婴儿致死性僵直性肌原纤维肌病的临床、骨骼肌病理和遗传学特征  

Clinical,skeletal muscle pathological and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy

作　　者：麦嘉卉 路新国[1] 马伟科[2] 武宇辉[2] 陈伟燕[1] 廖建湘[1] 江贤萍[3] 宋建明[3] 韩春锡[1] Mai Jiahui;Lu Xinguo;Ma Weike;Wu Yuhui;Chen Weiyan;Liao Jianxiang;Jiang Xianping;Song Jianming;Han Chunxi(Department of Neurology,Shenzhen Children′s Hospital,Shenzhen 518038,China;Intensive Care Unit,Shenzhen Children′s Hospital,Shenzhen 518038,China;Department of Pathology,Shenzhen Children′s Hospital,Shenzhen 518038,China)

机构地区：[1]深圳市儿童医院神经内科,深圳518038 [2]深圳市儿童医院重症医学科,深圳518038 [3]深圳市儿童医院病理科,深圳518038

出　　处：《中华实用儿科临床杂志》2022年第15期1156-1160,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：广东省高水平临床重点专科(深圳市配套建设经费)(SZGSP012);深圳市医学重点学科建设经费(SZXK033);深圳市医疗卫生三名工程(SZSM201812005);深港脑科学创新研究院开放课题(NYKFKT20190014);深圳市儿童医院院级课题(ynkt2020-zz20)。

摘　　要：目的探讨婴儿致死性僵直性肌原纤维肌病的临床、骨骼肌病理和遗传学特征。方法回顾性分析2017年2月至2021年4月深圳市儿童医院诊治的10例确诊为婴儿致死性僵直性肌原纤维肌病患儿的临床表现、实验室检查和基因检测结果。对其中3例患儿实施头颅、骨骼肌磁共振成像(MRI)、肌电图检查,2例实施肌肉活检。结果患儿分布为东北和华东地区各1例,华南地区8例。10例患儿中,男8例,女2例。患儿之间无血缘关系,出生时均正常。患儿发病年龄为2~12个月。10例患儿主要临床表现为进行性腹直肌(8例)、颈部肌(7例)、后背肌(2例)和肋间肌(1例)僵硬,导致呼吸衰竭。血清肌酸激酶轻度至中度升高(436~5 804 IU/L)(参考范围:24~229 IU/L)。肌电图示复合重复放电,未见肌强直电位发放。股外侧肌和腹直肌活检示肌纤维变性、坏死和空泡变性,未见明显炎症细胞浸润。改良格莫瑞染色部分视野可见红色颗粒状异常沉积物。骨骼肌免疫组织化学染色可见desmin蛋白大量沉积。电镜下可见肌纤维的肌节结构严重紊乱,Z盘破坏及颗粒状沉积物。10例患儿全外显子基因测序均表现为分别来自于父母的CRYAB基因的c.3G>A,p.Met1?纯合变异,父母均为杂合变异。结论腹直肌僵硬等中轴肌受累是婴儿致死性僵直性肌原纤维肌病的临床特征。CRYAB基因c.3G>A,p.Met1?变异是中国患儿的热点突变。Objective To investigate the clinical,skeletal muscle pathological,and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy(FIHMM).Methods The clinical manifestations,laboratory assessments data and gene sequencing results of 10 patients diagnosed with FIHMM in Shenzhen Children′s Hospital from February 2017 to April 2021 were retrospectively analyzed.Magnetic resonance imaging(MRI)of both musculoskeletal system and the brain,and electromyogram(EMG)were performed in 3 cases,while muscle biopsy was performed in 2 cases.Results Among these 10 cases,1 case was from Northeast China and 1 case from East China,while the rest 8 cases were from South China.Eight of the 10 patients were male,and the other 2 cases were female.They were all born normal and not related to each other.The age of onset varied from 2 to 12 months.The main clinical manifestations for all the patients were progressive rigidity of the rectus abdominis(8 cases),neck muscles(7 cases),rectus abdominis(2 cases)and intercostal muscles(1 case),resulting in respiratory failure.Mildly to moderately elevated serum creatine kinase level was detected(436-5804 IU/L)(reference range:24-229 IU/L).Complex repetitive discharges can be seen in the EMG,without any myotonic potential.Muscle fiber degeneration,necrosis,and vacuolar degeneration were noted in the histopathological examination of the vastus lateralis and rectus abdominis.An abnormal red granular deposit was observed in a portion of the field of the modified Gomory Trichrome staining.Immunohistochemistry showed substantial deposition of desmin.Under the electron microscopy,the sarcomere structure of the muscle fibers was seriously disordered,with the destruction of Z-bands and the presence of granular deposits.The whole-exome sequencing identified the same homozygous variation c.3G>A,p.Met1?of CRYAB gene in all the patients,but heterozygous variation in their parents.Conclusions Axial muscles involvement,such as rectus abdominis rigidity,is the main clinical characteristic of FIH

关 键 词：婴儿致死性僵直性肌原纤维肌病 肌肉僵直 呼吸衰竭 CRYAB基因 

分 类 号：R746[医药卫生—神经病学与精神病学]