Poulos Jordan, Samuels Martin, Palace Jacqueline, Beeson David, Robb Stephanie, Ramdas Sithara, Chan Samantha, Munot Pinki
Paediatrics, University College London Medical School, London WC1E 6BT, UK.
Respiratory Medicine, Great Ormond Street Hospital, London WC1N 3JH, UK.
Brain Commun. 2023 Nov 9;5(6):fcad299. doi: 10.1093/braincomms/fcad299. eCollection 2023.
Respiratory problems are a major cause of morbidity and mortality in patients with congenital myasthenic syndromes, a rare heterogeneous group of neuromuscular disorders caused by genetic defects impacting the structure and function of the neuromuscular junction. Recurrent, life-threatening episodic apnoea in early infancy and childhood and progressive respiratory failure requiring ventilation are features of certain genotypes of congenital myasthenic syndromes. Robb published empirical guidance on respiratory management of the congenital myasthenic syndromes, but other than this workshop report, there are little published longitudinal natural history data on respiratory outcomes of these disorders. We report a retrospective, single-centre study on respiratory outcomes in a cohort of 40 well characterized genetically confirmed cases of congenital myasthenic syndromes, including 10 distinct subtypes (DOK7, COLQ, RAPSN, CHAT, CHRNA1, CHRNG, COL13A1, CHRNE, CHRNE fast channel syndrome and CHRNA1 slow channel syndrome), with many followed up over 20 years in our centre. A quantitative and longitudinal analysis of key spirometry and sleep study parameters, as well as a description of historical hospital admissions for respiratory decompensation, provides a snapshot of the respiratory trajectory of congenital myasthenic syndrome patients based on genotype.
呼吸问题是先天性肌无力综合征患者发病和死亡的主要原因，先天性肌无力综合征是一组罕见的异质性神经肌肉疾病，由影响神经肌肉接头结构和功能的基因缺陷引起。婴儿早期和儿童期反复出现的、危及生命的发作性呼吸暂停以及需要通气的进行性呼吸衰竭是某些先天性肌无力综合征基因型的特征。罗布发表了关于先天性肌无力综合征呼吸管理的经验性指导意见，但除了这份研讨会报告外，几乎没有关于这些疾病呼吸结局的已发表的纵向自然史数据。我们报告了一项回顾性单中心研究，该研究针对一组40例基因确诊、特征明确的先天性肌无力综合征病例的呼吸结局进行了研究，包括10种不同亚型（DOK7、COLQ、RAPSN、CHAT、CHRNA1、CHRNG、COL13A1、CHRNE、CHRNE快通道综合征和CHRNA1慢通道综合征），其中许多病例在我们中心接受了20多年的随访。对关键肺功能测定和睡眠研究参数进行定量和纵向分析，以及对因呼吸失代偿而住院的历史情况进行描述，基于基因型提供了先天性肌无力综合征患者呼吸轨迹的概况。
