Exploring the Role of Genetic Testing in Infantile-Onset Epilepsy Syndromes: A Single-Center Experience in South India

Introduction: Epilepsy syndromes in infants, characterized by distinct clinical and EEG features, are often found to have underlying genetic etiology. A comprehensive analysis of the genetic landscape of infantile-onset epilepsy syndromes can provide insights into the prevalence, genotype–phenotype correlates, and identify new genetic variants.

Methodology: A retrospective observational study was conducted at a tertiary-care epilepsy center in South India. Children with seizure onset before 2 years of age and in whom genetic variation was identified as part of evaluation over a period of 7 years were included. Clinical characteristics such as seizure onset and types, developmental status, electro-clinical syndromes, and neuroimaging findings were noted. Demonstration of pathogenic, likely pathogenic and variants of uncertain significance (VUS) were documented.

Results: A total of 149 children demonstrated genetic variations. 67 children had seizure onset before 3 months of age. While 25 children had self-limited course, DEE was identified in 124 subjects. Among DEEs, 16 subjects were categorized as early-infantile developmental and epileptic-encephalopathy, 25 had infantile-epileptic spasms-syndrome, 7 had epilepsy of infancy with migrating focal-seizures, and 33 had Dravet syndrome. 34 children had abnormal neuroimaging findings, most commonly, diffuse cortical atrophy. Overall 37 pathogenic, 35 likely pathogenic and 92 VUS were identified. Most common genetic variation was observed in SCN1A (n = 33), followed by SCN2A (n = 8) and KCNT1 (n = 7).

Conclusion: This study helps in expanding our knowledge of the distribution of early-infantile monogenic epilepsies in our population. There is an urgent need for multi-centric prospective registries to get a better understanding of phenotype–genotype correlates in individual genetic epilepsies, which might aid in better targeted therapies.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
12 September 2024