FINAL DIAGNOSIS: BECKER MUSCULAR DYSTROPHY
The cause of death in this patient was most likely pulmonary hemorrhage resulting from anticoagulation therapy, given to prevent thrombus formation due to congestive heart failure resulting from his dilated cardiomyopathy. The cardiomyopathy was, in turn, caused by a Becker-type of muscular dystrophy.
Becker muscular dystrophy is a hereditary X-linked disease characterized by alteration of the dystrophin gene product, a structural protein important for maintaining the integrity of skeletal and cardiac muscle cell cytoskeleton. Alterations are usually due to inframe deletions, duplications or point mutations of the dystrophin gene, which is approximately 2500 kilobases in size and is located on chromosome Xp211. The related and more severe disease, Duchenne muscular dystrophy, results from complete lack of expression of dystrophin protein, usually as a result of larger deletions of the gene which result in shift of the reading frame. Molecular DNA deletion analysis of the dystrophin gene was performed on this patient when he was 24 years old and confirmed the presence of deletions consistent with a Becker muscular dystrophy genotype.
The skeletal muscle in this patient also showed nearly all of the histologic features of Becker muscular dystrophy, including necrosis, regeneration, endomysial fibrosis, splitting fibers and abnormal variation in fiber size.
Cardiac failure is the most common cause of death in Becker muscular dystrophy patients. It is postulated that impaired myocardium leads to an increased workload on the left ventricle, which in turn leads to left ventricular enlargement and mitral valve dilatation. This patient had severe cardiomyopathy with left and right ventricular enlargement and mitral and tricuspid valve annular dilatation. Pulmonary vascular thickening suggests the presence of left heart failure with subsequent development of pulmonary hypertension leading to right ventricular dilatation and possible right heart failure. The terminal event in this patient was an acute, severe pulmonary hemorrhage of the right lower lobe of lung possibly related to pulmonary hypertension, chronic congestive heart failure and possibly anticoagulation therapy necessitated by the chronic dilated cardiomyopathy. The vitamin K given on admission to reverse the Coumadin effects and his hemoptysis may also have played roles in the pulmonary hemorrhage.
It is interesting to note that the patient's younger brother, who was also clinically affected by Becker muscular dystrophy and who died at 14 years, had autopsy findings (Figures 8A and 8B) nearly identical to those seen in this patient.
Contributed by Marie C DeFrances, MD, PhD and Robert E Lee, MD