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Genetics Home Reference: your guide to understanding genetic conditions
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Central core disease

Reviewed October 2007

What is central core disease?

Central core disease is a disorder that affects muscles used for movement (skeletal muscles). This condition causes muscle weakness that ranges from almost unnoticeable to very severe.

Most people with central core disease experience persistent, mild muscle weakness that does not worsen with time. This weakness affects the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. Muscle weakness causes affected infants to appear "floppy" and can delay the development of motor skills such as sitting, standing, and walking. In severe cases, affected infants experience profoundly weak muscle tone (hypotonia) and serious or life-threatening breathing problems. Central core disease is also associated with skeletal abnormalities such as abnormal curvature of the spine (scoliosis), hip dislocation, and joint deformities called contractures that restrict the movement of certain joints.

Many people with central core disease also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.

Central core disease gets its name from disorganized areas called cores, which are found in the center of muscle fibers in many affected individuals. These abnormal regions can only be seen under a microscope. Although the presence of cores can help doctors diagnose central core disease, it is unclear how they are related to muscle weakness and the other features of this condition.

How common is central core disease?

Central core disease is probably an uncommon condition, although its incidence is unknown.

What genes are related to central core disease?

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, allowing calcium ions to "leak" through the abnormal channel or impairing the channel's ability to release stored calcium ions at the correct time. This disruption in calcium ion transport prevents muscles from contracting normally, leading to the muscle weakness characteristic of central core disease.

Related Gene(s)

Changes in this gene are associated with central core disease.

  • RYR1

How do people inherit central core disease?

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 mutated copy of the RYR1 gene, however, may be at increased risk for malignant hyperthermia.

Where can I find information about diagnosis or management of central core disease?

These resources address the diagnosis or management of central core disease and may include treatment providers.

  • Gene Review: Central Core Disease (http://www.ncbi.nlm.nih.gov/books/NBK1391/)
  • Genetic Testing Registry: Central core disease (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0751951)
  • MedlinePlus Encyclopedia: Hypotonia (http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm)
  • MedlinePlus Encyclopedia: Malignant Hyperthermia (http://www.nlm.nih.gov/medlineplus/ency/article/001315.htm)

You might also find information on the diagnosis or management of central core disease in Educational resources (http://www.ghr.nlm.nih.gov/condition/central-core-disease/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/central-core-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about central core disease?

You may find the following resources about central core disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for central core disease?

  • CCD
  • CCO
  • Central Core Myopathy
  • Myopathy, Central Core
  • Shy-Magee Syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about central core disease?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding central core disease?

acidosis ; autosomal ; autosomal dominant ; autosomal recessive ; calcium ; cell ; channel ; congenital ; dislocation ; fever ; gene ; hyperthermia ; hypotonia ; incidence ; ions ; ion transport ; joint ; motor ; muscle relaxant ; muscle tone ; mutation ; protein ; proximal ; receptor ; recessive ; rhabdomyolysis ; scoliosis ; surgery ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: Central Core Disease (http://www.ncbi.nlm.nih.gov/books/NBK1391/)
  • Jungbluth H. Central core disease. Orphanet J Rare Dis. 2007 May 15;2:25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17504518?dopt=Abstract)
  • Kossugue PM, Paim JF, Navarro MM, Silva HC, Pavanello RC, Gurgel-Giannetti J, Zatz M, Vainzof M. Central core disease due to recessive mutations in RYR1 gene: is it more common than described? Muscle Nerve. 2007 May;35(5):670-4. (http://www.ncbi.nlm.nih.gov/pubmed/17226826?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/14670767?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16917943?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16084090?dopt=Abstract)
  • 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. Epub 2006 Apr 18. (http://www.ncbi.nlm.nih.gov/pubmed/16621918?dopt=Abstract)
  • Zhou H, Jungbluth H, Sewry CA, Feng L, Bertini E, Bushby K, Straub V, Roper H, Rose MR, Brockington M, Kinali M, Manzur A, Robb S, Appleton R, Messina S, D'Amico A, Quinlivan R, Swash M, Müller CR, Brown S, Treves S, Muntoni F. Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies. Brain. 2007 Aug;130(Pt 8):2024-36. Epub 2007 May 4. (http://www.ncbi.nlm.nih.gov/pubmed/17483490?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2007
Published: July 7, 2014