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

J Neuromuscul Dis. 2020;7(4):407-417. doi: 10.3233/JND-190457.

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; force production; magnetic resonance imaging.

MeSH terms

  • Adult
  • Collagen Type VI / genetics*
  • Contracture* / diagnostic imaging
  • Contracture* / metabolism
  • Contracture* / pathology
  • Contracture* / physiopathology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Lower Extremity* / diagnostic imaging
  • Lower Extremity* / pathology
  • Lower Extremity* / physiopathology
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Muscle, Skeletal* / diagnostic imaging
  • Muscle, Skeletal* / metabolism
  • Muscle, Skeletal* / pathology
  • Muscle, Skeletal* / physiopathology
  • Muscular Dystrophies / congenital*
  • Muscular Dystrophies / diagnostic imaging
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophies / pathology
  • Muscular Dystrophies / physiopathology
  • Muscular Dystrophy, Duchenne* / diagnostic imaging
  • Muscular Dystrophy, Duchenne* / metabolism
  • Muscular Dystrophy, Duchenne* / pathology
  • Muscular Dystrophy, Duchenne* / physiopathology

Substances

  • Collagen Type VI

Supplementary concepts

  • Bethlem myopathy