背景:早期婴儿癫痫性脑病(EIEE)是一组高度异质性的疾病,表型和遗传。通常,它开始得很早,表现为顽固性癫痫,异常脑电图,和生长迟缓/智力障碍。随着下一代测序(NGS)的出现,其遗传病因引起了越来越多的临床关注。本研究旨在调查华东地区某中心医院EIEE患者的遗传特征和临床表型。
方法:这项研究回顾性地纳入了2021年1月至2022年1月期间在安徽省某医院收治的24名EIEE阳性患者的基因变异。中国。在所有病例中通过基于三重的全外显子组测序(WES)进行遗传诊断。此外,进行视频脑电图(VEEG)和神经影像学检查。
结果:共纳入24名儿童。第一次癫痫发作的平均年龄约为5个月。约42%的儿童有不同程度的发育迟缓,43%有脑结构异常,64%有VEEG异常。此外,其他表型,包括内分泌代谢和心脏结构异常,已独立报道。总的来说,在24例患者中发现了15种致病基因变异。确定的主要致病基因是SCN1A(25%,6/24),KCNQ2(8.3%,2/24),和TBC1D24(8.3%,2/24)。我们还发现了由双等位基因UGDH基因变异引起的极其罕见的EIEE84型病例,预测这种变异可能会影响蛋白质结构的稳定性。
结论:SCN1A致病变异是导致EIEE的主要因素,与以前发表的队列报告相似.NGS可用于准确的临床诊断和精确的治疗选择。我们还报道了一例中国患者UGDH基因变异引起的罕见EIEE84病例。这项研究进一步丰富了已知的致病性EIEE基因谱。
BACKGROUND: Early infantile epileptic encephalopathy (EIEE) is a group of highly heterogeneous diseases, both phenotypically and genetically. Usually, it starts early on and manifests as intractable epilepsy, abnormal electroencephalogram, and growth retardation/intellectual impairment. With the advent of next-generation sequencing (NGS), its genetic etiology has attracted increasing clinical attention. This study aimed to investigate the genetic characteristics and clinical phenotypes of patients with EIEE from a central hospital in Eastern China.
METHODS: This study retrospectively included the gene variants from 24 EIEE-positive patients admitted between January 2021 and January 2022 to a hospital in Anhui Province, China. The genetic diagnosis was performed in all cases by trio-based whole-exome sequencing (WES). Additionally, Video electroencephalogram (VEEG) and neuroimaging examinations were performed.
RESULTS: A total of 24 children were included. The average age at the first seizure was approximately 5 months. About 42% of children had developmental retardation of varying degrees, 43% had brain structural abnormalities, and 64% had VEEG abnormalities. In addition, other phenotypes, including endocrine metabolism and cardiac structural abnormalities, have been independently reported. In total, fifteen pathogenic gene variants were identified in 24 patients. The main pathogenic genes identified were SCN1A (25%, 6/24), KCNQ2 (8.3%, 2/24), and TBC1D24 (8.3%, 2/24). We also found an extremely rare case of EIEE84 type caused by biallelic UGDH gene variants, predicting that this variant might affect the stability of the protein structure.
CONCLUSIONS: SCN1A pathogenic variants are the main factor leading to EIEE, similar to previously published cohort reports. NGS is useful for accurate clinical diagnoses and precise treatment choices. We also reported a rare case of EIEE84 caused by variants in the UGDH gene in a Chinese patient. This study further enriches the known spectrum of pathogenic EIEE genes.