Rare case of severe cardiomyopathy in a 61 year–old man with mild muscle weakness caused by deletion of exons 48 and 49 in the dystrophin gene


Clinical Other

Poster Number: 4


Anasheh Halabi, MD, PhD, Perry Shieh, MD, PhD


1. UCLA, 2. David Geffen School of Medicine at UCLA

Becker muscular dystrophy (BMD) bears significant clinical heterogeneity with relatively milder skeletal muscle involvement when compared to Duchenne Muscular Dystrophy (DMD). Importantly however, the most common cause of morbidity in BMD patients is dilated cardiomyopathy with mean age of diagnosis in younger adolescents and mean age of death in the forties. Even in the absence of cardiomyopathy, BMD patients are at high risk for cardiac arrhythmias. Presently, the clinical heterogeneity of cardiomyopathy in BMD patients is hypothesized to be associated with in-frame dystrophin mutations, particularly at sites disrupting the rod-domain and the hinge-3 domains. Mutations at these sites presumably predispose an individual to more or less severe cardiac disease.

We present the case of a 61-year old man undergoing cardiac transplant evaluation and presenting to neuromuscular clinic for previously uncharacterized muscle disease. Patient’s history revealed he was first diagnosed with dilated cardiomyopathy around 44 years old and required ICD placement by 47 years old. At the onset of his cardiac symptoms, the patient endorsed subtle proximal leg weakness that did not interfere with his ability to perform activities of daily living. While undergoing work-up, it was also revealed he had twelve siblings of which three had died in their forties of heart-related reasons. On neurologic exam, the patient demonstrated symmetric quadriceps weakness (MRC 4/5 bilaterally) with intact reflexes. Genetic testing revealed hemizygous deletion of exons 48 and 49 in the dystrophin gene. Transthoracic echo presently demonstrates an ejection fraction of 26% and severely increased left ventricular size, normal wall thickness and severely reduced systolic function.

This case illustrates the value of molecular diagnosis and further substantiates evidence that in-frame deletions of exons 48 and 49 in the dystrophin gene cause severe cardiomyopathy in BMD patients.