Clinical and genetic characteristics of congenital myasthenia syndrome with episodic apnea caused by CHAT gene mutation: a report of 2 cases
10.3760/cma.j.issn.0578-1310.2018.03.012
- VernacularTitle:CHAT基因突变导致的先天性肌无力综合征伴发作性呼吸暂停二例
- Author:
Zhimei LIU
1
;
Fang FANG
;
Changhong DING
;
Weihua ZHANG
;
Jie DENG
;
Chunhong CHEN
;
Xu WANG
;
Jun LIU
;
Zheng LI
;
Xinlei JIA
;
Jiansheng ZENG
;
Suyun QIAN
Author Information
1. 100045 首都医科大学附属北京儿童医院神经内科
- Keywords:
Myasthenic syndrome congenital;
Apnea;
Loss of heterozygosity
- From:
Chinese Journal of Pediatrics
2018;56(3):216-220
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical and genetic features of congenital myasthenia syndrome with episodic apnea (CMS-EA) caused by gene mutation of choline acetyltransferase (CHAT)Methods The clinical data of 2 patients with congenital myasthenia syndrome were collected,and both were diagnosed from 2013 to 2015 in Beijing Children's Hospital,Capital Medical University.The clinical features and gene mutation characteristics were analyzed,and the patients were followed-up for therapeutic efficacy.Results The two patients (case 1 and case 2) had the onset soon after birth and at 3 months after birth respectively.The two patients were admitted to the PICU due to dyspnea,cyanotic episodes that required intubation.The patients had repeated apnea and became ventilator dependent.Case 1 died due to refusal of any treatment.Case 2 had a tracheotomy,and gradually weaned from ventilator after using pyridostigmine.The hospitalization of case 2 lasted 162 days.Case 2 was followed up to the age of 3 years and 4 months,and was extubated and was maintained on oral neostigmine but still had fluctuating ptosis and minor physical and mental retardation.Both cases were negative for anti-AChR,anti-acetylcholinesterase,anti-MuSK antibodies.Neostigmine test was negative in case 1 and suspiciously positive in case 2.Low-frequency repetitive nerve stimulation testing of case 2 was negative.Cranial MRI scans of both cases showed brain atrophy-like change.Genetic testing showed compound heterozygous deletions (exon 4,5,6) and pathogenic variant c.914T＞C (p.I305T) in CHAT in case 1,compound heterozygous variants c.1007T＞C (p.I336T) and c.64C＞T (p.Q22X) in CHAT in case 2.To our knowledge,compound heterozygous deletions (exon 4,5,6) and p.Q22X were novel,previously unreported variants.Conclusion CMS-EA usually presents at birth or in the neonatal period with hypotonia,ptosis,dysphagia due to severe bulbar weakness,and respiratory insufficiency with cyanosis and apnea.Early treatment with pyridostigmine is helpful to the improvement of clinical symptoms and prognosis.
