CHRNB1基因突变所致先天性肌无力综合征一家系报道

CHRNB1 gene mutations-related congenital myasthenic syndromes in a Chinese family

目的分析CHRNB1基因突变所致先天性肌无力综合征的临床表现、电生理及基因特点,提高对此病的诊断及鉴别诊断能力。方法观察2019年2月就诊于空军军医大学唐都医院的CHRNB1基因突变所致先天性肌无力综合征一家系先证者的临床特点、实验室检查,对其进行电生理检查及高通量全外显子测序,并对治疗反应及预后进行评估。结果先证者为16岁女性,4岁时出现双眼睑下垂,12岁时出现四肢无力。父亲有类似病史,母亲及一弟正常。心肌酶谱、甲状腺功能正常;重症肌无力抗体检测均为阴性;新斯的明试验阴性。双侧腋神经重复电刺激可见低频递减,针极肌电图未见肌源性损害。头颅磁共振成像、胸部CT检查结果大致正常。高通量全外显子测序:先证者CHRNB1基因8号外显子区域存在1个父源单杂合突变:c.865G>A(NM_000747)。予以氟西汀60 mg/d治疗,随访1年时四肢无力明显改善,眼睑下垂轻度改善。结论CHRNB1基因突变所致慢通道先天性肌无力综合征患者临床及电生理表现与获得性自身免疫性重症肌无力相似,极易误诊,高通量全外显子测序可明确诊断。

Objective To analyze the clinical,neurophysiological and genetic features of CHRNB1 gene mutations-related congenital myasthenic syndromes(CMS),and to facilitate the recognition and differential diagnosis of this disorder.Methods The clinical characteristics and laboratory features of the proband in a family with CHRNB1 gene mutations-related CMS were recorded,and the neurophysiological testing and high-throughput sequencing for the proband were performed.In addition,the response to the treatment and prognosis of the proband were reported.Results The proband is a 16-year-old female who had bilateral eyelid ptosis at the age of 4,presented with limb weakness at the age of 12.Her father has the similar symptoms and other family members are not affected similarly.Serum creatine kinase and thyroid function were normal.Needle electromyography results demonstrated no myopathic disorders.All myasthenia gravis-related antibodies tests including anti-acetylcholine receptor antibody were negative and she failed to respond to pyridostigmine.There was a decremental response of the compound muscular action potential on 5 Hz repetitive nerve stimulation.Brain magnetic resonance imaging and chest CT were unremarkable.The proband was found a heterozygous mutation(c.865G>A(NM_000747))in CHRNB1 gene exon 8 through high throughput sequencing.She started a 60 mg/d treatment of fluoxetine and showed beneficial response at one-year follow-up.Conclusions The clinical presentation of CHRNB1 gene mutation-related slow-channel CMS is similar to autoimmune myasthenia gravis,and is likely to be misdiagnosed.High-throughput sequencing accelerates the diagnosis.