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Lab 4 Online Assessment

  1. The allantois, identified in the placental cord, is continuous with what anatomical structure?
  2. Identify the 3 vascular shunts, and their location, in the embryonic circulation.
  3. Identify the Group project sub-section that you will be researching. (Add to project page and your individual assessment page)

Lab Attendance

--z3284061 20:36, 28 July 2011 (EST)

--z3284061 11:50, 4 August 2011 (EST)

--z3284061 11:08, 11 August 2011 (EST)

--z3284061 11:10, 18 August 2011 (EST)

--z3284061 11:24, 25 August 2011 (EST)

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--z3284061 11:13, 29 September 2011 (EST)

--z3284061 11:25, 6 October 2011 (EST)

--z3284061 11:05, 13 October 2011 (EST)

--z3284061 11:10, 20 October 2011 (EST)

Individual Assessment

Lab 1

1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique.

The origin of in Vitro Fertilization was firstly successful on 1978 with the born of world’s first test tube baby. The credit goes to the British scientist Robert Edwards who dedicated his research on the biology of fertilization during 1950s. He was finally awarded with the noble prize in 2010, for the development of human in vitro fertilization (IVF) therapy. Noble Prize winner 2010

2. Identify a recent paper on fertilization and describe its key findings.

This journal refers to the novel role for the rapid, fertilization-initiated calcium wave that triggers cell-cycle oscillations. Moreover, the oscillations of cell division of the embryo development could lead to a chaotic threat towards the formation of embryo.The outcome of this paper indicates a designed principle whereby the fast calcium-wave trigger following embryo fertilization harmonize cell divisions. [1]

3. Identify 2 congenital anomalies.

  • Patau syndrome: also called trisomy 13, is a congenital (present at birth) disorder associated with the presence of an extra copy of chromosome 13. This extra chromosome may lead to mental and physical abnormalities especially heart defects.
  • Harelip: "a congenitally deformed lip, usually the upper one, in which there is a vertical fissure causing it to resemble the cleft lip of a hare."

Lab 2

1. Identify the ZP protein that spermatozoa binds and how is this changed (altered) after fertilisation.

The Zona Pellucida protein which is responsible for specific sperm binding is known as Zona pellucida glycoprotein (ZP3). This protein is also thought to be an inducing factor to the acrosome reaction- by which the plasma membrane of sperm fuses with the membrane surrounding the acrosome. The reaction of the acrosome would involve the release or exocytosis of acrosome contents. When the membrane fusion occurs between the egg and sperm, the nuclei of sperm will pass towards the egg cytoplasm. Next, when Fertilization happens, the fusion of both nuclei ( sperm and egg) would case membrane depolarization in which penetration of other sperms (polyspermy) is prevented. Additionally, Cortical reaction is thought to play a vital role in preventing polyspermy by the release of cortical granules and removal of carbohydrate of ZP3. Consequently, ZP3 is altered and the binding of another sperm membrane will no longer occur.

2. Identify a review and a research article related to your group topic. (Paste on both group discussion page with signature and on your own page)

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. --z3284061 22:34, 10 August 2011 (EST)

1. Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation

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


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. [2]

3. Changes in strategies for optimal antibacterial therapy in cystic fibrosis.


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 [3]

Lab 3

Differentially expressed RefSeq genes in human trisomy 21

1.What is the maternal dietary requirement for late neural development?

Folate is improtant for neural development.

2.Upload a picture relating to you group project. Add to both the Group discussion and your online assessment page. Image must be renamed appropriately, citation on "Summary"

this is another image with allowance to use, transmit and share the work. I'm sorry, I was unaware of the copyright the time I've uploaded it. I hope this one suits the criteria

Cleft lip.jpg

window with link to original paper and copyright information. As outlined in the Practical class tutorial.

File:Cleft palate mice.jpg

--Mark Hill 16:28, 20 August 2011 (EST) You have uploaded an image ( that is not allowed to be reproduced without permission. Please remember what I told you in the practical class. Just because it appears in Pubmed Central does not allow anyone to reuse, you must see a copyright statement to that effect. I will delete this image.

--Mark Hill 21:12, 21 August 2011 (EST) You have not identified the source of this inmate in the image information panel.

