article explores the two molecular differences of the FMR-1 gene in normal individuals vs. those with Fragile X Syndrome. These differences are an increase in size of an FMR-1 exon containing a CGG repeat and abnormal methylation of a CpG island 250 bp proximal to this repeat. This research article also shows how these two abnormalities repress transcription of the FMR-1 gene, leading to the absence of the FMR-1 protein which is thought to be the contributing factor to the Fragile X phenotype.

--[[User:Z3290808|Sandra Issa]] 19:53, 9 August 2011 (EST)

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Here are some articles I have found for '''Fragile X syndrome''':

'''Research Article:''' The state of synapses in Fragile X Syndrome <ref><pubmed>19325170</pubmed></ref>

* Fragile X Syndrome is the most common inherited form of mental retardation and a leading genetic cause of autism.

* Evidence that suggests alterations in synapse number, structure and function are associated and contribute to both Fragile X Sydrome and autism.

* Fraile X Syndrome is caused by loss of function of the Fmr1 gene which encodes the RNA binding protein, FMRP (FMRP is present at synapses where it associates with mRNA and polyribosomes).

* FMRP is also has a role in synapse development, elimination and plasticity.

* An understanding of the molecular and synaptic function of FMRP, as well as the consequences of its loss, has led to the early developments of therapeutic strategies for Fragile X Syndrome.

'''Research Article:''' Fragile x syndrome: history, diagnosis, and treatment. <ref><pubmed>6348096</pubmed></ref>

'''Review Article:''' Systematic review of pharmacological treatments in fragile X syndrome <ref><pubmed>19822023</pubmed></ref>

'''Review Article:''' FMR1 and the fragile X syndrome: human genome epidemiology review <ref><pubmed>11545690</pubmed></ref>

--[[User:Z3290815|Tara Lofthouse]] 14:37, 16 August 2011 (EST)

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==='''Images'''===

[[File:FMR4 is silenced in fragile X syndrome.jpg|thumb|FMR4 is silenced in fragile X syndrome]]

[[File:FMR4 is silenced in fragile X syndrome.jpg|350px]]

File:FMR4 is silenced in fragile X syndrome

--[[User:Z3290808|Sandra Issa]] 10:20, 14 August 2011 (EST)

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[[File:Hippocampal_Formation.jpg‎|thumb|Hippocampal_Formation]]

[[File:Hippocampal_Formation.jpg‎|600px]]

File: Hippocampal_Formation

--[[User:Z3290815|Tara Lofthouse]] 13:49, 17 August 2011 (EST)

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Like?
[[File:Fragile site appearance and distribution.png|300px]]
File: Fragile site appearance and distribution
--[[User:Z3290618|Ziggy Harrison-Tikisci]] 08:55, 18 August 2011 (EST)

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[[File:Journal.pone.0013559.g001.png‎|thumb|FXR1 (A) and FXR2 (B) crystal structures]]

[[File:Journal.pone.0013559.g001.png‎|300px]]

File: FXR1 and FXR2 crystal structures

--[[User:Z3290689|Boris Zolotarev]] 11:00, 18 August 2011 (EST)

== '''Who's doing what?''' ==

* Introduction = DO AT THE END!!!!
* History of Disease = Tara
* Epidemiology = Tara
* Etiology = Boris
** Genetic contribution<ref>http://www.fragilex.org/html/premutation.htm</ref><ref><pubmed>10208170</pubmed></ref><ref><pubmed>11445641</pubmed></ref><ref><pubmed>12638084</pubmed></ref><ref>http://ghr.nlm.nih.gov/condition/fragile-x-syndrome</ref><ref><pubmed>8348153</pubmed></ref>
** Development of Disease
*** Fetal Development
*** At birth
*** In Adult
* Signs and symptoms = Ziggy
** Physical phenotype
** Social interaction
**Intellectual development
* Recent research = Sandra
** Fragile X and Autism
** Diagnosis
** Treatment
* References

==ZIGGY'S STUFF==
Just leaving this here for the next hour, so that I don't have to retype it all (can't get wifi in the embryo lab).

The hallmark of the fragile X syndrome is mental retardation, which was noted as early as 1943 in a report of a large family with 11 mentally retarded males and two mildly retarded females. 64 The clinical phenotype associated with the syndrome has since been widened to include a variety of cognitive, physical, and behavioral characteristics (reviewed in Mazzocco). 65 Almost all males with the full mutation exhibit some clinical features of the fragile X syndrome. Also, most affected males do not reproduce, presumably due to the severity of mental retardation. With regard to cognitive function, affected males often exhibit developmental delay very early in childhood. By the age of 3 years, most males will test in the mentally retarded range. 66 Ultimately, almost all males with the fragile X syndrome are mentally retarded, with severity ranging from profound (IQ <20) to mild mental retardation (IQ 50–70), with most being moderately retarded (IQ 40–54) (reviewed in Hagerman). 67 Physically, adult males often have a long narrow face, prominent ears, a prominent jaw, and macroorchidism (reviewed in Hagerman). 67 Other common physical features include a high arched palate, hyperextensible finger joints, double jointed thumbs, single palmar crease, hand calluses, velvet-like skin, flat feet, and mitral valve prolapse (reviewed in Warren and Sherman). 8 Males with the fragile X syndrome also tend to exhibit behavioral features such as hyperactivity, social anxiety, perseverative speech and language, tactile defensiveness, stereotypies (e.g., hand-flapping), and hand biting (reviewed in Hagerman). 67 Autistic-like behavior is also described in these males, with as many as 25% of males with the fragile X syndrome meeting the diagnostic criteria for autism. 68 The association of fragile X with autism, however, is not clear because the proportion of males with the fragile X syndrome meeting the diagnostic criteria for autism seems to diminish with age. 68

Physical phenotype
Before puberty, children with Fragile-X tend to have no discernable differences in physical appearance. They may have a broad forehead or a slightly larger size head. At puberty, these children begin to develop the physical signs recognized with Fragile-X, such as longer faces, larger jaws and ears. Furthermore, they tend to have impaired growth, and will not achieve a height that one might expect (based on familial relations, or population averages). Males may also develop macro-orchidism: enlargement of the testicles. Fragile-X patients may also have loose connective-tissues, allowing their joints to be more flexible that normal. This may cause complications arising from increased risk of hernia as well as problems associated with other connective tissues such as: heart-valve weaknesses resulting in murmur. Later in life, these men may develop a tremor and experience difficulty walking.

Social interaction
Children with Fragile-X tend to experience social anxiety, feeling awkward and uncomfortable in new environments and situations. Often, they may avoid social interactions, due to the anxiety, and tend not to seek contact with others. Their anxiety often manifests itself as discontinuous speech and a lack of eye contact.

Results indicate that compared to the control group, individuals with FXS exhibited decreased activation of prefrontal regions associated with complex social cognition, including the medial and superior frontal cortex, during successful face encoding. Further, the FXS and control groups showed significantly different relationships between measures of social anxiety (including gaze-fixation) and brain activity during face encoding. These data indicate that social anxiety in FXS may be related to the inability to successfully recruit higher level social cognition regions during the initial phases of memory formation.
Reference: Prefrontal social cognition network dysfunction underlying face encoding and social anxiety in fragile X syndrome.

Intellectual development
As a generalisation, the majority of Fragile-X patients have an IQ between 1 and 2 standard deviations below the population mean. This equates to around 40-85. Few Patients lie out-side this range, with approximately 20% within the ‘normal’ range (85-115) and less below 40. Females however, show lower impairment, with only one-third having IQs within the ‘mental retardation’ range.
Generally, Fragile-X patients have trouble with forming abstract ideas, planning and problem solving. Conversely, they tend to have a good memory for pictures and visual patterns, and may be better adept at following instructions if presented in picture format.
Compared to their unaffected siblings, children with FXS obtained significantly lower percentage correct scores on all subtests of the WISC at both time points. During the time between the first and second assessments, the annual rate of intellectual development was approximately 2.2 times faster in the unaffected children compared to the children with FXS. Levels of the fragile X mental retardation protein (FMRP) were highly associated with intellectual ability scores of the children with FXS at both time points.

Studies of intellectual function in FXS often demonstrate a mean IQ decline of 4 to 9 standardized points over intervals ranging from several months to 13 years.
Reference: Longitudinal Changes in Intellectual Development in Children with Fragile X Syndrome

Working Memory
First, when individuals affected by the premutation are examined as a group, they exhibit a weakness only for tasks that reflect functioning of the central executive subcomponent of working memory.

Second, when both permutation sub-groups are examined together, the extent of the central executive deficit is significantly correlated with larger CGG repeat expansions.

For permutation males who are asymptomatic, mild executive dysregulation, inhibitory deficits that worsen with age, and declarative verbal learning and memory are notable.

The detection of a deficit in the central executive component of working memory in the fourth decade of life that progressively deteriorates with age suggests a cumulative process that may be a cognitive correlate to the underlying degenerative process identified in premutation males.

The significant correlation between CGG repeat length and central executive working memory in asymptomatic carrier males suggests greater neuropathology in carrier males with larger expansions in FMR1 mRNA transcripts.
Reference: Lifespan changes in working memory in fragile X premutation males

Emotional characteristics
Fragile-X children often are easily upset or overwhelmed. New situations can easily frighten them. Upon entering an unfamiliar situation, some tend to cry, whilst others may become tense. These may often lead to tantrums or repetitive tics. During puberty and teen years, hormone levels may exaggerate this, making the tantrums more violent and the patients largely more aggressive. Furthermore, the usual anxiety experienced with difficult tasks may take longer to abate, meaning the patient may take longer to calm-down.

Language and Speech
Often these children have problems with coherence, word pronunciation and correct grammar use. This impairs their ability to properly communicate meaning. More serious speech problems are associated with vocal processing, such as: moderating tone, pitch or loudness as well as coordinating the movements needed to vocalize sounds. Furthermore, they may have difficulties processing spoken information and, as shown above, will be better at following instructions if presented in picture format. These children may stutter, omit sounds out of their words, repeat themselves, or restart the same sentence many times. They may also speak fast and/or mumble.
It is important to note, that some of their disability to communicate can be attributed to the shyness and social anxiety, while specific deficits may be due to sensory overload, rather than specific neural problems with control of speech and language.

== '''References''' ==
<references/>

Talk:2011 Group Project 4

2011-09-28T07:09:07Z

Z3279511: /* Peer Review */

[[2011_Group_Project_4|'''Group 4''']]: [[User:z3389806]] | [[User:z3290270]] | [[User:z3290379]] | [[User:z3290558]]

{{2011GroupDiscussionMH}}

==Peer Review==

'''Group 4: Peer Assessment'''
* Your page has a good balance of text, images and tables
* I like that your introduction is brief and to the point
* You history section is the best one have seen so far, it looks good and it easy to read
* The image in the pathogenesis has no copyright information
* In clinical manifestations are quite important I think and your section seems a little weak in comparison to the rest
* Treatment: I'm sure the table was a lot of work but it is quite complex ad all the drug names make me a bid dizzy. May be you can shorten it to the most relevant?
*Overall the page has a good content and it's fun to read. The diagrams and drawings are great --z3279511 17:09, 28 September 2011 (EST)

'''GROUP 4: Huntington's Disease'''
*Intro has good summary of the disease, however the first paragraph is a little too technical, could you maybe simplify it a little so you don't lose the reader right at the start (reference 5 is missing though)
*History is succinct and summarised well, i like the quote included, could you have gone a little further with the timeline? (maybe include some of the more recent developments), maybe the timeline could be better formatted in a table
*Good info from a variety of sources in epidemiology, good use of tables, I like how prevalence has been compared and how the table is explained (one little thing: could you maybe find more statistics for Australia?)
*Inheritance image needs student template added and maybe made a little bigger so detail can be seen
*Genetics section is informative but could use an image of the gene maybe
*Molecular Mechanisms & Pathogenesis section is well researched and good summary is provided. I like how key words have been highlighted. images need fixing (more descriptive legend is needed for the first image and what happened to the second image?
*I don't think you need to explain what the disease is again in the clinical manifestation segment (don't want to sound repetitive), image in this section isn't very clear, I feel that this section is a tad incomplete-maybe some expansion is needed e.g. classes 2 and 3 could be expanded on more
*I feel that diagnosis section could go further up? This section is very informative, but could be summarised a little more Some of the images in this section need better explaining, good balance of text and images in this section
*good use of table in treatment section, however more info could be provided as to how these drugs help the disorder
*Current/Future Research is very up to date, images here again need more description

Overall:
*it is evident that this project has been extensively researched
*good use of subheadings and headings
*maybe include the acronyms in the glossary and it would be good if glossary words were linked to text
*make sure all images include the student template required and legends of some images need to be expanded (more info on what the image is about)
*fix repetitive sentences
*good balance of images and text, good use of tables

--[[User:Z3331556|z3331556]] 15:27, 28 September 2011 (EST)

'''Peer Assessment Group 4'''

*Second sentence of intro is WAY too detailed for the intro, it means very little as the disease has not yet been explained to us and is too technical – OR, keep it but explain it in a more general way.
*What do you mean by familially or sporadical development? Define what you mean by this (intro)
*Timeline – events need to be explained. E.g. Venezuela Project – what is this? Why is it significant? (this is needed for most of the history entries)
*HTT and normal functions – can you explain what some of the processes are? E.g. dynactin complex, clathrin-mediated endocytosis are?
*Calcium signalling in pathogenesis – maybe explain why the calcium signalling pathway is important?
*The video file – make sure you write a little para about it. It has a new headings – shouldn’t it be a subheading?
*The paragraph of ‘Imaging’ in diagnostic tests needs to be pushed so its under the pics from neuropathology
*Tetrabenazine – I think have an intro sentence about it to highlight that this is the most commonly used one, as you only discuss it in depth (as a drug treatment) – unless you are going to add in explanations of other drugs?
*In Current/future research, refer to the pics on the RHS if they are relevant, otherwise I think they need to go somewhere else
*Overall comment: its good, lots of research, but even as someone who has a background in bio, we still don’t know everything about everything, so I think as you go, explain some of the more complicated processes so you can really understand what is going on.

