Ⅵ型胶原蛋白相关肌病的临床特点与致病基因分析

Clinical manifestations and gene diagnosis of collagen type VI related myopathy

目的总结Ⅵ型胶原蛋白相关肌病的临床表现、辅助检查结果和基因诊断，更好地识别和诊断这类少见遗传性肌病。方法对7例基因确诊的家族型或散发型Ⅵ型胶原蛋白相关肌病患者进行回顾性临床研究，总结其症状体征、肌酶谱、肌电图、肌肉MRI、肌肉活体组织检查（简称活检）病理以及基因型与表现型相关性等方面特点。结果7例患者中以COL6A1、COL6A2、COL6A3为致病基因的分别为3例、1例和3例。2例为家族型，5例为散发型。下肢为重的肢体近端无力、关节挛缩为主要临床表现。血肌酸激酶轻微升高。肌电图提示轻度肌源性损害。大腿肌肉MRI示特征性分布肌群受累。肌肉活检病理可见肌营养不良样改变，多数肌纤维结构清楚，肌纤维问胶原结缔组织增牛。结论对于渐进性肌肉无力伴早发关节挛缩，肌酸激酶轻度升高，下肢肌肉MRI呈选择性受累的患者，应注意Ⅵ型胶原蛋白相关肌病可能。临床工作中注意识别Ⅵ型胶原蛋白相关肌病临床特点，对疑诊患者进行高通量测序基因诊断，有助于提高诊断率。

Objective To summarize the clinical presentations, the findings of lab tests and procedures and the genetic investigation of collagen type VI related myopathy, and to help clinicians recognize and diagnose this rare disease. Methods Seven familiar or spontaneous collagen type VI related myopathy patients diagnosed by gene detection were analyzed. We emphasized on the features of clinical manifestations, serum creatine kinase level, eleetromyography, lower-limb muscle MRI, muscle biopsy and correlation between genotype and phenotype. Results Among 7 patients, 3 were caused by COL6AI mutation, 1 was caused by COL6A2 mutation and 3 were caused by COL6A3 mutation. Two patients were familiar while 5 were spontaneous. Highlighted clinical presentations were proximal weakness in lower limbs and joint contrature. Serum creatine kinase level was slightly elevated. Electromyography showed slight myogenic damage. Muscle MRI of thigh showed distinct pattern of muscle involvement. Muscle pathology revealed dystrophic myogenic changes with proliferation of connective tissue between muscle fibers. Conclusions Neurologists should recognize the features of collagen type gl related myopathy, such as progressive weakness, early-onset joint contractures, slightly elevated serum creatine kinase and selective muscle involvement on leg MRI scan, and then perform next-generation sequencing based genetic test on suspected patients. This approach would improve the diagnostic rate of the disease.