Clinical and histologic changes in the follow-up of a congenital myopathy

A 19-year-old woman was born with congenital hypotonia, generalized weakness, and dysmorphic features. A muscle biopsy performed at age 18 months found that type I fibers were smaller and more numerous than type II fibers, and she was diagnosed with congenital fiber type disproportion. She grew up with moderate motor impairment, but after a stationary period her weakness progressed gradually and she developed a severe ophthalmoplegia. When she was 18 years old a second muscle biopsy still indicated the predominance of type I fibers but also the presence of central nuclei and strong oxidative enzyme activity in the center of most of the fibers; this was compatible with centronuclear myopathy. The diagnostic reconsideration raises questions about the pathogenesis of these diseases and the recognition of congenital fiber type disproportion as a distinct nosologic entity.