2011 Group Project 2

From Embryology
Note - This page is an undergraduate science embryology student group project 2011.
2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip

DiGeorge Syndrome


A congenital disorder is one which is present at birth. They are often abnormalities that arise from errors that occur during development of the fetus. Some congenital abnormalities are genetic, and often run in families while others are spontaneous and have no genetic linkages. DiGeorge syndrome is a congenital abnormality that is caused by the deletion of a part of 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. [1].

About 1/4000 children born are affected by DiGeorge syndrome, with 90% of these cases involving a deletion of a section of chromosome 22 [2]. DiGeorge is quite often a spontaneous mutation, but it may be passed on in an autosomal dominant fashion. Some families have many members affected.

DiGeorge is a complex syndrome and patient cases vary greatly. The common symptoms present across numerous patients include

  • Abnormal faces
  • Congenital heart defects
  • Hypoparathyroidism with hypocalcemia
  • Cognitive, behavioral, and psychiatric problems
  • Increased susceptibility to infections
  • Hypoplasia or absence of the thyroid and parathyroid glands [3]

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 and a shortened lifespan for the patient. As there is currently no treatment education is vital to the wellbeing of those affected, directly or indirectly by this condition. [4] 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

  • Angelo DiGeorge. In the mid 1960's, Angelo DiGeorge noticed a similar combination of clinical features in some children. He named the syndrom after himself. The symptoms that he recognised were hypoparathyroidism, underdeveloped thymus, conotruncal heart defects and a cleft lip/palate. [5]
  • 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. [6]
  • Lischner and Huff determined that there was a deficiency in T cells was present in 10-20% of the normal thymic tissue of DiGeorge syndrome patients (1975). [7]
  • Cleveland determined that a thymus transplant in patients of DiGeorge was able to restore immunlogical function (1975). [8]
  • 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. [9]
  • 1980s technology develops to identify that these patients have part of a chromosome missing. [10]
  • De La Chapelle suspects that a chromosome deletion in 22q11l is responsible for diGeorge syndrome (1981) [11]
  • Ammann suspects that DiGeorge symdrome 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 (1982). [12]
  • Muller observes the clinical features and natural history of DiGeorge (1989) [13]
  • Pueblitz notes a deficiency in thyroid C cells in Digeorge patients (1993) [14]
  • Crifasi uses FISH as a definitive diagnosis of DiGeorge (1995) [15]
  • Davidson diagnoses DiGeorge prenatally using echocardiography and amniocentesis. This was the first reported case of prenatal diagnosis with no family history. (1998) [16]
  • Matsumoto confirms bone marrow transplant as an effective therapy of DiGeorge syndrome (1998) [17]
  • Lee links heart defects to the chromosome deletion in DiGeorge syndrome (2001) [18]
  • Lu determines that the genetic factors leading to DiGeorge syndrome are linked to the clinical features of Tetralogy of Fallot. (2001) [19]
  • Garg evaluates the role of TBx1 and Shh genes in the development of DiGeorge Syndrome (2001) [20]
  • 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 (2004) [21]
  • Fagman identifies Tbx1 as the transcription factor that may be responsible for incorrect positioning of the thymus and other abnormalities in Digeorge (2007) [22]
  • Oberoi uses speech, dental and velopharyngeal features as a method of diagnosing DiGeorge syndrome (2011) [23]
  • Yang notices dental anomalies associated with 22q11 gene deletions (2005) [24]


It appears that DiGeorge syndrome has a minimum incidence of about 1 per 2000-4000 live births in the general population, ranking among the most frequent causes of genetic syndromes at birth [25]. Due to the fact that 22q11.2 deletions can also produce Velocardiofacial syndrome as well, there is some overlap of the figures for epidemiology [26] as both syndromes have rather similar presentation. 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 [27]. The presentation of more severe cases of DiGeorge syndrome is apparent at birth, especially with malformations. Within the first 6 months of life, susceptibility to infection may raise suspicion of DiGeorge syndrome. However, it has been well documented that there individuals who have relatively minor cardiac malformations and normal immune function, and may show no presentation of DGS until later in life, which may be resultant form a learning dysfunction. DiGeorge frequently presents with cleft palate, as well as congenital heart defects[28]. 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 [29].


