CGH microarray studies in idiopathic developmental/cognitive impairment: association of historical and clinical features and the De Vries Score

Abstract

Objective. Studies have confirmed that copy number variations (CNV) in the human genome contribute to the etiology of mental retardation/ development delay/ congenital anomalies. We sought to evaluate the use of a microarray in the context of a clinical genetics practice, to determine if there were any specific clinical findings that predict the discovery of a CNV. Patients and methods. 334 cases with idiopathic mental retardation/impairment/development delay/disability or a combination of these findings were studied using array comparative genomic hybridization (Signature Chip Version 4). The subjects had previously had a non diagnostic medical genetics evaluation. Clinical findings were collated by a chart review. Each patient was scored according to a previously published clinical checklist by de Vries and colleagues. Results. Of 334 patients, 8 were excluded due to a syndromic diagnosis being established by clinical and/or microarray testing. Out of the remaining 326 patients, 33 (10%) showed CNVs, of which 5 were maternally inherited, 4 paternally inherited, 11 were de novo, and the origin of 13 remained unknown. The mean de Vries score was greater in the CNV group than in the non CNV group (4.17 and 3.95, respectively). No patient in the CNV group had a score of less than 3, while in the non CNV group, 12% of patients had scores less than 3. Conclusions. The De Vries clinical score was higher in CNV cases compared to those with no CNV (p=0.04) but this difference is unlikely to be clinically meaningful. Several features reached statistical significance of p<0.05 but we were unable to delineate patterns of features that might increase the yield of positive CNV results.

Keywords

• Copy number variation
• Developmental delay
• Dysmorphism
• Birth defects
• Prenatal