Findings from the Longitudinal CINRG Becker Natural History Study

Paula R. Clemens, Heather Gordish-Dressman, Gabriela Niizawa, Ksenija Gorni, Michela Guglieri, Anne M. Connolly, Matthew Wicklund, Tulio Bertorini, Jean Mah, Mathula Thangarajh, Edward C. Smith, Nancy L. Kuntz, Craig M. McDonald, Erik Henricson, S. Upadhyayula, Barry Byrne, Georgios Manousakis, Amy Harper, Susan Iannaccone, Utkarsh J. Dang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)201-212
Number of pages12
JournalJournal of Neuromuscular Diseases
Volume11
Issue number1
DOIs
StatePublished - Jan 2 2024

Bibliographical note

Publisher Copyright:
© 2024 - The authors. Published by IOS Press.

Keywords

  • Muscular dystrophies
  • dystrophin
  • muscle
  • natural history
  • skeletal

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