Central core disease

Central core disease (CCD), also known as central core myopathy or Shy-Magee syndrome, is a congenital myopathy primarily affecting skeletal muscle. It is caused predominantly by mutations in the RYR1 gene, which encodes the ryanodine receptor type 1, a calcium release channel critical for excitation-contraction coupling in skeletal muscle. The disease is characterized histologically by the presence of well-defined areas (cores) in the center of type 1 muscle fibers that lack mitochondria and oxidative enzyme activity. Clinical features typically present in infancy or early childhood and include hypotonia (floppy infant), delayed motor milestones, and proximal muscle weakness predominantly affecting the hip girdle and lower extremities. Many patients have associated orthopedic complications such as congenital hip dislocation, scoliosis, and foot deformities (pes planus or pes cavus). Facial weakness may be present but is usually mild. The severity of CCD is highly variable, ranging from mild weakness compatible with independent ambulation throughout life to more significant disability. Importantly, individuals with RYR1 mutations associated with CCD are at increased risk for malignant hyperthermia susceptibility (MHS), a potentially life-threatening reaction to certain anesthetic agents, particularly volatile anesthetics and succinylcholine. There is currently no curative treatment for central core disease. Management is supportive and multidisciplinary, including physical therapy to maintain mobility and prevent contractures, orthopedic interventions for skeletal complications, and respiratory monitoring in more severely affected individuals. Precautions regarding anesthesia are essential, and patients and family members should be counseled about malignant hyperthermia risk. Genetic counseling is recommended for affected families. The disease course is generally non-progressive or slowly progressive, and life expectancy is often normal in milder cases.

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

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