Muscle involvement in women carrying pathogenic DMD gene variants: A 6.5-year follow-up study

Women carrying pathogenic DMD gene variants can develop muscle affection, such as muscle weakness and fat replacement. The long-term progression of the muscle involvement is unknown. This study investigates the 6.5-year changes in muscle function and -fat fraction in women carrying pathogenic DMD gene variants to enhance understanding of disease progression and its natural history.

Muscle structure and -function were investigated at baseline and after 6.5 years in 34 women carrying pathogenic DMD gene variants (19 predicted to confer Duchenne Muscular Dystrophy (DMD), 15 Becker Muscular Dystrophy (BMD)). After a clinical evaluation, muscle fat fraction was assessed using Dixon MRI, muscle strength with isokinetic dynamometry, and muscle biomarkers with blood samples for creatine kinase and myoglobin.

Muscle fat fraction in the lower back, thigh, and calf increased significantly over 6.5 years. The average increases were generally less than 2%, but some carriers with significant baseline abnormalities experienced a more substantial increase in fat fraction, reaching as high as 31%. Although overall disease progression did not differ significantly between DMD and BMD carriers, all women who showed rapid progression were DMD carriers. Small but significant changes occurred in muscle strength and biomarkers.

The progression of muscle involvement in women carrying pathogenic DMD gene variants is generally slow. However, those with severe baseline abnormalities on MRI-often associated with a lower age of symptom onset-experience a more rapid progression of muscle fat fraction, suggesting that baseline MRI findings could help predict future disease progression in this population.