FAMILIAL DIGEORGE VELOCARDIOFACIAL SYNDROME WITH DELETIONS OF CHROMOSOME AREA 22Q11.2 - REPORT OF 5 FAMILIES WITH A REVIEW OF THE LITERATURE/

The DiGeorge (DG), velocardiofacial (VCF), and conotruncal anomaly-fac e (CTAF) syndromes were originally described as distinct disorders, al though overlapping phenotypes have been recognized, It is now clear th at all three syndromes result from apparently similar or identical 22q 11.2 deletions, suggesting that they represent phenotypic variability of a single genetic syndrome, We report on 12 individuals in five fami lies with del(22)(q11.2) by fluorescent in situ hybridization, and def ine the frequency of phenotypic abnormalities in those cases and in 70 individuals from 27 del(22)(q11.2) families from the literature. Comm on manifestations include mental impairment (97%), abnormal face (93%) , cardiac malformations (68%), thymic (64%) and parathyroid (63%) abno rmalities, and cleft palate or velopharyngeal insufficiency (48%). Fam ilial DG, VCF, and CTAF syndromes due to del(22) (q11.2) show signific ant inter- and intra-familial clinical variability consistent with the hypothesis that a single gene or group of tightly linked genes is the common cause of these syndromes. Up to 25% of 22q deletions are inher ited, indicating that parents of affected children warrant molecular c ytogenetic evaluation, We propose use of the compound term ''DiGeorge/ velocardiofacial (DG/VCF) syndrome'' in referring to this condition, a s it calls attention to the phenotypic spectrum using historically fam iliar names. (C) 1996 Wiley-Liss, Inc.