Collagen XII myopathy with rectus femoris atrophy and collagen XII retention in fibroblasts

Muscle Nerve. 2018 Jun;57(6):1026-1030. doi: 10.1002/mus.26067. Epub 2018 Feb 5.


Introduction: Mutation in the collagen XII gene (COL12A1) was recently reported to induce Bethlem myopathy. We describe a family affected by collagen XII-related myopathy in 3 generations.

Methods: Systematic interview, clinical examination, skin biopsies, and MRI of muscle were used.

Results: The phenotype was characterized by neonatal hypotonia, contractures, and delayed motor development followed by resolution of contractures and a motor performance limited by reduced endurance. DNA analyses revealed a novel donor splice-site mutation in COL12A1 (c.8100 + 2T>C), which segregated with clinical affection and abnormal collagen XII retention in fibroblasts. MRI disclosed a selective wasting of the rectus femoris muscle.

Discussion: COL12A1 mutations should be considered in patients with a mild Bethlem phenotype who present with selective wasting of the rectus femoris, absence of the outside-in phenomenon on MRI, and abnormal collagen XII retention in fibroblasts. Muscle Nerve 57: 1026-1030, 2018.

Keywords: Bethlem myopathy; MRI muscle; clinical phenotype; collagen 12A1 mutation; congenital muscular dystrophy; fibroblast stain.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Collagen Type XII / genetics
  • Collagen Type XII / metabolism*
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Humans
  • Male
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology*
  • Muscular Diseases / genetics
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology*
  • Mutation*


  • Collagen Type XII