Aliases: DiGeorge Syndrome (DGS); Velocardiofacial Syndrome (VCFS); Shprintzen Syndrome; Conotruncal Anomaly Face Syndrome (CTAF)
Gene(s) involved: Deletions of genes in the DiGeorge chromosomal region (DGCR) of 22q11.2.
Brief description of disorder: 22q11.2 deletion syndrome is a contiguous deletion syndrome characterized by congenital heart disease (74%), palate abnormalities (69%), immunodeficiency (77%), hypocalcemia (50%), dysphagia (30%), renal anomalies (37%), learning difficulties (70-90%), and characteristic facies. Other associated findings include hearing loss, seizures, autoimmune disorders, skeletal and laryngotracheoesophageal abnormalities, and deficiency in growth hormone. Autism or autistic-like behavior, delays in speech and motor milestones obtainment have been reported in approximately 20% of affected children.
The prevalence of 22q11.2 deletion syndrome is estimated as one in every 6,000; one in every 3,800 in the Hispanic population. It is purposed that the incidence is likely to be much higher than reported due to the high variability of expression.
Inheritance pattern: 22q11.2 deletion syndrome is caused by a de novo genetic deletion in 93% of cases and is inherited in an autosomal dominant fashion in 7%.
Genetics: Eighty-five percent of cases are found to have a deletion in the DGCR that occurs in a common 3-Mb region. The remaining 15% are found to have either alternate endpoints of the deletion or are found to have multiple, shorter segments deleted within the 3-Mb region that is typically deleted. Deletions in the DGCR are detectable by FISH in >95% of affected individuals. Conventional G-banded cytogenetic analysis should be run in conjunction with FISH due to the possibility of a chromosomal translocation involving 22q11.2, reported in <1% of individuals. Because of the high variability of phenotypic expressiveness and the chance of somatic mosaicism, parents of affected individuals should also be evaluated by FISH.
Test method: Conventional G-banded cytogenetic analysis, FISH, and array.
Test sensitivity: Cytogenetic analysis detects approximately 25% of deletions that are greater than 5 Mb. FISH and array will detect 98-100% of deletions/ duplications; however, deletions/ duplications smaller than 100 kb will not be detected on array and deletions/ duplications smaller than the FISH probe will not be detected by FISH.
Specimen requirements for Cytogenetic Analysis, FISH, and Array:
Adult: 3-5 ml peripheral blood in a sodium-heparin tube.
Newborn: 1-3 ml blood in a sodium-heparin tube.
Turn-around-time:
Newborns: 2-3 days
Non-STAT: 2-14 days
FISH: 6-8 days
Array: 7-14 days
References: GeneReviews
revised 5-24-2011
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