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Epilepsy with fever-sensitivity in patients with ATP6V0C pathogenic variants
Federica Martina Abigail Tanganelli1, Maria Francesca Di Feo2, Francesca Madia3
1Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genoa, Genoa, Italy; Child Neuropsychiatry Unit, IRCCS Istituto Giannina Gaslini, full member of ERN-Epicare, Genoa, Italy.
Seizure
|July 29, 2026
Summary
This study identifies ATP6V0C as a key gene in childhood fever-sensitive epilepsies. Early motor seizures triggered by fever, neurodevelopmental issues, and specific EEG changes characterize this condition.
Area of Science:
- Genetics
- Neurology
- Pediatric Epilepsy
Background:
- Fever-triggered seizures are seen in early-onset epilepsies.
- SCN1A-related conditions like Dravet Syndrome are well-known, but other genes are emerging.
- Genetic heterogeneity in fever-sensitive epilepsies requires further investigation.
Purpose of the Study:
- To assess genetic heterogeneity in individuals with fever-sensitive epilepsy.
- To investigate the role of ATP6V0C gene variants in fever-sensitive epilepsies.
- To define the electroclinical features associated with ATP6V0C variants.
Main Methods:
- Retrospective review of individuals tested with Next Generation Sequencing (NGS) panels or Whole Exome Sequencing (WES).
- Selection criteria included documented fever sensitivity.
- Variant filtering, segregation analysis, prediction tools, and ACMG guideline classification were employed.
Main Results:
- Of 721 individuals, 53 had fever-sensitive epilepsy (7.3%).
- Pathogenic variants were found in 30% of these cases.
- ATP6V0C variants were identified in 3.8% of fever-sensitive epilepsy patients, representing 12.5% of identified pathogenic variants.
Conclusions:
- ATP6V0C is a significant gene associated with childhood fever-sensitive epilepsy.
- The phenotype includes early febrile motor seizures, evolving EEG abnormalities, and neurodevelopmental impairment.
- Accurate molecular diagnosis is crucial for potential precision therapies in these children.
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