Defining the phenotype of FHF1 developmental and epileptic encephalopathy.

Autor: Trivisano M; Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Member of European Reference Network EpiCARE, Rome, Italy., Ferretti A; Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Member of European Reference Network EpiCARE, Rome, Italy., Bebin E; Department of Pediatric Neurology, University of Alabama at Birmingham, Birmingham, AL, USA., Huh L; Division of Neurology, Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, BC, Canada., Lesca G; Service de Génétique, Hospices Civils de Lyon, Lyon, France.; Institut Neuromyogène, Equipe Métabolisme énergétique et développement neuronal, CNRS, UMR 5310, INSERM U1217, Université Lyon 1, Lyon, France., Siekierska A; Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium., Takeguchi R; Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan., Carneiro M; Department of Pediatric Neurology, Femme Mère Enfant Hospital, Hospices Civils de Lyon, Lyon, France., De Palma L; Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Member of European Reference Network EpiCARE, Rome, Italy., Guella I; Division of Neurology, Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, BC, Canada., Haginoya K; Department of Pediatric Neurology, Miyagi Children's Hospital, Sendai, Japan., Shi RM; Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.; Department of Pediatrics, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Kikuchi A; Department of Pediatrics, Tohoku University Hospital, Sendai, Japan., Kobayashi T; Division of Child Development, Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan., Jung J; Service de Génétique, Hospices Civils de Lyon, Lyon, France.; Institut Neuromyogène, Equipe Métabolisme énergétique et développement neuronal, CNRS, UMR 5310, INSERM U1217, Université Lyon 1, Lyon, France., Lagae L; Department of Development and Regeneration, University Hospitals KU Leuven, Leuven, Belgium., Milh M; Department of Pediatric Neurology, Femme Mère Enfant Hospital, Hospices Civils de Lyon, Lyon, France., Mathieu ML; Department of Pediatric Neurology, Femme Mère Enfant Hospital, Hospices Civils de Lyon, Lyon, France., Minassian BA; Department of Pediatrics, University of Texas Southwestern, Dallas, TX, USA., Novelli A; Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Pietrafusa N; Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Member of European Reference Network EpiCARE, Rome, Italy., Takeshita E; Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan., Tartaglia M; Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Terracciano A; Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Thompson ML; Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA., Cooper GM; Hudson Alpha Institute for Biotechnology, Huntsville, AL, USA., Vigevano F; Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Member of European Reference Network EpiCARE, Rome, Italy., Villard L; Aix Marseille University, Inserm, MMG, Marseille, France., Villeneuve N; Department of Pediatric Neurology, APHM, Hopital de la Timone, Marseille, France., Buyse GM; Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium., Demos M; Division of Neurology, Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, BC, Canada., Scheffer IE; Austin Health, and Royal Children's Hospital, Florey and Murdoch Institutes, University of Melbourne, Melbourne, Australia., Specchio N; Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Member of European Reference Network EpiCARE, Rome, Italy.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2020 Jul; Vol. 61 (7), pp. e71-e78. Date of Electronic Publication: 2020 Jul 09.
DOI: 10.1111/epi.16582
Abstrakt: Fibroblast growth-factor homologous factor (FHF1) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 encodes a cytosolic protein that modulates neuronal sodium channel gating. We aim to refine the electroclinical phenotypic spectrum of patients with pathogenic FHF1 variants. We retrospectively collected clinical, genetic, neurophysiologic, and neuroimaging data of 17 patients with FHF1-DEE. Sixteen patients had recurrent heterozygous FHF1 missense variants: 14 had the recurrent p.Arg114His variant and two had a novel likely pathogenic variant p.Gly112Ser. The p.Arg114His variant is associated with an earlier onset and more severe phenotype. One patient carried a chromosomal microduplication involving FHF1. Twelve patients carried a de novo variant, five (29.5%) inherited from parents with gonadic or somatic mosaicism. Seizure onset was between 1 day and 41 months; in 76.5% it was within 30 days. Tonic seizures were the most frequent seizure type. Twelve patients (70.6%) had drug-resistant epilepsy, 14 (82.3%) intellectual disability, and 11 (64.7%) behavioral disturbances. Brain magnetic resonance imaging (MRI) showed mild cerebral and/or cerebellar atrophy in nine patients (52.9%). Overall, our findings expand and refine the clinical, EEG, and imaging phenotype of patients with FHF1-DEE, which is characterized by early onset epilepsy with tonic seizures, associated with moderate to severe ID and psychiatric features.
(© 2020 International League Against Epilepsy.)
Databáze: MEDLINE
Externí odkaz: