Centronuclear myopathy (CNM) is a rare muscle disease associated with non-progressive or slowly progressive muscle weakness that can develop from infancy to adulthood. On muscle histopathology, patients with CNM have increased frequency of central nuclei, as well as type 1 fiber predominance and hypotrophy, in the absence of other significant abnormalities. The majority of patients with autosomal dominant or later onset CNM [OMIM#160150], including DNM2-associated CNM, are ambulatory into adulthood. Some patients with DNM2-associated CNM have a more severe infantile onset and may have early feeding and respiratory issues, as well as delayed milestones. Intelligence is usually normal, but at least one family with a DNM2 mutation has been reported to have mild cognitive impairment, as well as mild axonal peripheral nerve involvement. NADH staining of patients with DNM2 mutations often reveals radial arrangement of sarcoplasmic strands, which is highly characteristic of DNM2-associated CNM. DNM2 [OMIM#602378] is the only gene currently known to be associated with autosomal dominant CNM. DNM2 mutations account for most, but not all, cases of CNM with autosomal dominant inheritance or later onset. Mutations in the PH domain of the protein are more likely to be associated with severe neonatal onset, whereas the milder phenotypes with later onset are often caused by mutations in the middle domain. Mutations in DNM2 have also been associated with dominant intermediate Charcot-Marie-Tooth disease, type B [OMIM#606482]. To date no deletions or duplications involving the DNM2 gene as causative of CNM or CMT have been reported.
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