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

Area of Science:

• Neurology
• Genetics
• Biostatistics

Background:

• Duchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disorder.
• Limited population-level models exist for DMD functional outcomes in real-world settings.

Purpose of the Study:

• To characterize longitudinal trajectories of key functional outcomes in DMD using registry data.
• To develop outcome-specific models for DMD disease progression.

Main Methods:

• Retrospective analysis of pseudonymised data from the Italian DMD/BMD Patient Registry.
• Linear mixed-effects models used to analyze age-dependent trajectories for North Star Ambulatory Assessment (NSAA), 6-minute walk test (6MWT), and Performance of Upper Limb (PUL) scores.
• Parsimonious model specifications selected to manage data sparsity and heterogeneity.

Main Results:

• NSAA and 6MWT demonstrated non-linear, age-dependent trajectories, best modeled quadratically.
• PUL 1.2 showed a piecewise linear decline, while PUL 2.0 followed a linear trajectory.
• Significant inter-individual variability observed across all functional outcomes.

Conclusions:

• DMD progression exhibits distinct patterns for ambulatory versus upper limb function.
• Mixed-effects modeling provides interpretable, outcome-specific reference trajectories for DMD.
• Highlights the necessity of tailored modeling approaches for understanding DMD disease progression.