CHRND基因突变所致慢通道先天性肌无力综合征一家系

A family of slow channel congenital myasthenic syndrome caused by CHRND gene mutation

目的分析CHRND基因突变所致慢通道先天性肌无力综合征家系的临床、电生理、肌肉病理和基因特点。方法先证者为19岁男性,儿童期出现眼睑下垂、运动易疲劳与四肢乏力,病情缓慢进展。其母亲、两个舅舅及其中一个舅舅的儿子有类似表现。对先证者进行血液学相关检测、电生理检查、肌肉病理和基因检测,并对父母、有症状的舅舅及舅舅的儿子进行家系验证。结果先证者重复神经电刺激检查可见低频递减现象。针极肌电图提示轻度肌源性损害。肌肉病理活检未见明确肌源性损害病理改变。基因检测发现CHRND基因c.826G>A突变,突变来源于母亲,有症状的舅舅及舅舅的儿子均有相同位点突变,该突变位点未经报告。予氟西汀治疗后肌无力症状较前好转。结论CHRND基因突变导致的慢通道先天性肌无力综合征可表现为早期出现的肌无力及运动不耐受,重复神经电刺激可见低频递减,有助于识别,诊断需通过基因检测。氟西汀可为首选治疗药物。

Objective To analyze the clinical,electrophysiological,muscular pathology and genetic characteristics of slow channel congenital myasthenic syndrome caused by CHRND gene mutation.Methods The proband was a 19 years old boy,presenting slow progression of muscle symptoms including ptosis,weakness of limbs and exercise intolerance since childhood.His mother,two uncles and one uncle’s son had similar symptoms.The proband underwent blood tests,electrophysiological studies,muscle biopsy and next generation sequencing.The genetic pedigree validation was conducted.Results The electrophysiological studies showed that the repeated compound muscle action potential in response to single nerve stimulus,decremental response to 2,3,5 Hz repetitive nerve stimulation.Electromyography(EMG)showed slight myogenic changes.The muscle biopsy was normal.DNA analysis revealed a compound heterozygous mutations,c.826 G>A,in CHRND gene.The pedigree tests validated the mutations were inherited from mother.His uncle and uncle’s son had the same mutation.Symptoms relieved after fluoxetine treatment.Conclusions Myasthenic syndrome caused by CHRND gene mutation can be manifested as early weakness of muscles and exercise intolerance.Repeated nerve stimulation is helpful for identification and diagnosis.Gene detection is required for diagnosis.Fluoxetine may serve as first line treatment for Myasthenic syndrome caused by CHRND.