Difference between revisions of "User:Z3290618"

From Embryology
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* [http://www.youtube.com/watch?v=RV3y_n5ZjFQ Lecture: Neurodevelopmental disorders - Fragile x and Autism]
* [http://www.youtube.com/watch?v=RV3y_n5ZjFQ Lecture: Neurodevelopmental disorders - Fragile x and Autism]
[[image:X-Linked_recessive_(affected_father).jpg|thumb|right|x-linked recessive]]
[[File:Fragile site appearance and distribution.jpg|Fragile site appearance and distribution]]
[[File:Fragile site appearance and distribution.jpg|Fragile site appearance and distribution|thumb|left|appearance]]
=== References ===
=== References ===

Revision as of 09:54, 13 October 2011

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 One

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

  • In 1973 the Monash University team achieved In Vitro Fertilisation (IVF). However, it only lasted a few days. On 25 July 1978, the first IVF baby was born in the UK.

Robert Edwards was awarded the 2010 Nobel Prize in Physiology or Medicine "for the development of in vitro fertilization"

Identify a recent paper on fertilisation and describe its key findings.

  • Hansen et al. (2002). The Risk of Major Birth Defects after Intracytoplasmic Sperm Injection and in Vitro Fertilization. The New England Journal of Medicine" 342:725-730
  • In a comparison of IVF conceived, intracytoplasmic sperm injection and naturally conceived children, the rate of major birth defects was seen to be double in assisted conception. At one year of age, the ratio of birth defects in the IVF and intracytoplasmic sperm injected children was 2.0. This figure was derived after adjustment for maternal age, sex of infant etc. Before adjustment the figure was higher (9:4.2).

Identify 2 congenital anomalies.

  • Spina bifida
  • Hydrocephalus

--Mark Hill 09:54, 3 August 2011 (EST) You need to answer these 3 questions before Lab 2.

Lab Two

Lab Three

What is the maternal dietary requirement for late neural development?

  • Iodine: 400-600mg through course of pregnancy. A deficiency can cause cretinism and hypothyroidism.

Upload a picture relating to you group project.

Fragile site appearance and distribution File: Fragile site appearance and distribution

--Mark Hill 23:41, 20 August 2011 (EST) Why did you upload this image as a screen shot? It has a lower resolution and may not accurately show the original image. It should have been downloaded from this page (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018726/figure/F7/) as a jpg file (CG-11-447_F7.jpg). Then renamed and uploaded to the site. Please do not use screenshots for uploading files. Repeat this exercise if you wish to get the marks for this part of the question.

Lab Four

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

The allantois is continuous with the Urachus to connect to the fetal bladder.

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

Ductus Arteriosus is located between the Arch of Aorta and the pulmonary artery. In adulthood, this shunt closes, forming the Ligamentum Arteriosum. Similarly, the Foramen Ovalis allows blood to bypass the pulmonary circulation by shunting blood from the right to left atria. The Ductus Venosus (later Ligamentum venosus) shunts fetal blood from the umbilical vein directly to the inferior vena cava.

Identify the Group project sub-section that you will be researching.

I will be doing Signs and Symptoms of Fragile-X syndrome.

Lab Five

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

The left side is the more common for diaphragmatic hernia due the early closure of the right side of the pluroperitoneal cavity.

Lab Six

Lab Seven

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

a) Satellite cells are not necessary for muscle hypertrophy. b) They are however generally involved as their numbers increase during this pathology.

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

Under chronic low frequency stimulation, fast-twitch fibres receive the same input as slow-twitch fibres. Over a period of stimulation, the fast-twitch fibres will undergo changes in their protein structure, responding to the cronic low frequency stimulation. These protein changes will result in the fast-twitch fibres resembling the slow-twitch fibres. Effectively, giving fast-twitch fibres prolonged slow-twitch stimulation causes the shift.

Trisomy 21 Assessment Criteria

The key points relating to the topic that your group allocated are clearly described.

This has been done fairly well. The key areas of Trisomy 21 have been well described. However, I would have liked to see a section on what proteins are over produced and what genes are over transcribed due to the trisomy and how this translates into the pathology.

The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.

The content, headings and sub-headings are appropriate. The diagrams and graphs are useful. A better explanation is needed for some (the growth charts for example) while others have been over-used (three diagrams of the karyotype is a little excessive).

Content is correctly cited and referenced.

The parts that have been referenced, are referenced well. However, there is no reference for the Heart Defects section. Furthermore, I feel there are too many large blocks of quote. The recent studies appears to all be copy + pasted as does the start of the growth charts section (though they are correctly referenced). A summary of this content would have been more appropriate.

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.

The wiki is clearly set out, well explained and the useful terms are defined to assist in learning. The diagrams and figures are basic, but I feel need explaining. They seem to just have been put there in order to have pictures.

Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.

Again, I would have preferred a gene - protein - pathology explanation. However, it appears that a lot of research has gone into the wiki.

Relates the topic and content of the Wiki entry to learning aims of embryology.

The wiki has been developed to illustrate the effects of Trisomy 21. No great emphasis has been placed on the development of the disorder. A stage by stage breakdown of the apparent pathology would be helpful and relate greater to the sequential nature of the embryology course.

