Etiologies, Clinical profile and Yield of Genetic Evaluation in an Indian cohort of Neonatal and Early onset Developmental and Epileptic Encephalopathy

Objectives To confirm the etiologies and follow up outcome of neonatal and early onset (<3 months) Developmental and Epileptic Encephalopathy (DEE) patients in a cohort of Indian patients Methods Retrospective single centre study of eligible patients seen over the last 8 years (January 2014- January 2022). The clinical details collected included: Age of seizure onset, seizures types, genetic evaluation and neuroimaging results, response to treatment and follow up outcome. All patients had a comprehensive genetic evaluation with Next Generation Sequencing (NGS) in form of initially Clinical Exome, and if normal then Whole Exome Sequencing (WES) trios. Results: Total 61 patients were eligible. Median seizure onset age was 35 days (Range: 1-90; M: F ratio: 1.3:1). Focal tonic seizures were the commonest (39/61-64%) seizures. MRI was abnormal in 33/61, with malformations in 8/61. A total of 44/61 (72%) patients had mutation identified on NGS [Clinical Exome- 17/29 (59%); WES trio-27/46 (58%)]. STXBP1 (5), SCN1A (3) and KCNQ, WWOX and TSC (2 each), were the commonest identified genes. After evaluation patients could be classified into- Genetic: 36 ; Structural Genetic: 4 ; Structural: 3 ; Metabolic 1; Vitamin responsive 4 , Unknown 13. At median follow up of 20 months (Range: 3-96 ), seizures were controlled in 24/61, and 12/61 had died. Conclusion: Neuroimaging and stepwise molecular testing could identify underlying etiologies in majority of our early onset DEE patients. STXBP1 was the commonest gene in our cohort. Most of the children continued to have refractory epilepsy with significant other associated co-morbidities.