Myopathy with respiratory failure and typical myofibrillar lesions

16 patients representing 7 different pedigrees exhibited an unusual, adult onset limb-girdle myopathy with typical clinical hallmarks. In a majority of cases there was evidence of an autosomal dominant inheritance. A prominent early finding in all cases was respiratory muscle weakness, and in many of these an acute respiratory incapacity was the reason for the first neurological examination. Neck flexor and sometimes foot extensor weakness were other early symptoms. The clinical picture seems to be at variance with that of the more well known hereditary myopathies. Electrophysiological analysis confirmed a myopathy and serum muscle enzyme concentrations were normal or slightly elevated. Muscle biopsy findings revealed myofibrillar changes which, at the light microscopy level, included plaques that stained strongly with rhodamine-conjugated phalloidin, a specific marker for F-actin. At the ultrastructural level, these plaques were observed to be composed of moderately dense, thin filaments and were related to splitting of Z-discs or formed extensions from Z-discs. We believe that the muscle biopsy changes revealed by cytochemical and ultrastructural observations indicate defective myofibrillogenesis, and the possibility of defective actin polymerization is discussed. A conclusive answer requires further immunocytochemical and immunoelectrophoretic studies and possibly the application of molecular genetics.