Abstracts

Rationale: Microarray or array-based Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism and pathogenesis. Array CGH technology has higher resolution and excellent throughput when compared with conventional and molecular cytogenetic. It can detect and identify genetic imbalances in subjects with normal karyotypes and reveal supernumerary markers and regions of loss of heterozygosity. Utility of chromosomal microarray analysis in patients with intellectual disability including autism has been reported. However experience in using this type of microarray analysis in children with seizures and unexplained global developmental delay is limited. We report our experience with chromosomal microarray analysis (CMA) among developmentally delayed children with and without epilepsy. Methods: To detect the frequency and compare results of copy number variations (CNV) in a single cohort of developmentally delayed children with and without epilepsy. All patients who had CMA analysis performed during July 2010- December 2010 were identified. Clinical, imaging, genetic testing results were compared between those children who had seizures and those who did not. Results: Seventy-one children (Male: 40; Female: 31) with developmental delay had CMA studies during July 2010- December 2010, and were included in the study. Ages ranged from 2.5 months-14 years. Twenty-two of the 71 had epilepsy( 31%). Infantile spasms, cryptogenic refractory epileptic encephalopathy and Lennox-Gastaut syndrome were some of the syndromic diagnoses. Forty-nine patients had no seizures, but had multiple congenital anomalies including cardiac and urogenital defects. Microarray studies were abnormal in 16/71 ( 22%). Among the epilepsy group 45% (10/22) were abnormal in comparison to the group without epilepsy 12% (6/49). Pattern of CNV abnormalities in epilepsy group were mainly deletion. In-silico analysis was done for identifying possible candidate genes and differentiating from de-novo CNVs.Conclusions: Copy number variations are more frequently seen in developmentally delayed children with epilepsy than without epilepsy. Pattern of genomic copy number variations in these children with epilepsy are secondary to deletions. Extension of this study to a comparative study in a larger cohort of patients with and without epilepsy (not limited to those with developmental delay or multiple congenital anomalies) is considered.