早发型面肩肱型肌营养不良1型三例临床和遗传学研究  

Clinical phenotype and genotype of early-onset facioscapulohumeral muscular dystrophy type 1

作　　者：陈晓瑜 常杏芝[1] 傅晓娜[1] 葛琳[1] 范燕彬 刘洁玉[1] 王志强[2] 张巍 熊晖[1] Chen Xiaoyu;Chang Xingzhi;Fu Xiaona;Ge Lin;Fan Yanbin;Liu Jieyu;Wang Zhiqiang;Zhang Wei;Xiong Hui(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Department of Neurology and Institute of Neurology,First Affiliated Hospital,Fujian Medical University,Fuzhou 350005,China;Department of Human and Molecular Genetics,Baylor College of Medicine,Houston 75800,USA)

机构地区：[1]北京大学第一医院儿科,100034 [2]福建医科大学附属第一医院神经内科福建省神经病学研究所,福州350005 [3]美国休斯顿贝勒医学院人类和分子遗传学系,75800

出　　处：《中华儿科杂志》2020年第5期408-412,共5页Chinese Journal of Pediatrics

基　　金：国家重点研发计划(2016YFC0901505)国家自然科学基金(81571220);。

摘　　要：目的:探讨早发型面肩肱型肌营养不良1型(FSHD1)的临床、病理及遗传学特征。方法:2012年6月至2018年6月在北京大学第一医院儿科门诊收集经分子遗传学检测确诊为早发型FSHD1的3例患儿,回顾性分析其临床资料,总结基因型、表型和肌活检病理特征。结果:3例患儿均为男性,分别为14岁、11岁、9岁11月龄,起病年龄均在婴幼儿期,起病后4~10年确诊,分子遗传学检测发现位于4qA的D4Z4重复单元数分别为2、3、4,符合早发型FSHD1的诊断,其共同临床表现为进行性、不对称性面部、肩胛带和下肢近端肌群无力,均有不同程度的脊柱畸形及高频为主的感音神经性听力损失,但D4Z4重复单元数为4的患儿临床表型最为严重。结论:早发型FSHD1起病隐匿,确诊困难精确诊断依赖分子遗传学检测,本组3例患儿的基因型与表型未发现明确关联,有待积累更多病例进一步分析,为疾病的基因型-表型关系和预后评估提供更为可靠的依据。Objective To explore the clinical,pathological and genetic characteristics of early-onset facioscapulohumeral muscular dystrophy type 1(FSHD1),in order to increase awareness of the disease.Methods In this retrospective study,the history of 3 patients,who were diagnosed with early-onset FSHD1 by molecular genetic test in Pediatric Outpatient Department of Peking University First Hospital from 4th June 2012 to 4th June 2018,were collected.Their clinical data,genotypes,phenotypes and pathological features of muscle biopsy were analyzed.Results All the three patients were males at the age of 14 years,11 years and 9 years 11 months,respectively,whose onset age was between infancy and early childhood and they got confirmed diagnosis within 4 to 10 years after the onset of illness.Their molecular genetic testing indicated that the number of D4Z4 repeat arrays located in 4qA were 2,3 and 4,which was consistent with the characteristics of early-onset FSHD1.Their common clinical manifestations were facial,scapular and proximal lower limb muscle progressively and asymmetrically weakness.All patients had different severity of spine deformity and high-frequency dominant sensorineural hearing loss,however,the phenotype of the third patient with 4 D4Z4 repeats was significantly the most severe.Conclusions Early-onset FSHD1 usually concealed onset and is difficult to diagnose.Its precise diagnosis depends on molecular genetic techniques,but the genotypes of 3 patients here are not corresponding to phenotypes strictly and it is necessary to accumulate more cases for further analysis in order to provide a more reliable basis for the relationship of genotype-phenotype and prognosis evaluation of the disease.

关 键 词：肌营养不良 面肩肱型 分子诊断技术 基因型 表型 

分 类 号：R74[医药卫生—神经病学与精神病学]