Department of Pediatric Neurology, Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
Ital J Pediatr. 2020 Feb 28;46(1):27. doi: 10.1186/s13052-020-0775-y.
CDKL5-related disorders (CDD) is an epileptic encephalopathy resulted of gene mutations of CDKL5. This study aimed to explore the development process of CDD and to expand its mutation spectrum.
Clinic datawas collected about three infantile epileptic encephalopathy cases diagnosed at Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine. Next generation sequencing technology was used to find three de novo mutations of CDKL5. We searched published literatures about CDKL5 in pubmed and made an analysis about our clinic data and the related literatures.
The three patients were all girls. Their average onset age of seizures was around 2 months, and all of them have intractable epileptic seizures, severe intellectual disability, and hypotension. Among them, two presented infantile spasm and high arrhythmia in EEG, and the other manifested clonic seizure and broad epileptiform discharge in EEG. Extracerebral space widening in cranial MRIs was demonstrated in two cases. Visual evoked potential was abnormal in two cases. Seizures were resistant to all kinds of antiepileptic drugs (AEDs). Gene tests showed three de novo mutations of CDKL5: one was a truncated mutation (c.2254A > T,P.R752X, stop279), which was pathogenic according to the ACMG guide, the other two were missense mutations (c.377G > T,p.Cys126Phe) and a frameshift mutation (c.362-362insG(p.Ala122GlyfsTer7), which were likely pathogenic according to the ACMG.
All three de novo mutations are first reported. Based on the combined related literature and the manifestations observed, we diagnosed the three children as CDKL5-related disorders, and concluded that the de novo CDKL5 mutations are the reason for their epilepsy.
CDKL5 相关疾病（CDD）是由 CDKL5 基因突变引起的癫痫性脑病。本研究旨在探讨 CDD 的发病过程并扩展其突变谱。
收集上海交通大学医学院附属新华医院诊断的三例婴儿癫痫性脑病病例的临床资料。采用下一代测序技术发现 CDKL5 的三个新生突变。我们在 pubmed 上搜索了已发表的关于 CDKL5 的文献，并对我们的临床数据和相关文献进行了分析。
这三个患者均为女孩，平均发病年龄在 2 个月左右，均有难治性癫痫发作，严重智力障碍，低血压。其中两例表现为婴儿痉挛症，脑电图高节律，另 1 例表现为阵挛性发作，脑电图广泛癫痫样放电。两例头颅 MRI 显示脑外间隙增宽。两例视觉诱发电位异常。癫痫发作对各种抗癫痫药物（AEDs）均耐药。基因检测显示 CDKL5 存在三个新生突变：一个为截断突变（c.2254A>T，p.R752X，stop279），根据 ACMG 指南判断为致病性突变，另两个为错义突变（c.377G>T，p.Cys126Phe）和一个移码突变（c.362-362insG[p.Ala122GlyfsTer7]），根据 ACMG 判断为可能致病性突变。
所有三个新生突变均为首次报道。根据综合相关文献和观察到的临床表现，我们诊断这三个孩子为 CDKL5 相关疾病，并且认为新生的 CDKL5 突变是他们癫痫的原因。
