Longitudinal motor function in proximal versus distal DMD pathogenic variants.

Area of Science:

• Neurology
• Genetics
• Clinical Medicine

Background:

• Duchenne muscular dystrophy (DMD) presents with significant clinical outcome variability.
• Understanding factors influencing DMD progression is crucial for patient management.

Purpose of the Study:

• To investigate if the location of dystrophin gene (DMD) pathogenic variants affects upper and lower extremity motor function in a large DMD cohort.
• To analyze motor function trajectories based on proximal versus distal DMD variant locations.

Main Methods:

• Longitudinal motor function data from 154 boys with DMD over 10 years were analyzed.
• Patients were categorized by DMD variant location: proximal (5' intron 44) vs. distal (including intron 44).
• Upper and lower extremity motor function measures were compared, adjusting for corticosteroid use.

Main Results:

• No significant difference in time to loss-of-ambulation or limb motor function trajectories between proximal and distal variant groups.
• Age significantly impacted motor function: younger boys (<7 years) showed functional gains, while older boys (≥7 years) exhibited decline.
• Motor function decline was independent of DMD variant location.

Conclusions:

• Proximal versus distal DMD pathogenic variant location does not influence the longitudinal decline in upper or lower motor function.
• Age is a critical determinant of motor function progression in Duchenne muscular dystrophy.