Clinical Features And Etiological Analysis Of Cerebellar Ataxia In Children (with A Report Of Four Cases Of Ataxia Telangiectasia In Children)

Part Ⅰ CLINICAL FEATURES AND ETIOLOGICAL ANALYSIS OF CEREBELLAR ATAXIA IN CHILDRENObjective: To summarize the clinical characteristics of children with cerebellar ataxia and analyze their etiological composition in order to guide the clinic and improve the prognosis.Methods: This study retrospectively reviewed the clinical data of children who were hospitalized in Children’s Hospital of Chongqing Medical University from January 2017 to June 2020,with "ataxia" as the main manifestation,and summarize the clinical characteristics and etiological composition of the children;according to age divided into infant group,toddler group,preschool children group,school-age children group and adolescent children group,analyze the clinical manifestations and auxiliary examination characteristics of children in five groups;then according to the course of the disease children are divided into acute group（course of disease<2 weeks）,subacute group（2 weeks≤course of disease<2 months）,and chronic group（disease course≥2 months）.The differences in indicators between the three groups are compared to analyze the difficulties in the diagnosis and therapy process.Results:（1）A total of 127 children with cerebellar ataxia were enrolled in this study,67 males and 60 females.The mean age of onset was 5.33±3.52years（age range from 6 months 10 days to 13 years）.（2）The most common causes were infection factors（46/127,36.2%）,genetic factors（25/127,19.7%）,immune factors（18/127,14.2%）.The top three diseases were postinfection cerebellar ataxia（58/127,45.67%）,GBS spectrum disease（9/127,7.09%）and cerebellar tumor（8/127,6.29%）.Among the infectious factors that induced the disease,the upper respiratory tract infection（33/127,25.98%）was the most common,followed by gastrointestinal infection（9/127,7.09%）.Epstein-Barr virus（11/127,8.67%）,Coxsackie virus（9/127,7.09%）and herpes simplex virus（7/127,5.51%）were the most common pathogens.（3）The most common first symptom of children with ataxia was unsteady walking,accounting for 49.60%,followed by vomiting（11.81%）and weakness of limbs（10.24%）.Unsteady walking,dysarthria,and limb tremor were the most important neurological symptoms,accounting for97.64%（124/127 cases）,47.24%（60/127 cases）and 35.43%（45/127 cases）of the entire group of cases respectively.（4）Among the 127 children,115 cases completed head MRI,47 cases（37.01%）showed abnormalities,cerebellar atrophy（9 cases,7.08%）and space-occupying lesions（8 cases,6.29%）were the most common.There were 70 cases（55.1%）completed EEG examination,finding 27 cases（38.57%）were abnormal,of which 14cases（11.02%）were background activity/rhythm abnormalities.（5）According to the age of the children,ataxia is most common in toddlers,and the top three causes of different ages are different.（6）According to the course of disease,the acute group was the most common（68 cases,53.5%）,followed by the chronic group（36 cases,28.3%）,and the subacute group（23cases,18.1%）.The history of infection（P=0.045）,whether there was motor development retardation（P<0.001）,and whether there was abnormal head MRI（P=0.001）had statistically different.Conclusion: Cerebellar ataxia was the most common in the toddler group,and the ratio of male to female is similar.Infection,genetic and immune factors were the most common causes;post-infection cerebellar ataxia,GBS spectrum diseases and cerebellar tumors were the most common diseases.The most common manifestations of the nervous system are instability of walking,dysarthria and tremor of the limbs.Acute ataxia is often accompanied by a history of pro-infection;chronic ataxia is common with delayed motor development or abnormal head MRI.;Part Ⅱ CLINICAL FEATURES AND GENETIC ANALYSIS OF FOUR CHILDREN WITH ATAXIA TELANGIECTASIAObjective: To discuss the clinical and molecular genetic characteristics of children with ataxia telangiectasia（AT）.Methods: The clinical data and genetic results of 4 unrelated AT patients were retrospectively analyzed,and the relevant literature was reviewed.Results: All 4 patients had progressive cerebellar ataxia and dysarthria,and 3 patients had bulbar conjunctival telangiectasia and cerebellar atrophy,and 2 patients had repeated respiratory infections.Seven mutation sites were identified in these 4 children by high-throughput sequencing,including c.974₉75del,c.7878₇882del,c.1899-1G>A,c.5706_c.5707 ins A,c.6679C>T,c.6115G>A,lossl（exon62-63）.Among them,c.974₉75del、c.5706_c.5707 ins A 、 lossl（exon62-63）were reported for the first time.Protein structure was predicted to be potentially harmful,and ACMG rates them as pathogenic or possibly pathogenic.Conclusion: The children who with clinical manifestations of cerebellar ataxia,dysarthria,telangiectasia,easy to suffer repeated respiratory infections,and cerebellar atrophy should be considered AT,and ATM gene screening is recommended to diagnose early intervention as early as possible to avoid repeated respiratory infections and ionizing radiation exposure.