Clinical and Genetic Spectrum of SCN8A-Related Disorders: A Retrospective Study From the Gulf Region.

Abstract

This multicenter retrospective study examined the clinical characteristics and outcomes of 26 patients with sodium channel protein type 8 subunit alpha (SCN8A)-related epilepsy and/or neurodevelopmental disorders across the Gulf region. Data were collected from August 2024 to January 2025. Most patients (80.77%) experienced epilepsy onset within the first year of life, with a mean onset age of 8.25 months. Common features included developmental delay (69.57%), epileptic encephalopathy (73.08%), intellectual disability (46.15%), and movement disorders (34.62%). Genetic testing identified SCN8A mutations, primarily loss-of-function variants (65.38%), with missense mutations being most frequent. Seizure types varied, with generalized tonic-clonic (53.84%) and focal seizures (42.31%) being common. Levetiracetam and sodium channel blockers were the most used treatments. A seizure reduction of >50% was achieved in 65.38% of patients, and 26.92% became seizure-free. Loss-of-function mutations were linked to better outcomes. The study underscores the clinical variability of SCN8A disorders and the importance of personalized genetic diagnosis and targeted therapy.