Differential detection of deletion 22q11.2 syndrome by specialty and indication

This study identified cytogenetic abnormalities in a population screened for deletion 22q11.2 syndrome (D22S) by fluorescence in situ hybridization (FISH) and G-banding and correlated these abnormalities to referring specialty and submitted indications. Requests for the D22S FISH assay were retrospectively reviewed over a 29-month period in our institution. Positive test results for D22S FISH and other abnormalities found by other FISH assays and G-banding were correlated to submitting specialist and indication. Thirteen medical services ordered D22S FISH testing on 297 patients over 29 months. The detection rate for all cytogenetic aberrations was 9.4% (28 of 297) including 5.4% (16 of 297) for D22S detection by FISH and 2.7% (8 of 297) for detection of additional cytogenetic anomalies by G-banding cytogenetics. Sixty-six of 297 patients negative by D22S FISH and G-banding were screened using other FISH assays and 3 of 47 (6.4%) patients screened using subtelomeric probes were positive for deletion and 1 of 3 (33%) patients screened for Prader-Willi syndrome was positive for deletion. Pediatric geneticists requested 53.9% (160 of 297) of the tests, yielding 60.7% (17 of 28) of positive test results. Tetralogy of Fallot and developmental delay were the indications associated with the most positive test results. In our institution, pediatric geneticists identify the largest spectrum of indications with D22S and appear most aware of the association of developmental delay with D22S. Performing conventional cytogenetics and other FISH assays, in addition to FISH for D22S, is important because there is considerable overlap between D22S and the phenotype of several other syndromes.