Characteristics of Japanese patients with becker muscular dystrophy and intermediate muscular dystrophy in a Japanese national registry of muscular dystrophy (Remudy): Heterogeneity and clinical variation

Abstract

Background: Obtaining an adequate number of patients to conduct a natural history study for rare diseases such as Becker muscular dystrophy (BMD) is difficult. Objectives: The present study used data from Remudy, a national registry for neuromuscular diseases in Japan, to conduct a phenotypic analysis of BMD. Methods:We analyzed Remudy data of participants with dystrophinopathy. All participants who were aged 17 and older and were ambulant at age 13 were included in this study. Participants were divided into two groups: Those with BMD who were ambulant at age 17, and those with intermediate muscular dystrophy (IMD) who lost ambulation by age 17. Frequent mutations were analyzed by age at ambulation, cardiopulmonary function, and genotype. For clinical comparisons, participants who were administered steroids were excluded. Results: From July 2009 through September 2015, 192 participants had registered with Remudy. Mean participant age was 34.80±13.3 (range, 17-78) years, and 52.1% of participants were ambulant. Of the entire study population, 50.5% had cardiomyopathy and 35.9% had respiratory failure. Three participants required invasive ventilation and 30 required non-invasive ventilation. Nineteen of the 30 non-invasive ventilator users were part-time users. In total, 138 (71.9%) had BMD and 54 (28.1%) had IMD. The most frequent mutation was ex45 ex47del (36 participants). Among participants with frequent in-frame mutations, those with the ex45-49del mutation lost their ambulation earlier than those with the ex45 ex47del mutation. A total of 67 different exon deletions and duplications were identified in the study population. Conclusion:We clarified the clinical phenotypes of Japanese patients with BMD/IMD using data from Remudy. Our results suggest that not only IMD but also BMD are associated with risk of respiratory dysfunction.