Skeletal muscle pathology in autosomal dominant Emery-Dreifuss muscular dystrophy with lamin A/C mutations

We present our observations on the skeletal muscle pathology of nine cases from seven families of autosomal dominant Emery-Dreifuss muscular dystrophy (ADEDMD) with identified mutations in the lamin A/C gene, aged 2-35 years at the time of biopsy. The severity of pathological change was moderate and the most common features were variation in fibre size (hypertrophy and atr ophy), an increase in internal nuclei and smaller diameter fibres with high oxidative enzyme activity. Only one case showed necrosis, which was presen t in two separate samples taken from the quadriceps and tibialis anterior, at different ages. Immunocytochemistry detected an age-related reduction of laminin beta1 on the muscle fibres in adolescent and adult cases. Antibodi es to lamins A and A/C, and emerin did not reveal any detectable difference s from controls. Electron microscopy of two out of three cases showed an ab normal distribution of heterochromatin in many fibre nuclei. Our results sh ow that dystrophic changes in skeletal muscle are not a major feature of AD EDMD, and that nuclear abnormalities may be detected with electron microsco py. Immunodetection of reduced laminin beta1 may be a useful secondary mark er in adults with this disorder, as immunocytochemistry of lamins is not ye t of diagnostic use.