22q11.2 deletion syndrome

22q11.2 deletion syndrome is caused by a missing piece (deletion) of part of chromosome 22 in each cell. The deletion occurs near the middle of the chromosome on the q arm at a location known as q11.2.

Most people with 22q11.2 deletion syndrome are missing a piece of chromosome 22 that contains about 30 to 40 genes, many of which have not been well characterized; however, some people have smaller deletions. Researchers are working to learn more about all of the genes that contribute to the features of 22q11.2 deletion syndrome. The deletion of a particular gene, TBX1, is thought to be responsible for many of the syndrome's characteristic signs and symptoms. Loss of this gene may also contribute to behavioral problems. The loss of another gene, COMT , may also cause increased risk of behavioral problems and mental illness. The other genes that are deleted likely contribute to the various features of 22q11.2 deletion syndrome.

Most cases of 22q11.2 deletion syndrome are not inherited from a parent and are caused by a random error during the formation of egg or sperm cells, or during early fetal development. In about 10% of cases, the deletion is inherited from a parent with the deletion.

When the deletion is inherited, it is inherited in an autosomal dominant pattern. This means that having the deletion in only one copy of chromosome 22 in each cell is enough to cause features of the condition. There is nothing that either parent can do, before or during a pregnancy, to cause a child to have this condition.

When a person with a deletion that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that deletion.

Most people with 22q11.2 deletion syndrome are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. This region contains 30 to 40 genes, many of which have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. We are unaware of any cases of homozygous 22q11.2 deletions. However, in addition to the loss of genes in the 22q11.2 region (e.g., TBX1 and COMT), the highly variable signs and symptoms of 22q11.2 deletion syndrome are in part due to changes outside the deleted region or on the remaining (non-deleted) copy of chromosome 22 (e.g., SNAP29).

We are not aware of published reports suggesting that feeling faint, or fainting (called syncope ) is a symptom directly associated with 22q11.2 deletion syndrome; however, syncope may occur as a result of features associated with 22q11.2 deletion syndrome. For example, syncope has been reported in people with hypoparathyroidism and people with low levels of calcium in the blood (hypocalcemia).

People who feel faint should speak with a health care provider to determine the underlying cause and discuss treatment options.

DiGeorge syndrome was once thought to be a distinct syndrome, but is now recognized to fall within the disorder spectrum known as 22q11.2 deletion syndrome. Symptoms of what was formerly known as DiGeorge syndrome were variable and the underlying cause (deletions of 22q11.2) is also responsible for related/overlapping syndromes. Terms such as 'complete' and 'partial' DiGeorge syndrome have been used in reference to individual cases which had all the characteristic signs and symptoms (e.g., hypoparathyroidism, absent thymus, and congenital heart disease) verses those with only some of them.

Yes. Some people with 22q11.2 deletion syndrome develop autoimmune diseases that can affect the thyroid. This includes Grave's disease, a disease that causes the thyroid gland to produce too much hormone (hyperthyroidism) and hypothyroidism, a condition in which the thyroid gland does not produce enough hormone.

Many people with 22q11.2 deletion syndrome develop hypoparathyroidism. Hypoparathyroidism is a condition in which too little parathyroid hormone (PTH) is produced. This condition causes low levels of calcium and high levels of phosphorus in the blood. Common symptoms may include tingling, muscle cramps, pain, dry hair, brittle nails, dry, scaly skin, cataracts, weakened tooth enamel in children, muscle spasms called tetany (can lead to spasms of the larynx, causing breathing difficulties), and seizures. The goal of treatment is to restore the calcium and mineral balance in the body.

We recommend you discuss concerns regarding your child's treatment with his physician.

Yes. 22q11.2 deletion syndrome can affect the central nervous system. Examples of central nervous system abnormalities, including brain abnormalities (e.g., cerebellar atrophy, polymicrogyria, enlarged sylvian fissures), neural tube defects, tethered cord, and seizures.

There are many treatment options available for children and adults with seizures. It can be challenging for a family to find the medication or procedure that works best for their child. We suggest that you speak with your child's health care provider about working with a physician who specializes in treating epilepsy. The Epilepsy Foundation provides information that can assist you in finding an epilepsy specialist in your area. To access this information, click here.

You can find more information on seizures and seizure disorders including information on treatment at the following links from MedlinePlus, the National Library of Medicine Web site designed to help you research your health questions.

Additional information on seizures can also be found by visiting the following Web page developed by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH).

Some individuals with 22q11.2 deletion syndrome do develop seizures. However, if you have questions regarding your son's diagnosis, we encourage you to speak with his healthcare provider. You may find it helpful to meet with a genetics professional, if you have not already done so.

Yes. Some people with 22q11.2 deletion syndrome have seizures. The seizures may be evidence of an underlying central nervous system abnormality or can result due to low levels of the parathyroid hormone.

Being overweight, or having difficulty losing weight, does not appear to be a symptom of 22q11.2 deletion syndrome specifically. However, an affected individual may have another condition causing this symptom that is associated with 22q11.2 deletion syndrome. For example, some autoimmune disorders such as hypothyroidism are associated with 22q11.2 deletion syndrome; hypothyroidism can cause weight gain or difficulty losing weight.

There is a wide range of symptoms and severity among people with 22q11.2 deletion syndrome. The long-term outlook for each person depends on the specific signs and symptoms each individual has.

Factors that may impact the severity of the disease and the likelihood for a shortened lifespan include whether or not a congenital heart defect is present and how severe the defect is, as well as the severity of immune system problems. For instance, individuals with complete absence of the thymus gland and absent T cells may pass away prematurely.

It is estimated that between 1 in 4,000 and 1 in 6,395 individuals have 22q11.2 deletion syndrome. It is suspected that 22q11.2 deletion is more common than previously reported given how much symptoms can vary and the likelihood that some individuals remain undiagnosed.

Fung WLA, Butcher NJ, Costain G, et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome. 2015;17(8):599-609. doi:10.1038/gim.2014.175.

The International 22q11.2 Deletion Syndrome Foundation, Inc. provides support, resources, and information for 22q11.2 deletion syndrome