Background: Duchenne Muscular Dystrophy (DMD) is a neuromuscular disorder with onset in early childhood, mainly affecting boys aged 2–4 years. It results from mutations in the DMD gene, which encodes dystrophin, a structural protein essential for membrane stability. Dysfunction leads to progressive muscle degeneration, with variability according to mutation type and location.
Objectives: To assess the impact of DMD in adulthood and examine the association between mutation type and clinical presentation, including muscular and systemic features.
Methods: We retrospectively reviewed records of patients over 18 years old, seen in the past 5 years, with clinical DMD, continuous corticosteroid use, and confirmed loss-of-function mutations. Loss of ambulation occurred before age 13, or up to 16 in intermediate cases.
Results: We included 89 patients (mean age 22; range 18–33). Mean age at diagnosis was 6 years, and at loss of ambulation 11.4 years. Mutation types: deletions (64%), duplications (16.8%), nonsense (11.2%), frameshift (4.4%), missense (1.1%), splice-site (1.1%), intronic (1.1%). Locations: 69.6% central rod domain, 14.6% N-terminal, 10.1% both, 1.1% dystroglycan-binding. Mean age at loss of ambulation: 11.2 years for deletions, 11.8 for duplications, 11.4
for nonsense; by domain, 11.2 for central, 11.8 for N-terminal, and 10 for dystroglycan-binding. Among 34 with cognitive data, 15 (44%) had intellectual disability. Cardioprotective therapy was used in 72 (80.8%), with 41 (46%) on ≥2 agents—more frequent in N-terminal
mutations (54% vs. 49% central). At least one cardioprotector was used in 80% of deletions, 93% duplications, 80% nonsense, 100% frameshift. Bone abnormalities on densitometry were more common in central domain mutations (70% vs. 63%), as were fractures (35% vs. 31%) and NIV use (35% vs. 31%) compared to N-Terminal mutations. Nonsense mutations showed higher frequencies of bone abnormalities, fractures, and NIV use compared to other mutation types.
Conclusion: DMD has a high clinical and functional impact, requiring a detailed understanding of its natural history to appropriately plan and provide transitions of care, ensuring comprehensive support throughout the different stages of life. Based on the findings of this study, mutations in the central domain have been associated with earlier loss of ambulation, more bone complications, and slightly less cardiac involvement compared with N-terminal mutations.