22q11.2 Deletion Syndrome

22q11DS is one of the most common genetic causes of learning disabilities and mild intellectual delay, with an incidence of 1 per 4,000 live births. Individuals with 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge syndrome or Velo-Cardio-Facial syndrome, have a number of physical and cognitive clinical features in common, such as congenital heart defects, learning difficulties and characteristic facial features although not everyone with 22q11DS has all of the features or is affected to the same degree of severity.

Genetics

22q11.2 deletion syndrome is caused by deletion of a small part of chromosome 22 at a location designated 22q11.2. The disorder is an autosomal dominant condition and so an individual is affected with 22q11DS when a deletion is present on one of their two copies of chromosome 22. An individual with a 22q11.2 deletion has a 50% chance of transmitting the chromosome 22 with the deletion to a child. Most patients (~90%) with 22q11DS are new occurrences (deletion is not inherited) while ~10% of individuals with 22q11.2 deletion syndrome have inherited the deletion from a parent.

Approximately 90% of individuals with 22q11DS have a “common” 3 Mb deletion that remove of over 40 genes detectable with chromosome FISH analysis. The remaining patients have smaller deletions that are nested within the 3 Mb common deletion region and a few patients with deletions outside this region. To date no correlation has been found between the size or extent of the deletion and the severity of the clinical phenotype. Molecular testing for 22q11DS involves the determination of the copy number of the genes in the 22q11 region to define the relative start and end point of the deletion (see Figure 1 below).

See related information sheet 22q11.2 Deletion Syndrome