Letter by Giglio and Mangiola Regarding Article, “Cardiomyopathy in Duchenne Muscular Dystrophy Carrier and Her Diseased Son: Similar Pattern Revealed by Cardiovascular MRI”
To the Editor:
Yilmaz et al1 provide a compelling report focused on the cardiac involvement in a Duchenne carrier and her affected child. They showed a similar late gadolinium enhancement (LGE) pattern revealed by cardiac MRI, relating genotype to the degree of cardiomyopathy. We believe that some additional comment is needed about the interpretation of their results.
Duplication of exons 8 to 11 of the dystrophin gene is a very rare rearrangement that requires in the carrier, for multiplex ligation-dependent probe amplification, testing of all 79 exons of the dystrophin gene.2 Moreover, the skewed X-chromosome inactivation assay must be performed because this factor is currently believed to be a main contributor to phenotypic manifestations in a Duchenne carrier.3
Both the Duchenne carrier and her son showed a mild cardiac involvement (ejection fraction, 45% in the former and 52% in the latter). Although the available evidence suggests that the amount of LGE is related to the left ventricular function, the authors did not report data on LGE in terms of percent myocardial left ventricular affected mass.
The authors emphasized and confirmed their observations (Figure 3 in their article) comparing the LGE pattern of the Duchenne carrier and child with the endomyocardial biopsy of a patient with “muscular dystrophy” who did not report a diagnosis. Dystrophin immunostaining of this subject showed in the same sample a mosaic pattern (feature of a Duchenne muscular dystrophy carrier and/or patient with Becker muscular dystrophy) and the absence of dystrophin in most cardiomyocytes (feature of a Duchenne patient). This approach seems frankly incorrect.
Subepicardial inferolateral LGE is acknowledged as a marker of fibrosis, but the simple association between LGE and severe cardiomyopathy in nonmanifesting carriers, although likely to occur, must be still proven. LGE might be present in very young carriers, remaining confined to the inferior wall even for long periods of time. In some patients (currently we do not know which ones), LGE might increase, thus causing the onset of cardiomyopathy. Notably, the same LGE pattern and location shown by the authors may be present even in limb-girdle and Becker muscular dystrophy,4 suggesting that LGE might represent in neuromuscular disease a nonspecific cardiac phenotype.
The observation of LGE in both a Duchenne carrier and her affected son is intriguing and reinforces the concept that the myocardium, as the skeletal muscle, could be genetically altered. Readers may be interested in the finding that the reported duplication might be associated with cardiomyopathy, but this appears random and unpredictable.5 The authors could help by contributing in this pivotal area, confirming that genetics is not a factor conditioning LGE pattern and onset and the clinical course of cardiomyopathy.