Gong Pan, Jiao Xianru, Yu Dan, Yang Zhixian
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Front Genet. 2021 Jun 30;12:649556. doi: 10.3389/fgene.2021.649556. eCollection 2021.
gene mutations had been described to cause developmental and epileptic encephalopathies (DEEs). In this study, we presented the detailed clinical features and genetic analysis of two unrelated patients carrying two variants in and reviewed eight different cases available in publications. Likely pathogenic variants were identified by whole exome sequencing; clinical data of the patients were retrospectively collected and analyzed. Our two unrelated patients were diagnosed with Ohtahara syndrome followed by infantile spasms (IS) and possibly the epilepsy of infancy with migrating focal seizures (EIMFS), respectively. They both manifested dysmorphic features with hirsute arms, thick hair, prominent eyebrows, long and thick eyelashes, a broad nasal tip, and short and smooth philtrum. In the eight patients reported previously, two was diagnosed with IS carrying a 'change-of-function' mutation and a gain-of-function mutation, respectively, two with EIMFS-like carrying a gain-of-function mutation and a loss-of-function mutation, respectively, one with EIMFS carrying a loss-of-function mutation, three with DEE without functional analysis. Among them, two patients with gain-of-function mutations both exhibited dysmorphic features and presented epilepsy phenotype, which was similar to our patients. Overall, the most common phenotypes associated with mutation were IS and EIMFS. Epilepsy phenotype associated with gain- and loss-of-function mutations could overlap. Additional cases will help to make genotype-phenotype correlations clearer.
基因变异已被描述为可导致发育性和癫痫性脑病（DEEs）。在本研究中，我们展示了两名携带两种变异的无关患者的详细临床特征和基因分析，并回顾了出版物中现有的八个不同病例。通过全外显子组测序鉴定出可能的致病变异；对患者的临床数据进行回顾性收集和分析。我们的两名无关患者分别被诊断为大田原综合征，随后出现婴儿痉挛（IS）以及可能的婴儿期迁移性局灶性癫痫发作（EIMFS）。他们均表现出畸形特征，如手臂多毛、头发浓密、眉毛突出、睫毛长且浓密、鼻尖宽阔以及人中短而平滑。在先前报道的八名患者中，两名分别被诊断为IS，携带一个“功能改变”突变和一个功能获得性突变；两名被诊断为类似EIMFS，分别携带一个功能获得性突变和一个功能丧失性突变；一名被诊断为EIMFS，携带一个功能丧失性突变；三名被诊断为DEE但未进行功能分析。其中，两名携带功能获得性突变的患者均表现出畸形特征并呈现癫痫表型，这与我们的患者相似。总体而言，与该突变相关的最常见表型是IS和EIMFS。与功能获得性和功能丧失性突变相关的癫痫表型可能会重叠。更多病例将有助于更清楚地建立基因型 - 表型相关性。
