Keywords

epilepsy, seizures, mTOR, DEPDC5, tuberous sclerosis complex, sudden unexpected death in epilepsy

Abstract

Mutations in the mTOR pathway can give rise to epileptic seizures in patients. While a variety of antiepileptic drugs are available to treat epilepsy, a large proportion of patients will experience refractory seizures (Chen et al., 2018). Additionally, patients with mTOR-related epilepsy may experience reduced efficacy in traditional therapeutic options to treat seizures (French et al., 2016; Hadzsiev et al., 2023; Kato et al., 2022; Moloney et al., 2023). Mutations resulting in mTOR-related epilepsy are genetically inherited; however, some variability in family histories of epilepsy may be due to second-hit somatic mutations in focal areas of the brain (Dawson et al., 2020; Ribierre et al., 2018). This patient population requires additional care, as they are more likely to experience cognitive disabilities, metabolic disorders, and an elevated risk of experiencing sudden unexpected death in epilepsy (McMahon et al., 2015; Mizuguchi et al., 2021; Thormeyer et al., 2026). Physicians should include screening specific to hyperactive mTOR activity and mutations within this pathway for the pediatric population presenting with their first seizure. Early diagnosis and targeted treatment may improve overall prognosis within this patient population.