CardiomyopathyLeft Ventricular Dysfunction in Duchenne Muscular Dystrophy and Genotype
Section snippets
Methods
Patients (n = 124) with a dystrophinopathy who were followed in the MetroHealth Medical Center Muscular Dystrophy Association Clinic over the years 1999 to 2011 were eligible for inclusion in the study. Patients with DMD and Becker muscular dystrophy have similar DMD mutations, and patients with Becker muscular dystrophy often develop severe cardiac dysfunction. Nevertheless, those with Becker muscular dystrophy were excluded from the present study leaving 104 patients having DMD, none of whom
Results
The clinical, genetic, and cardiac features of the 75 male patients are listed in Table 2. Most patients were Caucasian. Deletions were the most common type of mutation. The largest genetic group was C with the mutation starting from exon 41 to 55, and most patients had <5 exons involved.
Cardiomyopathy was evident in 43 patients (57.3%). The prevalence of cardiomyopathy increased with age, with the median age for the onset of cardiomyopathy being 21.0 years (95% confidence interval 18.2 to
Discussion
Our study is the largest study to date from a single institution to characterize the marked variability of cardiac dysfunction in patients with DMD. Because no previous reports systematically assessed the relative severity of the cardiomyopathy, we introduced a scale to reflect this variable severity; this classification encompassed both the age of onset and a quantitative assessment of the degree of LV dysfunction. We observed that some young patients had severe LV dysfunction and some older
Disclosures
The authors have no conflicts of interest to disclose.
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Cited by (49)
Cardiovascular Disease in Duchenne Muscular Dystrophy: Overview and Insight Into Novel Therapeutic Targets
2022, JACC: Basic to Translational ScienceCitation Excerpt :Additionally, the size of the gene also leads to hundreds of documented mutations of various types, including deletions, duplications, and missense mutations.30,31 DMD typically results from a deletion of more than 1 exon causing a premature stop codon, which in turn leads to a lack of dystrophin.32 Because cardiac dysfunction associated with DMD is quite variable, studies have investigated whether the underlying genetic mutations that cause DMD could predict the severity of cardiac dysfunction in DMD patients.
Cardiorespiratory management of Duchenne muscular dystrophy: emerging therapies, neuromuscular genetics, and new clinical challenges
2022, The Lancet Respiratory MedicineCitation Excerpt :Ideally, a patient's expected cardiorespiratory natural history could be predicted from his DMD genotype. However, related or unrelated patients who share a DMD genotype have been found to have highly divergent respiratory and cardiac phenotypes.15,88–91 For example, a patient's FVC might peak at a high absolute value and remain stable over time, while his brother's FVC peaks at a much lower level and declines rapidly.89
T<inf>1</inf>-Mapping and extracellular volume estimates in pediatric subjects with Duchenne muscular dystrophy and healthy controls at 3T
2020, Journal of Cardiovascular Magnetic ResonanceA Morpholino Oligomer Therapy Regime That Restores Mitochondrial Function and Prevents mdx Cardiomyopathy
2018, JACC: Basic to Translational ScienceCitation Excerpt :Conflicting reports on such an association are likely due to small sample size, variability in cardiac function analysis, clinical care and cardiac medications, and unverified consequences of the mutation on dystrophin transcript and/or protein (33–35). Patients with the same DMD genotype can show very different severity and age of onset of left ventricular dysfunction and, ultimately, survival (35). This confounds the interpretation of potential treatment-related effects.
DMD mutation and LTBP4 haplotype do not predict onset of left ventricular dysfunction in Duchenne muscular dystrophy
2018, Cardiology in the YoungThe IAAM LTBP4 Haplotype is Protective Against Dystrophin-Deficient Cardiomyopathy
2024, Journal of Neuromuscular Diseases
This publication was made possible by the Case Western Reserve University/Cleveland Clinic CTSA grant number UL1 RR024989 from the National Center for Research Resources, Bethesda, Maryland. Its contents are solely the responsibility of the authors and do not represent necessarily the official view of NCRR or NIH.
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