DiGeorge anomaly in the absence of chromosome 22q11.2 deletion.

OBJECTIVE: To test the hypothesis that the prevalence of deletion 22q11.2 among individuals who meet criteria for DiGeorge anomaly (DGA) is lower than the 90% commonly cited. STUDY DESIGN: Participants were identified through retrospective chart reviews on all patients who underwent testing for deletion 22q11.2 and all patients with a diagnosis of "DiGeorge" or any of the major criteria associated with DGA at a large pediatric hospital over a period of 6 years. DGA was confirmed in 64 individuals, based on the presence of at least 2 of the following features: (1) cellular immune deficiency and/or absence of part or all of the thymus; (2) hypocalcemia and/or parathyroid deficiency; (3) congenital heart disease. RESULTS: Of the 64 individuals with DGA, 29 (45%) did not have a chromosome 22q11.2 deletion. Among this deletion-negative subset, diabetic embryopathy and other chromosome abnormalities were the most commonly recognized underlying etiologies. CONCLUSIONS: These findings challenge a widely held belief that nearly 90% of DGA is due to chromosome 22q11.2 deletion. This study also calls attention to the heterogeneity of DGA, highlights similarities and differences between those with and without a chromosome 22q11.2 deletion, and attempts to resolve some confusing features of conditions associated with DGA.

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

OBJECTIVES: Cardiovascular malformations (CVMs) are reported to be common (approximately 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.