Missense variants in the A Isoform of FGF13 as a novel cause of paroxysmal dyskinesia

Mignot, Cyril, Papathanasiou Terzi, Matthildi Athina, Ravelli, Claudia, Bosch, Elisabeth, Lin, Xueqin, Trauffler, Adeline, Caumes, Roseline, Fry, Andrew E. ORCID: https://orcid.org/0000-0001-9778-6924, Fort, Clementine, Gauthe, Gaelle, Trollmann, Regina, Wirth, Thomas, Anheim, Mathieu, Meneret, Aurelie, Roze, Emmanuel, de Sainte Agathe, Jean-Madeilne, He, Hailan, Panagiotakaki, Eleni and Lesca, Gaetan 2026. Missense variants in the A Isoform of FGF13 as a novel cause of paroxysmal dyskinesia. Movement Disorders 10.1002/mds.70256

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Abstract

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.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Additional Information:	For the full list of authors, please refer to the article webpage: https://doi.org/10.1002/mds.70256. License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/
Publisher:	Wiley
ISSN:	0885-3185
Date of First Compliant Deposit:	19 March 2026
Date of Acceptance:	9 February 2026
Last Modified:	19 Mar 2026 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/185866

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