British Journal of Anaesthesia, Vol 83, Issue 2 217-222, Copyright © 1999 by The Board of Management and Trustees of the British Journal of Anaesthesia
J. L. Curran, W. J. Hall, P. J. Halsall, P. M. Hopkins, D. E. Iles, A. F. Markham, S. H. McCall, R. L. Robinson, S. P. West, L. R. Bridges and F. R. Ellis
Malignant hyperthermia (MH) is an autosomal dominant disorder presenting
under general anaesthesia. It is occasionally associated with a myopathy,
central core disease (CCD), named after its predominant histochemical
characteristic. The penetration of CCD is variable, but typically affected
individuals show delayed motor milestones in infancy and remain physically
compromised. It was thought until recently that individuals with CCD were
always susceptible to MH. Individuals from eight CCD families were screened
for the presence of 13 mutations in the skeletal muscle ryanodine receptor
gene, reported previously to be associated with MH and/or CCD: none was
detected. In seven of these families, where CCD and MH co-existed, we
examined the segregation of CCD, MH susceptibility and chromosome 19q
markers. In four families, there was complete co-segregation between MH,
CCD and the chromosome 19 markers, but in one large pedigree there was a
clear lack of segregation of CCD with either MH or chromosome 19 markers
and there was no segregation between MH and these markers. This is
unequivocal evidence that CCD, in common with MH, is genetically
heterogeneous. In the two other families, CCD segregated with chromosome 19
markers but not all individuals with CCD were susceptible to MH. We
recommend determination of MH susceptibility in all patients with CCD,
irrespective of the MH status of their relatives with CCD.
CLINICAL INVESTIGATIONS
Segregation of malignant hyperthermia, central core disease and chromosome 19 markers
Malignant Hyperthermia Investigation Unit, Academic Unit of Anaesthesia and Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK; Department of Genetics and Department of Pathology, University of Leeds, Leeds, UK; Northern Genetics Service, Newcastle Upon Tyne, UK
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