--[[User:Z3332824|z3332824]] 11:48, 28 September 2011 (EST)

Group 4: Huntington’s Disease

'''Group 4 Peer Review'''
* Good introduction, history seems adequate - although the timeline stops at 2002? Is there anything after this?
* Nice table for epidemiology; although some terms require explaining
* Excellent student-drawn diagrams and genetics section with a good balance between the text, bullet points and images. One image has been removed so be sure that that is re-uploaded!
* Video section: Formatting is a bit of a pain to read when the left hand margin keeps shifting with the images being placed here. Fix this please so that it is easier to track the page with our eyes.
* Treatment section is overwhelming, whilst some might have said that it looks great (and it really does), to suddenly be hit with such a huge table is exhausting. Perhaps shorten this section by mentioning that there is only treatment available for the symptoms, list them, and then link to an image containing the table in its entirety.
* Current/Future research section seems a bit short.
* Overall, it looks like an excellent project that has had a lot of thought put into it. Well done guys :)
--[[User:Z3288827|Leonard Tiong]] 10:25, 28 September 2011 (EST)

Initial thoughts, was wow! Clearly immense time and effort was put into this! Loved the structure of the headings and sub-headings.
*Introduction: Top notch, just needs an image to complete it.
*History: Nice use of the quote box, this section was done very well, except BOLD the years. Personally, I would have liked it more if the timeline itself was in a coloured table, no biggie.
*Epidemiology: Add “(Australia)” After Tasmania? Or just listing countries would be better? Overall, nicely done.
*Genetics: “Inheritance” part feels a little too short. Preferred if the image had black text over a white background. Everything else was great!
*Molecular Mechanisms & Pathogenesis: The space between the purple words and commas could be removed. The purple colour, made me think they were hyperlinks, maybe chose either to bold or colour the words, as having both is a bit much.
*Clinical Manifestations: The features would look better in a table, in my opinion. I like the image, very nice indeed! Good summary.
*Diagnostic Tests: Done well, though compared to the rest of the webpage, it looks very insignificant. I suggest adding more information!
*Video: Fix the formatting please!
*Treatment: Nice table, informative. The “Tetrabenzine” section, the text needs some formatting, sentences are cut off to the next line for some reason, to be honest Medications and Therapies seem to be most important part, so they should maybe be expanded on?
*Glossary: Looks good, just a few full stops missing!
--[[User:Z3332327|Lisa Xiao]] 01:24, 28 September 2011 (EST)

'''Group 4'''

*Very good introduction

*History: looks very nice, but the layout of the quote disrupts the page. I think it would be better to use bold letters, good idea though.

*Epidemiology: nice section, useful tables

*Genetics: good detailed content and drawings

*Pathogenesis: do not bold words in only one section, it disrupts the whole picture, good use of sub- headings.

*Clinical manifestations: good summary of the symptoms in the drawing, the classes and the five specific features would look better in a table, otherwise good section

*Diagnostic tests: the video subheading needs to be fixed, really irritating. Very detailed, I would put all images to the same side

*Treadment: mechanism of tetrabenazine inhibition image could have been done with more effort

*Research: very nice clear section
--[[User:Z3387190|Z3387190]] 21:27, 27 September 2011 (EST)

'''group peer assessment'''
*Introduction is well structured though image of the Huntington gene protein would be more beneficial to where I’m looking relating to genetics
*Genetics could expand more on the inheritance and the Huntington gene
*Role in transcription sub heading image removed
*Diagnostic test image needs to placed in correct section and the video should be placed at the end of the section, placement of the video cause confusion of the other diagnosis tests
*Treatment should have an introduction which introduces the drug used to manage diseases and therapies, better layout where most commonly used drug form management and therapies following the table to show alternative treatment.
*Current/future research should have some future research and images placed have no description which research project image belongs to
*References contain mistakes with repetitions and blanks also some done incorrectly such as reference “3” where not properly inputted on the wiki page
*Glossary was not linked to the web page as well while reading was lost without referring to a dictionary due to no indications definition is in the glossary
z3332250 23:46, 26 September 2011 (EST)

Group 4 Peer Review

*Punchy introduction-well done
*Timeline under history was excellent
*Seemed very scientific and wordy at times-a lot of detail is unnecessary; “less is more”
*Great balance of text and images-very readable
*Page flowed well in a logical manner
*Diagnosis section is very well done however there seems to be too much content/focus relative to the rest of the page. Perhaps add some more to other sections or make this section more concise?
*An extensive glossary and reference list-thorough research
*I learnt a lot from this page so well done!
*Overall, an impressive page. A few more things to tweak to make it excellent.
--[[User:Z3308965|Fleur McGregor]] 19:13, 26 September 2011 (EST)

'''Group 4 Critique'''

#• Introduction was quite good
#• History was good. I liked the timeline
#• Tables in the epidemiology were good
#• The genetics was clearly explained
#• Pathogenesis was really good. I quite liked it
#• Clinical manifestations is good
#• Diagnostic tests could be more detailed
#• Overall, quite a well written project. Well done. Maybe add a little more about the medications.

--[[User:Z3289991|Robert Klein]] 18:47, 24 September 2011 (EST)

'''Huntington's Disease'''

*The intro and history look really good, I like the timeline and the quote box
*What year was the information in the table in 'Epidemiology' sourced? Because from looking at the references, it seems to be within a 20yr period. Is this enitrely accurate to compare these?
*What are HTT and HD halotypes (in 'Epidemiology')? You've only put 'halotypes' in the glossary, you also need to a give a brief definition within the text, not just glossary
*Nice image in 'Genetics', lots of good easy to understand information there as well
*You need to fix the file under 'Role in Transcription Inhibition'
*The diagnosis section looks really good, make sure you get rid of that subheading for the video though
*Interesting table in 'Treatment', however the section on 'Tetrabenazine' does not has complete sentences and seems a bit unnecessary. Honestly I don't really care how the drug works (ie receptors) I'm more interesting in it's implications regarding HD
*The 'Therapies' section was good and succinct
*Current/Future Research looks really good
*Overall the page isn't bad, just need to confirm some details to improve it ie dates and definitions

Group 4
* On first looking at the project it looks like there is a good text/image ratio. However an image in the introduction would work well
* The content of the introduction is very clear and introduces the reader to the topic well
* I really like the history section. The story makes me a little excited about the condition in a way. I am left feeling keen to know more and there is an extensive list of discoveries. There needs to be more after 2002 though. I find it difficult to believe that nothing has been found in the last 9 years.
* The epidemiology table is a nice way of showing the data. But maybe you should put the Australian states in bold and at the top- also maybe include all of the states or Australia as a whole, not just NSW and TAS
* There is a file in the pathogenesis that is not accessible- either get the file up or remove the link
* The image in the pathogenesis has no copyright information
* A couple of grammar problems in the pathogenesis that could be fixed up- full stops mid sentence for example
* The clinical manifestations sections outlines the types of classes of manifestations but it is difficult to actually access the information on what the manifestations are. It would work well in a table with a little more detail on what the patient experiences
* The video is put as a new subheading within diagnosis. It needs to be made into the smaller subheading because I thought diagnosis section was over but it continues underneath
* The diagnosis section is in great detail, somewhat more detail than other sections. This is very interesting and shows that this team member worked hard on their section.
* Good work on the project, just a little editing and formatting to make it a finished product!

'''Group 4'''
* Nice structure of headings and subheadings, it breaks up the text and makes it a readable page. Extremely interesting topic!
* I found the history very interesting and enjoyed the quote from Huntington.
* maybe bold the dates in the timeline, just to make the page easy to follow. Or maybe a table could be appropriate.
* I liked the structure of the epidemiology section and the tabulated prevalences! good work!
* Molecular Mechanisms & Pathogenesis: unsure as to why some sentences were bolded.
* Differential Diagnosis: very interesting I liked that you added this in.
* Treatments table very succinct easy to understand and follow! Great!
* Good to see that most of your references were grouped. only a few that were doubled.
* Maybe have a continuos colour scheme for the page and type of table used.
* Good use of tables and I like that you explained what they were about.
* Make sure all acronyms and scientific language is in the glossary
* good student illustrations
* overall great ratio of text and pictures!

'''Group 4 Assessment'''
*This might be a bit nit-picky, but for the references given throughout the wiki, there isn’t any consistency. The [#] is sometimes right after the sentence, sometimes a space is given between the sentence and citation number, and the end of the sentence (period or comma) is sometimes before or after the reference #...
*The information within the introduction seems to be substantial. Only suggestion would be to add a picture to add to the overall look.
*In the history section, it was a good idea to have the single quote stand out in a colored box to itself. First time I’ve seen this. Looks professional. I question though, if all the events within the timeline are absolutely necessary…
*Epidemiology- Both tables are well organized and look extremely professional. Good information within this section, although it might be a good idea to reference a few more not-so-common terms in the glossary, such as SNP’s and others which may not be common knowledge for all.
*The Genetics section is well formatted with what I believe is the vital information needed in this section. Only complaint is the first picture (Inheritance Pattern…) doesn’t have the copyright information claiming that it is okay to use this image.
*The “Key cellular pathogenic mechanisms in HD” image likewise does not have the copyright information to verify its legal usage.
*Molecular Mechanisms and Pathogenesis section- Very well formatted and aesthetically appeasing. Why are some of the words in purple though? Are they meant to be defined the glossary, or just key points? “The Mutant Huntington gene…” file is also not on the page… Where is it?
*Diagnostic Tests  Research – I have no complaints. These sections look immaculate.
*In the glossary, try having a bullet list and also having the words within the wiki page to link to its definition in the glossary.
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
*Overall, good content within the page and very appealing visually. Just minor editing needs to be done I think. Good job!
--[[User:Z3391078|Z3391078]] 14:31, 27 September 2011 (EST)

'''Peer Assessment: Group Project 4'''
*The introduction and history sections are concise and well formatted.
*A few of the points in the timeline would be improved by containing a bit more information such as 'Mendel's work' and 'The Venezuala project'
*The tables used in the epidemiology section are clear and highly informative.
*The abbreviation HTT is used throughout the epidemiology section before it is stated what it means in the genetics section. This should be changed.
*The picture related to transcription factors needs to be fixed so that it can be displayed.
*The section entitled 'Video of Huntington's disease patient' should have a more appropriate heading to encompass the rest of the written information in that section.
*Under the information in some of the images you have uploaded, you still need to add <nowiki>{{Template:2011 Student Image}}</nowiki>.
*Some of the references are duplicated. They can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.
*Overall the project is highly informative, well written and formatted.
--[[User:Z3217345|z3217345]] 21:34, 27 September 2011 (EST)

==Discussion==

Hey Liz, I posted on the fb page regarding the genetics and pathogenesis part. The student drawn image I'm okay with doing yes. So far I was thinking about doing a picture showing the autosomal dominant nature of the gene. Basically a "tree diagram" of what happens when one parent is affected and the offspring has a 50% chance of inheriting HD.
But I'm okay at drawing so if someone else has something better they'd like me to draw I'm okay with it. :)
Girls please check fb, bit of a crisis.
:)

--[[User:Z3290270|Maeda Sadeghpour]] 06:00, 14 September 2011 (EST)

hey girls, i think we really need to start hurrying things along with our project. Maedeh, i know you said that peer reviews arnt getting marked, but we need to have our project FINISHED by then because after that we are only making finishing touches based on teh peer reviews. Also, are you still doing the student drawn image? Ta

--[[User:Z3290379|Elizabeth Blanchard]] 12:41, 13 September 2011 (EST)

Genetics + Pathogenesis

Yea I think so, it would make it more relative. If anyone comes across any studies just post the link here or on fb. :)

--[[User:Z3290270|z3290270]] 23:36, 24 August 2011 (EST)

Hmm, are epidemiological studies on HD? If there is, we should add. It will make our webpage more comprehensive.
And I don't mind doing that section.

--Nur Sharalyn Abdullah 20:24, 23 August 2011 (EST)

Girls, do you think we need an 'Epidemiology' heading??

--[[User:Z3290379|Elizabeth Blanchard]] 17:25, 23 August 2011 (EST)

Introduction + Clinical Manifestations.

--[[User:Z3290558|Lisa Lee]] 14:42, 23 August 2011 (EST)

Current + Future Research & Diagnostic Tests.

