22q11.2 Deletion Syndrome (DiGeorge Syndrome)

What is 22q11.2 deletion syndrome?

22q11.2 deletion syndrome is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2.

The features of this syndrome vary widely, even among affected members of the same family, and involve many parts of the body. Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a cleft palate) or other defects in the palate, recurrent infections caused by problems with the immune system, and mild differences in facial features. Affected individuals may also have kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, and autoimmune disorders such as rheumatoid arthritis and Graves' disease. Skeletal differences are possible, including abnormalities of the spinal bones (vertebrae), extra fingers or toes (polydactyly), and premature fusion of certain bones of the skull (craniosynostosis).

Many children with 22q11.2 deletion syndrome have developmental delays and learning disabilities. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia, depression, anxiety, and bipolar disorder. Additionally, affected children are probably more likely than children without 22q11.2 deletion syndrome to have developmental disorders (such as autism) that affect communication and social interaction.

Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called 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, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.

How common is 22q11.2 deletion syndrome?

22q11.2 deletion syndrome affects an estimated 1 in 4,000 newborns. This condition actually may be more common, however, because some people with the deletion have few signs and symptoms and therefore may not have been diagnosed.

What are the genetic changes related to 22q11.2 deletion syndrome?

22q11.2 deletion syndrome is a chromosomal condition related to chromosome 22.

The COMT and TBX1 genes are associated with 22q11.2 deletion syndrome.

Most people with 22q11.2 deletion syndrome are missing about 3 million base pairs (the building blocks of DNA) on one copy of chromosome 22 in each cell. This region contains about 30 genes, many of which have not been well characterised. A small percentage of affected individuals have shorter deletions in the same region. This condition is often described as a contiguous gene deletion syndrome because a deletion in chromosome 22 leads to the loss of many genes that are close together.

Researchers are working to identify all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of a particular gene on chromosome 22, TBX1, is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, and low calcium levels). The loss of another gene, COMT, in the same region of chromosome 22 may help explain the increased risk of behavioural problems and mental illness. Additional genes in the deleted region likely contribute to the varied features of 22q11.2 deletion syndrome.

Can 22q11.2 deletion syndrome be inherited?

The inheritance of 2q11.2 deletion syndrome appears to be autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition.

Most cases of 22q11.2 deletion syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the condition to their children. In fewer than 10 percent of cases, a person with this condition inherits the deletion in chromosome 22 from a parent. In inherited cases, other family members may be affected as well.

What other names do people use for 22q11.2 deletion syndrome?

  • Autosomal dominant Opitz G/BBB syndrome
  • CATCH22
  • Cayler cardiofacial syndrome
  • Conotruncal anomaly face syndrome (CTAF)
  • Deletion 22q11.2 syndrome
  • DiGeorge Syndrome
  • Sedlackova syndrome
  • Shprintzen syndrome
  • VCFS
  • Velocardiofacial syndrome
  • Velo-cardio-facial syndrome

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