Cardiomyopathy
Left Ventricular Dysfunction in Duchenne Muscular Dystrophy and Genotype

https://doi.org/10.1016/j.amjcard.2014.04.038Get rights and content

Prognosis in patients with Duchenne muscular dystrophy (DMD) is guarded, and most deaths are due to cardiac or respiratory causes. It is unclear if some DMD gene mutations might be predictive of either mild or severe cardiac dysfunction. We studied 75 patients with DMD followed at our institution. Cardiac function, as assessed by yearly echocardiography, showed marked variability in left ventricular (LV) function. Some patients in their 3rd decade had no or minimal dysfunction, whereas others in their 2nd decade had very severe dysfunction. Therefore, 4 severity groups were defined ranging from no or mild LV dysfunction to severe LV dysfunction using patient age at first abnormal echocardiographic finding and degree of LV dysfunction. Genetic data were collected for all patients. Most patients had mutations from exon 1 to 20 to exon 41 to 55. The distribution of the 4 severity groups of LV dysfunction did not significantly differ between these 2 mutation groups. An analysis based on the number of exons involved (<5 vs ≥5 exons) also found no significant difference in cardiac severity. When patients having identical mutations were compared with their cardiac course, concordance was often not evident. Steroid therapy had no apparent protection for the development of cardiomyopathy. In conclusion, 75 patients with DMD showed marked variability in the severity of LV dysfunction. Neither the age of onset nor the severity of cardiomyopathy correlated with any of the mutation groups.

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.

References (29)

Cited by (49)

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    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.

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    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

  • A Morpholino Oligomer Therapy Regime That Restores Mitochondrial Function and Prevents mdx Cardiomyopathy

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    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.

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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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