--[[User:Z3290379|Elizabeth Blanchard]] 09:30, 22 August 2011 (EST)

Sharalyn: History & treatment

--Nur Sharalyn Abdullah 20:15, 20 August 2011 (EST)

'''White blood cell populations from Huntington's Disease patients'''

[[File:White_blood_HD.gif]]

--[[User:Z3290558|z3290558]] 23:46, 17 August 2011 (EST)

===Establishment of HD hybrid cell line===

[[File:Establishment of HD hybrid cell line.jpg]]

(A) First polar body of mature rhesus macaque oocyte was removed by gentle squeezing through a slit of zona pellucida (A-a). Staining of 1st polar body DNA (arrowhead) and oocyte DNA (arrow) (A-b). HD monkey skin cell was placed under the zona pellucida (black arrow) (A-c). Reconstructed oocyte with HD monkey skin cell (A-d; yellow arrow) was placed between two electrodes for electrofusion (A-d). (B) Day 12 hatching blastocyst derived from HD monkey hybrid embryo (B-a; arrow indicated ICM). HD monkey hybrid blastocyst outgrowth at six days after attached onto feeder cells (B-b). High magnification of selected region (inset) of the ICM outgrowth (arrowhead). HD monkey hybrid cell line (TrES1) at passage 10 (B-c). (C) G-banding analysis of TrES1. Cytogenetic analysis of TrES1 demonstrated tetraploid chromosome (84; XXXY). (D) Expression of ES-cell specific markers: Alkaline phosphatase, Oct4, SSEA4 and TRA-1-60.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833146/?tool=pmcentrez

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

--[[User:Z3290270|Maeda Sadeghpour]] 21:30, 17 August 2011 (EST)

'''Large stem cell-derived neurospheres were generated from 33-week old HD hippocampus, but not WT hippocampus.'''

[[File:Stem cells neurospheres drived from Huntingtons Disease hippocampus.png]]

--[[User:Z3290379|Elizabeth Blanchard]] 15:06, 16 August 2011 (EST)

'''Melatonin levels in Huntington's disease patients and controls'''

[[File:Melatonin levels in HD patients and controls.jpg]]

The diurnal melatonin rise was significantly delayed in HD patients by about 01:30 h (p = 0.048). The black bar on the abscissa indicates the dark period (23:00–7:30 h).

--Nur Sharalyn Abdullah 12:21, 16 August 2011 (EST)

We decided on Huntington's Disease, I believe Nur spoke to you at the end of the class. :)

--[[User:Z3290270|Maeda Sadeghpour]] 16:44, 13 August 2011 (EST)

--[[User:S8600021|Mark Hill]] 18:28, 11 August 2011 (EST) Your group left the lab today without notifying me of your selected group topic.

Group 4 Topic: Neural Tube Defect

Research Article:

Conway S.J., Gosnell M., Rogers R., Simmons O., Snider P., Young R. (2011), Notochordal and foregut abnormalities correlate with elevated neural crest apoptosis in Patch embryos. Birth Defects Research Part A: Clinical and Molecular Teratology. doi: 10.1002/bdra.20802. Epub 2011 May 6.

http://www.ncbi.nlm.nih.gov/pubmed/21557455

Review Article:

Abdel-Hamed Z., Johnson C.A., Logan C.V. (2011), Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects. Molecular Neurobiology

http://www.ncbi.nlm.nih.gov/pubmed/21110233

--[[User:Z3290558|z3290558]] 02:07, 11 August 2011 (EST)

'''Neural Tube Defects'''

[[Review:]] Padmanabhan, R. (2006). Etiology, pathogenesis and prevention of neural tube defects. ''Congenital Anomalies'', 46(2), 55-67.

[[Research:]] Joó, J. G., Beke, A., Papp, C., Tóth-Pál, E., Csaba, A., Szigeti, Z., Papp, Z. (2007). Neural tube defects in the sample of genetic counselling. ''Prenatal Diagnosis'', 27(10), 912-21.

--[[User:Z3290270|z3290270]] 02:34, 11 August 2011 (EST)

''Review'': Bassuk AG, Kibar Z. '''Genetic basis of neural tube defects.''' Semin Pediatr Neurol. 2009 Sep;16(3):101-10 [http://www.ncbi.nlm.nih.gov/pubmed/19778707]

''Research'': De Marco P, Merello E, Cama A, Kibar Z, Capra V.''' Human neural tube defects: Genetic causes and prevention.''' Biofactors. 2011 Jun 14.[http://www.ncbi.nlm.nih.gov/pubmed/21674647]

--[[User:Z3389806|Nur Sharalyn Abdullah]] 14:24, 10 August 2011 (EST)

We are doing on neural tube defects!

--[[User:Z3389806|Nur Sharalyn Abdullah]] 13:47, 10 August 2011 (EST)

Neural Tube Defects

Article: <ref><pubmed>19120526</pubmed></ref>
Review: <ref><pubmed>18182339</pubmed></ref>

===References===
<references/>

--[[User:Z3290379|Elizabeth Blanchard]] 22:25, 9 August 2011 (EST)

Hi girls (: I actually managed to find some genetics-related articles on neural tube defects. It has something to do with folate and folate-related genes from what I have read so far. So how about it? Shall our website be based on neural tube defects? (:

--[[User:Z3389806|Nur Sharalyn Abdullah]] 08:12, 9 August 2011 (EST)

Hey girls,

So I've done a bit of research on a few of them.
One of the things we need to keep in mind is that it has to relate to the '''learning outcomes''', which I think is the embryological process, and how the genetic disorder relates to it or how its affected by it? (I tried looking it up but couldnt find it).

Here's a list of the topics I've been looking into:

[[Turner Syndrome:]] commonly known to have one missing sex chromosome, (or both) - LOTS of info on this. (only thing is, because its such a broad topic, we might have articles that contradict each other, or might not have that many embryology related new articles...?)

[[Klinefelter's Syndrome:]] the gigantic disease with the extra chromosome (XXY). there's a decent amount of info on this, but not as much as Turner.

[[Neural Tube defects:]] problems happening in the first month of baby formation because of the folate deficiency in the mother. But i'm not too sure where the genetics come into this..

Which topics have you guys been looking at? Let us know! cos we need to have some articles in '''[[2-3days time!]]''' :)

Ye it's better to research an area instead of just one disease then, because that will give us more to talk about... especially the genetic components which Mark commented on. So I was thinking Neural Tube Defects instead. That will give us Anencephaly, Encephaloceles, Hydranencephaly, Iniencephaly and Spina bifida. ?--[[User:Z3290270|Maeda Sadeghpour]] 01:09, 8 August 2011 (EST)

You need to think about what the genetic component will be for the disease you select. --[[User:S8600021|Mark Hill]] 23:51, 7 August 2011 (EST)

I don't think that having 4 categories will be a problem. I actually think that it will be good to have extra stuff to talk about. Have a look at the other pages from previous years, they are very elaborated so I think it's actually a good thing to have alot of things to talk about. But anyway lets decide on something so that we can post up our articles

--[[User:Z3290379|Elizabeth Blanchard]] 22:00, 7 August 2011 (EST)

Hey! I get what you mean, Maeda. Doing 4 categories can be quite heavy. Hmm, but I was thinking, since this is going to be a wikipage and the elaboration for the 'original' wikipage for spina bifida is not very deep for the 4 categories, maybe we could leverage on this weakness and make ours more detailed? :) But if you guys think it is too much, I don't mind doing the other suggestions too! Anyway, this is just a preliminary decision. It depends on the topics that other groups have chosen too. Would it be possible for us to finalise the topic by tomorrow?

--[[User:Z3389806|Nur Sharalyn Abdullah]] 17:18, 7 August 2011 (EST)

Hello people. I was basically trying to see which diseases had the most current information available online, and cystic fibrosis seems to be very well known. Spina Bifida is very interesting as well, my only concern with it is the 4 categories it's divided into, which I thought might make it a bit more work. What do you guys think? :)

--[[User:Z3290270|Maeda Sadeghpour]] 00:25, 6 August 2011 (EST)

Hey, girls! I'm thinking of spina bifida and hydrocephalus. Cheers!

--[[User:Z3389806|Nur Sharalyn Abdullah]] 20:26, 5 August 2011 (EST)

hey guys, had a quick look and Spina bifida and Turner's Syndrome both seem to have a decent amount of information on them

--[[User:Z3290379|Elizabeth Blanchard]] 14:26, 5 August 2011 (EST)

==Peer Assessments==
* Interesting but good use of a quote
* The introductory paragraph for the “history” section could probably be cut down or eliminated altogether
* Great inclusion of statistics in regards to epidemiology
* Student images were excellent, well drawn and were engaging
* Pathogenesis section could have been placed in a table just to change up the formatting
* The video inclusion was good and relevant
* You’re referencing needs to be tidied up; there are multiple entries from the same source that tends to clutter your reference section.
--[[User:Z3332629|z3332629]] 15:24, 22 September 2011 (EST)

Talk:2011 Group Project 3

2011-09-28T07:08:07Z

Z3279511: /* Peer Review */

[[2011_Group_Project_3|'''Group 3''']]: [[User:z3289066]] | [[User:z3289301]] | [[User:z3289829]] | [[User:z3289991]]

{{2011GroupDiscussionMH}}

==Peer Review==

'''Group 3: Peer Assessment'''
* You have constructed an informative page about an interesting syndrome
* At this stage it's a little text heavy, so may be you can cut it down and add some pictures instead
* In the history section it would be great to see these dates from the table with the text blended in, so it's on chronologic flow.
* You seem to take it very serious with the mitosis or not communicating with each other because you have four pictures of mitosis in three different sections. One picture and a good explanation would be sufficient. Then you could use the rest of the space for other pictures.
* The table for signs ad symptoms is great, but looks a bid empty. So may be you can change the format or add some more pictures.
* May be you could write a bid more about therapeutic options. I would find that more important then "similar abnormalities"
* Good referencing through the section. Just change the "double referencing"
* Overall, you page has a lot of information, may be you can balance it a little more out, communicate so you don't have "double" information and a few more pictures would be great.
--z3279511 17:08, 28 September 2011 (EST)

'''GROUP 3 Peer Assessment: Klinefelter's Syndrome'''
*I feel that the introduction is too lengthy, it should be summarised a little more. Although the info is informative, its structure needs some work- grammar and punctuation should be reviewed and sentence structure could be improved
*Figure 1 could use a more descriptive legend
*Historical information is ok, maybe could be improved by extending the timeline to a more resent years, also an image wouldn't hurt, just to break up the text a little
*epidemiology could use some proof reading to correct minor grammar mistakes e.g. "Males born with Klinefelter syndrome often fail to produce sperm, and have very low testosterone levels due to largely to them having small testes", sentence structure could also be reviewed so this section flows better (some sentences are short, but other than this, this section is informative
*Incidence is repeated twice, maybe could stick to one section, and it's different in each section (1 in 50 000 or 1 of every 1000 male births?)
*Aetiology (don't really know what this means), and the subheading "genetics" could be a better choice for the whole section, but info here is informative and understandable
*I do like the links made in Aetiology, the picture in this section could use a better legend and needs to be referenced properly (no copyright statement?)
*There is overlapping info in the Aetiology and Pathogenesis sections (both have Non-disjunction as subheading), and both have the same sort of images
*Table in signs and symptoms is too small should be a lot bigger so detail can be seen, it also needs to be referenced properly
*The info for signs and symptoms is good in a table, but it would be better if the table had colour so the reader can distinguish each section of the table
*diagnosis is informative

Overall:
*Reference list needs some work, some of the references have been repeated
*Project could be improved by finalising the glossary and maybe linking the words in the body to the glossary itself
*Images need to be referenced properly and some need more informative legends
*I feel some of the information is a little repetitive, maybe could read through and edit so it flows better
*subheadings and headings could be reviewed and re-organised so page flows better
*I do like the feature of links added throughout, maybe more would make it better

--[[User:Z3331556|z3331556]] 14:28, 28 September 2011 (EST)

'''Group 3 Peer Assessment'''
* Try to link your sentences in general - at times the reading is quite disjunct and difficult to read. Try to rewrite sections and see if it can be written in a more succinct manner.
* In general, keep the images on the right hand side of the page - I know you want to break things up, but if images are kept on the left then it disrupts the paragraph lining and makes the information difficult to track with the eye (just a minor thing, this is my opinion anyway)
* Some subsections just appear too short; is it really necessary to make a subsection for one or two sentences, as is the case of karyotyping? Try to implement all of the information into one paragraph
* The first image requires a proper reference to the work; is there any copyright information? And also protect your hand-drawn images - they are drawn excellently, but have no copyright information (unless you are happy with the images been used straight away by other students! :) )
* The current research section and possible treatment options section is far too brief; if this is a syndrome that causes many problems, then there should be a fair amount describing our direction of research and methods in which we can combat this syndrome. Try to find more information here!
* Overall, a good balance of the images and format, but reconsider the structure of paragraphs and subheadings so that the entire project has a better feel. Many sections feel like they have been started with great enthusiasm, but this has burnt out over time, giving the project a feel that some sections are just left incomplete. Try to fix this!
--[[User:Z3288827|Leonard Tiong]] 09:37, 28 September 2011 (EST)

'''Peer Assessment'''
*The first two paras of the introduction belongs in the genetics/etiology section. Need a broad intro to the actual syndrome and what happens in it. You don’t need to give a brief overview of all the sections, this isn’t an English essay.
*History- break up with bullet points?
*Figure 3 is a bit small – a bigger pic will look better I think
*Pictures in the Pathogenesis section look funny with the text – maybe have one under the other? It just squares the text in the middle and it looks odd.
*Don’t forget the missing pics in the signs and symptoms table
*History/timeline table might look better in purple – keep it consistent with the others.
*In the Current Research section, the 2nd paper that you have described is written with very colloquial language – can’t use that here! Maybe have a brief intro para about current research and where its headed etc, not just a description of papers. Also, maybe link them to other papers, e.g. This paper shows similar results to _______, surely there are similar findings in particular areas of research?
*Fertility picture needs to be in a ‘Figure’ box with a description and explanation of what it means.
--[[User:Z3332824|z3332824]] 23:30, 27 September 2011 (EST)

