儿童期发病的脊髓小脑性共济失调2型一家系及文献复习  

Childhood onset spinocerebellar ataxia type 2:a family report and literature review

作　　者：刘菁 梅道启 郭鹏波 肖梦君 谢振华 李娴 张强[1] 李东晓 Liu Jing;Mei Daoqi;Guo Pengbo;Xiao Mengjun;Xie Zhenhua;Li Xian;Zhang Qiang;Li Dongxiao(Henan Neurodevelopment Engineering Research Center for Children,Henan Key Laboratory of Children′s Genetics and Metabolic Diseases,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,China;Department of Neurology,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,China)

机构地区：[1]郑州大学附属儿童医院河南省儿童遗传代谢性疾病重点实验室河南省儿童神经发育工程研究中心,郑州450018 [2]郑州大学附属儿童医院神经内科,郑州450018

出　　处：《中华神经科杂志》2022年第5期490-496,共7页Chinese Journal of Neurology

基　　金：河南省自然科学基金(202300410415)。

摘　　要：目的探讨儿童期发病的脊髓小脑性共济失调2型(SCA2)患者的临床特点、遗传特征及诊断。方法收集郑州大学附属儿童医院神经遗传代谢病门诊2019年7月确诊的SCA2一家系临床资料,并结合已报道的儿童期发病的SCA2病例进行总结。采用聚合酶链反应、毛细管凝胶电泳以及Sanger测序技术对先证者及家系成员ATXN2基因CAG重复序列进行检测。结果该家系4代共9人患病,呈常染色体显性遗传。先证者为男性,3岁4个月,于9月龄发病,表现为发育落后,反应迟钝;1岁后出现进行性倒退,逐渐不能逗笑、不认人;不能独站、独走,无语言发育,吞咽困难,长期便秘,有抽搐史。先证者妹妹及母亲尚未发病;外祖母行走不能、口齿不清伴眼球震颤,头颅磁共振成像示小脑萎缩;外祖母的2位哥哥和2位姐姐均表现为行走不稳伴构音障碍;外祖母的父亲需借助轮椅行走。先证者、妹妹、母亲、外祖母的ATXN2异常等位基因CAG拷贝数分别为99、55、44次和43次,且均未检测出被打断的CAA序列。检索到的14篇文献(13篇英文和1篇中文)共报道20例经基因确诊的儿童期发病的SCA2患儿,绝大多数患者婴幼儿期起病、少数可至学龄期发病,临床表现以发育迟滞、肌张力障碍或不全、肌阵挛或婴儿痉挛、运动落后、眼动异常、色素性视网膜炎以及吞咽困难为主,而经典的小脑综合征仅部分存在;脑电图多数存在节律异常;头颅磁共振成像或CT主要表现为小脑萎缩。结论本病例是我国目前报道的发病年龄最小的SCA2患者。此类患者通常在婴幼儿期起病且ATXN2基因重复序列呈过度扩增状态,其临床特征不同于经典SCA2表型,需结合家族史并通过动态突变检测进行基因诊断。Objective To investigate the clinical characteristics,genetic characteristics and diagnosis of spinocerebellar ataxia type 2(SCA2)patients with childhood onset.Methods The clinical data of a SCA2 pedigree who diagnosed at Neurogenetic Metabolic Disease Clinic of Children′s Hospital Affiliated to Zhengzhou University in July 2019 were collected,and the reported cases of childhood-onset SCA2 were reviewed.The CAG repeat of ATXN2 gene was detected by polymerase chain reaction,capillary gel electrophoresis and Sanger sequencing techniques.Results A total of 9 people in 4 generations of the family were affected,showing an autosomal dominant inheritance.The proband was a 3 years and 4 months old boy,who showed abnormal symptoms at 9 months which manifested as developmental retardation.At 1 year old,he developed progressive regression which represented neither to be amused,recognize others,stand and walk alone,nor had language development.Meanwhile,he had difficulty swallowing,long-term constipation,and a history of convulsions.His sister and mother were not yet sick.His grandmother could not walk,had slurred speech accompanied by nystagmus,and magnetic resonance imaging showed cerebellar atrophy.His granduncles and grandaunts had unstable walking and dysarthria.His great-grandfather required wheelchair to walk.This pedigree showed an autosomal dominant inheritance.One of the ATXN2 gene alleles of the proband,his sister,mother and grandmother all showed abnormal amplification with 99,55,44,and 43 times respectively and no inserting CAA sequence.A total of 14 literatures reported 20 cases of childhood-onset SCA2 patients who were genetically diagnosed.The majorities had onset in infancy,and few can develop into school age.The main clinical manifestations were developmental delay,dystonia or insufficiency,myoclonus or infantile spasms,motor retardation,abnormal eye movement,retinitis pigmentosa and dysphagia,while the classic cerebellar syndrome was only partially present.Abnormal rhythm was found on electroencephalogra

关 键 词：脊髓小脑共济失调 儿童 三核苷酸重复扩增 系谱 ATXN2基因 

分 类 号：R744.8[医药卫生—神经病学与精神病学]