Bouma Sietse, Cobben Nicolle, Bouman Karlijn, Gaytant Michael, van de Biggelaar Ries, van Doorn Jeroen, Reumers Stacha F I, Voet Nicoline Bm, Doorduin Jonne, Erasmus Corrie E, Kamsteeg Erik-Jan, Jungbluth Heinz, Wijkstra Peter, Voermans Nicol C
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Pulmonary Diseases & Home Mechanical Ventilation, Maastricht University Medical Center+, Maastricht, the Netherlands.
Neuromuscul Disord. 2023 Jul;33(7):580-588. doi: 10.1016/j.nmd.2023.06.003. Epub 2023 Jun 11.
Centronuclear myopathy (CNM) is a heterogeneous group of muscle disorders primarily characterized by muscle weakness and variable degrees of respiratory dysfunction caused by mutations in MTM1, DNM2, RYR1, TTN and BIN1. X-linked myotubular myopathy has been the focus of recent natural history studies and clinical trials. Data on respiratory function for other genotypes is limited. To better understand the respiratory properties of the CNM spectrum, we performed a retrospective study in a non-selective Dutch CNM cohort. Respiratory dysfunction was defined as an FVC below 70% of predicted and/or a daytime pCO2 higher than 6 kPa. We collected results of other pulmonary function values (FEV1/FVC ratio) and treatment data from the home mechanical ventilation centres. Sixty-one CNM patients were included. Symptoms of respiratory weakness were reported by 15/47 (32%) patients. Thirty-three individuals (54%) with different genotypes except autosomal dominant (AD)-BIN1-related CNM showed respiratory dysfunction. Spirometry showed decreased FVC, FEV1 & PEF values in all but two patients. Sixteen patients were using HMV (26%), thirteen of them only during night-time. In conclusion, this study provides insight into the prevalence of respiratory symptoms in four genetic forms of CNM in the Netherlands and offers the basis for future natural history studies.
中央核肌病（CNM）是一组异质性肌肉疾病，主要特征为肌无力以及由MTM1、DNM2、RYR1、TTN和BIN1基因突变引起的不同程度的呼吸功能障碍。X连锁肌管性肌病一直是近期自然史研究和临床试验的重点。关于其他基因型呼吸功能的数据有限。为了更好地了解CNM谱系的呼吸特性，我们在一个非选择性的荷兰CNM队列中进行了一项回顾性研究。呼吸功能障碍定义为用力肺活量（FVC）低于预测值的70%和/或日间二氧化碳分压（pCO2）高于6kPa。我们收集了其他肺功能值（第一秒用力呼气容积/用力肺活量比值）的结果以及来自家庭机械通气中心的治疗数据。纳入了61例CNM患者。15/47（32%）的患者报告有呼吸肌无力症状。除常染色体显性（AD）-BIN1相关的CNM外，有不同基因型的33人（54%）表现出呼吸功能障碍。肺活量测定显示，除两名患者外，所有患者的FVC、第一秒用力呼气容积（FEV1）和呼气峰值流速（PEF）值均下降。16例患者使用家庭机械通气（HMV）（26%），其中13例仅在夜间使用。总之，本研究深入了解了荷兰四种遗传形式的CNM中呼吸症状的患病率，并为未来的自然史研究提供了依据。