'''Group 3'''

*I think the introduction should be a little more concise
*History could work better if all the information was summarised in a table/timeline rather than having paragraphs then a timeline. *Also, I find it a little hard to believe that no findings have been made since the 1970s.
*Epidemiology would probably benefit with subheadings
*Signs and symptoms are nicely set out
*I like that you have added a comparison of other diseases
*Maybe add a few more researches from 2011 rather than 2010 (if possible)
*Overall, quite a good project with some minor adjustments needed

Group 3:

*Whilst I appreciate the introduction and its content, I feel an introduction doesn’t need to be of the same size as some of the other sections of the project. It is to give a mere idea of the condition.
*History could be broken apart with dot points or bolded dates instead. How about a picture of Harry Klinefelter?
*Aetiology picture has no link to the article or where it was found, and no copyright notice.
*Pathogenesis has very little references, surely more would have been used.
*Images in table are blank and a lot more references would have been used than shown.
*space out the subheadings so they don’t look disjointed in diagnosis.
* references have not been listed properly (various links for same article)
--[[User:Z3291423|z3291423]] 18:09, 27 September 2011 (EST)

Group 3: Klinefelter’s Syndrome
*overall look: inconsistent formatting, imbalance of text and images in some sections, appropriate headings used.
*introduction: very broad, maybe too much detail?
*history is well researched; I really like the timeline at the end which summarises the major advancements. But it is very short and ends in the 1970s. It could include current research/advancements.
*Epidemiology: could benefit from a few subheadings or breaks in the text.
*Aetiology: I really like the use of external links.
*Signs and symptoms: works well in a table format but not sure why some cells are coloured and others are not.
*Other similar defects: interesting addition to the webpage, allows audience to continue research. Also demonstrates extensive knowledge of the syndrome. Great idea!
*Minor adjustment: just for convenience, glossary terms could be linked
--[[User:Z3332327|z3332327]] 16:14, 27 September 2011 (EST)

'''Group 3 assessment:'''
*Introduction begins in a confusing manner should begin explaining the disorder Klinefelter’s syndrome before explaining the genetic component of meiosis. Where the image was explained though would be more beneficial if the introduction have an image of the founder of the syndrome within this section or within the history heading.
*History has clear structure with explained information of the progress with relation to the timeline of the syndrome, images would have been more useful within this sub heading to make livelier instead or too much text.
*Epidemiology detains the male component though could explain female areas related to syndrome as well figure 3 .
*Pathogenesis is organised with images placed in areas which bring upon confusion where fig 5 and 6 both linking to Non-disjunction, image placement beneath text would be better placement.
*Signs and symptoms could have a little more elaboration and/or more images
*Sub heading of diagnosis at birth needs to place either in the centre or down 1 sentenced to become more organised.
*References should remove any repeats and the links below should be manually added to the references either under another subheading or normally
*Glossary should be linked throughout, either linking the word to the glossary or even bolding the terms so no confusion for people without any background in the area can understand.
z3332250 23:43, 26 September 2011 (EST)

Group 3 Peer Review

*Well structured and organised
*Timeline seems odd that it ends at 1970? If further information cannot be found, try to present this in a different way
*Figure 2 and 3 could perhaps be a little bigger
*Should a copyright statement be included in some of the images?
*Signs and symptoms table is great
*Some duplication of information throughout page-unnecessary
*Video link is a nice extra
*Well balanced text, images, and tables/graphs
*Overall, a well written page and visually appealing
--[[User:Z3308965|Fleur McGregor]] 18:48, 26 September 2011 (EST)

===Comments on Group Project 3===
'''Strengths:'''
*Smooth flow between headings and subheadings throughout the page.
*Timeline included provides a good summary of the block of text above it. Gives a reader a choice to read the summarised timeline or the block of text containing more details.
*The video links under Aetiology/Non-disjunction is very appropriate.
*The overall formatting of the page is well-done and neat.
'''Weaknesses:'''
*Introduction is a little bit too detailed. It should clear but concise.
*There is a lot of duplication of references.
*Some of the images did not include copyright statement which allows wiki users to re-use the image e.g. Figure 1
'''Specific corrections:'''
*What is aetiology?
*”These are anaphase lagging and nondisjunction. The latter of the two, nondisjunction, takes place more often.” Any statistics for this? If there is, it will be good to include it.
*Some of the signs and symptoms are not referenced.

--Z3389806 07:08, 26 September 2011 (EST)

'''Group 3'''

*Introducton: the beginning is a bit to abrupt, very nice image, otherwise good content

*History: very detailed information, useful timeline

*Epdidemiology: fig.3 would look better on the right side, the content is good

*Aetiology: no copyright information for the image, good use of subheadings.

*Pathodenesis: again, figure would look better on the right side, it disrupts the flow.

*Signs and symptoms: good table, the images look a little lost though, so maybe place them on the right edge, “age and intellect” could be bigger.

*Diagnosis: well done

*Management: good content, nice flow

*Similar defects: good content, but the structure could be better, maybe place the content in a table without the dots. Everything that belongs to e.g XO should start at the same hight

*Research: interesting section, well done

*Glossary: seems incomplete

*Make sure to include the copyright notice in all images
--[[User:Z3387190|Z3387190]] 12:13, 25 September 2011 (EST)

Group 3
* The first thing I noticed is that the project is very text heavy. Also- there are 4 images of mitosis. Is this really necessary? One is enough and you can use the other spaces to put other images in
* The introduction gives a nice, broad overview of the project. I understand immediately what is going to be said. But is there not an image of a patient to put here to draw the reader in? Maybe its just me that isn’t very excited about images of mitosis sorry.
* The history section would work better as a list of dates and names rather than a bulk of text
* Has there been no research since the 1970s? More recent findings need to be added to the history
* The epidemiology is very interesting- but there is a lot of clinical manifestations here that are described later. There is a double up in information.
* Signs and symptoms works well in a table- but more images of the condition would make it even better
* The comparison of other conditions is excellent! Great idea.
* Your information is there is just needs to be organised a little better and the fact that you have double ups on information and pictures indicates that there may not be any communication in the team- either that or laziness to find a different picture. Look forward to seeing your final project!

'''Group 3'''
* Good over all structure with the use of headings and sub headings. A very interesting syndrome and the page is easy to read.
* I think the intro could be condensed a little, as it should get straight to the point.
* I enjoyed reading the history section and good use of table and summary of history.
* I like figure 1, very nice that it was done by a student!
* figure 4 Maternal Non-Disjunction.. Is this a student drawn pic or did you use it from somewhere.. a little unclear.
* I was nice to see sign and symptoms tabulated, which made this section very easy to read and understand. good use of picture here. Could you find anymore relating to the signs and symptoms?
* I liked the addition of a movie link.
* The sub heading of diagnosis were very appropriate.
* Other Similar Defects- very interesting to add this in..
* Interesting current research: nice that it has been summarised.
* Make sure your reference list hasn't doubled up.
* Just for clarity it might be nice to use the same colour table throughout the page.
* It was good to see some of your pictures correctly labelled.

*'''Introduction''': Content is good, but it's a bit strange to start the introduction with an explanation about meiosis. Of course you need to include it, but generally one expects a few general sentences about the condition itself first, and then an explanation how problems in meiosis lead to it. Including a figure is good, but maybe put this one under the genetics section, and have a picture of somebody affected by the syndrome here instead?
*'''History''': It is one very long text, followed by a summary table under timeline. Maybe come up with a mix of the two, and make it one section? Would make keeping an overview easier. Keep the table, but put all the longer explanations you've written out under history into the table, next to the corresponding date? Content is good.
*'''Epidemiology''': Good, interesting content. The figures nicely break down the text. Well done!
*'''Aetiology''': Slight contradiction here - previously prevalance was said to be 1 in 500, now 1 in 1000? Also, you refer to Figure 1 which is all the way on top of the page - it would be nice to keep it closer to the text, in the relevant section itself. You might want to mention that MI = meiosis I and MII = meiosis II. I was also slightly surprised that you used the word "synapse" when talking about what happens between the homologous chromosomes - I might just never have come across it before (though I have taken quite a few genetics classes), but maybe double-check that? As far as I know it's called crossing over - that's what forms the chiasmata. In general, your whole explanation is very incomplete, you might wanna revise that. I know what you're trying to get at, but I don't think it's very clear for someone who doesn't have a genetics background. Also, I have a majour problem with Figure 4 - the way you illustrate it, I first thought you were showing two different chromosomes, say chromosome 1 & 2, of which there are two copies present each. Cause this is how it is pictured most of the time. Your explanation under the figure made me realise that it wasn't the case, but a) you need to improve that legend and explain more, and b) I'd strongly suggest you modify your figure so that the chromosomes look more like "X"ses - that'll make it much easier to understand that you're talking about one chromosome type, and are showing the sister chromatids and not separate chromosomes. I hope this makes sense?
The genetics part is good though.
*'''Pathogenesis''': Why does this section contain the subsection nondysjunction again? Nice, brief explanation of anaphase lagging. The nondysjunction section, unsurprisingly, mainly repeats what has already been said before. Your figures need a legend and more explanations. What are the different colours supposed to depict? Maternal vs paternal chromosomes? You need to point out that it's the size difference that shows chrom 1 vs chrom 2. Cause I thought first the colours mean homologous chromosomes, which then wouldn't be right cause it's the homologous chromosomes that align etc. Also, I'd suggest not talking about cells having three chromosomes instead of two, cause in reality, cells have so many more pairs of chromosomes than 2, instead maybe just say, 1 cell contains both of the homologous chromosomes instead of just one at the end of MI. You seem to be depicting a recombination event in Figure 6 - why? Does it have any relevance to this part? There's no mention of it in the text. Sorry this sounds terribly critical - good effort though!
*'''Signs & Symptoms''': Maybe explain more, and not just include a list with bullet points?
*'''Diagnosis''': Put the "featured imagine" right next to where it is mentionned? Otherwise seems fine to me.
*'''Management''': Looks good.
*'''Similar Defects''': Maybe rename it Syndromes instead of Defects? I was confused for a second that you were going to talk about further defects that affect KS patients, instead of similar diseases. Otherwise, looking good.
*'''Current research''': Nice long explanations of the research, though there surely are more than 3 current papers about this out there?
*'''Glossary''': How do we know which words from the sections can be found in the glossary? More terms could also be included.
*'''References''': Needs fixing. One and the same reference appears multiple times in the list.

'''Peer Assessment: Group Project 3'''
*The introduction is informative, however I think that the small paragraphs at the end detract from the section as a whole. It would be better to integrate these more so that they flow on from the previous text.
*The history section provides both detailed information and a timeline, which makes the historical stages easy to comprehend and refer back to.
*Is the image in the section on aetiology drawn by a student? If not, then copyright information and referencing needs to be included.
*In the section on diagnostic procedures, the image could be placed on the right for ease of reading.
*The figure in the signs and symptoms section and the figures in the epidemiology section are too small.
*Using colour borders in the signs and symptoms table would make it a bit clearer.
*The links to animations and a movie are great uses of additional material.
*Under the information in some of the images you have uploaded, you still need to add <nowiki>{{Template:2011 Student Image}}</nowiki>.
*The references should not be duplicated and can instead be linked together using the 'multiple instances on a page' editing guidelines: http://embryology.med.unsw.edu.au/embryology/index.php?title=References#Multiple_Instances_on_Page.
--[[User:Z3217345|z3217345]] 13:28, 27 September 2011 (EST)

'''Group 3 Assessment'''
*The Meiotic Non-disjunction jpg doesn’t have the proper citing or information about future referencing abilities.
*In the history section, I like how the occurances are both described in detail and set forth in an easy to read table format. Very organized.
*In the Aetiology section, where is the referencing for the Non-disjunction videos? Is video copyrighted?
*The Aetiology section and Pathogenesis sections seem to contain almost identical information. Are both necessary, or could they be combined/ one deleted?
*If you decide to keep the Non-disjunction videos, are the pictures in the Pathogenesis section necessary? Or do they just become redundant?
*In the Epidemiology section, both pictures need to be enlarged; they are so small I can’t make a distinction as to what’s on them.
*Signs and Symptoms- This section overall looks very good as far as information goes. The only thing I would suggest is to separate the different age sections a little bit more; their symptoms look to be running together from group to group. Also, try increasing the picture sizes, as they (especially the first one) is difficult to read.
*Again, for the video under Karyotyping, where is the referencing and copyright information on this?
*Action of Amoratase picture- This still needs to have the disclosure statement reguarding re-use and copyright guidelines. Also needs a descriptor sentence below the picture.
*Glossary- Shouldn’t there be references for these definitions?
*Both the Similar Defects and Research sections seem decent. Only suggestions:

-Similar defects chart: Try bigger pictures and sentences of less length.

