1例CHRB1基因变异导致的先天性肌无力综合征伴喂养困难、反复呛奶

Exploring the Clinical and Genetic Characteristics of One Case of Congenital Myasthenia Syndrome Complicated with Feeding Difficulty and Repeated Milk Choking Caused by Gene Variation of CHRB1

目的探讨CHRB1基因突变导致的先天性肌无力综合征(CongenitalMyastheniaSyndrome,CMS)伴喂养困难、反复呛奶的临床及遗传学特征。方法收集我院2018年5月收治的1例CMS家系的病例资料,对其临床特征和基因突变特点进行回顾性分析。结果本例患儿生后因进行性呼吸困难、青紫行气管插管后入住新生儿重症监护病房,拔管撤机后因喂养后反复呛奶发作,行气道肺部CT三维重建、食道造影术及支气管纤维镜检查排除食道气管瘘,诊断为咽部狭窄(舌后坠);先天性喉软骨发育不良(Ⅰ型);支气管黏膜炎;咽部反射欠佳伴反流,未见气道瘘。患儿撤去呼吸支持后,出现喂养困难,反复呛奶。出院后带胃管鼻饲注奶喂养,喂养中反复出现呛奶窒息。生后6个月仍不会自行吸吮、不能竖头、独坐、肌张力低下,体重及智力发育明显落后于同龄儿。基因检测显示CHRB1基因突变,其中c.452G> A及c.727C> T两个位点错意突变,为常染色体隐性遗传(AR),其父母均为杂合子。结论由CHRB1突变导致的先天性肌无力综合征,新生儿期即可起病,表现为喂养困难、反复呛奶,生长发育落后为特点,有家族遗传史(其父母均为杂合子,其哥哥出生后有喂养困难病史)。关于该病在新生儿期的发作形式及治疗方法以及预后,值得进一步探讨。

Objective To explore the clinical and genetic characteristics of Congenital Myasthenia Syndrome(CMS)complicated with feeding difficulty and repeated milk choking caused by gene variation of CHRB1.Methods The medical records of one case of CMS who was treated in Guangdong Hydropower Group Hospital in May 2018 were collected.Then retrospective analysis of the clinical characteristics and genetic mutation characteristics of the case was carried out.Results This case was admitted to neonatal ICU after endotracheal intubation due to progressive dyspnea and cyanosis after birth.After extubation and withdrawal of ventilator,the patient suffered from repeated milk choking following feeding.Therefore,three-dimensional CT reconstruction of airway and lung,esophagography,and bronchofibroscopy were conducted on the patient to eliminate esophageal fistula and tracheal fistula.As a result,the patient was diagnosed as pharyngeal stenosis(glossoptosis),congenital laryngeal cartilage dysplasia(typeⅠ),bronchial mucositis,and poor pharyngeal reflex complicated with reflux.No airway fistula was observed.After the removal of respiratory support,the patient suffered from feeding difficulty and repeated milk choking.After discharge from hospital,the patient was equipped with gastric tube and provided with nasogastric feeding of milk,during which the patient suffered from repeated milk chocking and asphyxia.Six months after birth,the patient still can not suck by him/herself,can’t raise the head and sit by him/herself,with low muscle tension.The weight and mental development were significantly behind the children at the same age.Gene test showed gene mutation of CHRB1 occurred to the patient,with missense mutations at two loci of c.452 G>A and c.727 C>T.The missense mutations were autosomal recessive inheritance(AR)since the parents of the patient were heterozygotes.Conclusion CMS caused by gene mutation of CHRB1 may suffer from onset of CMS at the neonatal stage,which is characterized by feeding difficulty,repeated milk choking,and backward growth and development.It is related to family genetic history(the parents are heterozygotes and the elder brother had a history of feeding difficulty after birth).It is worthy of further exploration of the attack forms,treatment methods,and prognosis of this disease in neonatal period.