Abstracts

Rationale: Microarray analysis is increasingly utilized for diagnostic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD) or multiple congenital anomalies (MCA). More recent studies have supported its important role in the etiologic diagnosis of patients with epilepsy. In this report we describe the results of performing microarray analysis on 97 children with unexplained epilepsy.Methods: Seven hundred and seventy patients seen at BC Children s Hospital from 2009 to 2011 had microarray analysis performed using Affymetrix Genome-Wide Human SNP Array 6.0 platform for a history of DD/ID, ASD, MCA and/or epilepsy of unknown cause. We retrospectively reviewed available clinical data and results of microarray testing on those patients with unexplained epilepsy. Results: Abnormal results were identified in 23 out of 97 children tested with unexplained epilepsy. Thirteen individuals had Copy Number Variants (CNVs) determined likely responsible for their clinical features based on identification of recognized recurrent microdeletion/duplication syndromes, and/or overlap with similarly reported case(s) (Table 1). Ten individuals had CNVs of unknown clinical significance based primarily on lack of previously reported cases. These numbers are comparable to the abnormal results identified in all 770 individuals tested (101 CNVs likely pathogenic and119 CNVs of unknown clinical significance). Of the 13 individuals with likely pathogenic CNVs, mean age of seizure onset was 2 years (2 months 9 years) and seizure types were variable, including focal and/or generalized seizures. All patients had DD/ID except for one individual diagnosed with a learning disability. Facial dysmorphisms and/or other anomalies were present in ten patients. Magnetic Resonance Imaging (MRI) head results were available in 9 individuals and abnormalities were identified in five. This included prominent bilateral white matter signal abnormalities in Patients 3, 4, and 5, reduced gyri in Patient 1 and mildly enlarged dysmorphic ventricles in Patient 13. Microdeletion or microduplication syndromes previously reported to be associated with seizures were identified in 9 patients (16p13.3, 16p13.11, 16p11.2 (2), 16p12.1, 17p13.3, 17q21.3, 22q11.2, and Xp28). A deletion disrupting the SCN1A gene and another involving UBE3A gene (Angelman syndrome) were also identified. Excluding Patient 6, the remaining CNVs overlapped with other cases in which seizures were reported. Conclusions: Thirteen out of 97 individuals with unexplained epilepsy were identified to have clinically significant CNVs. Most of the CNVs identified overlapped with previously reported microdeletion/duplication syndromes associated with various neurocognitive phenotypes, including epilepsy. These results support microarray analysis as an important diagnostic tool to use when evaluating children with unexplained epilepsy. Further study of these recurrent microdeletion/duplication regions could lead to the identification of novel candidate epilepsy genes.