Expanding the phenotypic spectrum of FGF12-epilepsy—does prompt precision therapy affect outcomes?

Arkush L, Karandasheva K, Ouellet F, D’Gama AM, Rosen Sheidley B, Liang NS, Chau V, Costain G, Smith L, Alwis A, Eltze C, Poduri A, D’Arco F, Adams J, Lee K, Singh J, Brown AP, Nagendran A, Pode-Shakked B, Tzadok M, Ben Zeev B, McTague A (2026)

Publication Type: Journal article

Publication year: 2026

Journal

npj Genomic Medicine Nature Publishing Group

Book Volume: 11

Article Number: 41

Journal Issue: 1

DOI: 10.1038/s41525-026-00581-0

Abstract

Fibroblast growth factor-12 (FGF12) variants have been associated with developmental and epileptic encephalopathy (DEE) with evidence of modulation of voltage-gated sodium channels Nav1.2 and Nav1.6. We aim to expand the phenotypic spectrum of FGF12-related epilepsy with emphasis on precision therapy. We describe 12 patients: eight with neonatal onset seizures with the recurrent p.Arg52His (c.155 G > A) variant, two with a previously unreported p.Glu153Gly (c.458 A > G) variant, one with a p.Gly50Ser (c.148 G > A) variant, and one with a de novo whole-gene duplication. Atypical absence seizures were present in 5/12 patients. Brain MRI was normal in 10/12; one patient’s MRIs showed progressive cerebellar atrophy, and one patient’s MRI showed a hemispheric infarct. 8 patients promptly started on sodium channel blockers became seizure-free with good developmental outcomes while 4 developed DEE. In summary, we expand the phenotypic spectrum of FGF12-related epilepsy and discuss the role of early precision therapy in developmental and epilepsy outcomes.

Involved external institutions

University of Michigan US United States (USA) (US) University Hospital Southampton NHS GB United Kingdom (GB) University College London (UCL) GB United Kingdom (GB) National Hospital For Neurology and Neurosurgery GB United Kingdom (GB) Tel Aviv University IL Israel (IL) Chaim Sheba Medical Center at Tel HaShomer / המרכז הרפואי עש חיים שיבא – תל השומר‎‎ IL Israel (IL) Great Ormond Street Hospital (GOSH) GB United Kingdom (GB) Boston Children's Hospital US United States (USA) (US) The Hospital for Sick Children (SickKids) CA Canada (CA) University of Toronto CA Canada (CA)

How to cite

APA:

Arkush, L., Karandasheva, K., Ouellet, F., D’Gama, A.M., Rosen Sheidley, B., Liang, N.S.,... McTague, A. (2026). Expanding the phenotypic spectrum of FGF12-epilepsy—does prompt precision therapy affect outcomes? npj Genomic Medicine, 11(1). https://doi.org/10.1038/s41525-026-00581-0

MLA:

Arkush, Leo, et al. "Expanding the phenotypic spectrum of FGF12-epilepsy—does prompt precision therapy affect outcomes?" npj Genomic Medicine 11.1 (2026).

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