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.
目的： 探讨胆碱乙酰基转移酶（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（CMS-EA）的临床及遗传学特征。 方法： 回顾性分析首都医科大学附属北京儿童医院2013年9月、2015年2月收治的2例CMS-EA家系的病例资料，分析其临床特征和基因突变特点，并进行随访。 结果： 2例患儿分别于生后和3个月余发病，均因呼吸困难、青紫发作气管插管下收住儿童重症监护病房，反复呼吸暂停，不能脱离呼吸机，例1患儿放弃治疗后死亡，例2给予气管切开及溴吡斯的明口服，住院162 d携带气管套管出院，随访患儿至3岁4个月，口服溴吡斯的明，已拔除气管套管，仍有波动性眼睑下垂，程度减轻，智体力发育略落后于同龄儿。2例患儿抗乙酰胆碱受体抗体、抗乙酰胆碱酯酶抗体、抗骨骼肌受体酪氨酸肌酶抗体均阴性；新斯的明试验阴性及可疑阳性各1例；低频神经重复电刺激未见特征性改变；头颅磁共振成像均提示脑萎缩样改变。2例均发现CHAT基因突变，例1为外显子4、5、6杂合缺失和p.I305T复合杂合突变，例2为p.I336T和p.Q22X复合杂合突变，其中，外显子4、5、6杂合缺失和p.Q22X为未报道的新突变。 结论： CMS-EA通常表现为自新生儿期或婴儿期起病的肌张力低下、肌无力、发作性眼睑下垂、喂养困难、伴呼吸暂停的呼吸困难，溴吡斯的明治疗有效，早期应用有助于改善临床症状和预后。.
Keywords: Apnea; Loss of heterozygosity; Myasthenic syndrome congenital.