Department of Neurology, Peking University First Hospital, Beijing, China.
Department of Neurology, Capital Medical University Affiliated Anzhen Hospital, Chaoyang-qu, China.
Ann Clin Transl Neurol. 2021 Apr;8(4):898-907. doi: 10.1002/acn3.51346. Epub 2021 Mar 23.
We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes.
The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up.
Thirty-five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb-girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha-dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long-term use in patients with COLQ or AGRN mutations.
The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb-girdle myasthenic syndrome, tubular aggregates, and decreased alpha-dystroglycan were indicative of the specific subtypes. Based on the follow-up findings, we suggest cautious evaluation of the long-term efficacy of therapeutic agents in congenital myasthenic syndrome.
总结中国先天性肌无力综合征患者的临床、遗传和肌病学特征，并随访治疗结果。
总结各型先天性肌无力综合征患者的临床谱、基因突变频率和病理诊断线索，并随访治疗效果。
共纳入 29 个家系的 35 例患者，发现 10 个致病基因：GFPT1（27.6%）、AGRN（17.2%）、CHRNE（17.2%）、COLQ（13.8%）、GMPPB（6.9%）、CHAT、CHRNA1、DOK7、COG7 和 SLC25A1（各占 3.4%）。AGRN（1/8）和 GFPT1（7/8）突变患者仅表现为单纯肢体无力，而 AGRN（6/8）突变患者均表现为远端肌无力。仅在 GFPT1 突变患者中发现管状聚集物（5/6）。AGRN 突变患者（2/2）的α- dystroglycan 减少。COLQ 突变患者乙酰胆碱酯酶抑制剂治疗无效或症状恶化，AGRN 突变患者治疗反应多样，其他亚型患者治疗效果良好。大多数亚型患者使用沙丁胺醇治疗有效或无害。COLQ 或 AGRN 突变患者长期使用治疗药物后，疗效减弱。
中国先天性肌无力综合征的遗传分布与其他种族不同。出现远端肌无力、选择性肢体无力型、管状聚集物和α- dystroglycan 减少提示特定的亚型。根据随访结果，我们建议谨慎评估治疗药物在先天性肌无力综合征中的长期疗效。
