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=12

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=<p><bold>Objective:</bold> To explore fat replacement, muscle strength, and clinical features in women heterozygous for a pathogenic <italic>DMD</italic> variant, we prospectively examined 53 women, assuming that some of these women—despite of the recessive X-linked inheritance—manifested clinical symptoms.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold><italic>DMD</italic> variant carriers were weaker and had higher fat fractions than controls in all investigated muscle groups (<italic>p</italic> &lt; 0.02). Fat fractions were 18% in carriers vs. 11% in controls in thighs (<italic>p</italic> = 0.008), and 15 vs. 11% in calf muscles (<italic>p</italic> = 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 (&lt;2 SDs from control mean) and/or elevated muscle fat fraction (&gt;2 SDs from control mean). Thirty of these had subjective symptoms. Blood creatine kinase and myoglobin were elevated in 57% of the carriers.</p><p><bold>Conclusion:</bold> Using quantitative methods, this study shows that both clinically symptomatic and asymptomatic women with pathogenic <italic>DMD</italic> variants show a high prevalence of muscle affection. Longitudinal studies in female carriers of pathogenic <italic>DMD</italic> variants are needed to follow the evolution of these changes.</p>