Skuteczność fenfluraminy u dziecka z epilepsją spowodowaną zmianą genetyczną w genie SV2A - opis przypadku

Pathogenic SV2A gene variants have been reported as causes of epilepsy and are often associated with drug resistance and susceptibility to fever-related seizures. No highly effective treatments have been established for this condition. We report a female patient with a family history of epilepsy who developed generalized seizures associated with fever and bathing from 6 months of age. Despite intensive treatment with multiple anti-seizure medications, the seizures remained refractory. Given the severe drug-resistant epilepsy characterized by fever sensitivity, seizure clustering, and multiple seizure types suggestive of Dravet syndrome, fenfluramine (FFA) was initiated at 2 years and 2 months of age. FFA at 0.2 mg/kg/day resulted in immediate and sustained seizure freedom. Subsequent whole-exome sequencing identified a pathogenic SV2A variant (p.Gly660Arg). This is the first report demonstrating the clinical efficacy of FFA for epilepsy associated with an SV2A variant. We propose that FFA's effectiveness stems from its ability to address two core pathologies of SV2A deficiency: correction of the excitatory/inhibitory imbalance by restoring inhibitory tone through its serotonergic mechanism, and mitigation of neuroinflammation, thereby stabilizing the neuronal network. FFA may represent a promising therapeutic option for patients with SV2A variant-associated epilepsy, particularly those with a fever-sensitive, drug-refractory phenotype; however, further studies with larger case series are needed to confirm its efficacy.