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.

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定义 FHF1 发育性和癫痫性脑病的表型

成纤维细胞生长因子同源因子 (FHF1) 基因变异最近与发育性和癫痫性脑病 (DEE) 相关。FHF1 编码调节神经元钠通道门控的胞质蛋白。我们旨在完善具有致病性 FHF1 变异的患者的电临床表型谱。我们回顾性收集了 17 名 FHF1-DEE 患者的临床、遗传、神经生理学和神经影像学数据。16 名患者具有复发性杂合 FHF1 错义变异：14 名具有复发性 p.Arg114His 变异，2 名具有新的可能致病性变异 p.Gly112Ser。p.Arg114His 变体与更早的发病和更严重的表型相关。一名患者携带涉及 FHF1 的染色体微重复。12 名患者携带了 de novo 变异，其中 5 名 (29. 5%) 遗传自有性腺或体细胞嵌合体的父母。癫痫发作在 1 天到 41 个月之间；76.5% 是在 30 天内。强直性癫痫发作是最常见的癫痫发作类型。12 名患者 (70.6%) 患有耐药性癫痫，14 名 (82.3%) 智力障碍和 11 名 (64.7%) 行为障碍。脑磁共振成像 (MRI) 显示 9 名患者 (52.9%) 出现轻度脑和/或小脑萎缩。总体而言，我们的研究结果扩展和完善了 FHF1-DEE 患者的临床、脑电图和影像表型，其特征是早发性癫痫伴强直性癫痫发作，与中度至重度 ID 和精神特征相关。6%) 患有耐药性癫痫，14 名 (82.3%) 智力障碍和 11 名 (64.7%) 行为障碍。脑磁共振成像 (MRI) 显示 9 名患者 (52.9%) 出现轻度脑和/或小脑萎缩。总体而言，我们的研究结果扩展和完善了 FHF1-DEE 患者的临床、脑电图和影像表型，其特征是早发性癫痫伴强直性癫痫发作，与中度至重度 ID 和精神特征相关。6%) 患有耐药性癫痫，14 名 (82.3%) 智力障碍和 11 名 (64.7%) 行为障碍。脑磁共振成像 (MRI) 显示 9 名患者 (52.9%) 出现轻度脑和/或小脑萎缩。总体而言，我们的研究结果扩展和完善了 FHF1-DEE 患者的临床、脑电图和影像表型，其特征是早发性癫痫伴强直性癫痫发作，与中度至重度 ID 和精神特征相关。