The Source of the image has been added to the Summary of the image. --z3284061 12:11, 25 August 2011 (EST)


  1. <pubmed>21779158</pubmed>
  2. <pubmed>21463524</pubmed>
  3. <pubmed>11165111</pubmed>
  4. <pubmed>2860913</pubmed>

Lab 4

1. The allantois, identified in the placental cord, is continuous with what anatomical structure?

In humans, allantois is an endodermal evagination of the developing hindgut which then becomes surrounded by the mesodermal connecting stalk.

2. Identify the 3 vascular shunts, and their location, in the embryonic circulation.

The Circulation of foetus differs from adult by the existence of 3 vascular shunts. These are:

  • Ductus venosus is located between the umbilical vein and IVC
  • Foramen ovale is located between the right and left atrium
  • Ductus arteriosus is located between the pulmonary artery and descending aorta

3. Identify the Group project sub-section that you will be researching. (Add to project page and your individual assessment page)



Genetic Configuration

External Links



Lab 5

1. Which side (L/R) is most common for diaphragmatic hernia and why?

The most common side at which diaphragmatic hernia occurs is the left side. The possible explanation for this is due to the fact that the right dome of diaphragm is protected by the liver for some degree. The diaphragm initially develops as a septum between the heart and liver. Next, progresses posterolaterally, and closes at what is known as Bockdalek foramen during the period of 8-10 weeks gestation.

Lab 6

1. What week of development do the palatal shelves fuse?

The fusion of palatal shelves occurs during week 9. This requires the early palatal shelves growth in the period of early embryonic development between stage 17 and 18.

2. What early animal model helped elucidate the neural crest origin and migration of neural crest cells?

The description of Wilhelm His for the population of neural crest cells in 1868, has brought inspirations to nowadays research by using vertebrate model animals. One of these animal models is the sequence of chicken embryo has helped to illustrate the migration of BiI-labeled neural crests towards branchial arches.

3. What abnormality results from neural crest not migrating into the cardiac outflow tract?

Some of the abnormalities which might result of neural crest defects include;

1) Persistent truncus arteriosus

2) Cushion hypoplasia

3) DiGeorge Syndrome

Lab 7

1) Are satellite cells (a) necessary for muscle hypertrophy and (b) generally involved in hypertrophy?

a) Satellite cells are not probably necessary for muscle hypertrophy. This is due to the fact that recent research have shown that the induciable activation of Akt can increase muscle mass without the satellite cells activation.

b) The role of Satellite cells can be mostly seen in the process of muscle regeneration after an injury. They seem to proliferate extensively.

A critical role for these cells in the process of muscle regeneration following injury has been clearly established. In that role, satellite cells have been shown to proliferate extensively

2) Why does chronic low frequency stimulation cause a fast to slow fibre type shift?

CLFS seems to have a major role in this shift that is relevant to the increase in myoneuclear content and satellite cell activation. The CLFS makes a shift in the oxygen and metabolite requirements of muscle fibers. Since the fast fibers are known to be glycolytic, there is probably no capacity of oxygen metabolism. The shift of fast to slow is needed because slow fibers have the ability to endure CLFS.

3) Trisomy_21 Review

The page seems to have a numerous amount of information and effort.

  • Introduction seems short for such a big topic. It would be great if it incorporates to what is actually in the page.
  • The Definition of Down Sydndrom and Aneuploidy can be possibly moved to the Terms.
  • The Location of the Links could be shifted to the External link sub heading, because the reader might find it disturbing to have plenty of links from the start.
  • The two sections “ Heart Defects” and “ Limb Defects” need more elaboration, rather than links. It is great to see other links in the middle that would lead you to another source, however, a couple of paragraphs would make the section more engaging.
  • In the Section “ Associated Congenital Abnormalities, the Image seems to miss a description!
  • The Prevalence can be shifted to the top of the page as the information is related to the introduction. Also the size of the image needs to be minimized because the section is not that large. In addition, the Limit of two countries can be expanded to a worldwide range.
  • “Screening by Country” seems to be limited to one country, it would look more professional if other countries were involved.
  • I liked how the diagram of “screening” shows the analysis process.
  • References can be moved towards the end of the page
  • Generally, a great deal of research has been put into this project, but with some alteration of the project structure, modify some minor mistakes ,and addition to global information could make it more superb.

Lab 8

Peer Review.

