17q21.31 microdeletion syndrome

17q21.31 microdeletion syndrome results when a small piece of chromosome 17 is missing. The deletion occurs on the long (q) arm of the chromosome at a location designated q21.31.

People with 17q21.31 microdeletion syndrome have developmental delay and intellectual disability. Typically their disposition is described as cheerful, sociable, and cooperative. They usually have weak muscle tone (hypotonia) in childhood. About half have recurrent seizures (epilepsy).

Affected individuals often have distinctive facial features including a high, broad forehead; droopy eyelids (ptosis); a narrowing of the eye opening (blepharophimosis); outer corners of the eyes that point upward (upward-slanting palpebral fissures); skin folds covering the inner corner of the eyes (epicanthal folds); a bulbous nose; and prominent ears. They may also have vision problems. Males with 17q21.31 microdeletion syndrome often have undescended testes (cryptorchidism). Defects in the walls between the chambers of the heart (septal defects) or other cardiac abnormalities, kidney problems, and skeletal anomalies such as foot deformities occur in some affected individuals.

The prevalence of 17q21.31 microdeletion syndrome is estimated to be 1 in 16,000; however, many affected individuals are never diagnosed with this disorder. Researchers estimate that 17q21.31 microdeletion syndrome may account for approximately 6 in 1,000 cases of unexplained intellectual disability.

People with 17q21.31 microdeletion syndrome are missing a sequence of about 500,000 DNA building blocks (base pairs), also written as 500 kilobases (kb), at position q21.31 on chromosome 17. The exact size of the deletion varies among affected individuals, but it contains at least six genes. This deletion affects one of the two copies of chromosome 17 in each cell.

The signs and symptoms of 17q21.31 microdeletion syndrome are probably related to the loss of one or more genes in this region. Researchers are working to determine how the loss of these genes contributes to the features of 17q21.31 microdeletion syndrome.

Read more about chromosome 17.

The inheritance of 17q21.31 microdeletion syndrome is considered autosomal dominant because a deletion in one copy of chromosome 17 in each cell is sufficient to cause the disorder. Most cases of 17q21.31 microdeletion syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. Affected people typically have no history of the disorder in their family. While it is possible for them to pass the condition on to their children, no individuals with 17q21.31 microdeletion syndrome have been known to reproduce.

In all known cases, people with 17q21.31 microdeletion syndrome have at least one parent with a common variant of the 17q21.31 region of chromosome 17 called the H2 lineage. This variant is found in 20 percent of people of European and Middle Eastern descent, although it is rare in other populations. In the H2 lineage, a 900 kb segment of DNA including the region deleted in 17q21.31 microdeletion syndrome has undergone an inversion. An inversion involves the breakage of a chromosome in two places; the resulting piece of DNA is reversed and reinserted into the chromosome.

People with the H2 lineage have no health problems related to the inversion. However, genetic material can be lost or duplicated when the inversion is passed to the next generation. Researchers believe that a parental inversion is probably necessary for a child to have 17q21.31 microdeletion syndrome, but other, unknown factors are also thought to play a role. So while the inversion is very common, only an extremely small percentage of parents with the inversion have a child affected by 17q21.31 microdeletion syndrome.