CDKL5综合征7例病例报告

摘要

目的 总结CDKL5综合征的临床表现和遗传学特点.方法 运用二代测序技术对2011至2017年中南大学湘雅医院诊断的7例不明原因早发型癫脑病患儿进行检测,结合其临床表现及相关文献,分析CDKL5综合征患儿临床及遗传学特征.结果 7例CDKL5综合征患儿中男2例,女5例.4例曾被诊断为"婴儿痉挛",3例被诊断为"无法分类的癫脑病";起病中位年龄2月龄,病初部分性发作或强直发作,后转变为痉挛及肌阵挛发作.5例脑电图可见高度失律.7例先证者二代测序检测到CDKL5基因3个错义突变[c.464G>A(p.G134P)、c.58G>C(p.G20R)、c.464G>A(p.G155D)],2个小片段缺失[c.1110del C(p.E370fs)、c.160-163del(p.K54fs)],1个碱基重复[c.278dupA(p.E93fs)],1个大片段重复缺失(3～8号外显子杂合缺失).父母外周血基因检测均未发现相同突变,均为新发突变.中位随访时间为36个月,发作均未完全控制.使用抗癫药物1～8种;4例行促肾上腺皮质激素(ACTH)治疗效果不佳;5例行生酮饮食,其中2例部分有效但症状不能完全控制.7例患儿的精神、运动和语言发育明显落后于正常儿童.结论 CDKL5综合征是由CDKL5基因突变引起一系列中枢神经系统综合征,不同突变位点可能有不同表型,不同表型预后存在差异.%Objective To explore the clinical and genetic features of CDKL5 disorder. Methods Using the next genomic sequencing technology to detect 7 cases of unexplained early infantile epileptic encephalopathy diagnosed by Xiangya Hospital of Central South University from the year 2011 to 2017, the clinical and molecular features of 7 cases with CDKL5 mutations were summarized ,and the related literatures were reviewed. ResuIts Five females and two males were diagnosed as CDKL5 disorder. Before the genetic tests,four patients were diagnosed as west syndrome and the other three patients were diagnosed as unclassified early onset epilepsy encephalopathy. The median age of seizure onset was 2 months,and the epilepsy started with partial seizure or tonic seizure,then turned into spasm or myoclonus. The EEG findings in five patients indicated hypsarrhythmia. Seven mutations of CDKL5 were found in seven patients,including three missenses mutations(c.464G>A / p.G134P、c.58G>C / p.G20R、c.464G>A /p.G155D),four frameshift mutations(c.1110del C / p.E370fs、c.160-163del / p.K54fs,c.278dupA / p.E93fs,heterozygous large deletion of the exon 3-8).All the mutations were not found in the parents.The median follow-up time was 36 months,the epileptic seizure of all patients could not be controlled.The number of antiepileptic drugs used ranged from 1 to 8.Four cases underwent the ACTH therapy but didn't get remarkable progress, five cases received ketogenic diet and only two of them achieved a little.All the patients had psychomotor develpoment retardation. ConcIusion CDKL5 disorder is a newly defined central nervous system syndrome caused by CDKL5 mutation,patients with different mutations have different phenotypes and prognosis.