Study of 250 children with idiopathic mental retardation reveals nine cryptic and diverse subtelomeric chromosome anomalies

TLDR

Cryptic subtelomeric chromosome anomalies are a significant cause of dysmorphology and mental retardation. The study aimed to determine whether routine screening for these aberrations should be performed in patients with idiopathic mental retardation/developmental delay. The authors tested 250 such patients, including 53 with isolated symptoms and 197 with dysmorphic features or malformations, using clinical cytogenetics. Among the 250 patients, normal karyotypes were observed in all, but subtelomeric anomalies were detected in 1.9% of isolated cases and 4.1% of cases with dysmorphic features, with a total of 10 anomalies, including one patient with both a deletion and a duplication, confirming these rearrangements as a significant cause of idiopathic mental retardation/developmental delay. © 2002 Wiley‑Liss, Inc.

Abstract

Abstract Cryptic subtelomeric chromosome anomalies have been recognized as a significant cause of dysmorphology and mental retardation. To determine whether the clinical cytogenetics laboratory should screen routinely for these aberrations, we have tested 250 patients with idiopathic mental retardation/developmental delay, either isolated (53) or associated with dysmorphic features and/or malformations in the absence of a recognizable syndrome (197). All had normal karyotypes at the 550–850 band level. Subtelomeric anomalies were found in 1/53 of the first group (1.9%) and 8/197 of the second group (4.1%). In one patient, two separate anomalies were present: a deletion (not inherited) and a duplication (inherited). It is possible that one of these 10 observed aberrations might represent a rare and previously unreported polymorphism and one a rare cross‐hybridization. Our study supports the proposition that cryptic subtelomeric rearrangements are a significant cause of idiopathic mental retardation/developmental delay, but both the diversity of the phenotypes of the positive cases and the wide diversity of their associated chromosome abnormalities emphasize the central problem for the clinical cytogenetics laboratory—that of choosing the most productive patient base for this useful diagnostic test. © 2002 Wiley‐Liss, Inc.