Group 1 Critique:

  • A great level of research is represented on the Page clearly. I would like to add some comments that could be useful in making the project better.
  • The introduction has lots of information as ( 3 paragraphs seems to be a lot for the introduction section ) It would look nicer in a shorter or summarised version and less details. Probably an image would make it look less wordy.
  • The images of Etiology Looks great and I like how they are labelled. Also, the highlighted words, which leads to another page are well done.
  • Diagnosis is one of the best presented sections on the page. The balance between images and words is greatly seen. You may consider minimizing the pictures in the tables so the extra white space is removed.
  • You have done a great job in gathering all the content into this page, I like how the Glossary is in alphabetical order. In the References, you may want to delete the repeated references. The last thing I would recommend is adding more pictures to make it more interesting and appealing especially after Diagnosis section.

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.

Group 3: A great Effort can been throughout the page. Some of these comments may be helpful.

  • Introduction is well researched and referenced but I reckon it’s too long for introducing the topic.
  • The History needs to be more organised in a way : like each year should have a separate paragraph. It will make it easier to read.
  • Aetiology is well structured, however, I noticed the image needs a reference and a source.
  • The Alignment of both images in the Pathogenesis section need to be adjusted to either sides.
  • images are missing from the Signs and symptoms. In the table, Puberty and adulthood seem to miss the reference of the source.
  • Great work on the table “Other Similar Defects” and the glossary.
  • in General, Solid work on the page, references are enough evidence. One Last comment, avoid the repetition of the references(1,3) and some others need to be re-formatted ( 35,36)

Group 4: Truly amazing work on this page. The balance between the images and text is phenomenal. It seems quite simple but easy to read well referenced. I like how you used tables to illustrate the epidemiology Nicely drawn images in Genetics Section. I really don’t see many things wrong with the page… It is well done.. the tables and images all speak up for the quality of the page. However, pay closer attention to the references because some of them are repeated or empty when you look at the list. Great work.

Group 5: Overall, Great work on the page:

  • The image in Epidemiology section needs a description and the copyright information. Also, the number of references is the same.
  • in the Signs and symptoms, more pictures would make it more interesting. Some of the paragraphs like Physical Phenotype needs to be references.
  • A reformatting is needed in the References instead of listing the websites.

Group 6: Nice introduction. The length is right. Perhaps what is missing is general image to make it less wordy. History seems to be well researched but if you can make into a timeline would be great. Nice layout in the Signs and symptoms Genetics/Aetiology. You may want to consider more images since the section are quite big. Also, add a description, copyright and reference for the images in the genetics and aetiology. Well done in the table of diagnostic Tests. Do not forget to add the images. In the Treatment and management, you may need to add some shading in the table because the lines of the table are not obvious and Prognosis needs more referencing. In the future Directions, you may consider deleting the in text referencing. Finally, some of references need to re-format.

Group 7: Fabulous work throughout the page. History seems to be a little long. Perhaps you can summarize it further. Also, add the reference for the images as you can only see the source. Since the Pathogenesis is quite long, have you considered addition of more images especially in the upper side of the section? Nice work on the signs and symptoms. But again, add the Reference. Not only the website  Diagnosis—amazing work and all but consider narrowing the space in some areas so it does not look empty and fix some of the unseen images. Some of the references need reformatting like 89, 1, 4, 5. Overall, good job

Group 8: Incredible work on the page. A balance between the text and images is greatly seen. The size of the image between history and introduction is quite big. Minimize it and place it in the right section. Epidemiology can be transferred into a column chart to see which one is more prevalent. Images in the Aetiology section are phenomenal but you want to make the drawings darker? Since they appear to be fading. Neuropathy section is spectacular. I can see a lot of effort in there from content to the drawn images. And I liked how in the table of diagnosis, the use of external links to deliver the information better. Finally, one of the references need to be reformatted as it refers to nothing (49) and the Gloassary could be shifted to be above the reference list.

Group 9 Obviously a lot of effort has been placed in this page. But it lacks of images in some sections like history or introduction. It is nice to know the history of the disease but It would be better it is summarised. Epidmiology seems to have many subheading under it. Perhaps a separate headings for each and more info on the epidmiolgy not one sentence only. The image of phenotype of Williams Syndrome can be in a separate box ( as an image ). Finally, Amazing work on all the details ( associations and medical conditions). Just be aware that references referring to 23 are empty.

Group 10: This project looks fine but it seems a little short? You want to expand the content in sections. History is well researched but it’s quite long. You can add more images (add the reference in the description) and make the dates in Bald. There are some spelling errors and extra signs that are not related to the work such as &&&. Some of the references are repeated and others need to be reformatted.

Lab 9

There is no lab Assessment.

