P.2.17 Hypertrophic cardiomyopathy in a patient with Duchenne muscular dystrophy

Dilated cardiomyopathy is observed in Duchenne muscular dystrophy (DMD). We report the case of a 28 year old DMD patient who exhibited a hypertrophic phenotype and preservation of cardiac function. On cardiac magnetic resonance imaging (CMR), the patient demonstrated severe asymmetric septal hypertrophy, raising the possibility of an underlying genetic cause distinct from DMD. Left ventricular systolic function was preserved with a normal ejection fraction. Additional CMR late gadolinium enhancement (LGE) imaging for myocardial fibrosis demonstrated an unusual LGE pattern. The sub-epicardial LGE in the left ventricular free wall was typical of those found in DMD patients. However, LGE was also present at the right and left ventricular insertion points typical of patients with hypertrophic cardiomyopathy. The patient has a commonly found DMD mutation, duplication in exons 3–4 of the dystrophin gene, predictive of the characteristic DMD dilated cardiomyopathy. Further genetic testing for genes known to cause hypertrophic cardiomyopathy identified two mutations: a heterozygous Glu542Gln mutation in the MYBPC3 gene and a heterozygous Glu195Lys mutation in the TNNT2 gene. Both mutations have been reported as disease causing in individuals with autosomal dominant hypertrophic cardiomyopathy. This case illustrates the co-occurrence of two relatively common genetic conditions: DMD and HCM. We postulate that these confounding gene mutations led to cardiac muscle hypertrophy, preventing the expected development of the typical dilated cardiomyopathy. The downstream pathways by which the cardiac hypertrophy and myocyte disarray resulting from MYBPC3 and TNNT2 mutations might abrogate cardiac dysfunction caused by dystrophinopathy are unknown but have important clinical implications. They may reveal a potential gene-based therapeutic strategy whereby insertion of a pro-hypertrophic gene variant may ameliorate or prevent dilated cardiomyopathy in DMD patient.