Cardiomyopathy in a patient with limb-girdle muscular dystrophy type 2D: Pathomorphological aspects

Abstract

Sarcoglycanopathies are a group of autosomal recessive limb-girdle muscular dystrophies caused by mutations in the genes encoding for α-, β-, γ- and δ-sarcoglycan, which are expressed in skeletal and cardiac muscle. Cardiomyopathy has rarely been reported in patients with mutations in the α-sarcoglycan gene and descriptions of heart pathology are lacking. To our knowledge, this is the first report on characteristic pathomorphological changes in cardiac muscle detected at autopsy in a patient with a proven mutation (nucleotide substitution 229C>T (R77C) in exon 3) in the α-sarcoglycan gene. The patient had the phenotype of Duchenne-like muscular dystrophy. Due to severe weakness of the respiratory muscles, permanent nocturnal mechanical ventilation via a tracheostomy had been necessary since the age of 24 years. The patient also suffered from mild pulmonary and systemic hypertension. At the age of 36, he lost consciousness and was brought to the emergency room in asystolia and unsuccessfully reanimated for half an hour. Gross heart examination disclosed scattered unsharply demarcated grey and yellow areas, characteristically localised in the outer (subepicardial) part of the lateral and posterior left ventricular wall, while the interventricular septum was spared. Similar changes were present in the apical region of the posterior right ventricular wall. Histopathological changes in focal subepicardial myocardial lesions in the free left ventricular wall consisted of myocardial degeneration in the absence of inflammatory infiltrates, fibrosis and fatty replacement of the myocardium, strikingly similar to changes in skeletal muscle. Since autopsy did not reveal any significant coronary stenosis or valvular pathology, both chronic myocardial ischemia and valvular disease could be excluded as causes of the above-described changes, which were ascribed to α-sarcoglycanopathy. Mild myocardial hypertrophy could be attributed to pulmonary and systemic hypertension. The progression of cardiomyopathy in α-sarcoglycanopathy was considered slow, since it had not reached the stage of dilated cardiomyopathy at the time of death. Focal subepicardial myocardial lesions, most pronounced in the posterobasal segment of the left ventricle, were characteristic of cardiomyopathy in α-sarcoglycanopathy. Since focal lesions may spread further, thorough cardiac monitoring is recommended in patients with α-sarcoglycanopathy.