State-of-the-art management of Dravet syndrome

Dravet syndrome is a severe developmental and epileptic encephalopathy caused by heterozygous, loss-of-function, pathogenic variants in the SCN1A gene. It is characterized by frequent, often prolonged convulsive seizures. Dravet syndrome is associated with diverse comorbid conditions, including developmental impairment, intellectual disability, and behavioral disturbances, in addition to high mortality rates. Prompt diagnosis and treatment initiation are essential to reduce seizure frequency, status epilepticus, and potentially improve neurodevelopmental outcomes. Currently available therapies such as fenfluramine, stiripentol, and cannabidiol have demonstrated significant reduction in convulsive seizure frequency, based on randomized controlled trials and real-world studies; however, they have not markedly affected non-seizure symptoms. Emerging therapies such as genetic modulation are promising given their potential for disease modification, seizure frequency reduction, and improvement of non-seizure outcomes. This review of observational studies and randomized clinical trials provides an overview of the natural history of Dravet syndrome, current treatment guidelines with recently approved medications, addressing both safety and efficacy, and new therapeutic approaches, including disease-modifying therapies. The therapeutic landscape in Dravet syndrome is evolving, with the use of new antiseizure agents and precision therapies that target the SCN1A variant. Goals of treatment include improvement of seizure burden, neurodevelopment, comorbidities, and quality of life in individuals with Dravet syndrome.