Broadening the phenotype associated with pathogenic variants in the <i>FGF12</i> gene: From developmental and epileptic encephalopathy to drug‐responsive epilepsy with favorable cognitive outcome

The fibroblast growth factor 12 (FGF12) gene encodes a protein interacting with voltage-gated sodium channels. Two variants, p.(Arg52His) and p.(Gly50Ser), have repeatedly been associated with developmental and epileptic encephalopathy-47 (DEE47; Mendelian Inheritance in Man #617166) with poor outcome. We aim to refine the electroclinical phenotype and outcomes of 10 unpublished patients (2-38 years old) with these recurrent pathogenic variants in the FGF12 gene without DEE (p.[Arg52His], n = 4; p.[Gly50Ser], n = 6). The patients with p.(Gly50Ser) showed later and more explosive epilepsy onset, whereas p.(Arg52His) cases had gradual onset. All developed epilepsy before 5 months, with 70% achieving seizure remission by 6 months with antiseizure medication (ASM), leading to good neurodevelopmental outcomes (median follow-up = 6.8 years). In contrast, the patients with mild intellectual disability had persistent epilepsy despite ASM. Additionally, patients with favorable neurodevelopmental outcomes and FGF12 pathogenic variants showed no signs of cerebellar atrophy. Moreover, we did not find a clear correlation between treatment with sodium channel blockers, its timing, and neurodevelopmental outcome. Here, we expand the phenotypic spectrum of FGF12 pathogenic variants and underscore cases with favorable neurodevelopmental outcomes.

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Publication Details

Journal
Epilepsia
Published
2025-06-09
DOI
https://doi.org/10.1111/epi.18495
Citations
2
Primary Topic
Epigenetics and DNA Methylation
Type
article
Field-Weighted Citation Impact
1.61
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article

Broadening the phenotype associated with pathogenic variants in the FGF12 gene: From developmental and epileptic encephalopathy to drug‐responsive epilepsy with favorable cognitive outcome

Béatrice Desnous, Laurent Villard, Florence Riccardi, Julien Neveu et al.
2 citations
Epilepsia
Epigenetics and DNA Methylation
1.61
article

Broadening the phenotype associated with pathogenic variants in the FGF12 gene: From developmental and epileptic encephalopathy to drug‐responsive epilepsy with favorable cognitive outcome

Béatrice Desnous, Laurent Villard, Florence Riccardi, Julien Neveu, Laure Lacan, Nicolas Chatron, Clément Pierret, Cécilia Altuzarra, Gaëtan Lesca, Sabrine Souci, Maryline Carneiro, Sébastien Boulogne, Marie Alesandrini, Stéphanie Valence, Mathieu Milh, Sylvie Nguyen, Bertrand Isidor, Diana Rodriguez
article en
2 citations

Abstract

The fibroblast growth factor 12 (FGF12) gene encodes a protein interacting with voltage-gated sodium channels. Two variants, p.(Arg52His) and p.(Gly50Ser), have repeatedly been associated with developmental and epileptic encephalopathy-47 (DEE47; Mendelian Inheritance in Man #617166) with poor outcome. We aim to refine the electroclinical phenotype and outcomes of 10 unpublished patients (2-38 years old) with these recurrent pathogenic variants in the FGF12 gene without DEE (p.[Arg52His], n = 4; p.[Gly50Ser], n = 6). The patients with p.(Gly50Ser) showed later and more explosive epilepsy onset, whereas p.(Arg52His) cases had gradual onset. All developed epilepsy before 5 months, with 70% achieving seizure remission by 6 months with antiseizure medication (ASM), leading to good neurodevelopmental outcomes (median follow-up = 6.8 years). In contrast, the patients with mild intellectual disability had persistent epilepsy despite ASM. Additionally, patients with favorable neurodevelopmental outcomes and FGF12 pathogenic variants showed no signs of cerebellar atrophy. Moreover, we did not find a clear correlation between treatment with sodium channel blockers, its timing, and neurodevelopmental outcome. Here, we expand the phenotypic spectrum of FGF12 pathogenic variants and underscore cases with favorable neurodevelopmental outcomes.

EpilepsiaVol. 66(8)
Université Claude Bernard Lyon 1 (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université de Versailles Saint-Quentin-en-Yvelines (FR), Aix-Marseille Université (FR), Université de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Sorbonne Université (FR), Hôpital Armand-Trousseau (FR), Assistance Publique Hôpitaux de Marseille (FR), Centre de Recherche en Neurosciences de Lyon (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Hôpital Raymond-Poincaré (FR), Fondation Lenval (FR), Hôpital d'Instruction des Armées Sainte-Anne (FR), Hôpital Saint-Jacques (FR), Génétique Médicale & Génomique Fonctionelle (FR), Hôpital de la Timone (FR), Centre de Génétique Médicale de Marseille (FR)
Good health and well-being
Openalex Percentile: Top 17%
Epigenetics and DNA Methylation
1.61
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