Genotype-related respiratory progression in Duchenne Muscular Dystrophy - multicentre international study.
Trucco F., Ridout D., Domingos J., Maresh K., Chesshyre M., Munot P., Sarkozy A., Robb S., Quinlivan R., Riley M., Wallis C., Chan E., Abel F., De Lucia S., Hogrel J-Y., Niks EH., de Groot I., Servais L., Straub V., Ricotti V., Manzur A., Muntoni F., UK NorthStar Clinical Network and AFM Network None.
INTRODUCTION/AIMS: Mutations amenable to skipping of specific exons have been associated with different motor progression in Duchenne muscular dystrophy (DMD). Less is known about their association with long-term respiratory function. We aimed to investigate the features of respiratory progression in four DMD genotypes relevant for ongoing exon skipping therapeutic strategies. METHODS: This was a retrospective longitudinal study including DMD children followed by the UK North Star network and international AFM network centres (May 2003-October 2020). We included boys amenable to skip exons 44, 45, 51 or 53, older than 5 years and ambulant at first recorded visit. Subjects who were corticosteroid-naïve or enrolled in interventional clinical trials were excluded. The progression of respiratory function (absolute forced vital capacity, FVC, and calculated as percentage of predicted, FVC%) was compared across the four subgroups (skip44, skip45, skip51, skip53). RESULTS: We included 142 boys. Mean (SD) age at first visit was 8.6 (2.5) years. Median follow-up was 3(0.3-8.3) years. In skip45 and skip51 FVC% declined linearly from the first recorded visit. From the age of 9 years FVC% linearly declined in all genotypes. Skip44 had the slowest (2.7%/year) and skip51 the fastest (5.9%/year) annual FVC% decline. The absolute FVC progressively increased in skip44, skip45, skip51. In skip53 FVC started declining from 14 years of age. DISCUSSION: The progression of respiratory dysfunction follows different patterns for specific genotype categories. This information is valuable for prognosis and for the evaluation of exon skipping therapies. This article is protected by copyright. All rights reserved.