Genetic analyses in two extended families with deletion 22q11 syndrome: Importance of extracardiac manifestations

Objectives Cardiovascular malformations (CVMs) are reported to be common (∼75%) in patients with deletion 22q11.2 (del22q11) syndrome. To better understand why deletions go unrecognized, we characterized the phenotype in deleted individuals in two large kindreds with particular emphasis on the presence or absence of CVM. Study design After the diagnosis of del22q11 in two unrelated probands with CVM, we sequentially evaluated family members with clinical evaluation and cytogenetic analysis. Results Del22q11 was identified in 13 individuals; all exhibited characteristic dysmorphic facial features, but a CVM was present in only 6 of 13 (46%) individuals. Conclusions We speculate that in the absence of CVM, diagnosis of del22q11 is hampered by a failure to recognize extracardiac features of the del22q11 syndrome spectrum. The data highlight the need for primary care physicians and specialists to familiarize themselves with the extracardiac stigmata of del22q11 to ensure timely diagnosis in all family members.