Longitudinal functional trajectories in Duchenne muscular dystrophy: outcome-specific patterns from a registry-based...

Duchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disorder characterised by loss of motor function. Despite a broadly predictable disease course, robust population-level reference models for multiple functional outcomes under real-world conditions remain limited. This study characterises longitudinal trajectories across key functional outcomes in DMD using registry data. This retrospective registry-based study used pseudonymised data from the Italian DMD/BMD Patient Registry. Age-dependent trajectories for NSAA, 6MWT and PUL (versions 1.2 and 2.0) were modelled using linear mixed-effects models with outcome-specific age functions. Parsimonious model specifications were selected to account for data sparsity and heterogeneity. A total of 368 genetically confirmed patients were included. NSAA and 6MWT showed non-linear age-dependent trajectories, both best described by quadratic mixed-effects models. In contrast, upper limb function declined more gradually: PUL 1.2 followed a piecewise linear trajectory, whereas PUL 2.0 was adequately captured by a linear random-intercept model. Substantial inter-individual variability was observed across all outcomes. These findings indicate outcome-specific progression patterns, with non-linear trajectories in ambulatory function and more gradual, approximately linear decline in upper limb function. A mixed-effects modelling approach provides interpretable reference trajectories for multiple functional outcomes in DMD under real-world conditions and highlights the need for outcome-specific modelling of disease progression.