Lower Extremity Muscle Involvement in the Intermediate and Bethlem Myopathy Forms of COL6-Related Dystrophy and Duchenne Muscular Dystrophy: A Cross-Sectional Study

Article type: Research Article

Authors: Batra, Abhinandan^a | Lott, Donovan J.^a | Willcocks, Rebecca^a | Forbes, Sean C.^a | Triplett, William^a | Dastgir, Jahannaz^b | Yun, Pomi^b | Reghan Foley, A.^b | Bönnemann, Carsten G.^b | Vandenborne, Krista^a | Walter, Glenn A.^{c; *}

Affiliations: [a] Department of Physical Therapy, University of Florida, Gainesville, Florida, USA | [b] Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA | [c] Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA

Correspondence: [*] Correspondence to: Glenn A. Walter, Ph.D., Professor, Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL-32610. Tel.: +1 (352) 294 5996; E-mail: glennw@ufl.edu.

Abstract: Collagen VI-related dystrophies (COL6-RDs) and Duchenne muscular dystrophy (DMD) cause progressive muscle weakness and disability. COL6-RDs are caused by mutations in the COL6 genes (COL6A1, COL6A2 and COL6A3) encoding the extracellular matrix protein collagen VI, and DMD is caused by mutations in the DMD gene encoding the cytoplasmic protein dystrophin. Both COL6-RDs and DMD are characterized by infiltration of the muscles by fatty and fibrotic tissue. This study examined the effect of disease pathology on skeletal muscles in lower extremity muscles of COL6-RDs using timed functional tests, strength measures and qualitative/ quantitative magnetic resonance imaging/spectroscopy measures (MRI/MRS) in comparison to unaffected (control) individuals. Patients with COL6-RD were also compared to age and gender matched patients with DMD. Patients with COL6-RD presented with a typical pattern of fatty infiltration of the muscle giving rise to an apparent halo effect around the muscle, while patients with DMD had evidence of fatty infiltration throughout the muscle areas imaged. Quantitatively, fat fraction, and transverse relaxation time (T2) were elevated in both COL6-RD and DMD patients compared to unaffected (control) individuals. Patients with COL6-RD had widespread muscle atrophy, likely contributing to weakness. In contrast, patients with DMD revealed force deficits even in muscle groups with increased contractile areas.

Keywords: Collagen VI-related dystrophies, duchenne muscular dystrophy, magnetic resonance imaging, force production

DOI: 10.3233/JND-190457

Journal: Journal of Neuromuscular Diseases, vol. 7, no. 4, pp. 407-417, 2020