Abstracts

Rationale: Diagnosis of specific underlying genetic etiologies of epilepsy may guide specific treatment. Here we present a novel correlation between genetic epilepsy syndrome and treatment response, to highlight the utility of genetic testing in epilepsy and suggest medication options for similar patients. Methods: Two cases of intractable non-lesional frontal lobe epilepsy in childhood presented to our clinic for evaluation and treatment. Their cases are reviewed retrospectively to describe their unanticipated response to a next choice of medication. Results: Each patient underwent presurgical evaluation, concordant with clinical semiology suggesting frontal lobe seizure onset. Invasive surgical monitoring to recommend candidacy for resection was considered in both cases. Clinical genetic panel testing (Invitae, San Francisco CA) identified unique novel pathogenic variants in the DEPDC5 gene (table) in each patient. Each patient tried multiple newer ('second-' and 'third-generation') antiepileptic medications, including at least one sodium-channel agent, with ongoing seizures despite monotherapy and polytherapy trials. Clinical response to phenytoin was dramatic, with both patients achieving seizure freedom immediately upon reaching stable therapeutic serum levels. Each has sustained response to phenytoin monotherapy, currently at >6 and >14 months seizure freedom, without significant side effects. Conclusions: In modern clinical practice, 'first-generation' antiepileptic drugs such as phenytoin are often eschewed for newer medications with improved side effect profiles. Select conditions may, however, have pharmacogenetic profiles suggesting targeted treatment. To our knowledge, such a response has not previously been reported in DEPDC5-related epilepsy. Our experience highlights the importance of continued medication trials in refractory focal epilepsy, highlights differences between medication response even within the same class, and suggests preliminarily suggests a potential specific responsiveness of this condition to phenytoin. Funding: No funding