Lab 10

1. Besides fetal alcohol syndrome, identify another environmental teratogen that can lead to hearing loss.

Cytomegalovirus (CMV) is and extraordinarily common herpes virus is one of the tratogens that contribute to hearing loss in infants.

2. Identify 3 factors that contribute to poor neonatal drainage of the middle ear.

  • In neonates, the auditory tube is thought be orientated more horizontally (angle about 10 degrees) compared to adults ( angle about 45 degrees). Consequently, the fluid builds up in the middle ear and it will be more susceptible to bacterial and viral infection.
  • The size of Eustachian tube in neonates is thought to be shorter and narrower. As a result, the speed at which the fluid accumulates will be quicker than adults.
  • In Adults, the two muscles controlling the auditory tube are tensor palati and the levator palati. However, the anatomy of neonates middle ear only permits the use of one of these muscles (the tensor palati) to work. This causes poor drainage due to the poor function of that muscle (levator palate).

3. Identify 1 genetic abnormality that affects hearing development and link to the OMIM record. (Your individual abnormality should be different from all other students)

Alport syndrome X-linked inherited disorder that is caused by mutations in COL4A3, COL4A4 or COL4A5. The result of phenotype is progressive sensorineural deafness and renal failure. Alport syndrome

Lab 11

1. Name the components that give rise to the interatrial septum and the passages that connect the right and left atria.

The formation of interatrial septum occurs at the beginning of week 5 development. It all begins with what is known as septum primum, a piece of tissue forming the initial divider between the right and left atria. A gap remains known as foramen primum. From the myocardium and next to the septum primum, the second component arises referred to as septum secundum, the second incomplete interatrial septum of the embryo, containing the foramen ovale; it develops to the right of the septum primum and fuses with it to form the adult interatrial septum.

2. Identify the cardiac defects that arise through abnormal development of the outflow tract

  • Double outlet of the right ventricle
  • Transposition of the great vessels
  • Tetralogy of Fallot
  • Stenosis of the aortic valve with can lead to hypertrophy of the left ventricle
  • Common Arterial Trunk
  • Ventricular septal defect and aorticopulmonary septal defect

Lab 12

1.Give examples of 3 systems that continue to develop postnatally.

  • Reproductive system ( Testis | Spermatozoa - about 2 months of age, primordial germ cells (gonocytes) are replaced by adult dark (Ad) and pale (Ap) spermatogonia forming the spermatogonial stem cell (SSC) population that at puberty will commence differentiation into spermatozoa. )
  • Nervous System (Neural Hearing (6 months to 5 years) ) during the period of year 1.
  • Endocrine System e.g. ( Adrenal - Year 3 zona reticularis present ) at the age of 3.

2.Identify the abnormalities detected by the Guthrie Test and link to one abnormality listed in OMIM. Some of the Abnormalities that are detected by the test may include:

  • Phenylketonuria (PKU)
  • Biotinidase Deficiency (OMIM)
  • Congenital Adrenal Hyperplasia (CAH)
  • Congenital Hypothyroidism (CH)
  • Congenital Toxoplasmosis
  • Cystic Fibrosis (CF) (OMIM)
  • Galactosemia (GAL)
  • Homocystinuria
  • Maple Syrup Urine Disease (MSUD)
  • Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)
  • Toxoplasma gondii IgM antibodies

Student Contribution to the page:

  • Introduction Image:
Cleft palate and lip


  • Ultrasound Images and All drawn pictures in the Animation
Three-dimensional imaging indicates the presence of a facial cleft in a fetus of 22 weeks gestational age
Palate and lip development animation

Genes Involved in Clefting

Research interest, in the origin of cleft lip/palate as well as the genetic and environmental factors that induce the condition, picked up in the 1940s. Since then, various studies have been undertaken to elucidate the ambiguity behind this embryonic abnormality. It is widely accepted now that a combination of environmental and genetic factors contribute to the increase in likelihood of clefting of the palate or upper lip during development. Some of the genes that have been identified to have a vital role in the development of CL/CP include:

Mice mutants exhibit cleft palate and umbilical hernia

Glutamate decarboxylase 1 (Gad1) and Vesicular inhibitory amino acid transporter (Viaat)

