Congenital myopathy associated with the triadin knockout syndrome

Neurology. 2017 Mar 21;88(12):1153-1156. doi: 10.1212/WNL.0000000000003745. Epub 2017 Feb 15.

Abstract

Objective: Triadin is a component of the calcium release complex of cardiac and skeletal muscle. Our objective was to analyze the skeletal muscle phenotype of the triadin knockout syndrome.

Methods: We performed clinical evaluation, analyzed morphologic features by light and electron microscopy, and immunolocalized triadin in skeletal muscle.

Results: A 6-year-old boy with lifelong muscle weakness had a triadin knockout syndrome caused by compound heterozygous null mutations in triadin. Light microscopy of a deltoid muscle specimen shows multiple small abnormal spaces in all muscle fibers. Triadin immunoreactivity is absent from type 1 fibers and barely detectable in type 2 fibers. Electron microscopy reveals focally distributed dilation and degeneration of the lateral cisterns of the sarcoplasmic reticulum and loss of the triadin anchors from the preserved lateral cisterns.

Conclusions: Absence of triadin in humans can result in a congenital myopathy associated with profound pathologic alterations in components of the sarcoplasmic reticulum. Why only some triadin-deficient patients develop a skeletal muscle phenotype remains an unsolved question.

Publication types

  • Case Reports

MeSH terms

  • Arrhythmias, Cardiac / complications*
  • Arrhythmias, Cardiac / genetics*
  • Carrier Proteins / genetics
  • Child
  • Electrocardiography
  • Humans
  • Male
  • Microscopy, Electron, Transmission
  • Muscle Proteins / deficiency*
  • Muscle Proteins / genetics
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / ultrastructure
  • Mutation / genetics
  • Myotonia Congenita* / complications
  • Myotonia Congenita* / genetics
  • Myotonia Congenita* / pathology
  • Sarcoplasmic Reticulum / pathology
  • Sarcoplasmic Reticulum / ultrastructure

Substances

  • Carrier Proteins
  • Muscle Proteins
  • TRDN protein, human