Background Chromosome MicroArray-based genomic copy-number analysis (CMA) has an important role in the discovery of both novel and recurrent epilepsy-associated copy number variants (CNVs) in patients with epilepsy. In case of an additional neuro-developmental disorder the diagnostic accuracy may be as high as 15%.

Objectives The purpose of this study is to describe the results of performed CMA on 706 children with unexplained epilepsy associated with developmental delay/intellectual disability, autism spectrum disorders and/or multiple congenital anomalies (‘epilepsy plus’).

Design/method Retrospective chart review on clinical and genetic aspects of CNVs identified in 706 patients with ‘epilepsy plus’, seen at the Vancouver BC Children’s Hospital from 2009 to 2014. All patients had CMA performed using Affymetrix Genome-Wide Human SNP Array 6.0 or CytoScanHD®.

Results Abnormal CMA results were identified in 191 out of 706 children with ‘epilepsy plus’. 122/706 (17.3%) patients had variants of unknown significance (VUS), and 80/706 (11.3%) patients had pathogenic CNVs. This group included 19 patients that had CNVs in genomic “hotspots” predisposing to epilepsy, including 1q21.1 (n = 1), 15q11.2 (n = 2), 15q13.3 (n = 4), 15q11-q13 (n = 3), 16p11.2 (n = 1046), and 16p13.11 (n = 3). Among other known microdeletion/microduplication syndromes (n = 20) was 22q13.3 deletion (Phelan-McDermid Syndrome) (n = 4). One of the four 22q13.3 deletion patients had treatment resistant epilepsy and a small deletion (47kb) of the SHANK3 gene.

Conclusions CMA revealed pathogenic CNVs in epilepsy “hotspots”, and known microdeletion syndromes like Phelan-McDermid syndrome in 11.3% of children with ‘epilepsy plus’. Examination of CNVs also plays an important role in the identification of possible epilepsy genes i.g. SHANK3 mutations in patients with 22q13.3 deletions.