目的 分析智力障碍共患癫痫(ID-E)儿童的临床特征及基因组拷贝数变异(CNVs)情况,为ID-E的临床治疗提供参考依据。方法 选取2013年1月—2017年1月唐山市妇幼保健院收治的60例ID-E患儿为研究对象,收集患儿的一般临床资料,采集患儿及其父母外周血进行全外显子CNVs检测,并对数据进行分析。结果 ID-E患儿中男性较多(61.67%),年龄主要集中在1~3岁(31.67%),大多数患儿BMI正常或偏高(93.33%)、出生体重正常(86.67%)、顺产(90.00%),大多数呈重度ID受损(83.33%)、临床表型以生长发育迟缓(76.67%)和语言表达障碍(68.33%)为主;治疗药物主要为丙戊酸钠,31例(51.67%)患儿双联治疗,预后良好率为46.67%;60例ID-E患儿中检出6例(10.00%)异常CNVs,其中2例诊断为已知综合征(Wolf-Hirschhorn综合征、Smith-Magenis综合征),2例诊断为致病性CNVs,1例为可疑CNVs,1例为临床意义不明CNVs;父母起源分析,仅有1例临床意义不明的患儿为母源性,其他均为新发性改变。结论 ID-E患儿具有一定临床特点,CNVs可作为ID-E遗传病学病因分析的重要检测手段,帮助明确ID-E病因,指导疾病诊治。
Abstract
Objective To analyze the clinical features and copy number variants (CNVs) of intellectual disabilities-epilepsy (ID-E), so as to provide basis for clinical treatment of the disease. Methods From January 2013 to January 2017, 60 children with ID-E admitted to Tangshan Maternal and Child Health Hospital were enrolled in the study, and their general clinical data were collected. Meanwhile, peripheral blood samples were collected from the children and their parents for whole exome CNVs testing, and the data were analyzed. Results Children with ID-E included in this study were mainly male (61.67%), aged 1 to 3 years (31.67%), with normal or slightly higher BMI (93.33%), with normal birth weight (86.67%), born naturally (90.00%). Moreover, most children with ID-E in this study were with severe ID impairment (83.33%), mainly characterized by growth retardation (76.67%) and expressive language disorder (68.33%).Therapeutic agents mainly included sodium valproate, and 31 children (51.67%) received dual therapy. The rate of better prognosis was 46.67%. Six (10.00%) of the 60 children with ID-E were detected with abnormal CNVs, including 2 cases diagnosed with known syndrome (Wolf-Hirschhorn syndrome, Smith-Magenis syndrome), 2 cases with pathogenic CNVs, 1 with CNVs, and 1 with clinically unknown CNVs. Parental origin analysis showed that the cause of clinically unknown CNVs was maternal, and the others were new mutations. Conclusions Children with ID-E have certain clinical characteristics. CNVs can be used as an important detection method for genetic epidemiological analysis of etiological factors of ID-E, which can help to clarify the cause of ID-E and guide the diagnosis and treatment.
关键词
智力障碍 /
癫痫 /
基因组拷贝数变异 /
遗传病学
Key words
intellectual disabilities /
epilepsy /
genomic copy number variants /
genetic epidemiology
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基金
河北省医学科学研究课题计划(20181321)
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