P.1.2 Natural history of pulmonary function in collagen VI-related myopathies: An international study

Abstract

Robust natural history studies are essential for clarifying and validating phenotypic classifications, optimizing clinical care and preparing for clinical trials. We studied the natural history of pulmonary function in correlation to motor function in the collagen VI-related myopathies by analyzing longitudinal forced vital capacity data in a large international cohort. Retrospective chart reviews of molecularly and/or biochemically confirmed collagen VI-related myopathy patients were performed at 10 neuromuscular centers. A total of 486 forced vital capacity (FVC) measurements obtained in 145 patients were analyzed. Ullrich congenital muscular dystrophy (UCMD) patients were easily identified by severe muscle weakness preventing ambulation or resulting in early loss of ambulation and demonstrated a cumulative decline in FVC of 2.6% per year (<i>p</i><0.0001). Patients with better functional abilities, in whom walking with/without assistance was achieved, were initially combined. One subset of patients demonstrated a continuous decline in pulmonary function while the other had stable pulmonary function. None of the patients with declining pulmonary function attained the ability to hop or run and were categorised as intermediate collagen VI-related myopathy and the remaining patients as Bethlem myopathy. Intermediate patients demonstrated a decline in FVC of 2.3% per year (<i>p</i><0.0001) while the relationship between age and FVC in Bethlem myopathy patients was not significant (<i>p</i>=0.1432). Kaplan Meier curves depicting ventilation-free probability demonstrated a statistically significant (<i>p</i>=0.006) difference between UCMD and intermediate patients with 50% of UCMD patients on nocturnal non-invasive ventilation by age 11.0years and 50% of intermediate patients by age 21.5years. The relationship between maximal motor ability and FVC was highly significant (<i>p</i><0.0001) with 50% of UCMD patients losing ambulation by age 10years and 50% of intermediate patients by age 19years.