A prospective study of etiologies and phenotype of an Indian cohort of childhood onset (less than five years) epilepsies

Objectives To confirm the etiology and phenotype of new onset epilepsy in an Indian cohort of children below five years age. Methods A prospective single centre study over 12 months (February 2021- February 2022). The clinical details documented included: Epilepsy classification and epilepsy syndrome, electroencephalogram (EEG) and neuroimaging results. All patients without an acquired cause (Neuroimaging was normal or had malformation), underwent comprehensive genetic evaluation with Whole Exome Sequencing (WES) trios and if normal, had microarray. Results: Total 265 patients were eligible. Median epilepsy onset age was 14.5 months (Range: 0-58; M: F ratio: 2:1). Etiology could be confirmed in 189/265 (71%) patients, with acquired cause [120/265-45%; Neonatal hypoglycaemic brain injury (NHBI) being the commonest-60/265] being more frequent than a genetic etiology (59/265-22%). Total 105/265 patients had an identifiable epilepsy syndrome, of these 98 had a severe epilepsy syndrome with West syndrome (50) being the commonest. Seventy (26%) patients also had associated global developmental delay. EEG was abnormal in 180/265 (68%), and MRI in 146/265 (55%) patients. Genetic evaluation had a yield of 52% with a molecular diagnosis confirmed in 59/112 patients tested (WES trio 52/112; and in 5/55 WES negative patients copy number variants, two patients had Angelmann syndrome). The commonest single gene mutation identified were SCN1A and TSC2 genes, in 4 each. Conclusion: In our epilepsy patients, a cause could be identified in majority. NHBI was the single most common etiology. Comprehensive genetic evaluation could give a molecular diagnosis in more than half of patients tested.