伴有震颤的先天性肌病的临床、肌肉病理和基因突变特点  

Clinical,muscle pathology and gene mutation characteristics of congenital myopathy with tremor

作　　者：赵影 焉传祝[1] 纪坤乾 Zhao Ying;Yan Chuanzhu;Ji Kunqian(Department of Neurology,Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]山东大学齐鲁医院神经内科,济南250012

出　　处：《中华神经科杂志》2024年第5期451-459,共9页Chinese Journal of Neurology

基　　金：国家自然科学基金(82171394)。

摘　　要：目的总结并探讨伴有震颤的先天性肌病的临床表现、肌肉病理和基因突变特点,以提高临床医师对该病的认识。方法报道2021年4月于山东大学齐鲁医院就诊的1例伴有震颤的先天性肌病患者的临床资料,对患者的肌肉组织进行酶组织化学染色及免疫组织化学染色,通过蛋白质印迹法及实时荧光定量聚合酶链反应对患者肌肉慢肌型肌球蛋白结合蛋白-C(sMyBP-C)的表达水平及线粒体拷贝数进行检测。同时对既往报道的伴有震颤的先天性肌病的相关文献进行复习,并对报道的病例进行总结。结果先证者为35岁男性,幼年起病,主要表现为震颤及运动不耐受,伴轻度四肢近端肌无力,肌肉活组织检查(活检)示轻度肌源性损害伴线粒体异常改变,基因检测发现MYBPC1基因c.788T>G杂合突变,进一步检测发现患者sMyBP-C表达水平明显降低,线粒体拷贝数增多。患者伴有震颤的先天性肌病诊断明确,长期随访症状无进展。对本家系以及既往报道的10个家系共26例患者的临床特点进行总结发现:震颤为该疾病的突出临床表现,合并轻到中度的肌无力,可有不同程度的肌张力降低、粗大运动发育迟缓和骨骼关节畸形,症状多无进展或慢性进展。肌肉活检多表现为肌源性损害,包括Ⅰ型纤维优势、Ⅰ型纤维萎缩和Ⅰ型纤维轴空样改变,可伴有轻度线粒体异常。MYBPC1基因c.788T>G突变为该病的热点突变。结论对于早发的不明原因的震颤合并肌无力、肌张力减低、粗大运动发育迟缓、骨骼关节畸形等,需考虑伴有震颤的先天性肌病可能,并完善肌电图、肌肉活检及基因检测以明确诊断。肌肉活检多表现为肌源性损害,MYBPC1基因c.788T>G突变为该病的热点突变。Objective To summarize and discuss the clinical manifestations,muscle pathology and gene mutation characteristics of congenital myopathy with tremor and to improve clinicians′understanding of the disease.Methods The clinical data of a patient of congenital myopathy with tremor who visited Qilu Hospital of Shandong University in April 2021 were reported.Enzyme histochemical staining and immunohistochemical staining were performed on the muscle tissues of the patient,and the expression level of slow skeletal myosin binding protein-C(sMyBP-C)and mitochondrial DNA copy numbers were detected by Western blotting and quantitative real-time polymerase chain reaction.The literatures of congenital myopathy with tremor reported previously were reviewed and patients reported were summarized.Results The proband is a 35 years old male,whose clinical symptoms occurred from childhood,mainly manifested as irregular muscle vibration of the limbs and exercise intolerance,with mild proximal limb muscle weakness.Muscle biopsy showed mild myogenic damage with abnormal mitochondrial changes,and gene detection showed MYBPC1 gene c.788T>G heterozygous mutation.Further detection showed that the expression level of sMyBP-C was significantly reduced,and the number of mitochondrial DNA copies was increased in the patient.The diagnosis of congenital myopathy with tremor was clear,and the symptoms did not progress during long-term follow-up.The clinical characteristics of 26 patients from this family and 10 families previously reported were summarized,and the results indicated that tremor was a prominent clinical manifestation of this disease,combined with mild to moderate muscle weakness,which could be accompanied with varying degrees of myasthenia,delayed gross motor development and skeletal joint malformation.The symptoms usually had no progress or chronic progress.Muscle biopsy usually indicated myogenic damage,including typeⅠfiber predominancy,typeⅠfiber atrophy and central cores in typeⅠfibers,which may be accompanied by mild mit

关 键 词：震颤 肌病 肌球蛋白结合蛋白-C 活组织检查 

分 类 号：R746[医药卫生—神经病学与精神病学]