Clinical and histologic findings in autosomal centronuclear myopathy.

Centronuclear myopathy (CNM) is a congenital myopathy characterized by chains of centrally located nuclei in a large number of muscle fibers. Clinically, an early-onset form was reported in several autosomal-recessive (AR) families and many sporadic patients, whereas a late-onset form was found in most autosomal-dominant (AD) families. The boundary between these two forms remains unclear, and the molecular basis of autosomal CNM is still unresolved. To better define the clinical and morphologic characteristics of autosomal CNM, the authors analyzed a series of 29 patients from 12 families. Two subgroups were identified in three AD families: two families had a relatively late onset of disease and a slow progression of diffuse weakness, whereas the third family, who had a similar clinical course, also presented a unique diffuse muscle hypertrophy. Two presumed AR families and seven sporadic patients were analyzed together, and three subgroups were identified: 1) an early-onset form with ophthalmoparesis; 2) an early-onset form without ophthalmoparesis; and 3) a late-onset form without ophthalmoparesis. Overall, 23 muscle biopsies were reviewed; a majority of patients had >20% central nuclei, fiber type 1 predominance, and a radial distribution of sarcoplasmic strands on oxidative stains. A marked endomysial fibrosis was observed in three sporadic patients with a relatively severe clinical course. The classification reported in this study will be useful for the diagnosis and the follow-up evaluation of patients with autosomal CNM and for the research into the molecular defects underlying the condition.