Abstracts

Rationale: Epileptic encephalopathies (EE) are severe early-onset neurodevelopmental disorders with refractory epilepsy and developmental delay or intellectual disability. The majority of these disorders were previously of unknown etiologies. However, advances in cytogenetic and genomic investigation techniques are starting to unveil the molecular basis of these genetically heterogeneous disorders. The diagnostic yield of various approaches in EE of unknown etiology remains uncertain as these are seldom tested in parallel. Methods: In this study, we recruited 103 patients with unexplained sporadic pediatric EE and performed targeted resequencing of 35 known EE genes (n=95 patients) or whole-exome sequencing of familial trios (n=8) and compare the yield of these two approaches in this population. Results: We find that targeted resequencing provides a molecular diagnosis in 12.6% (n=12/95) patients while whole-exome sequencing identifies an etiology in 37.5% (n=3/8) of patients. Conclusions: Although whole-exome sequencing remains expensive, it carries a significant higher diagnostic yield and allows the identification of new putative candidate EE genes. In turn, the non-biased identification of new EE genes through whole-exome sequencing will enhance our understanding of the molecular basis of these heterogeneous disorders and should increase the diagnostic yield of targeted resequencing in coming years.