脊髓小脑共济失调3型临床特征及遗传学分析

Clinical Features and Genetic Analysis of Spinocerebellar Ataxia Type 3

目的探讨遗传性脊髓小脑共济失调3型(SCA3)的临床及遗传学特征,为临床诊断提供依据。方法回顾性分析2016年1月至2021年9月郑州大学第一附属医院收治的36例SCA3患者,分析其临床资料及基因检测结果,应用聚合酶链反应(PCR)技术对就诊于神经内科的1例典型家系进行SCA3动态突变基因检测,并进行遗传学分析。结果36例患者病程1~20 a,平均8(4,9)a,发病年龄(39.72±11.00)岁,异常基因CAG重复次数55~79(64.86±5.09)次,CAG重复长度与发病年龄呈负相关(r=-0.762,P<0.001),与病程呈正相关(r=0.331,P=0.049)。30例(83.3%)以步态不稳为首发症状,主要临床表现为进行性小脑性共济失调,可伴有构音障碍、锥体束征、眼球震颤、锥体外系表现、焦虑抑郁等。典型家系的5代20人中14例发病,其中12例临床诊断为SCA3;6例进行了基因检测,其中5例SCA3基因CAG重复次数异常(>60次),1例基因结果正常。先证者以双下肢无力伴震颤起病,该家系具有明显的遗传早现现象。结论SCA3临床异质性显著,主要表现为进行性小脑性共济失调,该病发病年龄早,CAG重复长度与其临床特征相关。临床上应特别注意识别非典型症状起病的患者。头MRI、神经系统查体等可以协助诊断,基因检测是确诊的金标准。

Objective To investigate the clinical and genetic features of hereditary spinocerebellar ataxia type 3(SCA3),and to provide evidence for clinical diagnosis.Methods A total of 36 patients with SCA3 who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2016 to September 2021 were retrospective analysed,and summarized the clinical data and genetic test results.In addition,the SCA3 dynamic mutation gene was detected by polymerase chain reaction(PCR)in a typical family in the Department of Neurology,and the genetic analysis of this family was performed.Results The disease course of 36 SCA3 patients were ranged from 1 to 20 years,with an average of 8(4,9)years,and the average age of onset was(39.72±11.00)years.The number of CAG repeats of abnormal genes ranged from 55-79(64.86±5.09)times,and CAG repeat length was negatively correlated with the age of onset(r=-0.762,P<0.001),but positively correlated with the course of disease(r=0.331,P=0.049).In 30 cases(83.3%),walking instability was the first symptom,and the main clinical manifestations were progressive cerebellar ataxia,accompanied by dysarrhythmia,pyramidal tract sign,nystagmus,extrapyramidal manifestations,anxiety and depression.There were 14 cases in 20 people of 5 generations in typical families developed symptoms,and 12 cases of which were clinically diagnosed as SCA3.There were 6 cases underwent genetic testing,among which 5 cases with abnormal CAG repeats of SCA3 gene,while 1 case had normal gene results.The proband began with weakness of the lower limbs and tremor,this family showed the phenomenon of genetic anticipation.Conclusion SCA3 has significant clinical heterogeneity,mainly manifested as progressive cerebellar ataxia.The onset age of the disease is early,and CAG repeat length is related to clinical features.Special attention should be paid to the identification of patients with atypical onset symptoms.Brain MRI and nervous system physical examination can assist in diagnosis,but genetic testing is the gold standard for diagnosis.