Zhang Huiting, Yang Liu, Duan Jing, Zeng Qi, Chen Li, Fang Yu, Hu Junjie, Cao Dezhi, Liao Jianxiang
Shenzhen Children's Hospital, China Medical University, Shenzhen, China.
Guangdong Women and Children Hospital, Guangzhou, China.
Front Neurosci. 2021 Dec 2;15:761473. doi: 10.3389/fnins.2021.761473. eCollection 2021.
We aimed to explore the associated clinical phenotype and the natural history of patients with gene variations during early childhood and to identify their genotype-phenotype correlations. This study used a cohort of 13 patients with epilepsy and developmental disorder due to mutations, namely, 7 patients from Shenzhen Children's Hospital between September 2014 and January 2020 and 6 patients from previously published studies. Their clinical data were studied. A total of 13 children with gene variants (eight boys and five girls) were identified. The age of disease onset was in infancy. Mutations were located between exons 8 and 15; most were frameshift or truncated mutations. Four mutation sites (c.924G > A, c.1532-2_1532del, c.1747_1755dup, and c.1735_1738del) had not been reported before. All patients had global developmental delay within the first year of life, and intellectual impairment became gradually apparent. Some of them developed behavioral problems. The developmental delay occurred before the onset of seizures. All seven patients in our cohort presented with epilepsy; myoclonic seizures, absence seizures, and epileptic spasms were the most common seizure types. Abnormal electroencephalograms were identified from five patients before the onset of their seizures. All patients suffered from drug-resistance seizures. However, comorbidities such as behavioral problems were less frequently observed. The most common age of disease onset in gene mutations is in infancy, while neurodevelopmental delay and epilepsy are the major phenotypes. They have a higher percentage of drug-resistant epilepsy and epileptic spasms than those in previous reports. We should give attention to the patients with abnormal EEGs without seizures and think about the suitable time of the anti-seizure medications for them. We have not found the genotype-phenotype correlation. Chinese Clinical Trial Registry, Registration number: ChiCTR2100049289 (https://www.chictr.org.cn/listbycreater.aspx).
我们旨在探讨幼儿期基因变异患者的相关临床表型和自然病史，并确定其基因型与表型的相关性。本研究使用了一组因基因突变导致癫痫和发育障碍的13例患者，其中7例来自2014年9月至2020年1月期间的深圳儿童医院，6例来自先前发表的研究。对他们的临床数据进行了研究。共鉴定出13例携带基因变异的儿童（8名男孩和5名女孩）。发病年龄在婴儿期。突变位于外显子8至15之间；大多数为移码或截短突变。四个突变位点（c.924G>A、c.1532-2_1532del、c.1747_1755dup和c.1735_1738del）此前未被报道过。所有患者在出生后第一年内均出现全面发育迟缓，智力障碍逐渐明显。其中一些患者出现行为问题。发育迟缓发生在癫痫发作之前。我们队列中的所有7例患者均患有癫痫；肌阵挛发作、失神发作和癫痫痉挛是最常见的发作类型。5例患者在癫痫发作前脑电图异常。所有患者均患有耐药性癫痫。然而，行为问题等合并症较少见。基因突变最常见的发病年龄在婴儿期，而神经发育迟缓与癫痫是主要表型。与先前报道相比，他们的耐药性癫痫和癫痫痉挛比例更高。我们应关注脑电图异常但无癫痫发作的患者，并考虑为他们使用抗癫痫药物的合适时机。我们尚未发现基因型与表型的相关性。中国临床试验注册中心，注册号：ChiCTR2100049289（https://www.chictr.org.cn/listbycreater.aspx）。