Earlier studies have indicated that GABA signalling plays a significant role in the development of central nervous system and palate formation. It has been hypothesised that two of the variants of GABA signalling pathway contribute to the normal formation of craniofacial structures. These are namely; glutamate decarboxylase 1 (Gad1) and vesicular inhibitory amino acid transporter (Viaat). In a study conducted in mice, the alteration or mutation of these two genes has lead to the development of oral clefts such as cleft palate. This has been performed by the inactiviation of the GABA receptors during the CNS development. As a result, inactivation of these two genes causes a disruption in the palate development. This suggested that the presence of Gad1 and Viaat is important for the central nervous system for normal development of the palate. Therefore, mutations or alterations of these genes in the GABA signalling pathway lead to the non-neural defects including cleft palate as fetal movements during development have been altered.[1]

Transforming Growth Factor α (TGFA)

TGFA is regarded as one of the significant genes that have been studied extensively due to its relevance to the oral clefts. TGFA is a trans-membrane protein that is expressed at the medial edge epithelium (MEE) of fusing palatal shelves. The receptor of this gene, epidermal growth factor receptor (EGFR) is expressed on the degenerating MEE. In a study conducted on mice, it was found that the deletion or alteration of this receptor contributed mostly to the facial medio-lateral defects and high occurance of cleft palate formation. [2] [3]

Transforming Growth Factor β 3 ( TGF β3)

Transforming growth factor family consists of more than 30 ligands, which is believed to be involved in a numerous number of biological functions such as proliferation, differentiation, epithelium-mesenchymal transformation, and apoptosis. TFG β3 is a type of protein, known as a cytokine, which is involved in cell differentiation, embryogenesis and development.

MSX 1 Gene

This protein was detected in the epithelial component of the vertical palatal shelf which peaks between 14-14.5 days, prior to the contact of the palatal shelves. Potential roles of the TGF β3 in cellular adhesion, and extracellular formation during the process of palate development have been demonstrated both in vivo and in vitro. The alteration or mutation of this factor via smoking or other factors may result in the failure of epithelial cells during the development of the palate to fuse together. Consequently, the foetus is likely to develop cleft palate abnormality. [3]

[4] [5]

Muscle segment homeobox 1 (MSX1)

Muscle segment homeobox 1 (MSX1) is a protein which is encoded by MSX1 gene. The transcripts of this protein are found in several locations such as thyrotrope-derived TSH cells, and thyrotropic tumor TtT97, pituitary cells, and most importantly expressed during embryogenesis. [6] [7] Due to the abundant expression sites of MSX family, it is hypothesized that these proteins might have an essential role in early development of the embryo. [8] It has been discovered that MSX1, a transcriptional repressor, is significant in craniofacial, limb, odontogenesis, and nervous system development and tumor growth inhibition. Alteration in any kind, including mutation of this gene, may result in the formation of nonsyndromic cleft lip and/or palate. The phenotypes of MSX1 merely depends on the locus of mutation which can affect the protein structure and function. For instance, Ser105Stop mutation was found to cause a complete deletion or absence of the MSX1 homoeodomain. This in particular impairs the development of craniofacial structures and causes clefts. [3]

Environmental Factors in Clefting

Environmental factors have been noted to play a large role in inducing clefting during the developmental process. Certain toxins and drugs, as well as the lack of proper nutrition, have been identified to induce especially detrimental effects in certain processes within development as a whole. Three major environmental factors that are able to induce clefting during embryonic and fetal development are smoking, the consumption of alcohol and the lack of proper nutrition.

Smoking Cleft lip and palate is considered to be one of the possible defects associated with maternal smoking. It was found that smoking cigarettes during the period of pregnancy sometimes is associated with cleft defects. The maternal glutathione s-transferase θ-1 (GSTT1) genotype, together with smoking was found to elevate the risk of cleft lip and/or cleft palate by a ratio of 4.9. Moreover, the gene MSX1 genotypes along with maternal smoking resulted to an even higher ratio of oral defects by 7.16 times. [3] [9]

Alcohol Several studies have shown that the teratogenic impacts of heavy alcohol exposure contributed to the incidence of cleft lip and/or cleft palate. It was reported that about 9-18% of infants who have experienced high alcohol exposure ended up with oral abnormalities such as cleft lip/cleft palate. [10] However, a low level of alcohol consumption does not seem to elevate the risk of oral defects. The gene MSX1 was reported to be a major gene that could result in cleft palate or cleft lip. Furthermore, the gene MSX1 was more likely to be altered with the consumption of four drinks or more. It was found that cytochrome proteins may play a significant role in metabolism of endogenous morphogens in the developing fetus. Variants such as CYP2E1, or CYP1A2 were found to increase the risk of oral defects when they were altered or mutated. As a result, the structural development of the fetus was affected. [3] [11]

