Paediatric Laboratory Medicine
Paediatric Laboratory Medicine

22q11 Deletion Syndrome

Clinical features
Who should be tested?
Testing Method
Potential Outcomes Interpretation of test results
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Clinical features

22q11DS is one of the most common genetic causes of learning disabilities and mild mental retardation, 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.


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).

Who should be tested?

  • individuals clinically suspected of being affected with 22q11DS and negative on FISH analysis
  • individuals with a family history of 22q11DS
  • pregnancies at increased risk of being affected with 22q11DS

Testing Method

Gene Dosage Analysis: Multiplex Ligation-dependent Probe Amplification (MLPA) is used to determine the relative copy numbers of 29 genes in the 22q11-13 region (see Fig.1).

Test sensitivity: Approximately 90% of 22q11DS deletions are due to the common 3Mb deletion, with another 5% of patients having a smaller nested deletion within the 22q11 region. These cases will be detected with MLPA.

Fig. 1. Map of the 29 genes in the 22q11-13 region analyzed with MLPA kit P250. The common 3Mb deletion which extends from the CTCL1 gene to the LZTR1 gene is indicated

Potential Outcomes & Interpretation of Test Results

Reason for referral

Chromosome 22 gene dosage



none detected

  • This result does not confirm a diagnosis of 22q11.2 deletion syndrome.


deletion detected

  • This result confirms a diagnosis of 22q11.2 deletion syndrome


  1. Chromosome analysis should be performed on all patients clinically suspected of being affected with 22q11.2 deletion syndrome prior to molecular analysis. These studies may identify patients with a translocation involving chromosome 22 and another chromosome.
  2. Current molecular testing may not detect all possible mutations for this disease. A negative test does not rule out the diagnosis of 22q11.2 deletion syndrome.
  3. The clinical course or severity of symptoms cannot be predicted by molecular analysis.
  4. Test results should be interpreted in the context of clinical findings, family history, and other laboratory data.
  5. This test was developed and its performance characteristics validated by the Molecular Genetics Laboratory at the Hospital for Sick Children. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes.

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