Defining the phenotype of FHF1 developmental and epileptic encephalopathy
| العنوان: | Defining the phenotype of FHF1 developmental and epileptic encephalopathy |
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| المؤلفون: | Marina Trivisano, Julien Jung, Lieven Lagae, Marco Tartaglia, Nathalie Villeneuve, Berge A. Minassian, Ilaria Guella, Ruo Ming Shi, Luca De Palma, Gregory M. Cooper, Alessandro Ferretti, Michelle L. Thompson, Ingrid E. Scheffer, Eri Takeshita, Antonio Novelli, Gunnar M. Buyse, Michelle Demos, Alessandra Terracciano, Linda Huh, Federico Vigevano, Tomoko Kobayashi, Laurent Villard, Atsuo Kikuchi, Ryo Takeguchi, Gaetan Lesca, Maryline Carneiro, E. M. Bebin, Marie Laure Mathieu, Nicola Specchio, Mathieu Milh, Kazuhiro Haginoya, Aleksandra Siekierska, Nicola Pietrafusa |
| المساهمون: | Gall, Valérie, Children's Hospital Bambino Gesù IRCCS [Rome], University of Alabama at Birmingham [ Birmingham] (UAB), University of British Columbia (UBC), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospitals Leuven [Leuven], Asahikawa Medical University, Hospices Civils de Lyon (HCL), Miyagi Children’s Hospital, Xi'an Jiaotong University (Xjtu), Tohoku University [Sendai], University Hospitals KULeuven, University of Texas Southwestern, National Center of Neurology and Psychiatry, HudsonAlpha Institute for Biotechnology [Huntsville, AL], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), University of Melbourne, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | Epilepsia Epilepsia, 2020, 61 (7), ⟨10.1111/epi.16582⟩ Epilepsia, Wiley, 2020, 61 (7), ⟨10.1111/epi.16582⟩ |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], ILAE COMMISSION, [SDV.GEN] Life Sciences [q-bio]/Genetics, Bioinformatics, Germline, Epilepsy, 0302 clinical medicine, Gene duplication, Medicine, Missense mutation, Child, Brain Diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Brain, Electroencephalography, Phenotype, 3. Good health, [SDV] Life Sciences [q-bio], Neurology, Child, Preschool, Female, medicine.symptom, Life Sciences & Biomedicine, POSITION PAPER, Adult, Adolescent, FHF1, Clinical Neurology, Prenatal diagnosis, Status epilepticus, Article, CLASSIFICATION, neonatal onset, Young Adult, 03 medical and health sciences, Intellectual Disability, Humans, developmental and epileptic encephalopathy, Retrospective Studies, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, business.industry, Infant, Drug Resistant Epilepsy, medicine.disease, Fibroblast Growth Factors, 030104 developmental biology, FGF12, epilepsy, Neurology (clinical), Neurosciences & Neurology, genetic, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | International audience; Objective: Fibroblast-growth-factor homologous factor (FHF1) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 gene encodes a cytosolic protein that interacts with neuronal sodium channel. Aim of this study is to report the largest series of patients with pathogenic FHF1 genetic variants in order to define electro-clinical phenotype, genotype-phenotype correlation, and information about management and prognosis. Methods: Through an international collaboration, we retrospectively collected detailed clinical, genetic, neurophysiologic and neuroimaging data of 17 patients with FHF1-related epilepsy. Results: Fourteen patients carried heterozygous missense variant c.341G>A (p.Arg114His) in FHF1 gene, two patients heterozygous missense variant c.334G>A (p.Gly112Ser) and one patient carried a chromosomal microduplication involving FHF1 gene. The majority of variants were de novo, although in 29% of cases somatic or germline parent mosaicism occurred. Patients with c.341G>A variant presented with a phenotype consisting of early onset DEE. Drug resistant epilepsy, intellectual disability, psychiatric features and status epilepticus were also common features. Tonic seizures were the most frequent seizure type. Patients who carried c.334G>A variant and FHF1 gene duplication showed a delayed epilepsy onset compared with patients carring the hotspot variant (c.341G>A). Brain MRI was normal at onset while a mild cerebral and/or cerebellar atrophy appeared during follow-up in 8 out of 17 patients (47%). Conclusion: FHF1-related DEE is characterized by an almost homogeneous clinical phenotype characterized by early-onset and drug-resistant epilepsy, intellectual disability, and psychiatric features in patients with c.334G>A variant. Few cases with a milder phenotype can occur, although a genotype-phenotype correlation had been identified. Because of the possibility of germline or somatic mosaicism, it is appropriate to offer prenatal diagnosis to couples with a child with FHF1related DEE. |
| وصف الملف: | application/pdf; Print-Electronic |
| اللغة: | English |
| تدمد: | 0013-9580 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d4d1a11078ecaf1ba0275c15ca52819Test https://hal-amu.archives-ouvertes.fr/hal-03149027Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6d4d1a11078ecaf1ba0275c15ca52819 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00139580 |
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