Desminopathies form a heterogeneous group of myopathies characterised by pathological aggregations of desmin. We report a family, where mother and daughter presented with an atrioventricular block and a slowly progressive distal muscular weakness, with non-homogeneous focal atrophy on computed tomography scans. The mother developed a severe global heart insufficiency necessitating a heart transplantation at 56 years of age. Skeletal muscle biopsies were characterised by inclusion bodies strongly expressing desmin and alpha B-crystallin, with a predominantly subsarcolemmal localisation. Ultrastructurally most inclusions corresponded to non-membrane bound granulo-filamentous material with disruption of myofibrils. An immunoblot showed a hyperintense desmin band at 53 kDa and a second band at 49 kDa, the latter being absent in controls. The cardiac muscle of the explanted heart showed very similar inclusions. These cases illustrate that in this distinct subtype of desminopathies the cardiac muscle alterations are comparable with those observed in skeletal muscle, and suggest the possibility of a primary desmin pathology.