Phenotypic Variability of Dystrophinopathy Symptomatic Female Carriers

Can J Neurol Sci. 2017 May;44(3):304-310. doi: 10.1017/cjn.2016.448. Epub 2017 Feb 9.

Abstract

Background: Dystrophinopathies are X-linked muscular dystrophies characterized by pathogenic mutations in the dystrophin gene. Symptomatic dystrophinopathy female carriers may present with limb-girdle weakness. The diagnosis may be challenging in the absence of affected male relatives. We aimed to describe the phenotypic variability in a series of molecular-confirmed female dystrophinopathy patients.

Methods: This is a retrospective analysis of medical records from 1997 to 2015.

Results: Ten female dystrophinopathy patients were selected, two with unusual phenotypes: one with early joint contractures muscular dystrophy and the other with very late onset myopathy. Muscle imaging studies demonstrated predominant asymmetric fat replacement. Muscle biopsy immunohistochemistry demonstrated clear mosaic pattern in two cases and only subtle reduction of dystrophin intensity in three.

Conclusions: Adequate diagnosis is fundamental for genetic counseling and cardiologic follow-up. Female patients with dystrophinopathy may present unusual phenotypes such as early contractures and very late onset myopathy.

Keywords: Xp21; contractures; dystrophinopathy; imaging; rimmed vacuoles; symptomatic carrier.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Dystrophin / genetics*
  • Female
  • Heterozygote*
  • Humans
  • Middle Aged
  • Muscular Dystrophies / diagnostic imaging*
  • Muscular Dystrophies / genetics*
  • Phenotype*
  • Retrospective Studies

Substances

  • Dystrophin