Development of cardiomyopathy in female carriers of Duchenne and Becker muscular dystrophies

JAMA. 1996 May 1;275(17):1335-8.

Abstract

Objective: To characterize the presence and behavior of the dystrophinopathic myocardial damage in female carriers of a gene defect at the Xp21 locus of the X chromosome that causes Duchenne and Becker muscular dystrophies (DMD and BMD).

Design: Cohort study from April 1, 1985, to April 30, 1995, with cardiologic follow-up performed yearly for a minimum of 3 to a maximum of 10 years.

Setting: Counseling center for genetic muscular disorders.

Patients: A total of 197 women and girls aged 5 to 60 years ascertained to be carriers of the DMD (n = 152) or BMD (n = 45) gene.

Main outcome measures: Cardiac status at yearly examinations as determined by 12-lead electrocardiogram (ECG), 24-hour ambulatory ECG, M-mode and 2-dimensional echocardiography, and carotid pulse tracing. Myocardial scintigram was performed on each individual at least twice during the study. Immunohistochemical analysis of dystrophin from myocardium and/or skeletal muscle biopsy was performed in 12 carriers.

Results: Preclinical or clinically evident myocardial involvement was found in 166 cases (84.3%), without significant differences in percentage and behavior between DMD and BMD carriers. Its occurrence increased significantly with age, from 54.5% (18 cases) in carriers aged between 5 and 16 years to 90.2% (148 cases) in carriers older than 16 years. Dystrophin anomalies were detected at the membrane level of the myocardial fibers in all endomyocardial biopsy specimens.

Conclusions: Genetic anomalies can be considered the primary cause of myocardial damage in carriers of dystrophinopathic myopathies; myocardial damage shows the same behavior already described in DMD and BMD patients and progresses from preclinical to dilated cardiomyopathy, passing through stages of myocardial hypertrophy or dysrhythmias.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / physiopathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dystrophin / metabolism
  • Female
  • Heart Function Tests
  • Heterozygote
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / physiopathology*
  • Myocardium / metabolism
  • Myocardium / pathology

Substances

  • Dystrophin

Grants and funding