22q11.2 deletion syndrome: DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes.

A microdeletion of chromosome 22q11.2 is found in most patients with velocardiofacial syndrome, DiGeorge syndrome, and conotruncal anomaly face syndrome, and in some patients with Cayler cardiofacial and autosomal dominant Opitz-G/BBB syndromes. A wide spectrum of clinical findings accompanies the 22q11.2 deletion, without genotype or phenotype correlation even among affected family members. Classic features are dysmorphic facies, conotruncal cardiac defects, hypocalcemic hypoparathyroidism, T-cell mediated immune deficiency, and palate abnormalities. Less well recognized are learning, speech, feeding, and psychiatric disorders, and renal and musculoskeletal defects. Parathyroid and immune deficiencies in the same individual can progress or resolve with time. The 22q11.2 deletion can be inherited as an autosomal dominant or arise as a de novo deletion or translocation. Fluorescent in situ hybridization using cosmid probes mapping to the DiGeorge chromosomal region is a widely available method to detect the 22q11.2 deletion in metaphase chromosomes from cultured lymphocytes, amniocytes, or chorionic villi. The ubiquitin-fusion-degradation-1-like gene, expressed in embryonic branchial arches and in the conotruncus, appears to play a prominent role in the pathogenesis of the 22q11.2 deletion syndrome.