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

Abstract

Monogenic epilepsies are a significant etiology of paediatric epilepsy. These are now more easily identified due to advances in genetic testing. However, the utility of genetic testing in Low- Middle- Income Countries (LMICs) has not been explored. A retrospective review was carried out in Karachi, Pakistan. Patients with symptoms suggestive of genetic epilepsy underwent Next-Generation Sequencing (NGS) panel testing. 77 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 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 a third of our population. The proportion of P/LP variants found in SCN1A is higher than that found in other populations, and we reported two novel variants in SCN1A. 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.