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. Other neuromuscular conditions can have similar findings on muscle biopsy, so these features are not always diagnostic for CNM. Patients with RYR1-associated CNM typically present at birth with profound weakness and hypotonia. Reduced fetal movement and polyhydramnios may also be noted in the prenatal period. Frequent respiratory tract infections and feeding difficulties associated with bulbar involvement are common, but often exhibit substantial improvement over time. Slow improvement in muscle strength is typically observed, and there is no known association with cognitive involvement. Patients share similar phenotypic features including myopathic facies with inverted V-shaped mouth, and external ophthalmoplegia. Key histopathological findings include a lower total number of central nuclei than is seen with other genetic forms of CNM, fibers with internal nuclei (often multiple), a marked increase in fat and connective tissue, and a notable absence of necrosis and regeneration. Mutations in RYR1 have also been associated with malignant hyperthermia, central core disease and multi-minicore disease.
Specimen Types Accepted