-Research- Try adding a picture to the section to make it more aesthetically appealing
*Some of the references are repetitive. Make sure to fix this so they all link to a single reference instead of numerous ones of the same resource.
--[[User:Z3391078|Ashley Smith]] 14:00, 27 September 2011 (EST)

'''Group 3:'''
* The introduction is very lengthy, some parts feel as though they would be more appropriate in other sections. The image here fits nicely with the text but it could benefit from a more descriptive legend and needs to include <nowiki>“{{Template:2011 Student Image}}”</nowiki>.
* In the history, you begin to use the short hand “KS” without an initially stating that this is the abbreviation for “Klinefelters syndrome (KS)”. The dates that are mentioned are very detailed although it ends in 1970, were there any other breakthroughs since then? A picture of Klinefelter would be a nice touch here.
* Epidemiology requires some proof reading as there are a couple of little mistakes and the images would have more of an impact if they were slightly larger.
* I like how you have linked figure 1 to the non-disjunction sub-heading under aetiology. The image in this section could benefit from a coloured legend, ie. Instead of saying “Blue circles are male cells”, in a box include an actual blue circle = male cells along with the other descriptions. It also needs to be properly cited.
* There is too much repetition between pathogenesis and aetiology, maybe discussion between these two students is needed to minimise repetition. Good hand drawn images but you need to include the student template as mentioned previously.
* Signs and symptoms would look better in a coloured table and with more images. I don’t think it is necessary to repeat the image comparing age and intellect here.
* Diagnosis; nice use of another form of media – a video. The abbreviation of KS in this section needs to be established first by placing KS after the first time you mention Klinefelters syndrome.
* Management is very concise and thorough
* Other similar defects; nice touch, it could look more appealing with the use of colour and larger images though.
* Current research is formatted nicely and flows well

--z3290815 15:54, 28 September 2011 (EST)

==Discussion==

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Hey i have been looking for a profile pic for some time and none have come up. So prob better if you don't look for it because I am afraid that you will waste time. Nice! birthday cake :) I should do that for my dad's bday which is coming up.
Anyways see you tomorrow
--[[User:Z3289301|Dona Cho]] 23:55, 21 September 2011 (EST)

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Hey Dona, thats a good idea! i like all the pics that you have added, and pathogenesis looks good! I just baked my dad a birthday cake and planning on doing some work on this now. So i will probably be up for a while. I am also looking for pics of H. Klinefelter. Good work!--[[User:Z3289829|Souti Khalil]] 21:12, 21 September 2011 (EST)
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I am looking for a profile picture of Mr Klinefelter. I think it will be good to put one in in the introduction section. I am having trouble finding any - but you do come across one pls put one up -I think it will look great!
--[[User:Z3289301|Dona Cho]] 20:19, 21 September 2011 (EST)

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Guys I thought that it would look good if all the images were order 'figure 1, figure2...'
Just so that it all looks uniform
Hope your ok with it but if you don't like it you can just change it back.

--[[User:Z3289301|Dona Cho]] 17:52, 21 September 2011 (EST) :)

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That looks interesting, but I'm not really up to adding any of that tonight. Feel free to add whatever you like.
--[[User:Z3289066|Elisabeth Karsten]] 22:57, 14 September 2011 (EST)

Hi guys ;)

I was just reading some stuff - found some interesting info related to management (I think it is liz?)

The part of the review is as follows:

'Decreased energy and libido, which are associated with postpubertal testosterone deficit, improve with hormone therapy and often are accompanied by improved confidence and sense of well-being.Androgen therapy should be started when there is direct laboratory evidence of a testosterone deficit or when hypergonadotrophism, which suggests such a deficit, is present. This may occur by the time the patient begins middle school...

Because gynecomastia predisposes men to breast cancer—the frequency of breast cancer is 20 to 50 times greater than in men who do not have Klinefelter syndrome1,2—monthly breast self-examination should be encouraged. If necessary for cosmetic reasons, gynecomastia may be treated surgically.'

The review also mentioned something about 'cryopreservation' so that the precious sperm can be stored and used for later IVF.

If the above sound interesting, it might be good reading the review article (particularly the management section. Follow the link below for the review.

http://www.aafp.org/afp/2005/1201/p2259.pdf

ps. I dont think I will be sleeping much tonight!!

--[[User:Z3289301|Dona Cho]] 22:32, 14 September 2011 (EST)

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I don't think we can use those pictures, unfortunately. Safest to stick with papers and hand-drawn I think. The timeline looks really really good. If anything, I would be inclined to put a bit less info in the main bit of history and focus on that time line. I think it's a nice visual respresentation of the information.
--[[User:Z3289066|Elisabeth Karsten]] 21:17, 14 September 2011 (EST)

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I found this website which has alot of picture's of KS, and there are only a few copyright statements, can we use them? [http://carregwenimages.com/klinefelters-syndrome-pictures]

Haha, I just saw them! thanks for that! I just edited the history and the timeline. Is the information in the timeline just repetitive of what i have written, should i just remove it? --[[User:Z3289829|Souti Khalil]] 20:09, 14 September 2011 (EST)
----

It did end up happy in the end lol. Yeh they look really good. We're allowed to add links to our page, so I think that'd be best. I'll put those on now. Thanks!
--[[User:Z3289066|Elisabeth Karsten]] 18:46, 14 September 2011 (EST)

Thanks for fixing up the table in signs and symptoms, it looks great!

That video was mean, i was eating when i watched it and i felt so sorry for the little boy, i couldnt watch the rest. :(

If you think we need an animation i found these two websites, but i have no idea of how we would put them on to our page.

[[http://www.biostudio.com/d_%20Meiotic%20Nondisjunction%20Meiosis%20II.htm]]
[[http://www.biostudio.com/d_%20Meiotic%20Nondisjunction%20Meiosis%20I.htm]]
--[[User:Z3289829|Souti Khalil]] 18:09, 14 September 2011 (EST)

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That video is so funny! I was laughing to the point of tears while watching this! I don't think Dr. Hill would be too happy if we added the video to our webpage though. Great job Liz once again with the editing. Keep up the good work!--[[User:Z3289991|Robert Klein]] 15:22, 14 September 2011 (EST)

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Hey everyone, I just uploaded our 1 Wikipedia image. It's the karyotype of Klinefelter's syndrome. If anyone founds anything better on Wiki, just make sure you say something and take that one off.
--[[User:Z3289066|Elisabeth Karsten]] 09:52, 14 September 2011 (EST)

So I found this video, it's super cute and lame. But I think it's a nice representation? Not sure how applicable it is though... http://www.youtube.com/watch?v=6q2JxMDaNys
--[[User:Z3289066|Elisabeth Karsten]] 10:08, 14 September 2011 (EST)
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[[File: Signs and Symptoms by Age Group.PNG|right|300px| Signs and Symptoms by Age Group.PNG|thumb]]

Thanks Liz! I really loved the intro and the picture that you created! Maybe we don’t have to remove it, however I will also be on the lookout for a picture which may better suit the introduction. In the meantime, I was thinking maybe we should order the subsections better, for example; Introduction, History, Epidemiology, Aetiology, Pathogenesis, Signs and symptoms, diagnosis, management, other similar defects and then current research. I just think we should explain the cause and pathogenesis of the disease before the signs and symptoms and diagnosis.

Lastly, I found a table on a website and have created a similar one on signs and symptoms. I'll just upload it here, and we can decide if we want to use it.

That is all. --[[User:Z3289829|Souti Khalil]] 13:13, 12 September 2011 (EST)

That table looks really really good, though it could be easier if we upload it like the other table I put up, as opposed to a picture. I'm happy to do that if you like. And yeh that order looks good too, I'll change it now and if anyone disagrees they can change it back. --[[User:Z3289066|Elisabeth Karsten]] 22:29, 12 September 2011 (EST)
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Our page is starting to looking really good!! I just fixed up the aetiology, it may need more work to be done though. Liz the picture i made, is really similar to the one you have in the introduction, is it too much?? Sorry about the delay in uploading it. --[[User:Z3289829|Souti Khalil]] 00:50, 12 September 2011 (EST)

That's fine, I kind of expected that. You use it since it fits in with your topic and I'll do another one for the intro. Aetiology looks really good, nice work!

--[[User:Z3289066|Elisabeth Karsten]] 09:07, 12 September 2011 (EST)

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Hey Liz, Great job with the editing! It looks really good. I will keep on the lookout for gathering more information. --[[User:Z3289991|Robert Klein]] 20:31, 11 September 2011 (EST)

----

Hey everyone, I've just fiddled with the formatting of the page a bit. If you don't like it, of course feel free to change. I also changed the formatting of the table t make it a bit clearer to read, if you preferred the old one though I've saved a copy of it so just let me know. Just looking at the page, some things in epidemiology I think would fit a bit better in signs and symptoms; and eitiology and pathogenesis are a little repetive of each other which I guess we should of expected. But we'll be able to discuss it properly on this coming thursday.

--[[User:Z3289066|Elisabeth Karsten]] 20:24, 11 September 2011 (EST)

To help out a bit, I found some links to articles that are 'Open Access'. This should save time for you guys:
http://www.springerlink.com/content/g68408vq74752421/fulltext.pdf
http://psy.hull.ac.uk/Staff/t.jellema/VantWout_PlosONE.pdf
http://www.autismresearchcentre.com/docs/papers/2011_BCetal_Plos%20biology_unsolvedmystery.pdf
http://www.ojrd.com/content/pdf/1750-1172-5-15.pdf
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0020292
http://www.hogrefe.nl/fileadmin/user_upload/Documenten/PDF/Wetenschappelijk_onderzoek/Bruining_et_al_-_Dissecting_clinical_heterogeneity_of_ASD_through_genotypes.pdf
http://www.ijponline.net/content/36/1/36

Hope this helps!--[[User:Z3289991|Robert Klein]] 12:23, 9 September 2011 (EST)

Looks good, thanks rob.

--[[User:Z3289066|Elisabeth Karsten]] 20:24, 11 September 2011 (EST)

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I had to remove the photo from 'signs and symptoms so that I can confirm it's copyright restrictions. Sorry about that. --[[User:Z3289991|Robert Klein]] 07:44, 9 September 2011 (EST)

----

I edited the Epidemiology and fixed it up as best I could. As well, I found and added a picture to the signs and symptoms section to make it a little clearer. I still seem to be having difficulties with formatting. If anyone comes across charts that I can use for Epidemiology, that would be much appreciated. I still can't find anything that I can use. I will fix up the 'other similar defects' section and have it ready very soon. --[[User:Z3289991|Robert Klein]] 06:39, 9 September 2011 (EST)

----

Hey guys, sorry I've been a bit MIA recently. But yeh I agree totally, I was planning to finish off the intro once everything else is finished, but for the moment I'll make sure I'll finish off my other sections.
And yeh you're ideas re:tables and diagrams sounds great. I'll have a go at drawing a couple on paint as well
--[[User:Z3289066|Elisabeth Karsten]] 21:39, 8 September 2011 (EST)

----
Good idea Souti! As well as that, I will retype my sections and try and fix them according to what Dr.Hill wishes. Maybe for treatments, you could speak about the drugs used to manage the condition. We do need to edit the other sections and add much more content and diagrams. Perhaps a few handrawn diagrams wouldn't go astray?--[[User:Z3289991|Robert Klein]] 18:40, 8 September 2011 (EST)

----
Hey guys, I noticed earlier today that Mark Hill has put comments on our page that we need to change and improve. So i'm going to take out 'case study', and replace it with 'treatments'. What do you guys think? Make sure you have a look at what he has said.
--[[User:Z3289829|Souti Khalil]] 17:44, 8 September 2011 (EST)

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Rob, 'Other Similar Defects' is looking great! I am committing the next couple of hours to Klinefelter's syndrome. Do you guys think we could elaborate a bit more in the introduction, just to give a larger scope of our disease?

--[[User:Z3289829|Souti Khalil]] 11:48, 8 September 2011 (EST)

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I added images to 'Other Similar Defects'--[[User:Z3289991|Robert Klein]] 07:55, 7 September 2011 (EST)

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I have constructed a table for Other similar defects! I think that it should be alright, however there may not be enough info so the conditions may not properly be explained. We are still waiting on a table for signs and symptoms as well as a diagram for pathogenesis--[[User:Z3289991|Robert Klein]] 10:01, 6 September 2011 (EST)

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What we should do is add a table to 'similar defects', a diagram for pathogenesis, a and a table for signs and symptoms--[[User:Z3289991|Robert Klein]] 12:49, 1 September 2011 (EST)

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Glossary, Epidemiology and Similar defects have all been added. Let me know if anything else needs to be done!--[[User:Z3289991|Robert Klein]] 06:04, 1 September 2011 (EST)

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Alright Everyone,
For the different genotypes dotpoint, I will cover that when I complete the section to do with 'similar defects'. I have fixed up the referencing system. --[[User:Z3289991|Robert Klein]] 13:53, 27 August 2011 (EST)

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Hey guys,
I have included a list of things that Mark Hill emphasised in regards to our group project in the lab today;

- Different genotypes

- Animal models

- Review articles

- Importance of how the disease comes about (pathogenesis).

So, by next Thursday our main page should have plenty of content under each subheading. 
--[[User:Z3289829|Souti Khalil]] 14:14, 25 August 2011 (EST)

----

Hey Guys,
I have added a discussion tab for any enquires and updates on the progress of our assessment, as well as a referencing tab (or whatever they are actually called) at the bottom of the page. So for each section, if anyone finds relevant articles/images etc. they can place it there.
Oh, and please remember to add new content to the top.
--[[User:Z3289829|Souti Khalil]] 00:53, 18 August 2011 (EST)

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Hey Guys,
Sorry to be a bother. I am having trouble referemcing properly in the Wiki format, as what can be seen in my Epidemiology piece and also my messing up of the reference list. Would one of you mind showing me how to fix this problem? Thanks so much and I will have the piece on 'other similar defects' prepared by Saturday. The glossary will be uploaded on Monday.
--[[User:Z3289991|Robert Klein]] 05:40, 18 August 2011 (EST)

----

'''Referencing'''
PMID is the reference number that you need

without the ':' will act as an link to the article
--[[User:Z3289301|Dona Cho]] 12:51, 25 August 2011 (EST)

==References==

If you find any good papers relating to someone elses topic, you can put them under these subheadings to help out.

