Missense Variants in the A Isoform of FGF13 as a Novel Cause of Paroxysmal Dyskinesia

BACKGROUND: Pathogenic variants within the unique N-terminal inactivation particle of FGF13 isoform A (FGF13A) have so far been associated only with an X-linked dominant epileptic encephalopathy (DEE). OBJECTIVE: The aim was to expand the clinical and molecular spectrum of FGF13A-related disorder. METHODS: We performed exome or genome sequencing of patients with unexplained nonepileptic paroxysmal dyskinesia (PxD). RESULTS: Four unrelated boys with three novel de novo or inherited pathogenic missense variants in FGF13A were identified. Variants were also located within the inactivation particle, proximal to the DEE variants. Carrier mothers were unaffected, indicating an X-linked recessive inheritance. All patients presented with PxD in infancy, consisting of both hyperkinetic and hypokinetic-hypotonic phases, and a variable neurodevelopmental disorder. The frequency of attacks was high (60-100 per day). Treatment with caffeine with or without methylphenidate partially improved PxD in 2 patients. CONCLUSIONS: FGF13A variants cause a partially caffeine-responsive PxD phenotype with variable cognitive impairment, albeit without epilepsy. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.