Dietary (Folic Acid) Maternal nutrition during pregnancy contributes highly to the normal development of the fetus, especially oral and palate development. In studies conducted on mice, the development of the palate was delayed due to the deficiency in folic acid supply. Moreover, insufficient dietary intake of B-complex vitamins and deficiency or excessive amount of vitamin A have been associated with high incidence of abnormal cleft formation. [12] MTHFR (5,10 methylenetetrahydrofolate reductase) is an enzyme of the metabolism of folate and homocysteine and is involved in substrate methylation and in the synthesis of nucleotides. The gene is located on chromosome 1p36.3. It was found that the absent or reduced levels of MTHFR could homocystinuria. It was observed that a high level of homocysteine was detected in mothers with cleft babies as compared with mothers who have normal levels of MTHFR. It has also been hypothesised that variants of enzymes managing the folate metabolism contribute to the oral cleft formations. The gene encoding of the MTHFR enzyme is known to have two common variants; C677T and A1298C. The link between MTHFR variants and cleft lip and/or palate incidences has been much less studied in the literature. [13] [11]


The embryonic development of the upper lip and nose requires a precise genetic sequence of events. This cranio-facial development pathway is a very complex process and therefore there are several points during development at which cleft lip or palate can occur. During the third and eighth week, five major facial prominences are fused together. The lips then develop between the third and seventh week followed by the palate between the fifth and twelfth week. Due to this intricate process, multiple genetic and environmental factors will vary in their affect on the type and severity of cleft lip and palate and lead to the malfunction of the various tissues involved.

Diagram Shows 5-week embryo with five major prominences

The maxillary, medial nasal and lateral prominences fuse together via a combination of processes including apoptosis, epithelial bridging and subepithelial-mesenchymal penetration. Cleft lip and cleft palate result when these tissues fail to fuse. Some research suggests that this abnormality is secondary to a defect of mesenchymal growth or epithelial bridging. There is evidence that intracellular signaling pathways and a wide range of errors in genetic programming may interfere with the fusion of median nasal and maxillary prominences. Consequently, the blood supply and musculature are often compromised and lead to malfunction of the lip and palate.[14]

For example, in a unilateral cleft lip, the deep fibres of the orbicularis oris muscle are interrupted by the presence of the cleft and insert into the nasal base (the side of the defect), however, in a normal infant, these muscles will form a concentric muscle around the mouth. Furthermore, the superficial layer of the orbicularis oris muscle changes direction and forms superiorly, parallel to the edges of the cleft and inserts inferior to the columella. This can be seen when infants smile as the base of the nose would spread out laterally.[15]

Usually, fusion of both lateral palatal shelves as well as nasal septum in the anterior posterior direction from the incisive foreman to the uvula is essential for the palate development to progress. The occurrence of cleft palate is often linked with a split uvula. Functional impairment and secondary complications often occur with the gap between both the nasal and oral cavities including problems with speaking, ear infections/hearing loss, aesthetic problems, dental anomalies, psychosocial problems and hyper-nasal voice resonance due to the leakage of air from the nasal cavity. [16]

In Diagnosis:

Ultrasound images:

Figure 2.A, Coronal, B, sagittal, C, transverse, and D, 3D rendered US images of a cleft lip (arrows) and palate in a fetus at 21 weeks gestational age. Image in D is viewed frontally. White line indicates plane depicted in C.

Figure 3. Three-dimensional rendered frontal oblique US image shows a median cleft lip (arrow) in a fetus at 32 weeks gestational age.


Editing on the page as well as writing up some of the glossary words and editing some of the references.


  1. <pubmed>20333300</pubmed>
  2. <pubmed>16495466</pubmed>
  3. 3.0 3.1 3.2 3.3 3.4 <pubmed>18383123</pubmed>
  4. <pubmed>14729481</pubmed>
  5. <pubmed>10433915</pubmed>
  6. <pubmed>9369446</pubmed>
  7. <pubmed>10215616</pubmed>
  8. <pubmed>1973146</pubmed>
  9. <pubmed>3565662</pubmed>
  10. <pubmed>9632044</pubmed>
  11. 11.0 11.1 <pubmed>19881024</pubmed>
  12. <pubmed>12672677</pubmed>
  13. <pubmed>11967921</pubmed>
  14. <pubmed>2938624</pubmed>
  15. <pubmed>21331089</pubmed>
  16. <pubmed>3100859</pubmed>