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22q11.2 Deletion Syndrome

Last updated March 24, 2018

Approved by: Krish Tangella MD, MBA, FCAP

22q11.2 Deletion Syndrome is a genetic condition that is caused by deletion of genetic material from the long arm of chromosome 22.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Conotruncal Anomaly Face Syndrome (CTAF)
  • Digeorge Anomaly
  • Velocardiofacial Syndrome (VCFS)

What is 22q11.2 Deletion Syndrome? (Definition/Background Information)

  • 22q11.2 Deletion Syndrome is a genetic condition that is caused by deletion of genetic material from the long arm of chromosome 22. About 30-40 genes coexisting in this region are lost in the deletion. Very few genes have been characterized from this region. Among them are TBX1 and COMT, which are believed to contribute to the characteristic facial features and behavioral traits of this disorder
  • 22q11.2 Deletion Syndrome is inherited as an autosomal dominant trait in a minority of the affected individuals, who inherit the condition from one of the parents. In these individuals, a single defective copy of chromosome 22 in their body cells is sufficient to cause the condition
  • The deletion of part of chromosome 22 can affect almost any part of the body. The symptoms may be mild or severe, and often varies even among affected members of the same family
  • Since 22q11.2 Deletion Syndrome is a genetic disorder, having a family history of the disorder is a known risk factor for developing it. Nonetheless, only 10% of the reported cases are inherited. The other 90% occur due to spontaneous mutations in the egg and sperm, or during early fetal development. The risk factors for the spontaneous development are currently unknown
  • Some major symptoms of the disorder include characteristic facial features, such as upslanted eyes, broad nasal bridge, cleft palate, congenital cardiac defects, recurrent infections, missing thymus gland, delay in achieving developmental milestones, learning disabilities, autism spectrum disorders, and mental disorders such as schizophrenia
  • The diagnosis for 22q11.2 Deletion Syndrome can be made in the prenatal stages with fetal ultrasound or genetic testing of fetal cells. A diagnosis of the condition after birth is typically done through physical examination, evaluation of family medical history, and genetic testing
  • Presently, there are no cures available for 22q11.2 Deletion Syndrome. Treatment is usually tailored to address individual symptoms. While cleft palate, skeletal defects, and cardiac defects may be corrected through surgery, continued monitoring may be required for infections and other symptoms
  • The prognosis associated with 22q11.2 Deletion Syndrome has improved in the recent past. However, it is also dependent upon the severity of the signs and symptoms, with milder cases having a better prognosis

Who gets 22q11.2 Deletion Syndrome? (Age and Sex Distribution)

  • 22q11.2 Deletion Syndrome is reported to affect 1 in 4,000 newborns. The condition manifests itself in the fetus during gestation
  • It is believed that the condition may be more common due to misdiagnosis, as the symptoms overlap with those of other conditions. Additionally, those with mild symptoms may not be diagnosed at all, in certain cases
  • Both male and genders are susceptible to 22q11.2 Deletion Syndrome
  • No racial or ethnic group predilection is observed

What are the Risk Factors for 22q11.2 Deletion Syndrome? (Predisposing Factors)

  • 22q11.2 Deletion Syndrome is a genetic disorder, but only 1 in 10 affected individuals inherit the condition. Hence, a family history of the condition is a risk factor for developing the same
  • In cases where the condition develops as a result of spontaneous mutation in the gamete cells (ova and sperms), the risk factors are not known

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of 22q11.2 Deletion Syndrome? (Etiology)

22q11.2 Deletion Syndrome is caused by the deletion of a portion of the long arm (q) of chromosome 22 in the middle of the chromosome, at locus q11.2.

  • Approximately, 3 million base pairs are missing from the DNA in this region, which houses 30-40 genes. Since the loss of genetic material leads to loss of several closely located genes, this disease is also known as a “contiguous gene deletion syndrome”
  • Only 2 of the genes from the deleted region have been characterized, which include:
    • TBX1 - the deletion of which is believed to cause some of the characteristic symptoms of the condition, such as the distinctive facial features, heart defects, and low calcium levels. The absence of this gene is also though to contribute to behavioral issues
    • COMT - the deletion of this gene is believed to result in the characteristic behavioral problems associated with this syndrome
  • About 90% of affected individuals develop the disease as a result of spontaneous deletion in either the genetic material during the formation of gamete cells (egg and sperm) of the parents or during early fetal development
  • In 10% of cases, the condition is inherited in an autosomal dominant manner from one parent who carries the deletion on chromosome 22

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of 22q11.2 Deletion Syndrome?

