Surgical decision-making in adult patients with epilepsy related to germline mutations: A single-center study

ObjectivesGenetic testing is not routinely performed during presurgical evaluation of adult patients with epilepsy.MethodsIn this retrospective observational study, we analyzed the diagnostic yield of an epilepsy multigene panel and patient characteristics in adult epilepsy surgery candidates from 2014 to 2024. We compared data collected from patients with GTPase-activating protein activity toward Rags 1 (GATOR1) and non-GATOR1 pathway mutations.ResultsIn total, 31 of the 236 (13%) patients tested positive for monogenic epilepsy disorders. The epilepsy multigene panel diagnostic yield was 12% (28 of the 233 patients). Overall, 9 of the 31 patients had GATOR1 pathway mutations. Moreover, 15 of the 31 patients underwent invasive electroencephalography evaluations, with 6 exhibiting GATOR1 and 9 exhibiting non-GATOR1 pathway mutations. In the GATOR1 mutations group, three of the six (50%) patients had focal ictal onset. In the non-GATOR1 mutations group, two of the nine (22%) patients had focal ictal onset. Overall, 8 of the 31 patients underwent resection or laser ablation, with 4 exhibiting GATOR1 and 4 exhibiting non-GATOR1 pathway mutations. In the GATOR1 mutations group, four of the nine (44.4%) patients underwent resection or laser ablation, and all had favorable outcomes (Engel I-II). In the non-GATOR1 mutations group, 4 of the 22 (18.2%) patients underwent resection. One patient had a favorable outcome (Engel I).ConclusionsGenetic testing may be helpful for selection of epilepsy surgery candidates and for counseling regarding expected epilepsy surgery outcome. These findings may be valuable for large multicenter studies with the goal to streamline the surgical journey of epilepsy patients with germline mutations.