先天性副肌强直R1448C家系的临床、电生理及骨骼肌影像研究

Clinical and genetic study of a Chinese family with paramyotonia congenital

目的:研究1个中国先天性副肌强直(paramyotonia congenita,PC)家系的临床、电生理及影像学特征,为该病的诊治提供依据。方法:收集1个PC家系(包括4代共6例患者)临床资料,对先证者进行肌电图(针极肌电图、短时间运动试验、长时间运动试验和肌肉降温试验)及双下肢磁共振检查,对该家系部分患者行候选基因SCN4A全部24个外显子测序,明确是否存在责任突变。结果:该家系患者均自幼出现遇冷后面部及肢体发僵、无力,温暖及轻度活动后可缓慢缓解,部分患者剧烈运动、疲劳及饥饿亦可诱发肌无力发作。先证者肌电图可见肌强直样放电,短时间运动试验正常,长时间运动试验及肌肉降温试验均有CMAP振幅显著下降;双下肢磁共振检查示T2WI抑脂相散在高异常信号。该家系3例患者(Ⅲ3、Ⅲ5、Ⅳ1)的SCN4A基因第24外显子上均存在c.4343 c>t杂合突变,该突变导致氨基酸序列R1448C改变。结论:中国PC家系中存在R1448C突变,其临床特点、肌电图及影像学检查有助于疾病诊断。

Objective To investigate the characteristics of the clinic, electrophysiology and skeletal muscle imageology in a paramyotonia congenita （PC） family, and to provide more evidence for diagnosis of PC. Methods Clinical features of a PC family （including six patients in four generations） were collected. The EMG （electromyogram, short time exercise test, prolonged exercise test and muscle cooling test） and lower limbs MR imaging were performed on the proband. We detected 24 exons of candidate SCN4A gene of the proband by polymerase chain reaction and DNA sequencing to discover disease-related mutations. Results All patients from the PC family showed facial and limb muscle stiffness or muscle weakness provoked by cold exposure since childhood, which could be relieved slowly by warm or mild exercise. The symptoms usually lasted some hours to days. Muscle weakness could also be induced by strenuous exercise, fatigue or huger in part of the patients. When it became severe, patients were even forbidden in bed. Electromyogram assay showed that spontaneous electrical myotonia in the proband. Short time exercise test was normal, while remarkable reduction in compound muscle action potential （CMAP） amplitude was observed in prolonged exercise test as well as in muscle cooling test. Result of lower limbs MRI of the proband showed that there was abnormal signal in parts of skeletal muscles, especially in right soleus. A heterozygous point mutation c.4343 （c〉t） leading to R1448C was found in exon 24 of SCN4A gene of all the tested patients. Conclusions R1448C mutation exists in Chinese paramyotonia congenita family. The clinical features, EMG and skeletal muscle MR imaging assays contributes to the diagnosis of paramyotonia congenita.