Frequency
The exact prevalence of central core disease is unknown. However, it is thought to be the most common of the congenital myopathies, which are a group of muscle disorders that cause weakness very early in life. As a group, congenital myopathies affect 6 per 100,00 newborns.
Causes
Mutations in the RYR1 gene cause central core disease. The RYR1 gene provides instructions for making a protein called ryanodine receptor 1. This protein plays an essential role in skeletal muscles. For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of charged atoms (ions) into muscle cells. The ryanodine receptor 1 protein forms a channel that releases calcium ions stored within muscle cells. The resulting increase in calcium ion concentration inside muscle cells stimulates muscle fibers to contract, allowing the body to move.
Mutations in the RYR1 gene change the structure of ryanodine receptor 1 and the calcium channel that it forms. The abnormal calcium channel alters the normal flow of stored calcium ions within muscle cells. Specifically, calcium ions "leak" slowly but continually through the abnormal channel or calcium ions cannot pass through the channel when they are needed. This disruption in calcium ion transport prevents muscles from contracting normally, leading to the muscle weakness characteristic of central core disease.
Inheritance
Central core disease is most often inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.
Less commonly, central core disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but typically do not show signs and symptoms of the condition. People who carry one RYR1 gene mutation, however, may be at increased risk for malignant hyperthermia.
Other Names for This Condition
- CCD
- CCO
- Central core myopathy
- Myopathy, central core
- Shy's disease
- Shy-Magee syndrome
Additional Information & Resources
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Clinical Trials
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Fusto A, Moyle LA, Gilbert PM, Pegoraro E. Cored in the act: the use of models to understand core myopathies. Dis Model Mech. 2019 Dec 19;12(12):dmm041368. doi: 10.1242/dmm.041368. Citation on PubMed or Free article on PubMed Central
- Jungbluth H, Treves S, Zorzato F, Sarkozy A, Ochala J, Sewry C, Phadke R, Gautel M, Muntoni F. Congenital myopathies: disorders of excitation-contraction coupling and muscle contraction. Nat Rev Neurol. 2018 Mar;14(3):151-167. doi: 10.1038/nrneurol.2017.191. Epub 2018 Feb 2. Citation on PubMed
- Jungbluth H. Central core disease. Orphanet J Rare Dis. 2007 May 15;2:25. doi: 10.1186/1750-1172-2-25. Citation on PubMed or Free article on PubMed Central
- Lawal TA, Todd JJ, Meilleur KG. Ryanodine Receptor 1-Related Myopathies: Diagnostic and Therapeutic Approaches. Neurotherapeutics. 2018 Oct;15(4):885-899. doi: 10.1007/s13311-018-00677-1. Citation on PubMed or Free article on PubMed Central
- Quinlivan RM, Muller CR, Davis M, Laing NG, Evans GA, Dwyer J, Dove J, Roberts AP, Sewry CA. Central core disease: clinical, pathological, and genetic features. Arch Dis Child. 2003 Dec;88(12):1051-5. doi: 10.1136/adc.88.12.1051. Citation on PubMed or Free article on PubMed Central
- Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P. Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat. 2006 Oct;27(10):977-89. doi: 10.1002/humu.20356. Citation on PubMed
- Treves S, Anderson AA, Ducreux S, Divet A, Bleunven C, Grasso C, Paesante S, Zorzato F. Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders. Neuromuscul Disord. 2005 Oct;15(9-10):577-87. doi: 10.1016/j.nmd.2005.06.008. Citation on PubMed
- Wu S, Ibarra MC, Malicdan MC, Murayama K, Ichihara Y, Kikuchi H, Nonaka I, Noguchi S, Hayashi YK, Nishino I. Central core disease is due to RYR1 mutations in more than 90% of patients. Brain. 2006 Jun;129(Pt 6):1470-80. doi: 10.1093/brain/awl077. Epub 2006 Apr 18. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.