DiGeorge Syndrome (DGS) is a developmental field defect that is presumed to be of heterogenous etiology. Reported cases have shown autosomal dominant, autosomal recessive, X-linked and chromosomal modes of inheritance for DGS [30].

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 [31].

One study demonstrated the presence of large deletions across multiple loci in 22q11. Hence it was determined by the researchers that it is unlikely that a point mutation or a small deletion of a single locus could lead to DGS, as the detection of these large deletions suggests that the loss of function of more than a single gene is required for pathogenisis of DGS [32].

  • more to come guys, just off to work, will try and get it completed tonight.

--Timothy Ellwood 10:12, 5 September 2011 (EST)


As mentioned in the introduction, the pathogenesis of DiGeorge is a 22q11.2 microdeletion. More precisely, 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 microdeletion, which is a result of complications that occur during meiosis. It seems that multiple genes exist in this region, which results in similar symptoms being seen across a large number of 22q11.2 microdeletion syndromes. As mentioned previously, 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[33].

A specific gene that seems to be critical in DiGeorge syndrome is the TBX1 gene which, when deleted, causes the exact presentation of DiGeorge syndrome. [34] 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[35].

Dianostic Tests

Diagnostic Test How it works Relevance to DiGeorge
Fluorescence in situ hybridisation (FISH) [36] FISH is a technique that attaches DNA probes that have been labeled with fluorescent dye to chromosomal DNA. 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. [37] 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.
Based on symptoms 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 [38]
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 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.
Ultrasound 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. [39] 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.
Amniocentesis 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 symdrome 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. [40]
BACS- on beads technology 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. [41]

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 [42]. 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 [43] [44]. The most common signs and symptoms 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 [45]. 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 [46].

Abnormality Clinical presentation How it is caused
Congenital heart defects Congenital malformations of the heart can present with varying severity ranging from minimal symptoms to mortality [47]. 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 lead to pathological changes (causing shortness of breath) that will be described on the right. These changes can usually be prevented or corrected with surgery if detected early [48] [49]. 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. Cardiac development involves multiple genes, some of which play a role in the formation of the conotruncus, are located on the chromosome 22 and may be deleted in DiGeorge syndrome [50]. In 22q11.2 deletion syndrome various disorders can lead to congenital heard disease. Some of the most common ones include patient ductus arteriosus, tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities [51]. To give one example, the tetralogy of Fallot will be described below and illustrated in image on the right. The four features of the teralogy of Fallot are:
  1. Ventricular septal defects

The healthy heart has four chambers, two atria and two ventricles, where the left and right ventricle are separated by the 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)[52].

  1. 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) [53].

  1. "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)[54].

  1. 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)[55].

Defect of palate/velopharyngeal insufficiency Velopharyngeal insufficiency or cleft palate is the failure of the roof of the mouth to close during embryonic development. Apart from facial abnormalities whe the upper lip is affected as well, it presents with hypernasality (nasal speech) and nasal air emission [56].

In the english language only the sounds "m", "n" and "ng" should resonate nasally, however in hypernasality other sounds resonate through the nose as well to varying degrees. In order to pronounce strong consonants ("p", "b", "g", "t", and "d") the velopharygeal spincter must close off the nose, which does not occur in velopharyngeal insufficiency, resulting in difficulties to pronounce these strong consonantes[57].

The roof of the mouth, also called soft palate or velum, the lateral pharyngeal wall and the posterior 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 during embryologic development and commonly occurs in DiGeorge syndrome [58].
Recurrent infections due to immunodeficiency Many newborns with a 22q11.2 deletion present with difficulties in mounting an immune response against infections or with problems after vaccination. In most cases these problems cease before the first year of life, however some patients may have a persistent immunodeficiency and develop autoimmune diseases such as juvenile rheumatoid arthritis or graves disease [59]. The immune system has a specialized T-cell mediated immune response in which T-cells recognize and eliminate (kill) foreign antigens (bacteria, viruses etc.) that are presented to T-cell receptors by antigen-presenting cells [60]. T-cells arise from and mature in the thymus. Especially during childhood T-cells arise from 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. This in turn causes the difficulties in dealing with infections [61].

