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. 2003 Dec;88(12):1051–1055. doi: 10.1136/adc.88.12.1051

Central core disease: clinical, pathological, and genetic features

R Quinlivan 1, C Muller 1, M Davis 1, N Laing 1, G Evans 1, J Dwyer 1, J Dove 1, A Roberts 1, C Sewry 1
PMCID: PMC1719384  PMID: 14670767

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.

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Figure 1 .

Figure 1

Muscle biopsies stained for NADH-TR. A: normal two fibre pattern. A1: type 1 fibre uniformity (all dark fibres), central cores, and increased adipose and connective tissue. B1 (B2 similar): type 1 fibre uniformity with uneven staining and small core-like areas. B3: type 1fibre uniformity and multiple central and eccentric cores. C1: type 1 fibre uniformity. C2: abundant well defined central and eccentric cores with type 1 fibre uniformity. C3: type 1 fibre predominance, uneven stain, and small eccentric cores. D1: type uniformity, with cores in most fibres, a wide variability in fibre size, and excess adipose tissue.

Figure 2 .

Figure 2

Case B1, showing mild facial weakness with an inability to bury the eyelashes and early onset scoliosis.

Figure 3 .

Figure 3

Family tree of family 3.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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