Background:

Congenital myasthenic syndrome is a group of rare genetic disorders affecting transmission across the neuromuscular junction. Patients present with variable ocular, bulbar, respiratory, and extremity weakness that may respond to symptomatic therapies.

Methods:

We identified 18 patients with congenital myasthenic syndrome from a pediatric neuromuscular center over a decade. Through a retrospective chart review, we characterize demographic profile, clinical features, genetic variants, treatment, and follow-up of these patients.

Results:

Patients had the following genetic subtypes: CHRNE (6), CHAT (2), MUSK (2), DOK7 (2), COLQ (1), RAPSN (1), PREPL (1), GFPT1 (1), CHRBB1 (1), and CHRNA1 (1). The phenotype varied based on the genetic variants, though most patients have generalized fatigable weakness affecting ocular, bulbar, and extremity muscles. There was a significant delay in the diagnosis of this condition from the onset of symptoms. Although most patients improved with pyridostigmine, some subtypes showed worsening with pyridostigmine and others benefited from albuterol, ephedrine, or 3,4-diaminopyridine treatment.

Conclusion:

Increasing recognition of this rare syndrome will lead to early diagnosis and prompt treatment. Prompt utilization of genetic testing will identify novel variants and the expanding phenotype of this condition.

中文翻译：

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单一中心的先天性肌无力综合征：表型和基因型特征

背景：

先天性肌无力综合征是一组影响神经肌肉接头传递的罕见遗传疾病。患者表现出不同的眼部、延髓、呼吸和四肢无力，可能对对症治疗有反应。

方法：

十多年来，我们从一个儿科神经肌肉中心确定了 18 名先天性肌无力综合征患者。通过回顾性图表审查，我们描述了这些患者的人口统计学特征、临床特征、遗传变异、治疗和随访。

结果：

患者具有以下遗传亚型：CHRNE (6)、CHAT (2)、MUSK (2)、DOK7 (2)、COLQ (1)、RAPSN (1)、PREPL (1)、GFPT1 (1)、CHRBB1 ( 1) ) 和CHRNA1(1)。表型因遗传变异而异，但大多数患者具有影响眼部、延髓和四肢肌肉的全身乏力无力。从症状出现开始，这种疾病的诊断显着延迟。尽管大多数患者在使用吡斯的明后病情有所改善，但一些亚型在使用吡斯的明后病情恶化，而其他亚型则从沙丁胺醇、麻黄碱或 3,4-二氨基吡啶治疗中获益。

结论：

越来越多地认识到这种罕见的综合征将导致早期诊断和及时治疗。迅速利用基因检测将识别新的变异和这种疾病的扩大表型。