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Arch Dis Child 88:1051-1055 doi:10.1136/adc.88.12.1051
  • Community child health, public health, and epidemiology

Central core disease: clinical, pathological, and genetic features

  1. R M Quinlivan1,
  2. C R Muller2,
  3. M Davis3,
  4. N G Laing4,
  5. G A Evans1,
  6. J Dwyer5,
  7. J Dove5,
  8. A P Roberts1,
  9. C A Sewry1
  1. 1Neuromuscular Clinic and Departments of Pathology and Radiology, The Robert Jones and Agnes Hunt District and Orthopaedic NHS Trust, Oswestry, Shropshire SY10 7AG, UK
  2. 2Department of Human Genetics, University of Wuerzberg, Wuerzberg 97074, Germany
  3. 3Department of Anatomical Pathology, Royal Perth Hospital, Perth, Australia
  4. 4Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australian Neuromuscular Research Institute, QE11 Medical Centre, Perth, Australia
  5. 5Department of Paediatric Orthopaedics and Paediatrics, North Staffordshire Royal Infirmary, Stoke on Trent, UK
  1. Correspondence to:
    Dr R Quinlivan
    Neuromuscular Clinic, Children’s Unit, Robert Jones and Agnes Hunt NHS Trust, Oswestry SY10 7AG, UK; Rcmq37aol.com
  • Accepted 27 April 2003

Abstract

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.

Footnotes