Hey guys! this is a publication which seem to be pretty good!!

http://www.nichd.nih.gov/publications/pubs/klinefelter.cfm
--[[User:Z3289301|Dona Cho]] 12:54, 25 August 2011 (EST)

===Description/Introduction===

===History===

Natural history of seminiferous tubule degeneration in Klinefelter syndrome<ref><pubmed>16172111</pubmed></ref>

===Signs and Symptoms===

===Epidemiology===

Abramsky L, Chapple J.47, XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling. Prenat Diagn. 1997;17:363–368.

Bojesen A, Juul S, Gravholt CH.Prenatal and postnatal prevalence of Klinefelter syndrome: anational registry study. J Clin Endocrinol Metab. 2003;88:622–626

[http://www.aafp.org/afp/2005/1201/p2259.pdf Klinefelter Syndrome]

===Diagnosis===

Hey guys, it's Dona. I put my name down for this section. I will try to get mine done by the end of this week. :)

--[[User:Z3289301|Dona Cho]] 17:23, 24 August 2011 (EST)

===Treatment===

===Etiology===

===Pathogenesis===

===Case Study===

===Similar Defects===

===Current Research===
http://www.ncbi.nlm.nih.gov/pubmed/7446531
Check this out!!--[[User:Z3289991|Robert Klein]] 05:03, 1 September 2011 (EST)

<ref><pubmed>21342258</pubmed></ref>

===References===
<references/>

==Pictures==
[[File:Magnetic Resonance of Head MRI from patient with Down Syndrome and Klinefelter's Syndrome.jpg|thumb|Magnetic Resonance of Head MRI from patient with Down Syndrome and Klinefelter's Syndrome]]

--[[User:Z3289829|Souti Khalil]] 23:57, 17 August 2011 (EST)

[[File:Klinefelter's Syndrome.jpg|thumb|center|Klinefelter's Syndrome]]

--[[User:Z3289066|Elisabeth Karsten]] 23:31, 13 August 2011 (EST)

[[File:Overview of human testicular sample from a patient with Klinefelter's syndrome.png|thumb|center|Klinefelter's Syndrome patient testicular sample]]

--[[User:Z3289991|Robert Klein]] 10:17, 16 August 2011 (EST)

[[File:Kleinfelter syndrome.jpg|thumb|center|Facial dysmorphic features in a child with double aneuploidy—Down syndrome and Klinefelter syndrome]]

--[[User:Z3289301|Dona Cho]] 20:35, 17 August 2011 (EST)

==Topic Choice==

Hey guys, so after having a look at that list I quite like the sound of
*Anencephaly or
*Klinefelter's syndrome

There's loads of resources for Klinefelter's syndrome, but I think Anencephaly sounds really interesting. It's a type of neural tube defect, so we may even be able to do that as a topic - neural tube defects (it's on the list as well).
Just let us know what you think, thanks guys!

I've just attached a review for each

[http://www.ncbi.nlm.nih.gov/pubmed/21397196 Klinefelter Syndrome]

[http://www.ncbi.nlm.nih.gov/pubmed/21110233 Neural Tube Defects] or [http://www.ncbi.nlm.nih.gov/pubmed/17089587 Anencephaly]

--[[User:Z3289066|z3289066]] 09:32, 6 August 2011 (EST)

Hey Everyone,
I am leaning towards Klinefelter syndrome as it seemed interesting to learn about. I found a couple of articles on the internet which explore more the epidemiology of the condition amongst the population. Liz, I read through your artiles and they were quite interesting in the way that they explored the genetics behind the condition. We will be able to perhaps link these in with the epidemiology to make our argument more convincing.

Below is a review article:

[http://onlinelibrary.wiley.com.wwwproxy0.library.unsw.edu.au/doi/10.1002/(SICI)1097-0223(199909)19:9%3C808::AID-PD637%3E3.0.CO;2-B/pdf]

The Research Article:

[http://jcem.endojournals.org/content/88/2/622.full.pdf+html]

Both articles explore more the epidemiology of klinefelter's syndrome as I felt that it would be interesting to look at its prevalence, and frequency of distribution within a population. The first review article that I hasve linked to explores the frequency of Klinefelter's syndrome in a population along with various other genetic anomalies.

--[[User:Z3289991|z3289991]] 07:02, 9 August 2011 (EST)

Yeh that sounds good to me, if anyone has any objections just let us know. We can figure out exactly what we want in the page on thursday, but yeh should def's talk about the epidemiology.

--[[User:Z3289066|z3289066]] 14:53, 9 August 2011 (EST)

Hey guys!

I think that Klinefelter's syndrome is definitely an interesting disease and it has lots of resources. I think we still need a plan B though, a few other diseases which I thought were really interesting are;
- Thalassaemia
- Anencephaly (good pick Liz!)
- Spina Bifida
I found a really good review article on Klinefelter’s syndrome, although it’s pretty dated.
[http://archinte.ama-assn.org.wwwproxy0.library.unsw.edu.au/cgi/content/full/158/12/1309]
[http://onlinelibrary.wiley.com.wwwproxy0.library.unsw.edu.au/doi/10.1002/ajmg.b.30163/pdf]

I shall see you all thursday!

--[[User:Z3289829|z3289829]] 22:15, 9 August 2011 (EST)

Hey guys, this is dona - I guess I am the last one to write on the board (sorry!)

I personally like the topic; neural tube defects. Reasons are 1. there is so much information because it is an umbrella term that includes many conditions like spina bifida and anencephaly
and 2. we will be learning the developing of the neural tube next week in lecture - so it will not be difficult to understand the etiology of neural tube defects

Here are the links:

review article [http://www.ncbi.nlm.nih.gov/pubmed/10899792]

research article [http://www.tandfonline.com.wwwproxy0.library.unsw.edu.au/doi/pdf/10.1080/19485565.1991.9988793]

p.s Hey could everyone identify themself by writing their name before writing on this discussion forum, that way people know whose talking. (please)

--[[User:Z3289301|Z3289301]] 17:23, 10 August 2011 (EST)

===Sections===

*Description/Introduction - Liz
*History - Souti
*Signs and Symptoms - Dona
*Epidemiology - Rob
*Treatment - Liz
*Eitology - Souti
*Pathogenesis - Dona
*Similar defects - Rob

I was thinking it'd be good to also do a topic on recent research, I'm happy to do that one, and should also do a glossary. So we should have someone finalise that, but it'd be really helpful if everyone could just add words in they think would be good as you go. Does anyone want to volunteer for editing that? Just put your name in the spot below so everyone knows.

*Recent research - Liz
*Glossary - Rob
*Diagnosis - Dona
*Case Study - Souti

--[[User:Z3289066|Elisabeth Karsten]] 12:15, 13 August 2011 (EST)

----

Hey Guys,
I have uploaded an image to the Epidemiology section of the Group webpage, however it appears to have distorted the whole webpage in that all the other categories below epidemiology have been pushed to the side. Also, I am having trouble trying to enlarge the image. Do you know how I can fix this problem? The table was referenced appropriately.
Cheers

--[[User:Z3289991|z3289991]] 10:14, 13 August 2011 (EST)

Hey, yeh that should be fine for the moment, don't worry too much about the formatting. You can fix it, but it'll be easier to do once there's text there too move around it.
There should be a page explaining all the details about picture formatting, but I can't qutie remember how to do it off the top of my head. Is that the size of the original image? Because that could be part of the problem.

--[[User:Z3289066|Elisabeth Karsten]] 12:09, 13 August 2011 (EST)

Oh I've just realised what's happened, see how you've put the file name then "thumb"? The default for thumb is to make it slightly smaller and move to the right where it will wrap around whatever text is there. You can try [File name|thumb|left|name] if you want it on the left, or else instead of 'left' you can say 'center'. But it's gotta be 'center', not 'centre' (I think). Or else you don't have to use thumb at all, and just leave it out completely.

Hope this helps.

--[[User:Z3289066|Elisabeth Karsten]] 14:02, 13 August 2011 (EST)

Thanks Liz,
You know what? I will add some text during next week and then play around with the formatting. You are right in your first comment, because that way I can format the picture and text properly. Thanks so much for your help though.
--[[User:Z3289991|Robert Klein]] 15:21, 13 August 2011 (EST)

----
==Peer Assessments==

* Great amount of depth, you have covered each subheading quite well
* It was great to see a comparison to other similar defects
* Non-disjunction is discussed twice, can it be summarised into just the one section?
* In the signs and symptoms section, the images seem to be arranged in a disorderly fashion, maybe place them elsewhere. Also your image comparing age and intellect is extremely small. The sizing of a larger majority of your photos needs to b adjusted
* You’re referencing needs to be tidied up; there are multiple entries from the same source that tends to clutter your reference section.
* There were only two examples of management strategies, are there anymore out there? Maybe you could do a comparisons table for this section
--[[User:Z3332629|z3332629]] 15:23, 22 September 2011 (EST)

Talk:2011 Group Project 1

2011-09-28T07:06:33Z

Z3279511: /* Peer Review */

[[2011_Group_Project_1|'''Group 1''']]: [[User:z3060621]] | [[User:z3217043]] | [[User:z3217345]] | [[User:z3391078]]

==Peer Review==

'''Group 1: Peer Assessment'''
* An image would make your introduction more engaging
* The second paragraph of the introduction is already quite explanatory and might fit better into aetiology/pathogenesis. Instead one or two simple but engaging sentences would be goo.
* The epidemiology section is good but if I wouldn't have learned about chromosomes I would feel a little confused.
* There are writing mistakes and there is no copyright information in the table in the epidemiology section
* The direct links to the glossary (blue words) in the aetiology section are great. If you would have those for all sections it would make your page look more whole
* There are too few references in the aetiology section
* Clinical Manifestations contain useful information, however it's also good to have a more detailed description. May be you could outline the most common clinical presentation a bid more explanatory.
* The tables in the diagnostic section are great, just a different format, so that you don't have huge white gaps would be better
* The treatment and research section are good. May be you could put a little introduction into the treatment section before you go straight into the subheadings.
* Overall, your page has a good structure and is informative. The links to the glossary are great but should be used through the whole page. A few more pictures would make your page more engaging. --z3279511 17:06, 28 September 2011 (EST)

'''Group 1 Peer Assessment"
*Few grammatical errors found in the introduction, such as missing words in the sentences but overall the introduction was well written.
*Would have been good to include an image in the introduction eg. Chid diagnosed with the syndrome indicating the characteristic short stature.
*Hyperlinks to the glossary are missing in the introduction and epidemiology sections.
*Images named ‘stats abnormal’ and “turner syndrome X chromosome variations” does not include any copyright information.
*The etiology section was well written but it would have easier to understand concepts such as ‘dysjunction’ if the image was linked after the section in paragraph that explains it. At the moment the image looks a bit random and is hard to understand the processes illustrated in it.
*I liked how the clinical manifestations were divided into different parts.
*Great use of table and images in the “Prenatal Diagnosis” section. Summarises the information quite well.
*The text in the ‘current research’ section is a bit heavy and confusing. Either try and summarise the key points in a table or use an image to break up the text. The information presented in the future research section seems lacking compared with the ‘current research’ section.
*Some words listed in the glossary do not include there definitions.
*Overall good work. Just small things to fix up.
--[[User:Z3291622|Z3291622]] 15:53, 28 September 2011 (EST)

'''Group 1 Assessment'''
* Key Points: Clinical manifestations could probably have a better explanation, as opposed to a list? Perhaps try discussing the presentation of the disease, etc. Is there any history of the disease? Generally sections are of good length and the information is relevant.
* Content is difficult to assess because there are sections that are lists of terms. Many items in the project rely heavily on this point-form, especially the clinical manifestations. Perhaps try using more images to support the clinical presentation/complications of the disease, as well as the prenatal diagnosis. The diagrams are used well when they are used.
* Referencing is generally fine, although the first image doesn't seem to have a correct copyright license. As for the double references in the reference section, we have the same problem too!
* The student-drawn diagram is simple but effective, and the images chosen are adequate to the project. However, the entire project seems a little brief in each section; try to ensure that you've written everything that you can!
* All of the information is well-cited with a large number of sources and clearly shows that further research has been done. However, to make the project flow a bit better maybe have some more images and phrases to allow an explanation as opposed to just dot points on the work.
--[[User:Z3288827|Leonard Tiong]] 09:17, 28 September 2011 (EST)

'''Group 1'''

*An image would nicely complement your introduction.
*A history timeline would be nice to include
*A few sentences should be restructured in epidemiology
*Clinical manifestations should be explained a little or include an image to break up the text
*Nice tables in diagnosis- although some pictures should be made a little smaller
*The student drawn maternal serum sampling image is really good
*Treatment would benefit a picture
*Good research section
*Overall, good project you just need to fix a few things

'''Peer Assessment 1'''
*Intro: sentences should be divided up into shorter ones, not 2 sentences
*The picture next to epidemiology may look better on the other side? Balance it with the abnormalities graph
*The 3rd sentence of the Epidemiology para could be worded better – you don’t need to use the word ‘remaining’
*Hyperlink to glossary words from intro and epidemiology (like you have in the etiology section)
*Clinical manifestations section is good – I like the layout
*Wording of Diagnosis is funny – re-read it out loud and you will see 
*Good use of tables, but 2nd is incomplete and needs a pic for the baby box
*Perhaps expand on some of the treatments e.g. Speech and Future Research
*Current research section is confusing with so many parts bolded, maybe use different formatting or colours to break it up a bit?
*Referencing – some are repeated several times one after another, I think there is a way to condense them? (e.g. references 39-42 are all the same)

