C.1 Utility of genetic testing in the pre-surgical evaluation of children with drug-resistant epilepsy

Abstract

Background: All patients with drug-resistant focal epilepsy, should undergo an evaluation to determine if non-medical options, including surgical intervention, are appropriate. This evaluation involves a thorough work-up, typically including some or all of neuropsychological evaluation, prolonged video EEG monitoring, and advanced neuroimaging. The utility of genetic testing as part of this evaluation has not been thoroughly investigated. Methods: In this retrospective study, we reviewed the charts of pediatric patients referred for epilepsy surgery evaluation over a 5-year period. We extracted and analyzed results of genetic testing as well as clinical, EEG, and neuroimaging data. Results: 125 patients were referred for epilepsy surgical evaluation, 86 of whom had some form of genetic testing. Of these, 18 had a pathogenic or likely pathogenic variant identified. Genes affected included NPRL3, TSC2, KCNH1, CHRNA4, SPTAN1, DEPDC5, SCN2A, ARX, SCN1A, DLG4, and ST5. One patient had ring chromosome 20, one a 7.17p12 duplication, and one a 15q13 deletion. A specific medical therapy choice was allowed due to genetic diagnosis in three patients who did not undergo surgery. Conclusions: Obtaining a molecular diagnosis may dramatically alter management in children with drug-resistant focal epilepsy. Genetic testing should be incorporated as part of standard investigations in the pre-surgical work-up of such patients.