AUTHOR=Fornander Freja , Solheim Tuva Åsatun , Eisum Anne-Sofie Vibæk , Poulsen Nanna Scharff , Andersen Annarita Ghosh , Dahlqvist Julia Rebecka , Dunø Morten , Vissing John 

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

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.707837

DOI=10.3389/fneur.2021.707837

ISSN=1664-2295

ABSTRACT=Objective: To explore fat replacement, muscle strength and clinical features in women heterozygous for a pathogenic DMD variant, we prospectively examined 53 women, assuming that some of these women – despite of the recessive X-linked inheritance – manifested clinical symptoms.
Methods: 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.
Results: DMD variant carriers were weaker and had higher fat fractions than controls in all investigated muscle groups (p<0.02). Fat fractions were 18% in carriers vs. 11% in controls in thighs (p=0.008), and 15% vs. 11% in calf muscles (p=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. 
Conclusion: Using quantitative methods, this study shows that both clinically symptomatic and asymptomatic women with pathogenic DMD variants show a high prevalence of muscle affection. Longitudinal studies in female carriers of pathogenic DMD variants are needed to follow the evolution of these changes.