Seizure freedom after vagus nerve stimulation in a patient with SCN3A-related network epilepsy and incomplete penetrance: A case report

Genetic-based epilepsies often present as distributed neural network disorders, challenging traditional focal versus generalized classifications. We report a 20-year-old male with drug-resistant epilepsy associated with a previously unreported SCN3A missense variant (c.5970C > G; p.Ser1990Arg). Despite failure of multiple anti-seizure medications and a non-localizing electroclinical profile, the patient achieved complete seizure freedom following Vagus Nerve Stimulation (VNS) therapy. Segregation analysis revealed the variant in asymptomatic relatives, including a parent with subclinical interictal discharges, confirming incomplete penetrance. This case underscores the role of VNS as a transformative therapeutic strategy for genetic network epilepsies where resective surgery is not feasible.