Central core disease

This is part of Rare diseases.

Diagnosis: Central core disease

Synonyms: --


Date of publication: 2011-12-29
Version: 3.0

ICD 10 code


The disease

Central core disease is an inherited neuromuscular disorder causing muscle weakness.

In 1956, American physicians George Milton Shy and Kenneth Raymond Magee described the disease for the first time. The description was of a congenital form of muscle weakness found in three generations of the same family. The weakness was non-progressive and remained stable over time. A microscopic analysis of muscle fibres using coloured dyes revealed very specific changes. Some areas did not stain, revealing a central core in the middle of many muscle fibres. (See figure below.) In 1958 the disease was named by Joseph Godwin Greenfield and it refers to the characteristic abnormalities in the cores of muscle cells. There is no Swedish name for the disease.

Figure: Microscopic image of a cross section of muscle fibre
Figure: Microscopic image of a cross section of muscle fibre


It is not known how many people have the disease, but it is estimated that there are at the most fifty people with central core disease in Sweden.


Central core disease is caused by a mutation in gene RYR1, which is located on 9q13.1 and controls the production of (codes for) the ryanodine receptor 1 protein. The ryanodine receptor is an ion channel located in a membrane found within muscle fibres (the sarcoplasmic reticulum). This ion channel acts as a type of valve, allowing calcium ions to pass through. The precise reason why muscles do not function normally is unknown. However it is known that the central cores of the affected muscle fibres do not contain mitochondria. Mitochondria are small units within cells and are responsible for providing them with energy. To date (2011) more than forty different mutations in the ryanodine receptor gene have been identified.

Mutations in the RYR1 gene can cause other diseases, including inherited malignant hyperthermia. Separate information on this disease is available in the Swedish Rare Disease Database.


In most affected families the inheritance pattern of central core disease is autosomal dominant. This means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disease and do not pass it down.

Figure: Autosomal dominant inheritance

The inheritance pattern can also be autosomal recessive. This means that both parents are healthy carriers of a mutated gene. When two healthy carriers have a child, there is a 25 per cent risk that the child will inherit the mutated genes (one from each parent) in which case he or she will have the disease. In 50 per cent of cases the child inherits only one mutated gene (from one parent only) and like both parents, will be a healthy carrier of the mutated gene. In 25 per cent of cases the child will not have the disease and will not be a carrier of the mutated gene.

Figure: Autosomal recessive inheritance

A person with an inherited autosomal recessive disease has two mutated genes. If this person has a child with a person who is not a carrier of the mutated gene, all the children will inherit the mutated gene but they will not have the disorder. If a person with an inherited autosomal recessive disease has children with a healthy carrier of the mutated gene (who has one mutated gene) there is a 50 per cent risk of the child having the disorder, and a 50 per cent risk of the child being a healthy carrier of the mutated gene.


Central core disease is characterised by muscle weakness, the severity of which varies between individuals. Some individuals are only mildly affected, while others have such severe symptoms that they have problems walking.

Muscle weakness is often evident at birth or in early childhood. The condition results in delayed motor development, and children with the disease are late learning to sit, stand and walk. Muscle weakness primarily affects the hips and legs, but also the back, neck, and shoulders. The condition remains relatively stable throughout life and is non-progressive. Many people with central core disease experience muscle stiffness during strenuous physical activity, and may also suffer muscle cramps. Facial muscles are not affected.

People with the disease often develop deformities of the joints, particularly in the back and feet. Some patients have cardiac defects causing irregular heart rhythm or cardiac insufficiency.

People with central core disease may react to certain anaesthetics by developing a dangerously elevated body temperature (malignant hyperthermia.) Carriers of the mutation who have no symptoms of muscle weakness are also predisposed to malignant hyperthermia. Malignant hyperthermia is a complication leading to a dangerous rise in body temperature, and if not treated is a life-threatening condition. It is important that medical personnel are aware of the risks associated with malignant hyperthermia, to ensure that the right type of anaesthesia is administered. Further information about the inherited form of malignant hyperthermia can be found in the the Swedish Rare Disease Database.


