Utility of genetic testing in pediatric epilepsy: Experience from a low to middle-income country

Abstract

Monogenic epilepsies are a significant etiology of pediatric epilepsy. These are now more easily identified due to advances in genetic testing. However, the utility of genetic testing in low to middle-income countries (LMICs) has not been fully explored. A retrospective review was carried out in Karachi, Pakistan. Patients with symptoms suggestive of genetic epilepsy underwent next-generation sequencing (NGS). Seventy-seven patients were tested, of which 27 % (n = 21) initially had pathogenic (P) or likely pathogenic (LP) results. This increased to 32 % (n = 25) after clinical reclassification of some variants of uncertain significance (VUSs) based on American College of Medical Genetics and Genomics (ACMG) guidelines. Initially, 6 % of patients (n = 5) had no P/LP or VUS, and 66 % (n = 51) had at least one VUS. After variant resolution and reclassification, results were negative for 25% (n = 19) and 43% (n = 33) had VUSs. Genetic testing was positive in one-third of our population. The proportion of P/LP variants found in <i>SCN1A</i> is higher than that found in other populations, and we report two novel variants in <i>SCN1A</i>. The yield of genetic testing in our population is comparable to that found in North America. Initially, a higher proportion of our population had inconclusive results, indicating the need for better characterization of the South Asian genotype.