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

Women who carry the genetic defect for muscular dystrophy have a high risk of developing heart disease, especially as they age. The muscular dystrophy defect occurs on the X chromosome in the gene that produces the protein dystrophin. Researchers followed 197 female carriers of the muscular dystrophy defect for 3 to 10 years. At each annual examination, electrocardiograms and echocardiograms were included. Heart or skeletal muscle biopsies were taken from 12 of the women. Approximately 10% of the women had heart disease at the start of the study and less than 10% had any evidence of skeletal muscle disease. By the end of the study, 15% of the women 15 years or younger had developed heart disease, but 44.5% of those older than 15 had developed heart disease. Over 56% of those older than 50 with the Duchenne mutation had heart disease and 62.5% of those older than 50 with the Becker mutation had heart disease. Five women died, three of heart failure. Biopsies revealed abnormal dystrophin in the myocardial fibers.
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 fiber's 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. JAMA. 1996;275:1335-1338)