Central core disease: clinical, pathological, and genetic features

• Published in: Archives of disease in childhood Vol. 88; no. 12; pp. 1051 - 1055
• Main Authors: Quinlivan, R M, Muller, C R, Davis, M, Laing, N G, Evans, G A, Dwyer, J, Dove, J, Roberts, A P, Sewry, C A
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health 01-12-2003; BMJ; BMJ Publishing Group Ltd; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Biological and medical sciences; Biopsy; CCD; central core disease; Child; Congenital diseases; Connective tissue; Development and progression; Diagnosis; Family (Sociological Unit); Female; Fever; forced vital capacity; FVC; General aspects; Genetic aspects; Genetic disorders; Genetics; Humans; Hyperthermia; in vitro contracture test; Infant; IVCT; Kinases; Male; malignant hyperthermia; masseter muscle spasm; Medical sciences; MMR; Muscle diseases; Muscle, Skeletal - pathology; Muscular diseases; Mutation; Mutation - genetics; myopathy; Myopathy, Central Core - genetics; Myopathy, Central Core - pathology; Original; Orthopedics; Pediatrics; Pedigree; ryanodine receptor; RYR1; Scoliosis; Severity (of Disability); Human; Pediatrics; Symptomatology; Striated muscle disease; Genetics; Central core myopathy; Congenital disease; Child; Genetic disease
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/adc.88.12.1051

Central core disease (CCD) is a dominantly inherited congenital myopathy allelic to malignant hyperthermia (MH) caused by mutations in the RYR1 gene on chromosome 19q13.1. Eleven individuals with RYR1 mutations are described. Four index cases showed features consistent with a congenital myopathy (hypotonia, delayed motor milestones, and skeletal abnormalities including congenital hip dislocation and scoliosis). All four cases and subsequently seven other family members were found to possess novel mutations in the RYR1 gene. The degree of disability varied from one clinically normal individual, to another who had never achieved independent ambulation (the only patient with a de novo mutation). Four cases showed a mild reduction in vital capacity, repeated nocturnal polysomnography showed hypoxaemia in one case. A variety of muscle biopsy features were found; central cores were absent in the youngest case, and the biopsy specimens from two others were more suggestive of mini-core myopathy. In all cases missense mutations in exons 101, 102, and 103 of the RYR1 gene on were found. Future laboratory diagnosis of suspected cases and family members will be less invasive and more accurate with DNA analysis. Clinicians, especially paediatricians and orthopaedic surgeons, should be aware of this disorder because of the potential risk of MH.