Quantitative Muscle MRI and Clinical Findings in Women With Pathogenic Dystrophin Gene Variants.

To explore fat replacement, muscle strength, and clinical features in women heterozygous for a pathogenic variant, we prospectively examined 53 women, assuming that some of these women-despite of the recessive X-linked inheritance-manifested clinical symptoms. We performed a cross-sectional observational study using MRI and stationary dynamometry of lower extremities, extracted blood muscle biomarkers, and investigated subjective complaints. Results were compared with 19 healthy women. variant carriers were weaker and had higher fat fractions than controls in all investigated muscle groups ( < 0.02). Fat fractions were 18% in carriers vs. 11% in controls in thighs ( = 0.008), and 15 vs. 11% in calf muscles ( = 0.032). Seventy-two percent had fat fractions deviating from controls by two standard deviations (SDs) in one or more of the 16 investigated muscle groups. On strength testing, 40% of the carriers had results deviating from control muscle strength by two SDs in one or more dynamometry assessments. Forty-three carriers (81%) had either reduced muscle strength (<2 SDs from control mean) and/or elevated muscle fat fraction (>2 SDs from control mean). Thirty of these had subjective symptoms. Blood creatine kinase and myoglobin were elevated in 57% of the carriers. Using quantitative methods, this study shows that both clinically symptomatic and asymptomatic women with pathogenic variants show a high prevalence of muscle affection. Longitudinal studies in female carriers of pathogenic variants are needed to follow the evolution of these changes.