3例先天性肌强直的临床特点和基因分析

Clinical and genetic features of three Chinese patients with myotonia congenita

目的探讨3例先天性肌强直(myotonia congenita,MC)患者的临床特点和基因突变情况。方法回顾性分析河南省人民医院神经内科2016年1月至2018年11月收治的无亲缘关系的3例MC患者的临床和病理资料,并进行基因检测。结果3例患者均幼年或少年早期起病,其中例1和例2的首发症状均为下肢肌强直、之后波及或不波及上肢、均出现于运动起始时,例3的首发症状为上肢强直,之后波及口轮匝肌、眼肌及下肢肌,除运动起始时出现强直外、久跑时也出现强直;3例患者症状均于反复活动后缓解,其中2例于寒冷时加重、另1例于劳累或紧张时加重。3例患者的CK均正常,肌电图均显示有强直电位,其中2例查下肢肌肉核磁无异常、另1例未查肌肉核磁。3例患者中2例的肌肉病理示轻微肌源性病理改变,另1例病理无异常。基因检测示3例患者均发现氯离子通道蛋白-1(chloride channel 1,CLCN1)基因突变,例1为p.W303R单杂合突变,例2为p.C254W单杂合突变,例3为p.R626*和p.M470V复合杂合突变。结论运动起始时出现肌强直、反复活动后缓解为MC的特征性临床表现。p.C254W和p.M470V为我们新发现的错义突变。

Objective To investigate the clinical,pathological features and gene mutation of three Chinese patients with myotonia congenita(MC).Methods The clinical,muscle pathology and molecular information of 3 unrelated Chinese patients with MC were analyzed retrospectively from January 2016 to November 2018 at Department of Neurology,Henan Provincial People’s Hospital,1 of which had a family history.Results Onset of the disease of the 3 patients with MC started at infancy or early adolescence.Among the 3 patients,patient 1 and patient 2 had the first symptom of lower limb stiffness,later the upper limbs were or were not involved as the disease progresses,which appears upon initiating movement,and patient 3 had the first symptom of upper limb stiffness,later the orbicularis oris,eyelid muscles and lower limbs were also involveded as the disease progresses,which appears upon initiating movement and long time running.The symtoms of the 3 patients all improved after repetitive muscle contractions.The symptoms of patient 2 and patient 3 tended to aggravate during cold weather,patient 1 tended to aggravate when she was tired or stressed.Electromyography in the 3 patients all showed myotonia discharges.Muscle pathlogy of the 3 patients showed mild myopathic changes or normal.Genetic testing revealed that patient 1 had a heterozygous p.W303R mutation in the chloride channel 1(CLCN1)gene,patient 2 had a heterozygous p.C254W mutation in the CLCN1 gene,and patient 3 had the compound heterozygous mutations of p.R626*mutation and p.M470V mutation in the CLCN1 gene.Conclusions Muscle stiffness at motor initiation and improved with several repetitions of the same movement are the classic characteristics of MC.The p.C254W and p.M470V mutations may be two new missense mutations in the CLCN1 gene.