Genetic Epilepsies With Onset in Infancy and Toddlerhood: A Prospective Single-Center Study in India

The burden of genetic causes of epilepsy is higher in infants and toddlers. Early diagnosis helps in precision therapy and prenatal diagnosis. The spectrum of genetic causes can vary depending on the location and prevalence of consanguinity practices.

Children having epilepsy with onset before age three years were enrolled after ruling out acquired causes. Neuroimaging, electroencephalography, and whole exome sequencing (WES) were done and seizure outcome was assessed after six months.

We enrolled 147 participants (82 boys, 65 girls). Mean age at seizure onset was 5.5 ± 6.5 months. WES gave an overall yield of 61.9% (91/147) and 71.4% (40/56) in cases with epilepsy onset before three months. Seventy (76.7%) cases had developmental delay. Commonly implicated genes were SCN1A, KCNQ2, ALDH7A1, STXBP1, TBC1D24, CDKL5, CPLX1, BRAT1, WWOX, and RHOBTB2. The common comorbidities of autism, attention-deficit/hyperactivity disorder, and intellectual disability had a significant association with genetic epilepsy. WES helped in precision medicine in over 40% of cases. While normal development was associated with higher rates of seizure freedom, those with severe microcephaly, a seizure burden of >200/month, or rigidity had higher mortality rates.

Genetic etiology for epilepsy is common in children with seizure onset below age three years, with yield being the highest for onset in the first three months. Presence of comorbidities increased the yield of genetic diagnosis. Autosomal recessive disorders are more common in India due to higher consanguinity rates. Higher seizure burden, severe microcephaly, or infantile epileptic spasm syndrome are associated with higher mortality.