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.

As written above, the wiki appears to be well researched. I would have expected more than 20 references though. The key areas of Trisomy 21 are covered and adequately "inform peers in their learning". Further depth would be appreciated. Having said that, there are links available throughout the wiki if one is interested in further research.

Lab Eight

Group One

Look of the presentation - A little work needs to be done on your formatting. Your pictures need to be aligned with the text better. "Stats abnormal.jpg" intrudes into the text. It makes the page look a little sloppy. Further, You have large blocks of texts that would be better put into tables to break down and simplify the information presented.

Your clinical manifestions is very basic. It looks like you have read a number of articles and just listed terms. It would be better if each manifestation was coupled with the reason for that sign/symptom. For example, write down the term, what it means and how the non-disjuntion causes it at a protein/molecular level.

Positives - Your topic is very well researched. You seem to understand and convey that understanding very well. The body of the work is done. I would suggest looking at other pages and presenting/formatting yours so that it looks a little neater. GOOD JOB!

Group Two

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.

Group Three

You need to break up the large amount of text with more tables. The amount of text is quite overwhelming up until 'Signs and Symptoms'. Speaking of this section: The table looks FANTASTIC. Really neat, simple, love it! However... you haven't alternated the colours correctly. You need to end with light purple... you have two dark blocks next to eachother.

Your 'Action of inhibitors' picture needs to be better segregated. Put a border around it or something.

Try to keep your formatting of headings consistant. In further research, the headings do not appear in the contents, but in Diagnosis, they do.

Group Four

The page is laid out really well. The formating is basic but effective. Make sure your pictures are all working e.g. Mutant Huntington Disease.

Group Six

The first striking feature is the long block of text from the start. You need to break this up with more tables. Your Genetics/Aetiology section could be laid out more simply. A table with columns for the Gene, gene profile and then description. In Pathophysiology, you already have the numbered list. Don't put the numbers next description and format this so that each of the following:

Pulmonary stenosis Overriding aorta Ventricular septal defect Right ventricular hypertrophy

are a subheading in your contents.

In treatment and managment, I would suggest that you colour each row of the table differently. I agree that tables without borders look better. However, if is hard to see which bit of information is associated with Pott's shunt, Watersons shunt etc.

Lastly: only 41 references? I would have expected a lot more. The average number for the other groups is in the 125-150 region. You might want to do a bit more research.

Group Seven

Group Eight

Group Nine

Group Ten

Group Eleven

Lab Nine

Lab Ten

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

Cytomegalovirus is an environmental teratogen that can lead to hearing loss, prenatally.

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

In the neonate, the auditory tube, that runs toward the nasopharynx, is almost horizontal. Whereas in the adult, it runs downward. This tube is also far smaller and narrower prenatally, restricting the amount of fluid that can drain through it. Finally, the auditory tube has few muscles, neonatally, that contribute to opening it. In the adult there are more.

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


Lab Eleven

Lab Twelve

Group Page Contribution

Content Added

Signs and Symptoms

Fragile X syndrome is characterised by mental retardation, a variety of cognitive, physical and behavioural signs. Most males with the full FMR mutation exhibit the clinical features of fragile X displayed below. Furthermore, males affected tend not to reproduce, but this is possibly due to the severity of mental retardation.

Physical phenotype

Before puberty, children with Fragile-X tend to have no discernible 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[1]. 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 macroorchidism: enlargement of the testicles. Fragile-X patients may also have loose connective-tissues[2], 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.

Physically, adult males often have a long narrow face, prominent ears, a prominent jaw, and macroorchidism. 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[1][2]. Mitral valve prolapse has been shown to in late adolescence[3]. Males with the fragile X syndrome also tend to exhibit behavioral features such as hyperactivity, social anxiety, perseverative speech and language, tactile defensiveness, stereotypes (e.g., hand-flapping), and hand biting.

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[4]. Their anxiety often manifests itself as discontinuous speech and a lack of eye contact.

Studies into the social cognition network underlying face encoding, show profound causation relating to cortical activation [5] Individuals with FXS show decreased activation of prefrontal regions that are shown to affect social cognition. These areas include the medial and superior frontal cortex. The data suggests that social anxiety in Fragile-X patients may be related to the inability to successfully activate higher level social cognition regions during the early phases of memory formation. [5]

Intellectual development

Males with FXS tend to exhibit developmental delays in childhood. By age 3, these males will test in the mentally retarded range. As a generalisation, the majority of Fragile-X patients have an IQ defined as moderately retarded (IQ 40-54). However, the mental retardation ranges from profound (IQ<20) to mild. Females however, show lower impairment, with only one-third having IQs within the ‘mental retardation’ range.

In sibling studies, children with Fragile-X syndrome obtain lower percentage correct scores in all subtests of the WISC (Wechsler Intelligent Scale for Children) [6]. Over time, the gap between the FXS afflicted and the non-affected siblings grew dramatically. The unaffected children had a rate of intellectual development approximately 2.2x that of their FXS counterparts.

