FHF1 developmental and epileptic encephalopathy: recurrent p.Arg114His is cause of neonatal onset epilepsy
Abstract number :
935
Submission category :
4. Clinical Epilepsy / 4B. Clinical Diagnosis
Year :
2020
Submission ID :
2423268
Source :
www.aesnet.org
Presentation date :
12/7/2020 1:26:24 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Marina Trivisano, Bambino Gesù Children's Hospital, IRCCS; Alessandro Ferretti - Bambino Gesù Children's Hospital, IRCCS, Rome; E. Martina Bebin - University of Alabama at Birmingham School of Medicine; Linda Huh - BC Children's Hospital | University of B
Rationale:
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 electro-clinical phenotypic spectrum of patients with pathogenic FHF1 variants.
Method:
We retrospectively collected detailed clinical, genetic, neurophysiologic and neuroimaging data of 17 patients with FHF1-DEE.
Results:
Sixteen patients had recurrent heterozygous FHF1 missense variants: fourteen had c.341G >A (p.Arg114His) and two c.334G >A (p.Gly112Ser). One patient carried a chromosomal microduplication involving FHF1. Twelve patients carried a de novo variant, five (29.5%) inherited the variant 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 MR showed mild cerebral and/or cerebellar atrophy in 9 patients (52.9%).
Conclusion:
FHF1-DEE has an electro-clinical phenotypic spectrum characterized by early onset DEE. The p.Arg114His variant is associated with an earlier onset and more severe phenotype. Because of the high frequency of parental mosaicism, it is especially important to offer targeted reproductive counselling.
Funding:
:NO funding
Clinical Epilepsy