Defining the phenotype of FHF1 developmental and epileptic encephalopathy.
Defining the phenotype of FHF1 developmental and epileptic encephalopathy.
复制标题
DOI：
10.1111/epi.16582
复制
发表时间：
2020-07
期刊：
影响因子：
5.6
通讯作者：
Specchio N
中科院分区：
文献类型：
--
作者：
Trivisano M;Ferretti A;Bebin E;Huh L;Lesca G;Siekierska A;Takeguchi R;Carneiro M;De Palma L;Guella I;Haginoya K;Shi RM;Kikuchi A;Kobayashi T;Jung J;Lagae L;Milh M;Mathieu ML;Minassian BA;Novelli A;Pietrafusa N;Takeshita E;Tartaglia M;Terracciano A;Thompson ML;Cooper GM;Vigevano F;Villard L;Villeneuve N;Buyse GM;Demos M;Scheffer IE;Specchio N
最近，成纤维细胞生长因子同源因子（FHF 1）基因变体与发育性和癫痫性脑病（DEE）有关。FHF 1编码调节神经元钠通道门控的胞质蛋白。我们的目的是完善患者的电临床表型谱致病FHF 1变异。我们回顾性收集了17例FHF 1-DEE患者的临床、遗传学、神经生理学、神经影像学资料。16例患者有复发性杂合FHF 1错义变异：14例有复发性p.Arg114His变异，2例有新的可能致病的变异p.Gly112Ser。p.Arg114His变异与较早发作和更严重的表型相关。1例患者携带涉及FHF 1的染色体微重复。12例患者携带从头变异，5例（29.5%）遗传自性腺或体细胞嵌合的父母。癫痫发作在1天至41个月之间，76.5%在30天内发作。强直性发作是最常见的发作类型。耐药癫痫12例（70.6%），智力障碍14例（82.3%），行为障碍11例（64.7%）。头颅MR显示9例（52.9%）轻度脑和/或小脑萎缩。总的来说，我们的研究结果扩展和完善了FHF 1-DEE患者的临床，EEG和成像表型，其特征是早发性癫痫伴强直性发作，与中度至重度ID和精神病学特征相关。
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. We retrospectively collected clinical, genetic, neurophysiologic, neuroimaging data of 17 patients with FHF1-DEE. Sixteen patients had recurrent heterozygous FHF1 missense variants: fourteen 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, 11 (64.7%) behavioral disturbances. Brain MR showed mild cerebral and/or cerebellar atrophy in 9 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.
登录
查看更多内容
影响因子：
5.6
作者：
Scheffer IE;Berkovic S;Capovilla G;Connolly MB;French J;Guilhoto L;Hirsch E;Jain S;Mathern GW;Moshé SL;Nordli DR;Perucca E;Tomson T;Wiebe S;Zhang YH;Zuberi SM
通讯作者：
Zuberi SM
影响因子：
8
作者：
Berg, Anne T.;Nickels, Katherine;Camfield, Carol S.
通讯作者：
Camfield, Carol S.
影响因子：
5.6
作者：
Rochtus, Anne;Olson, Heather E.;Poduri, Annapurna
通讯作者：
Poduri, Annapurna
影响因子：
3.5
作者：
Oda, Yoichiro;Uchiyama, Yuri;Matsumoto, Naomichi
通讯作者：
Matsumoto, Naomichi
影响因子：
3.1
作者：
Guella, Ilaria;Huh, Linda;Demos, Michelle
通讯作者：
Demos, Michelle