Congenital Centronuclear Myopathy Type 1

Abstract

Autosomal dominant centronuclear myopathy is a congenital, slowly progressive myopathy, which is pathologically characterized by high proportion of muscle fibers with centrally located nuclei, radial arrangement of sarcoplasmic strands around the nuclei, and predominance and hypotrophy of type 1 fibers. The onset of symptoms occurs usually in adolescence, but the disease may not become evident until the third decade of life, when weakness involves mainly limb girdle, trunk, and neck muscles but may also affect distal muscles. Some patients become wheelchair bound in their 50s. On MRI imaging, there is an early involvement of the ankle plantar flexors and the medial gastrocnemius, followed by posterior and anterior compartment of the thighs. Marked ocular involvement including ptosis and ophthalmoplegia are common, while contractures other than those affecting the Achilles tendon and/or long finger flexors are rare.

Patients with early onset may improve in muscle strength but may develop restrictive respiratory impairment over time. The disease is genetically heterogeneous: half of patients have been recognized to be due to mutations in the DNM2 gene, encoding dynamin-2 (Table 38.1).