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Lookup NU author(s): Professor Michela GuglieriORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
BACKGROUND: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype. OBJECTIVE: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials. METHODS: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes. RESULTS: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter. CONCLUSIONS: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.
Author(s): Clemens PR, Gordish-Dressman H, Niizawa G, Gorni K, Guglieri M, Connolly AM, Wicklund M, Bertorini T, Mah J, Thangarajh M, Smith EC, Kuntz NL, McDonald CM, Henricson E, Upadhyayula S, Byrne B, Manousakis G, Harper A, Iannaccone S, Dang UJ
Publication type: Article
Publication status: Published
Journal: Journal of Neuromuscular Diseases
Year: 2024
Volume: 11
Issue: 1
Pages: 201-212
Print publication date: 02/01/2024
Online publication date: 17/11/2023
Acceptance date: 18/10/2023
Date deposited: 23/01/2024
ISSN (print): 2214-3599
ISSN (electronic): 2214-3602
Publisher: IOS Press
URL: https://doi.org/10.3233/JND-230178
DOI: 10.3233/JND-230178
Data Access Statement: The data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
PubMed id: 37980682
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