The signs and symptoms of 22q11.2 Deletion Syndrome include:

  • Facial features
    • Cleft palate
    • Small ears
    • Broad nose
    • Upslanted eyes
  • Heart abnormalities
    • Pulmonary atresia, where the valve that regulates the blood flow to a part of the lungs is not formed properly
    • Absent pulmonary valve
    • Ventricular septal defects: The connection between the lower chambers of the heart is not normal
    • Defective septum and pulmonary atresia may coexist
    • Incomplete development of aorta (interrupted aortic arch)
  • Autoimmune disorders may be present such as:
    • Rheumatoid arthritis causing signs and symptoms including swelling and tenderness of the joints, decreased range of joint movement, and stiff joints
    • Graves disease causing signs and symptoms  including anxiety, enlarged thyroid gland, unexplained weight loss, bulging eyes, and abnormal heartbeats
  • Absence of the thymus gland, on very rare occasions
  • Respiratory problems
  • Problems with the structure and function of kidneys
  • Low blood calcium levels
  • Low blood platelet levels (thrombocytopenia)
  • Problems with feeding, digestion
  • Mild skeletal abnormalities (short stature, malformation of bones in the spine)
  • Delay in achieving developmental milestones
  • Risk of behavioral issues such as attention deficit hyperactivity disorder (ADHD)
  • Autism spectrum disorders
  • Risk of mental disorders such as:
    • Schizophrenia
    • Bipolar disorder
    • Depression
    • Anxiety

Note: Affected individuals may not exhibit all of the above symptoms. The symptoms may be mild to severe, and may even vary among affected individuals belonging to the same family.

How is 22q11.2 Deletion Syndrome Diagnosed?

A diagnosis of the disorder is undertaken based on the following evaluations:

  • Prenatal diagnosis of 22q11.2 Deletion Syndrome:
    • Ultrasound scans: It may help identify congenital heart and kidney defects
    • Prenatal genetic testing of fetal cells using techniques such as fluorescence in-situ hybridization (FISH), multiplex ligation-dependent probe amplification assay (MLPA), quantitative polymerase chain reaction (qPCR), and array comparative genomic hybridization (array-CGH)
  • Diagnosis of 22q11.2 Deletion Syndrome after birth of the child:
    • Complete physical examination
    • If characteristic facial features and other abnormalities are present, then an evaluation of family medical history is performed
    • X-rays for checking skeletal abnormalities
    • Ultrasound scan of the kidneys to check for abnormalities
    • Magnetic resonance imaging (MRI) scans to check for congenital abnormalities
    • Electrocardiogram (EKG) and echocardiogram for heart defects
    • Genetic testing to confirm diagnosis, using techniques such as fluorescence in-situ hybridization (FISH), multiplex ligation-dependent probe amplification assay (MLPA), quantitative polymerase chain reaction (qPCR), and array comparative genomic hybridization (array-CGH)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of 22q11.2 Deletion Syndrome?

Some potential complications in individuals with 22q11.2 Deletion Syndrome include:

  • Developmental delays
  • Arthritis
  • Repeated infections
  • Celiac disease (rare)
  • Thyroid gland abnormalities including hypothyroidism or hyperthyroidism (rare)
  • Susceptibility to depression and other mental disorders
  • Early onset Parkinson’s disease
  • Severe congenital heart defects may be fatal

How is 22q11.2 Deletion Syndrome Treated?

There are currently no established methods for treating 22q11.2 Deletion Syndrome. The treatments are generally geared towards addressing individual symptoms. A concerted and coordinated effort by a number of specialists may be required in order to successfully treat the symptoms of 22q11.2 Deletion Syndrome.

The treatment measures may include the following:

  • Feeding difficulties can be addressed by a dietitian, since cleft palate may present difficulties with breastfeeding
  • Surgery for cleft palate
  • Infections may be treated with antibiotics
  • Low blood calcium levels can be treated with calcium and vitamin D supplements
  • Hearing aids for hearing abnormalities; tests for frequent ear infections
  • If the thymus gland is absent, thymus transplantation may be recommended
  • If possible, surgery to correct cardiac defects
  • Speech therapy, to help a child develop proper speech
  • Special education
  • Psychiatric therapy for mood disorders

How can 22q11.2 Deletion Syndrome be Prevented?

  • Currently, there are no specific methods or guidelines to prevent 22q11.2 Deletion Syndrome since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as 22q11.2 Deletion Syndrome
  • Regular medical screening at periodic intervals with tests, and physical examinations are strongly recommended for this condition; life-long treatments and monitoring may be necessary

What is the Prognosis of 22q11.2 Deletion Syndrome? (Outcomes/Resolutions)

  • The prognosis of 22q11.2 Deletion Syndrome has improved in the last several years, owing to available treatments for congenital heart defects
  • The severity of the signs and symptoms may dictate the outcome; individuals with mild signs and symptoms have better prognosis than those with severe features
  • Life-long monitoring and treatment measures may be required for an affected individual

Additional and Relevant Useful Information for 22q11.2 Deletion Syndrome:

The signs and symptoms of 22q11.2 Deletion Syndrome are so varied; hence, different groupings of features were once described as separate conditions. Researchers and medical experts named these conditions variously as DiGeorge Syndrome, Velocardiofacial Syndrome (also known as Shprintzen syndrome), and Conotruncal Anomaly Face Syndrome.

In addition, some children with the 22q11.2 deletion were diagnosed with the autosomal dominant form of Opitz G/BBB Syndrome and Cayler Cardiofacial Syndrome. Once the genetic basis for these disorders was identified, healthcare providers and scientists determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, the term 22q11.2 Deletion Syndrome is used; a description that is based on its underlying genetic cause.

What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Aug. 1, 2016
Last updated: March 24, 2018