Characterization of the muscle involvement in dynamin 2-related centronuclear myopathy

Brain. 2006 Jun;129(Pt 6):1463-9. doi: 10.1093/brain/awl071. Epub 2006 Apr 3.

Abstract

Centronuclear myopathy (CNM) is a slowly progressive congenital myopathy characterized by abnormal centrally located nuclei in a large number of muscle fibres. Recently, different missense mutations affecting the middle domain of the dynamin 2 (DNM2) have been shown to cause autosomal dominant CNM. In order to better define the phenotype of DNM2-related CNM, we report here on the clinical and muscle imaging findings of 10 patients harbouring DNM2 mutations. DNM2-CNM is characterized by slowly progressive muscular weakness usually beginning in adolescence or early adulthood. In addition to bilateral ptosis, our data show that distal muscle weakness often exceeds proximal involvement. Furthermore, electrophysiological investigations frequently demonstrated signs of mild axonal peripheral nerve involvement, and electromyographical examination may show neuropathic changes in addition to the predominant myopathic changes. These features overlap with findings seen in the phenotype of DNM2-related autosomal dominant Charcot-Marie-Tooth disease type 2B. In all 10 DNM2-CNM patients, muscle computer tomography assessment showed a consistent pattern of muscular involvement and a characteristic temporal course with early and predominant distal muscle involvement, and later affection of the posterior thigh compartment and gluteus minimus muscles. The recognition of this specific imaging pattern of muscle involvement--distinct to the reported patterns in other congenital myopathies--may enable a better selection for direct genetic testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Child
  • Dynamin II / genetics*
  • Humans
  • Middle Aged
  • Muscle Weakness / diagnostic imaging
  • Muscle Weakness / genetics
  • Muscle Weakness / pathology
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / pathology
  • Mutation, Missense
  • Myopathies, Structural, Congenital / diagnostic imaging
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology
  • Myopathies, Structural, Congenital / physiopathology
  • Phenotype
  • Tomography, X-Ray Computed

Substances

  • Dynamin II