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

• Published in: Frontiers in neurology Vol. 12; p. 707837
• Main Authors: Fornander, Freja, Solheim, Tuva Åsatun, Eisum, Anne-Sofie Vibæk, Poulsen, Nanna Scharff, Andersen, Annarita Ghosh, Dahlqvist, Julia Rebecka, Dunø, Morten, Vissing, John
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 03.09.2021
• Subjects: Dixon MRI; dynamometry; dystrophinopathy; female carriers; muscle fat infiltration; muscle strength; Neurology
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2021.707837

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.