Introduction: Infantile onset epileptic encephalopathies (IOEE) have always been a diagnostic dilemma for pediatric neurologists worldover. With recent modifications in epilepsy classification, a syndromic diagnosis is achieved, however underlying etiology stays elusive. This specifically holds true for infants with refractory seizures who do not have any identifiable neurometabolic or structural substrate. The role of exome sequencing (ES) in this subset of patients was explored in this study.

Methods: A retrospective review (January 2016 to May 2017) of cases presenting with infantile onset epileptic encephalopathy to Pediatric Neurology clinic at a tertiary care institute was performed.

Results: A total of 226 children (169 with a structural etiology) with IOEE were identified. Fifty seven caseswere without any structural substrate on MRI brain; 45/57 underwent ES. Twenty seven (27/45) had seizure onset < 6 months of age (early onset); 18/46 had seizure onset > 6 months of age (late onset). Electroclinical syndromic diagnosis was attained in 07/45 (16%) with West syndrome being the commonest.Genetic diagnosis could be reached in 37/45; 80% infants (24/27 (88%) in early onset group and 13/18 (72%) in late onset group. SCN1A, SCN2A, GRIN2A and GRIN2B were the most common genetic mutations identified. Metabolic disorders identified on ES were Leigh’s disease in 3, GLUT1 deficiency and Glycine encephalopathy in one each.

Conclusion: Clinical exome sequencing has a significantly high etiological yield in children with non structural IOEE.