Genetic Predictors and Remodeling of Dilated Cardiomyopathy in Muscular Dystrophy

Abstract

Background-Dystrophin gene mutations cause 2 common muscular dystrophies, Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Both are frequently associated with dilated cardiomyopathy (DCM) and premature death. We hypothesized that early diagnosis and treatment of DCM in DMD/BMD patients would lead to ventricular remodeling and that specific dystrophin gene mutations would predict cardiac involvement. Methods and Results-Sixty-nine boys with DMD (nϭ62) and BMD (nϭ7) (mean age, 12.9 and 13.7 years, respectively) were referred to our Cardiovascular Genetics Clinic for evaluation, including echocardiography and DNA analysis. Follow-up evaluations were scheduled yearly until the first abnormal echocardiogram indicative of DCM and quarterly thereafter. After the first abnormal echocardiogram, angiotensin-converting enzyme inhibitor or ␤-blocker therapy was started. ␤-Blockers were added if echocardiography showed no ventricular remodeling in angiotensin-converting enzyme inhibitor-treated patients after 3 months. DCM was diagnosed in 31 subjects (DMD, 27/62, 44%; BMD, 4/7, 57%) (mean age at onset, 15.4Ϯ2.8 years; range, 10.4 to 21.2 years). All 31 subjects were begun on pharmacological therapy after diagnosis. On follow-up (nϭ29), 2 subjects (both DMD) showed stable DCM, 8 subjects (all DMD) showed improvement, and 19 subjects (16 DMD; 3 BMD) showed normalization of left ventricular size and function (total improvement, 27/29 [93%]). DNA analysis in 47 cases (68%) revealed a significant association between DCM and exon 12 and 14 to 17 mutations, possible protection against DCM by exon 51 to 52 mutations, and a trend toward significant association between onset of DCM and exon 31 to 42 mutations. Statistical significance was based on nominal probability values. Conclusions-Early

Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management

“…Further studies are awaited to allow firm recommendations to be made. 108,[119][120][121][122][123] Signs or symptoms of abnormalities of cardiac rhythm should be promptly investigated with Holter or event monitor recording and should be treated. [124][125][126][127] Sinus tachycardia is common in DMD, but is also noted in systolic dysfunction.…”

Characteristics and outcomes of cardiomyopathy in children with Duchenne or Becker muscular dystrophy: A comparative study from the Pediatric Cardiomyopathy Registry

“…11,12 When started early in the course of cardiac dysfunction, these therapies may also slow progression of cardiac abnormalities. 13,14 , In our DMD+BMD group, ACE inhibitors and beta-blockers were prescribed between 1990 and 2005 in fewer than 40% at the time of cardiomyopathy diagnosis, despite 31% having CHF symptoms. Educating caregivers about this consensus may improve long-term outcomes including quality of life in these patients.…”

Muscular Dystrophies: Key Elements for Everyday Diagnosis and Management

“…Knowledge of disease-specific complications, implementation of anticipatory care, and medical advances have changed the standard of care, with an overall improvement in the clinical course, survival, and quality of life of affected people. [5][6][7][8][9][10][11] Muscular dystrophies can present an autosomal dominant, autosomal recessive, or Xlinked pattern of inheritance and can result from mutations affecting structural proteins localizable to the sarcolemma, nuclear or basement membrane, sarcomere, or non-structural enzymatic proteins. 1,4 In recent years, cardiac involvement has been observed in a growing number of genetic muscle diseases, and considerable progress has been made in understanding the relationships between disease skeletal muscle and cardiac muscle disease.…”

“…[5][6][7][8][9][10] Electrocardiography (ECG) and echocardiography are typically advocated for screening, 1,12 although very recently, cardiovascular magnetic resonance has shown promise in revealing early cardiac involvement when standard cardiac evaluation is unremarkable. [15][16][17] This review will focus on the skeletal muscle diseases most commonly associated with cardiac complications that can be diagnosed by echocardiography, such as dystrophin-associated diseases or dystrophinopathies that include Duchenne (DMD) and Becker (BMD) muscular dystrophies, cardiomyopathy of DMD/BMD carriers and X-L dilated cardiomyopathy.…”