Predictors of disease severity and progression in patients with Duchenne muscular dystrophy: A literature review

Objective: Duchenne muscular dystrophy (DMD) is a degenerative, fatal neuromuscular disease caused by gene mutations that prevent dystrophin expression, and DMD progression follows a predictable disease course, with irreversible decline. We conducted a review of published literature to identify factors that may predict disease severity in DMD patients. Methods: PubMed was searched using terms related to DMD, age, mutation type, treatment utilization, corticosteroid use, 6-Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), ambulation loss, longitudinal natural history, and clinical trial design. Results were limited to English language publications from January 1, 2010–January 11, 2017. Results: More than 50 potentially relevant articles were identified and screened for inclusion. Age dichotomy reported in several studies showed that younger boys gained in function until ≈7 years of age, when muscle loss outpaced growth and maturation, leading to progressive functional decline. Baseline 6MWT distance was also shown to be predictive of subsequent loss of ambulation, particularly in patients >7 years. Mutation type was reported to affect disease severity. In particular, patients with mutations amenable to exon 44 skipping were shown in several studies to experience slower disease progression than the general DMD population and patients amenable to skipping other exons. NSAA score was predictive of loss of ambulation. Rise time, an NSAA subanalysis, together with 6MWT was reported to be predictive of 6MWT changes. Additional studies evaluated correlations between corticosteroid use and quantitative muscle strength with disease progression and functional measures. Patients who initiated corticosteroids before age 5 had a functional gain of ≈3 units/year on the NSAA versus patients who started corticosteroids later. Conclusion: These findings are important to consider when designing clinical trials of potential disease-modifying treatments for DMD. The findings also highlight the importance of genetic testing and may provide important prognostic information that can be shared with patients.