Autoimmune diseases are thought to be due to T-cell regulatory defects and impair of central tolerance [62].

Hypocalcaemia due to hypoparathyrodism Hypoparathyrodism (lack/little function of the parathyroid gland) causes hypocalcaemia (lack/low levels of calcium in the bloodstream). Hypocalcaemia in turn may cause seizures in the fetus [63]. 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[64]. 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 [65].
Learning difficulties 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 [66].

DiGeorge syndrome children appear to have an IQ in the lower range of normal or mild mental retardation[67]. Furthermore, these children appear to have average verbal short-term memory abilities, while problems arise in the visuospatial short-term memory, in executive control, and in the working memory[68].

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 [69]. Additionally studies found correlation between 22q11.2 and abnormally small parietal lobes [70].
Abnormal facial features To the common facial features of individuals with DiGeorge Syndrome belong [71]:
  • 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
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 right [72].


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 [73]. 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 [74]. This often complicates the diagnosis. In fact, some patients are not diagnosed until early adulthood or not diagnosed at all, especially in developing countries [75] [76]. 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 [77]. Despite the high variability, a range of typical symptoms raise suspicion for DiGeorge over a range of ages and will be listed below [78][79]:

  • Newborn: heart defects
  • Newborn: cleft palate, cleft lip
  • Newborn: convulsion due to hypocalcaemia
  • Newborn: other birth defects such as kidney abnormalities or feeding difficulties
  • Late-occurring features: 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 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.

Area Medical condition Therapy options
Cardiology Some of the most common congenital heart defects in DiGeorge syndrome include patient ductus arteriosus, tetralogy of Fallot, ventricular septal defects and aortic arch abnormalities [80].

Signs and symptoms are:

  • Shortness of breath
  • Purple-blue skin due to insufficient oxygen supply
  • Loss of consciousness
  • Heart murmur
  • Poor feeding
  • Underdevelopment of limbs and muscles

However, mild cases of congenital heart defects might not be detected through life[81].

The classical treatment for severe cardiac deficits is surgery, where the surgical prognosis depends on both DiGeorge syndrome itself and the anatomy of the cardiac defects. Because individual with DiGeorge commonly have other conditions besides possible cardiac anomalies, the other conditions such as a deprived immune system, hypocalcaemia and platelet deficiency, may influence the diagnosis after surgery. In terms of the anatomy, some cardiac defects are easier to repair surgically than others [82]. In order to achieve the best outcome, with the best perisurgical care, timing becomes important[83].

Overall techniques in cardiac surgery have been adapted to the special conditions of patients with 22q11.2 deletion, which decreased the mortality rate significantly [84].

Cleft palate A cleft palate will be detected right after birth. The main features of a cleft hypernasality and nasal air emission [85]. Additionally facial abnormalities and speech difficulties can have psychological effects on the child [86]. Plastic surgery in clef palate patients is performed to counteract feeding difficulties, hypernasality and nasal air emulsion. 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[87]. Outcomes of surgery show that about 50 percent of patients attain normal speech resonance while the other 50 percent retain hypernasality [88]. However, depending on the severity, resonance and pronunciation problems can be reversed or reduced with speech therapy [89].
Child development and psychology

Further research possibilities


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

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

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

Congenital preset from birth

Facies appearance of facial expression of an individual that is typical for a particular disease or condition

Graves disease symptoms due to too high loads of thyroid hormone, caused by an overactive 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

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

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

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

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.

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

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


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  85. PMID: 21861138
  86. <pubmed> 3757858</pubmed>
  87. <pubmed>11772163</pubmed>
  88. <pubmed> 21740170</pubmed>
  89. <pubmed>8884403</pubmed>

2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip