Centronuclear myopathy

Centronuclear myopathy (CNM) is a group of rare inherited neuromuscular disorders characterized by the abnormal central positioning of nuclei within skeletal muscle fibers, which are normally located at the periphery. The condition is also known as myotubular myopathy, though this term is most often reserved for the severe X-linked form (X-linked myotubular myopathy, XLMTM). Centronuclear myopathies primarily affect the skeletal muscular system, leading to progressive muscle weakness and wasting. The severity and age of onset vary considerably depending on the genetic subtype. The X-linked recessive form (caused by MTM1 mutations) is the most severe, typically presenting at birth with profound hypotonia (low muscle tone), respiratory insufficiency requiring ventilatory support, feeding difficulties, and ophthalmoplegia (weakness of eye muscles). The autosomal dominant form (caused by DNM2 mutations) generally has a milder course with onset in childhood, adolescence, or adulthood, featuring slowly progressive limb weakness, ptosis (drooping eyelids), and ophthalmoplegia. The autosomal recessive forms (caused by BIN1, RYR1, or TTN mutations) are of intermediate severity, often presenting in infancy or childhood with generalized muscle weakness, facial weakness, and respiratory compromise. Additional features across subtypes may include elongated facial appearance, high-arched palate, scoliosis, and foot deformities. There is currently no cure for centronuclear myopathy. Management is supportive and multidisciplinary, focusing on respiratory support (including mechanical ventilation when needed), physical therapy to maintain mobility and prevent contractures, orthopedic interventions for skeletal complications, and nutritional support including gastrostomy feeding in severe cases. Gene therapy approaches, particularly for the X-linked form, are under active clinical investigation and represent a promising area of research.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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