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[Cardiac dysfunction in female gene carriers of Duchenne muscular dystrophy]
1First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Insights
Female Duchenne muscular dystrophy (DMD) gene carriers often show cardiac dysfunction and subclinical skeletal muscle involvement. Early cardiac screening is crucial to prevent heart failure in these individuals.
Area of Science:
- Cardiology
- Neurology
- Genetics
Context:
- Duchenne muscular dystrophy (DMD) is a genetic disorder primarily affecting males, but female carriers can also experience health issues.
- Cardiac and skeletal muscle involvement in female DMD carriers is not fully understood.
- This study investigates the prevalence and correlation of cardiac and skeletal muscle dysfunction in female DMD carriers.
Purpose:
- To assess the frequency of cardiac dysfunction in female DMD gene carriers.
- To evaluate skeletal muscle involvement in these carriers.
- To explore the correlation between cardiac and skeletal muscle dysfunction.
Summary:
- 31.3% of 16 female DMD carriers had cardiac symptoms, and 75% showed signs of dilated cardiomyopathy.
- Electrocardiographic abnormalities were found in 56.3% of carriers.
- While carriers lacked clinical muscle weakness, 87.5% had elevated creatine kinase and subclinical skeletal muscle changes on CT scans.
- A negative correlation was observed between left ventricular dimensions and skeletal muscle CT values, indicating a link between cardiac and skeletal muscle dysfunction.
Impact:
- Findings highlight a high incidence of both clinical and subclinical cardiac and skeletal muscle issues in DMD carriers.
- Emphasizes the need for proactive cardiac monitoring and treatment in female DMD carriers to prevent symptomatic heart failure.
- Suggests that early detection and management of cardiac dysfunction can improve outcomes for DMD carriers.
Abstract:
Cardiac dysfunction and its correlation with skeletal muscle dysfunction were examined in 16 definite female gene carriers of Duchenne muscular dystrophy (DMD). Five out of 16 carriers (31.3%) had cardiac symptoms and 8 carriers (50.0%) showed an increased cardio-thoracic ratio on chest X-ray. Electrocardiographic abnormalities including a high R:S ratio (> or = 1.0) in the V1 lead, deep Q wave (> 3 mm) in the I, II, aVL, V5, and V6 leads, complete right bundle branch block and premature ventricular beats, were observed in 9 carriers (56.3%). On echocardiographic examination, an increase in the end-diastolic dimension of the left ventricle and a decrease in the ejection fraction suggestive of dilated cardiomyopathy were found in 12 carriers (75.0%). Tl-201 myocardial SPECT scan was performed in 2 symptomatic carriers and showed an area of hypoperfusion in the inferio-posterior wall. These findings were similar to previously reported findings in DMD patients. A biopsy of the myocardium was obtained in one carrier with her informed consent for the biopsy. Immunohistochemical staining demonstrated that 75.4% of the myocardial fibers were negative for dystrophin, suggesting that her cardiac dysfunction is caused by the abnormal expression of dystrophin in the cardiac muscle. On examination of the skeletal muscle function, none of the carriers had clinical evidence of muscle weakness or atrophy. However serum creatine kinase activity was elevated in 14 of 16 carriers (87.5%). Computed tomography (CT) of the lower limb muscles demonstrated widened spaces among muscles and moss-eaten appearance of low density areas within muscles and CT value was decreased, suggesting the subclinical involvement of the skeletal muscle. In the carriers without cardiac symptoms, there was a negative correlation (p < 0.05) between the end-diastolic dimension of the left ventricle and the CT value of the biceps femoris muscle (a muscle with the lowest CT value among the lower limb muscles). This indicates that there was an apparent correlation between the cardiac and skeletal muscle dysfunction. These findings suggest a high frequency of clinical and subclinical involvement of the cardiac and skeletal muscles in DMD carriers. To protect them from cardiac failure, cardiac dysfunction in DMD carriers needs to be examined closely and treated appropriately before the carriers become symptomatic.