Epilepsja wrażliwa na gorączkę u pacjentów z wariantami patogennymi genu ATP6V0C

OBJECTIVE: Fever can trigger seizures in several early-onset epilepsies. SCN1A-related epilepsies, including Dravet Syndrome, are the best characterised conditions in this spectrum, but a growing number of genes implicated in fever-sensitive epilepsies have emerged. We assessed the genetic heterogeneity of individuals who underwent testing because of seizures or epilepsy with fever sensitivity. In particular, we investigated the occurrence of ATP6V0C pathogenic variants and delineated its associated electro clinical features. METHODS: We retrospectively reviewed individuals tested with epilepsy-targeted Next Generation Sequencing (NGS) panels and/or Whole Exome Sequencing (WES) between 2022 and 2025, selecting those with documented fever sensitivity (defined as seizure occurrence or exacerbation temporally linked to febrile episodes in subjects who suffer from both febrile and afebrile seizures). Variants were filtered for frequency, evaluated through segregation and prediction tools, and classified according to ACMG guidelines. RESULTS: Among 721 individuals tested with NGS or WES for neurological indications, 418 (58%) had a history of seizures, including 53 (7.3%) with fever-sensitive epilepsy. Pathogenic or likely pathogenic variants were identified in 30% of these cases. Notably, ATP6V0C variants accounted for 2/16 (12.5%) of all pathogenic/likely pathogenic findings and were identified in 3.8% of tested fever-sensitive epilepsy patients, ranking among the most frequently implicated genes in this cohort. SIGNIFICANCE: Our findings support ATP6V0C as a relevant gene in the landscape of childhood epilepsies with fever sensitivity. The associated phenotype appears characterized by early febrile-triggered motor seizures, initially normal EEG followed by multifocal abnormalities, normal MRI and subsequent onset of neurodevelopmental impairment. These results highlight the importance of accurate molecular diagnosis in children presenting with fever-sensitive seizures, with potential implications for future precision therapies.