Is cardiac dysfunction a feature of dysferlinopathy? Data from the clinical outcome study of dysferlinopathy

Dysferlinopathies are muscular dystrophies due to recessive mutations in the DYSF gene, and are not traditionally considered to cause cardiac dysfunction. However, occasional reports of patients having left ventricular dysfunction raise the possibility of dysferlinopathy associated cardiomyopathy. We sought to evaluate the frequency of cardiac test abnormalities in patients participating in the international multicentre clinical outcome study of dysferlinopathy. All 193 patients had genetically confirmed dysferlinopathy. Patients were followed over a three year period and underwent echocardiogram and ECGs at baseline assessment and after 36 months. Where indicated by abnormalities on echocardiogram, cardiac MRI was subsequently performed. Analysis of baseline cardiac assessments indicates that in the cohort as a whole, left ventricular ejection fractions (LVEF) were comparable with reported normal values for patient age and sex. Left ventricular systolic dysfunction was evident of echo-imaging in 7/193 individuals. Cardiac MRI was obtained in 5 of these 7 individuals, and confirmed the presence of clinically relevant findings in 3 individuals, demonstrating hypertrophic cardiomyopathy (n = 1), mildly impaired left ventricular function (n = 1) or segmental cardiomyopathy (n = 1). Two additional individuals had LVEF <55% on baseline echocardiograms, suggesting dysfunction, and are awaiting further assessment. Cardiomyopathy was diagnosed prior to study involvement in one further individual. Baseline ECGs did not identify abnormalities beyond that which might be typically encountered in the normal population. Data collection from the majority of 36 month assessments will be completed by summer 2017 and we allow presentation of longitudinal echocardiogram and ECG data in these patients. The clinical outcome study of dysferlinopathy will allow definitive conclusions about whether dysferlinopathy also has a cardiac phenotype and its prevalence.