--[[User:Z3332824|Z3332824]] 22:48, 27 September 2011 (EST)

===Comments on Group Project 1===

Group 1:

*Intro seems a bit to mundane, there is no ‘hook’ and a picture wouldn’t look bad either.
* Spelling and grammatical mistakes in the epidemiology also the common abnormalities table/pic has no copyright permission in the journal either.
* very little references in eitiology, surely all that information was gathered from somewhere.
* the clinical manifestations section could be put in a table, maybe with a brief description of each item listed. How about some photos in this section?
* table in diagnostic procedures is good and succinct, however the picture has no copyright notification.
* A short table for treatment? Maybe some photos to relate the procedures used to what is being said.
*current & future research is good however the sheer amount of reading is too much, so maybe find a way to space it out?
*glossary is very awesome and I love the links!
* multiple references need to be fixed!
--[[User:Z3291423|z3291423]] 17:43, 27 September 2011 (EST)

'''Peer Assessment'''
Group 1: Turners Syndrome
*The introduction is very extensive and provides a good overview to the website. Maybe a bit too much information/detail for the introduction.
* Headings and Subheadings are appropriate and demonstrate a good understanding of the topic. Information flows from each heading to the next and is quite easy to follow.
*Perhaps adding a few more terms to the glossary from the epidemiology section such as: ‘gonadoblastoma’.
* Etiology: good use of glossary, very useful
*Clinical Manifestations: easy to understand but perhaps consider a table format? And particularly in the physical attribute subheading, this could be improved with an image.
* The diagnosis section is well balanced in terms of images and text. The tables are a good idea, however could be formatted a bit differently so that the text and images are in proportion – eliminates excessive blank space in the age and phenotypic manifestation column.
*Research: good layout; may benefit from use of external links or links to the glossary.
--[[User:Z3332327|z3332327]] 14:52, 27 September 2011 (EST)

'''Peer Assessment'''

*Introduction terms not bold or linked to the glossary “monosomy” made the introduction most confusing. Referencing of this heading contain only links should manually reference if possible.
*Image from the epidemiology need to be explained of the congenital disorders from turners a small paragraph would suffice. Also similar to the introduction the referencing of the 4th reference can be found on “Pubmed” and could be referenced properly instead of having links.
*Etiology had good flow and genetic terms linked to glossary which was useful. Content links to the images with some elaboration, only issue is the referencing is not done properly and should be done properly.
*Clinical manifestation contains useful information of the disorders related though has many referencing repeating and should be fixed. Not only this but maybe the heading would be better to be below the diagnosis to have better flow to know what your diagnosing .
*Diagnosis has good use of tables and images to display the methods to diagnose the disorder with labelled diagrams though would be better more separation between text looks to cramped together .
*Treatment seems unorganised with no clear way to know what a treatment is or not as first paragraphs is a routine check-up and should be placed as another sub heading or below with management.
*Referencing in general should be major concern removing the repeats and those not done properly altered.
*Research id layout is clear with sufficient amount if description of the research done in this field.
*If possible timeline would be best in understanding the origin of the disorder and link to the current research.
z3332250 23:35, 26 September 2011 (EST)

GROUP 1 peer review: Turner Syndrome
*Introduction is informative and well summarised, however a few sentences are a bit lengthy and can be better structured so paragraphs flow easily. e.g. "It is caused by complete or partial X monosomy in some or all cells and occurs in approximately 1 in 2000 live female births, however the morbidity rate of spontaneous abortions is 10% and only about 1% of fetuses survive to term." can be better structured. In addition there are several spelling mistakes that are distracting e.g. "The affected organ systems and tissues may are effected to a lesser or greater extent amongst that are affected by turner syndrome" - this sentence doesn't make sense at all
*You may also want to incorporate an image to break up the text in the intro
*One of the requirements for the group project is to include the history of the disease, the intro contains very minimal background information but besides this there's no evidence of research into how this disease was discovered and developments in its understanding
*The image beside epidemiology is obstructing the break up of the introduction and epidemiology, you may want to fix this. This image may also be better if made a little bigger
*The prevalence is repeated in both intro and epidemiology, maybe just mention it in just one section
*Epidemiology info is very informative but really needs to be proof read, this lets down the whole section. Some of the sentences contain spelling mistakes and grammar needs to be reviewed e.g. "The phenotype of Turner Syndrome is varies but it involves anomalies of the sex chromosome" and "Turner Syndrome can be transmitted from mother to daughter, and thus can it could be described as a heredity linked syndrome"
*"The remaining third have structural abnormalities of the X chromosomes, and two thirds are mosaics. Whereby, the maternal X is retained in two-thirds of women and the paternal X in the remainder." - sentences like this need to be fixed to make more sense
*Some sentences are also very abrupt and short, could be revised so they flow more
*The Karyotype image is incorrectly referenced and does not contain the copyright clearance statement, this needs to be fixed
*The abnormalities graph really needs fixing, not correctly referenced, no copyright clearance statement and title isn't very descriptive
*I really like how the words relevant to this syndrome are linked to the glossary, this really helps the reader, saving us from having to scroll down to the bottom of the page. This could be applied to the whole page
*The non-disjunction image is informative but needs to be properly referenced
*The info in etiology is very informative and comprehensive, but again grammar is a problem e.g. "When an uneven distribution is such that one of the gametes does not have any of a chromosome" -consider revising this sentence
*The image 22+23=45 could be better placed so that it doesn't overlap into the next section
*The clinical manifestations section has an extensive list, but could be improved by maybe having a paragraph or two describing these not just a link to a reference, an image of some of these manifestations may also enhance this section
*The diagnosis section has a good balance of text and image and there is great use of tables. Also the links to the glossary again is helpful
*maybe consider making the images in the table a little smaller
*Student drawn images are included and comprehensive
*Treatment and research sections are succinct and informative, easy to go through
* I really like the way the glossary is formatted, makes it very easy to access
*The extensive reference list is impressive and indicative that a lot of research has gone into this page

Over all:
*There really needs to be thorough proof reading to correct grammar, better structure your sentences, and generally make better sense of some sentences, this particularly applies to epidemiology section
*You should also fix the referencing of the images, copyright statements are missing
--[[User:Z3331556|z3331556]] 22:08, 26 September 2011 (EST)

Group 1 Peer Review

*Introduction gives brief history-is there any timeline or more detailed history available?
*Sub headings are in a logical order, flows well
*Picture next to epidemiology is too small
*Prenatal diagnosis-well done. Good use of information
*Needs to be proof read especially introduction. Some structuring of sentences and paragraphs throughout page needs work
*Images need to be checked for correct referencing and copyright
*Glossary is well structured however it could be extended a little, especially in relation to the first half of site
*Overall referencing is well done however some duplication
*Overall, well researched. Most of the content is there, need to finalise presentation eg. Spelling, grammar, layout, etc.
--[[User:Z3308965|Fleur McGregor]] 16:36, 26 September 2011 (EST)

'''Strengths:'''
*The alphabetisation of the glossary helps readers to search for terms more easily. I really like this bit.
*The link of some of the words under Etiology to Glossary is really good. The reader can directly find out the meaning of a particular word without scrolling down much.
*All the characteristics and diseases are supported by scientific articles.
*The summaries given for each of the articles under Research gives the reader a gist of each article. It gives the reader a rough idea of where research for Turner Syndrome is heading towards.
*Overall: It has a good flow to the page with headings and sub-headings appropriately placed.
'''Weaknesses:'''
*The wikipage needs to be vetted. There are quite a few grammatical and punctuation errors.
*The placements of some images are disrupting the format of the page e.g the image of “22+23=45”.
*There are duplication in referencing. It will be good to combine the references to only one reference number per article to avoid duplication
*Some of the images did not include copyright statements which allow wiki users to reuse the images e.g. the karyotype image & image on abnormalities.
*Some of the references are just website links. This will need to be corrected.
*History of Turner Syndrome is not available. How was the syndrome first discovered? When was it discovered?
'''Specific corrections:'''
*The second sentence of introduction “It is caused by…survive to term” is a bit too long. Breaking it into two sentences might be better.
*“During normal fetal development, each ovary contain as many as 7 million oocytes”. The word “contain” should be “contains”.
*“The oocytes gradually reduced to 400,000 during menarche and during menopause fewer than 10,000 remains.” Insert the word “are” after “oocytes”.
*Standardise the term “Turner Syndrome”. Either all should be “Turner Syndrome” or “Turner syndrome”
*“…which is complete by the time the infant, is aged 2.” The word “complete” should be “completed”.
*“Genetically menopause” I’m not sure what this means. Is it supposed to be “Genetically-induced menopause”?
*“For example short stature is caused by a deletion of the Xp chromosome and the deletion of Xq causes gonadal dysfunction”. There should be a comma after the word “example”.
*The image on abnormalities associated with Turner Syndrome might be more suitable to be placed under clinical manifestations.

--Z3389806 22:40, 25 September 2011 (EST)

'''Group 1'''

*Interesting introduction, but includes quite a few spelling mistakes, make sure you correct them.

*The epidemiology section includes lots of information, but the sentences make sometimes no sense, or include writing mistakes.

*Maybe place the “karyotype” image on the right, it interrupts the epidemiology section.

*I like the “malfunctions” image, but it looks a bit lost at this position, and lacks a copyright information.

*The sperm + egg image is genius, but it disrupts the flow on the left side, so maybe put in to the right.

*Clinical manifestations: the heading should be on the left edge of the page, the content is ok but would look better in a table.

*Diagnostic procedures: very good section, but the tables seem a bit too big.

*The treatment section looks fine, except for the “speech ” and ”appearance” part. Those could include more information.

*The research section seems very well done.

*The glossary is incomplete. You should decide, if you want to link the words or not, but if you do, it must be for the hole
page, and not only one section.

*Make sure all images include a copyright notice.

'''Group 1 Critique'''

#• The introduction is quite interesting. Clinical features of the disease, even if given as an example, should not be mentioned in the introduction
#• The graph comparing common malformations of Turner Syndrome in the epidemiology is quite good, however it should be explained a little more clearly. Also, where is the copyright information for the graph?
#• The aetiology has terms in it which are not properly explained e.g. random assortment. Give clearer explanations
#• Clinical manifestations are explained ok. Maybe put it in sentence form instead of listing it in bullet points
#• Diagnostic Procedures is labelled and explained ok. Maybe expand upon the techniques a little more instead of just summarizing them in a table
#• Treatment is ok. Could have a little more explanation though
#• Research and future research is good
#• Glossary is incomplete- random assortment, sister chromatids

--[[User:Z3289991|Robert Klein]] 18:26, 24 September 2011 (EST)

Group 1

Firstly, nice progress with the group project. After reading your page, I have a good general knowledge of Turner Syndrome, so thanks. Overall, most sections were well done, though the writing style and layout could be more consistent, but you could work on that when you've finalised the content of the page.

#The key points relating to the topic that your group allocated are clearly described.
#* Introduction: Good intro, very first image of the karyotype should include the actual statement of the 'Open access' not just 'copyright'
#* Epidemiology: Grammatical errors disrupt the flow of the content, in addition, graph has no copyright info, title could be improved
#* Etiology: Nice simple diagram of 22 eggs and 23 sperms, good example of when a picture can tell more than a thousand words! I feel there needs to be consistency either use Turner Syndrome or TS throughout the page
#* Clinical: liked how you have further classified the symptoms to its associated titles, nice idea; very easy to read, but a table would also be good
#* Diagnosis: image of TS maternal serum sampling doesn't contain {Template:2011 Student Image}, but a very good table
#* image of the TS X chromosome variations shouldl contain {Template:2011 Student Image}. Furthermore, if you use A-E in image descriptions, you should include A-E within the image
#* Research: very good layout and explanations, informative
#The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
#* Could include more images especially in clinical manidestations, and some images do not fit the requirements set by Mark, as I've highlighted above
#Content is correctly cited and referenced.
#* seems to be cited well. However, although you have more than 100 referencees, a lot of them are repeated references, maybe you could try to use more pubmed articles, a greater variety
#The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
#* Glossary: could include more words such as echocardiogram
#Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
#* Although you have more than 100 referencees, a lot of them are repeated references, maybe you could try to use more pubmed articles, a greater variety
#Relates the topic and content of the Wiki entry to learning aims of embryology.
#Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
#Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
#The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
#* Although the content is informative, I'm left feeling like I want more variety of resources, so maybe some further research will improve the overall impression of your page
#Develops and edits the wiki entries in accordance with the above guidelines

"What would improve this project...."
* consistency in writing style
* more images and cited correctly

--[[User:Z3291643|z3291643]] 14:44, 24 September 2011 (EST)

'''Turner Syndrome'''

*Just make sure you’re consistent with the capital letters for Turner syndrome, you’ve got ‘Turner syndrome’, ‘turner syndrome’ and ‘Turner Syndrome’ throughout the page
*The page looks good, just a bit of final rearrangement of the images would be even better
*You’ve got a lot of good information in "Clinical Manifestations" but perhaps the information would look better in a table as opposed a long list? Some pictures wouldn’t go astray either
*I like the links down to the glossary, it makes it very efficient
*The table in "Diagnosis" looks really good, but try to shrink the pictures in it down a bit so it’s not so huge
*It would be good to expand some of the sections in “Treatment”, you’ve got a really good basis but you need more than one line in “Speech” etc
*Your "Research" is very detailed with lots of good papers
*Overall it is quite a good page, it just needs a little bit of reformatting

Group 1
* first glance of your project it appears that there is a lack of consistency with the image/text ratio. There are areas with lots of images and areas where there is a bulk of text with no images. It would be better if you spread the images out evenly between the sections rather than clumping them all together.
*The epidemiology is very word heavy. There are a number of terms in there that I think would benefit from having a link to the glossary. By the end of the section I was left feeling a little overwhelmed.
* The etiology section is good. Links to the glossary are very helful.
* The clinical manifestations is ultimately just a list. There are no images and nothing exciting about this- I was almost inclined to skip over it because it did not draw my attention. This is the perfect place to have interesting images and yet there is none. This section needs to be reformatted.
* The diagnostic material was easily accessible and interesting.
* As a whole, the information you need is all there, you just need to reformat your page so that it is more appealing and more easily accessed by the audience.

