由SCN4A基因错义突变导致的严重新生儿发作性喉痉挛1例及文献复习

New phenotype of severe neonatal episodic laryngospasm due to a missense mutation in SCN4A:A case report and literature review

严重新生儿发作性喉痉挛(severe neonatal episodic laryngospasm,SNEL)是一种离子通道病,该病因钠电压门控通道4亚基(sodium voltage-gated channel alpha subunit 4 gene,SCN4A)基因突变导致反复发作性咽喉肌强直而危及新生儿生命。现报告1例在出生后出现阵发性发绀和四肢强直的新生儿病例,随访期间,患儿还出现四肢肌肥大和生长发育迟缓。全外显子测序证实该患儿存在SCN4A基因新型杂合突变(c.2395G>A,p.Ala799Thr)。卡马西平是治疗该病的有效药物。此病例扩展了我们对SCN4A基因突变表型的认识。总结已报道的16例SNEL病例特点,发现他们主要发生p.G1306E位点错义突变。相似症状表现为新生儿期上气道肌紧张和喂养困难,长大后多数患者表现为不同程度的发作性肌强直和进行性的肌肥大。一些患者出现"运动员"特征外貌,但几乎所有患者肌电图均有肌强直放电。

Severe neonatal episodic laryngospasm(SNEL)is an ion channel disease characterized by recurrent life-threatening myotonia of respiratory muscle due to mutations in the voltagegated sodium channel genes.Here we reported a newborn manifested as paroxysmal cyanosis and limb myotonia after birth.The neonate also developed muscle hypertrophy and stunted growth during the follow-up.Whole exome sequencing confirmed c.2395 G>A,p.Ala799 Thr heterozygous mutation of SCN4A.Carbamazepine was found to be effective on treating the disease.This case expands our understanding of the phenotype resulting from SCN4A mutations.By summarizing the characteristics of reported 16 cases in SNEL,we found they were mainly in the p.G1306 E mutation.The common symptoms were upper airway muscle stiffness and feeding difficulties during neonates.When grow up,most patients have different degrees of recurrent attacks of myotonia and progressed muscle hypertrophy.Some of them have athlete-like special faces but all showed myotonic discharge in eletromyogram.