Specifically, a deficit in working memory has been attributed to the FXS mutation. When studied, they exhibit a weakness for tasks that reflect function of the central executive subcomponent of working memory[7]. Furthermore, the extent of the central executive deficit is correlated significantly with larger CGG section repeat. This correlation between repeat length and working memory (specifically in asymptomatic carrier males) suggests that carrier males have greater neuropathology with larger expansions in FMR1 mRNA transcripts[7].

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.

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.

Behavioural characteristics

There are a number of of phenotypic behavioural characteristics associated with Fragile-X syndrome. It is important to note that a number of these are purely observational. Many do not have scientific studies associated with proof of the characteristic nor explanations of by which mechanism they occur. For information on these see National Institute of Child Health & Human Development and The National Fragile X Foundation.

Males with the fragile X syndrome also tend to exhibit behavioral features such as hyperactivity, social anxiety, perseverative speech and language, tactile defensiveness, stereotypes (e.g., hand-flapping), and hand biting[8]. ADHD and a short attention span are associated with Fragile-X patients. Girls are less likely to be diagnosed with hyperactivity, however, they do tend to exhibit an inattentiveness and a failure to focus on long, difficult tasks[9].

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[10]. 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[11]. 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[12]. 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[13].

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.

x-linked recessive



Year Discovery
1910 Thomas Hunt Morgan demonstrated that when a gene is located on the X chromosome of the fruit fly, the characteristic appears more frequently in males than in females[1].
1943 Martin and Bell inferred and first reported that the excess number of retarded males in the population was due to a sex linked inheritance. The two also noted that there was a lack of unusual physical features related to the mental retardation, including the shape of the head and face. Therefore Martin and Bell were also the first to report sex linked mental retardation without microcephaly or microphthalmia [2].
1969 Herbert Lubs first documented report of the existence of the marker X chromosome.[2]. Lubs developed the chromosomal test for Fragile X however it was not used extensively until the late 1970's[3].
1977 Sutherland showed Lubs findings to be a reliable through cells cultured in a folate deficient medium. [4].
1980 Turner and colleagues recognized the combination of macroorchidism and mental retardation in males in conjunction with a fragile site on the X chromosome to be a separate clinical entity[5].
1991 Verkerk discovered and described the FMR1 gene and encouraged the medical and psychopedagogic research of Fragile X Syndrome[6].
2001 Hagerman and colleagues first recognized Fragile X-associated tremor/ataxia syndrome (FXTAS)[7].
2010 Paul and colleagues deduced that the elevated mRNA in FXS premutation carriers are vulnerable to neurotoxin, leading to early cell death and brain disease, consistent with FXTAS symptoms. [8].
Signs & Symptoms Treatment Option and Description
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.” [9]

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.” [9]


FXS patients are known to be at an increased risk for seizures, with rates of 5% for girls and 13% to 18% for boys. Many types of seizures have been reported in individuals with FXS; the most common type being complex partial seizures.

A single anticonvulsant is usually the treatment of choice to control seizures in FXS. Following administration of anticonvulsant, general health and blood-specific monitoring is required. [9]

Excessive mGluR5 (metabotropic glutamate receptor 5 pathway)Signaling

Enhancement of mGluR-mediated processes and excessive mGluR5 signaling that normally would be inhibited by FMRP has been shown to contribute to many of the phenotypic features of FXS, such as cognitive deficits, behavioural abnormalities, enhanced anxiety, seizures, coordination problems and more.

mGluR5 antagonists have been studied in animal models of FXS and have demonstrated benefits in decreasing problems associated with excessive mGluR5 signaling, such as reducing seizures, enhancing cognitive skills and improving behaviour. mGluR5 antagonists trials are beginning with FXS individuals. [9]

Behavioural Deficits

Studies have shown that environmental variations impact on behaviour. For instance, fewer autistic behaviours as well as enhanced IQ scores in children with FXS are associated with a higher-quality home environment. Educational services are also known to improve behaviour and decrease autistic symptoms in FXS patients. Higher-functioning individuals with FXS may also benefit from counseling or psychotherapy. [9]


--z3290618 12:55, 28 July 2011 (EST)

--z3290618 12:38, 4 August 2011 (EST)

--z3290618 12:22, 18 August 2011 (EST)

--z3290618 11:29, 25 August 2011 (EST)

--z3290618 11:37, 1 September 2011 (EST)

--z3290618 12:50, 15 September 2011 (EST)

--z3290618 11:49, 22 September 2011 (EST)

--z3290618 11:56, 29 September 2011 (EST)

--z3290618 11:22, 6 October 2011 (EST)

  1. http://www.fragilex.org/html/history.htm
  2. 2.0 2.1 Cite error: Invalid <ref> tag; no text was provided for refs named PMID6348096
  3. http://www.friendsforfragilex.org/research/history.php
  4. http://www.medlink.com/medlinkcontent.asp
  5. http://www.medlink.com/medlinkcontent.asp
  6. Cite error: Invalid <ref> tag; no text was provided for refs named PMID19718005
  7. http://www.medlink.com/medlinkcontent.asp
  8. http://www.medlink.com/medlinkcontent.asp
  9. 9.0 9.1 9.2 9.3 9.4 <pubmed>19117905</pubmed>