Group 1 - Turner Syndrome
*'''Introduction''': The second paragraph of the introduction partly observes poor sentence structure, and in general needs a little bit more clarification. Also, I wouldn't necessarily include that information in the introduction, but put it under a different heading, etiology maybe? The following paragraph is good, just watch out with this sentence: "Each person who has turner syndrome all vary" - that doesn't quite make sense. Each person varies, or people with TS all vary...
*'''Epidemiology''': This sentence really doesn't make sense to me: "Whereby, the maternal X is retained in two-thirds of women and the paternal X in the remainder." Furthermore, the whole paragraph needs editing in terms of sentence structure. The content is good, though could do with slightly more explanation.
*The table with the common abnormalities is good, but in a slightly random place.
*None of these first sections include links to the glossary. Explaining some of the terms in more detail could easily be achieved by linking them to the glossary.
*'''Etiology''': Be careful when saying meiosis creates genetic diversity. Yes, meiosis creates diversity by shuffling existing alleles and producing new combinations, but the underlying mechanism, which is the main drive for genetic diversity, is mutation because that is what creates new alleles. (I'm just saying this because my lecturer in genetics was very keen on making us understand this difference!) Other than that, excellent explanation of how the genotype of Turner Syndrome occurs. Considering some of the genetic component was also explained under epidemiology, it would be useful to relate this information to what has already previously been mentionned.
*'''Clinical Manifestations''': Poor. Referencing not done properly, no explanations, a simple list really tells hardly anything about the manifestations. Linking them to articles is useful, but not doing anything else makes the whole exercise of creating a page dedicated to a disease pointless if there won't actually be any descriptions or explanations.
*'''Diagnostic Procedures''': Very well explained, good use of diagrams and figures to illustrate the text.
*'''Treatment''': Links to the glossary would be good. Content is good, but the referencing isn't done properly, and some figures would be nice to illustrate things, it looks a little bit dry as such a long blurb of text.
*'''Current research''': Looks fine to me
*'''Future research''': Good idea!
*'''Glossary''': Could be more extensive, mainly because some sections do not contain any links to the glossary.
*'''References''': Needs fixing. it appears as though it hasn't been done right a single time... (ie one and the same paper occurs multiple times in the list)
*General: There are obvious quality differences between the different sections, which is a shame. Parts are done really well, others not so much. The content and subsections would be fine if they all had the same standard as the well-written ones.

'''Group 1'''
* Good overall structure with headings and subheadings, it breaks up the text and makes it easy to follow.
* Very interesting topic with a lot of good relevant information.
* Pictures and tables are great. Just make sure your pictures are referenced properly eg. karyotype picture. also it might make the page look cleaner if the pictures are either all on the left or all on the right. this also may avoid the headings being shifted.
* Maternal Serum Sampling, very nicely drawn, could you maybe label the picture as to what everything is so the reader can identify the structures easily.
* Might be nice to add in a history timeline.
* maybe you could use sub headings in the aetiology section.
* Clinical manifestations had good use of subheading and collated information. I like the simplicity of dot points... could you maybe add a picture here to break up the text and keep the reader engaged.
* Make sure your references aren't doubled int the list.

'''Group 1:'''
* The introduction is very thorough, however the use of too many statistics and scientific terms like “partial x monosomy” make it difficult to read, especially for an introduction. By hyper-linking the glossary terms or by using a simple explanation of the word in the sentence could help make this section more reader friendly.
* The introduction also needs to be re-read to fix little mistakes such as those in the following sentences “The affected organ systems and tissues may are effected to a lesser or greater extent amongst that are affected by turner syndrome.” and “However, there still further research to be completed.” An image added to this section also wouldn’t hurt.
* I would suggest that you play around with the placement of the images in the epidemiology section. Where they are placed now disrupts the flow of the text or leaves a large blank space between the next heading, which is also disruptive. The first image can be made a little larger and the second image does not have the correct copyright or title format.
* The epidemiology section also needs to be proof read to fix little mistakes.
* The etiology section is done very well, it is very easy to read and made easier with the hyper-links to the glossary.
* Image 1 under etiology is missing <nowiki>“{{Template:2011 Student Image}}”</nowiki> and image 2 has a little mistake in the explanation “Complete absence of on effected of the X sex chromosomes...” and needs to be moved slightly so that it doesn’t indent the next heading.
* Nice referencing in the clinical manifestation section although the symptoms need to be explained more. What is it? What are the implications of it? A picture could be useful where text can’t explain a symptom.
* Diagnostic procedures section is done very well. Good balance between images, text and tables however all the images need to include<nowiki>“{{Template:2011 Student Image}}”</nowiki>. Very good student drawn images and explained very well - I didn’t even realise they were student drawn until I read that they were! Hyper-linking to the glossary is also a bonus.
*Treatment is done well especially by breaking up the text into sub-headings, some spelling mistakes though such as “Also if convex gorwth of toenails”.
*Research is very informative but by bolding the reference, it makes it hard to follow and read. Maybe if you include a space in between the findings of the paper or a table could help this section.
*The reference section needs to be fixed as references should not be listed more than once under the reference section. Read the section on “multiple referencing” under “editing basics”.

--z3290815 13:01, 28 September 2011 (EST)

'''Uploaded Student Images -''' Please include the following template in all uploaded image information. Copy the text shown below including the curly brackets in page view mode, and paste at the end of the information box area when uploading your image.

<nowiki>{{Template:2011 Student Image}}</nowiki>

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Hey guys, I'm sorry I'm just now getting on here so late... I've been really really sick ever since I came back from Cairns a couple days ago, then couldn't find my flashdrive that all my information was on I was going to upload. :( I'm working on my sections now again (had to start from semi-scratch) and should have them complete by the end of the night.
I'm kind of worried about the rest of the page though... It seems like only one (maybe two) other people have even contributed??? Did someone drop out of the class? We need to figure this out ASAP to pick up the slack.
Also, I couldn't help but notice that nothing so far has been cited...? Maybe people are having trouble with how to cite the works? I guess we can talk about it in class on Thursday.
I think it would be a good idea if we could get together sometime this weekend to work on the overall page as a group.
Let me know what you all think.
Ashley

Hi Ashley,
I am happy to meet up this Sunday sometime if that suits you. I have completed some of my sub-sections and will put them up soon.

Great! I'm still working on mine... My internet kept messing up last night, so we had to get it fixed today; working on it now. Unforunately Sunday's the ONLY day this weekend I'm not free. We can talk more tomorrow in lecture/lab! :)

--[[User:S8600021|Mark Hill]] 10:44, 8 September 2011 (EST) Some of the existing sub-sections have appropriate content, but there are also empty sub-sections, a total lack of referencing/citation and no glossary.
* The referencing issue needs urgent progress.
* Existing figures/table are appropriate.
* There needs to be more images in this work.
* Where is the student drawn figure?
* Project recent history shows a single group member wiring on this topic.

So I guess we are doing Turner's Syndrome? Or are we still discussing?

I think Thalassemia sounds really interesting and there is more scope for research/ learning something new rather than the sex chromosome abnormalities.

Here are two articles which were interesting I found:

[http://www.ncbi.nlm.nih.gov.wwwproxy0.library.unsw.edu.au/pubmed/21806986 A rapid detection for α-thalassemia by PCR combined with dissociation curve analysis]

[http://www.ncbi.nlm.nih.gov.wwwproxy0.library.unsw.edu.au/pubmed/21239835 Hematopoietic stem cell transplantation in thalassemia]

--[[User:Z3217043|z3217043]] 20:24, 10 August 2011 (EST)

== Thalassemia ==

Hey guys I'm going to do the History and the Treatment of Thalassemia. --[[User:Z3217043|z3217043]] 10:32, 25 August 2011 (EST)

Ashley Smith- I'm doing Etiology and Clinical Manifestations --[[User:Z3391078|Ashley Smith]] 10:58, 25 August 2011 (EST)

The two sub-sections that I will be researching are diagnostic procedures and current/future research possibilities. --[[User:Z3217345|z3217345]] 11:03, 25 August 2011 (EST)

== Discussion ==

There a number of research and review articles, particularly on PubMed, so maybe post ones that you find interesting up and then we can maybe assign sections to everyone next lab so that we can further research those particular areas individually?--[[User:Z3217345|z3217345]] 13:55, 10 August 2011 (EST)

I had found two of the same articles that had already been posted, so I had to go back and find different ones. I'm not sure if we really are going to do Turner's Sydrome since not all of us were present when we named it. We can decide in class tomorrow I guess. --[[User:Z3391078|Z3391078]] 02:23, 11 August 2011 (EST)

Maybe we can begin thinking about the general sections we might have? Introduction, History, Causes, Symptoms, Treatment, Prognosis, Prevention, Current Research, Future Research, Glossary? Any thoughts? --[[User:Z3217345|z3217345]] 09:00, 18 August 2011 (EST)

Here are some free full text articles that might be helpful:

http://www.ncbi.nlm.nih.gov/pubmed/21840746

http://www.ncbi.nlm.nih.gov/pubmed/16821224

http://eje-online.org/content/151/6/657.long

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1273980/?page=3

http://jcem.endojournals.org/content/84/12/4345.long

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1511250/?page=1

http://jcem.endojournals.org/content/86/7/3061.long

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118376/?tool=pubmed

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883963/?tool=pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20361125

http://humupd.oxfordjournals.org/content/7/6/603.long

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613558/?tool=pubmed

== Research Articles ==

[http://www.ncbi.nlm.nih.gov/pubmed/21802870 Turner syndrome and metabolic derangements: Another example of fetal programming.]--[[User:Z3217345|z3217345]] 13:44, 10 August 2011 (EST) (Prior topic)

[http://www.ncbi.nlm.nih.gov/pubmed/21802870 Turner syndrome and sexual differentiation of the brain: implications for understanding male-biased neurodevelopmental disorders.] --[[User:Z3217345|z3217345]] 13:44, 10 August 2011 (EST)(Prior topic)

[http://www.ncbi.nlm.nih.gov/pubmed/21793702 Estrogen requirements in girls with Turner syndrome; how low is enough for initiating puberty and uterine development?]--[[User:Z3217345|z3217345]] 13:44, 10 August 2011 (EST)(Prior topic)

[http://www.sciencedirect.com.wwwproxy0.library.unsw.edu.au/science/article/pii/S0015028211005152 Outcomes of spontaneous and assisted pregnancies in Turner syndrome: the U.S. National Institutes of Health experience.] --[[User:Z3391078|Z3391078]] 02:18, 11 August 2011 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/21813448 How I treat thalassemia]--[[User:Z3217345|z3217345]] 11:45, 11 August 2011 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/21810090 Pulmonary function in thalassaemia major and its correlation with body iron stores]--[[User:Z3217345|z3217345]] 11:45, 11 August 2011 (EST)

== Review Articles ==

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082783/?tool=pubmed Optimising management in Turner syndrome: from infancy to adult transfer.]--[[User:Z3217345|z3217345]] 13:44, 10 August 2011 (EST)(Prior topic)

[http://www.nlm.nih.gov/medlineplus/turnersyndrome.html Turner Syndrome] --[[User:Z3391078|Z3391078]] 02:31, 11 August 2011 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/20492708 Beta-thalassemia]--[[User:Z3217345|z3217345]] 11:45, 11 August 2011 (EST)

== Images ==

I found a pic of what the cells look like under a microscope.

[[File:Thala.jpg|200px|thumb|left|alt text]]
--[[User:Z3060621|Aisyah Barchia]] 19:19, 17 August 2011 (EST)

[[File:Thalassemia_pic.jpg|200px|thumb|left|Miotic Cell Defects]] --[[User:Z3217043|z3217043]] 11:06, 18 August 2011 (EST)

[[File:ThromboembolicEvents.jpg |Thromboembolic Events In Thalassemia Intermedia (TI) VS Thalassemia Major (TM)|framed|none]]--[[User:Z3217345|z3217345]] 08:57, 18 August 2011 (EST)

[[File:PULMONARY HYPERTENSION.JPG|350px|thumb|left|Pulmonary Hypertension]]

Nothing going on here guys? There should be some discussion within your group on the possible topic. --[[User:S8600021|Mark Hill]] 23:53, 7 August 2011 (EST)

{{2011GroupDiscussionMH}}

==Peer Assessments==
Group 1:
* Your page was extremely in depth which was really great.
* Its great that you’ve linked words to the glossary
* The use of a range of different images was good and I like how you made the effort to copyright your own image!
* You’re referencing needs to be tidied up; there are multiple entries from the same source that tends to clutter your reference section.
* The dot point form of clinical manifestations perhaps could have been better formatted into a table as I personally found your formatting confusing and slightly not a well-organised.
--[[User:Z3332629|z3332629]] 15:20, 22 September 2011 (EST)