Science News: Muscle Involvement in Women Carrying Pathogenic DMD Gene Variants: A 6.5-Year Follow-up Study

Submitted by: Shaohua Xu, MD
Edited by: Rebecca O'Bryan, MD

Citation: Lyu Z, Poulsen NS, Joensen H, et al. Muscle involvement in women carrying pathogenic DMD gene variants: A 6.5-year follow-up study. J Neuromuscul Dis. Published online January 9, 2026. doi:10.1177/22143602251408549

Summary:
This 6.5‑year longitudinal study followed 34 women carrying pathogenic DMD gene variants and demonstrated that while most carriers experience slow, minimal progression of muscle involvement, a small subgroup—particularly those with high baseline muscle fat fraction, childhood‑onset symptoms, or variants typically causing Duchenne phenotypes—show substantially faster increases in muscle fat replacement. MRI revealed gradual fat accumulation mainly in the lower back, posterior thigh, and calf, with only modest changes in strength and function overall. These findings highlight that baseline MRI abnormalities are a meaningful predictor of future progression, offering important insight into prognosis and long‑term monitoring needs for female dystrophinopathy carriers.

Comments: 
This study fills a major gap in the natural history of female carriers of DMD variants—a population known to be clinically heterogeneous but historically understudied. By providing prospective, quantitative MRI‑based progression data over more than six years, it establishes that most carriers remain stable while identifying a distinct fast‑progressing subgroup with clear prognostic markers. The work also clarifies which clinical measures are sensitive (MRI) versus insensitive (strength testing, 6MWT) to change in this population, informing both clinical care and future trial design.

Why is this interesting/relevant to the AANEM audience?
This study is valuable for neuromuscular clinicians because it provides rare, long‑term, quantitative data on how muscle involvement evolves in women carrying pathogenic DMD variants, a population that is frequently seen in clinic but historically understudied. It offers practical insight into prognosis, surveillance, and counseling for female dystrophinopathy carriers.