Muscle weakness is evaluated by measuring the blood concentration of the enzyme creatine kinase (CK). An electromyography examination (EMG), measuring the electrical activity of muscles, will usually reveal signs of muscle disease. The diagnosis is confirmed by a muscle tissue analysis under a microscope. This will usually reveal characteristic abnormalities, in particular a central core in muscle fibres. Samples of muscle tissue are taken from an arm or leg muscle (muscle biopsy) under local anaesthesia.

A DNA analysis can also be used to confirm whether a person has the disease. Pre-natal diagnosis is therefore possible when the mutation causing the disease is known.


There is currently no cure for the disorder, and efforts are directed at relieving symptoms. Much can be done to support the individual and compensate as much as possible for functional limitations.

The heart should be examined at an early stage, and subsequently at regular intervals, as it can be affected by the disease.

The risk of the patient developing malignant hyperthermia should be assessed as early as possible. If an investigation is not carried out, everyone suspected or known to have the disease should be treated as if they risked developing malignant hyperthermia. Before an operation it is important that the anaesthetist is informed about the disorder so that dangerous complications are avoided.

While growing up, children with the disease require contact with various specialists including a paediatric neurologist, paediatric orthopaedic surgeon and paediatric cardiologist. It is important that investigations and treatment are coordinated by a paediatrician. Habilitation may also be necessary, in which case it should be based on the needs of the individual child. A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. Help is available within the medical, educational, psychological, social and technical fields. Measures may include assessments, treatment, assistance with choice of aids, information about disabilities and counselling. Information about support offered by the local authority as well as advice on changes to the individual’s accommodation and environment should also be available.

Regular contact with a physiotherapist is necessary to stimulate the child’s motor development, and to devise an individualised exercise programme to maintain muscle function. To prevent deformities developing, it is important to maintain joint mobility through daily exercise. It is also important to try to maintain muscle strength. Reports indicate that training programmes can help improve muscle strength in people with the disease. If the heart is affected by the disease, the training programme should take this into account. School and preschool staff should be informed about physical activities which are suitable for the child.

Abnormalities presenting in the back or joints should be assessed and followed up by an orthopaedic surgeon.

It is helpful to be well-informed about the disorder when making choices about education and what games and sports to participate in. When deciding on a suitable career, it is important to avoid jobs requiring physical exertion. When necessary, the Swedish Public Employment Services can provide support and information on choice of occupation and the Swedish Regional Social Insurance Office can help in adapting the work environment.

It is important that the psychological and social needs of the whole family are met. Support may be offered by a social worker and/or psychologist.

Adults with the condition require continued contact with the same kinds of specialists they had when growing up. Continued contact with, for example, a physiotherapist may also be necessary.

Central core disease has not been associated with any increased risk of complications in pregnancy.

Patients diagnosed with central core disease should be offered genetic counselling.

Medical warning card

In order to avoid misdiagnosis and inappropriate treatments, individuals with confirmed central core disease can carry a medical warning card, issued by NHR, The Swedish Association of Persons with Neurological Disabilities (see under “Organizations for the disabled/patient associations”) to be shown to all health care providers. The card confirms the diagnosis and provides information about potential risks, including those associated with anaesthesia.

Practical advice


National and regional resources in Sweden

Assessments of people with muscle diseases are carried out primarily at neurology clinics at Swedish university hospitals. People with central core disease should be examined by a neurologist with specialist knowledge of neuromuscular diseases.

Assessments of malignant hyperthermia are carried out at the Malignant Hyperthermia Unit, Anaesthesia Clinic, Skåne University Hospital, Lund, Sweden.

Resource personnel

Senior Physician Gunilla Islander, The Malignant Hyperthermia Unit, Anaesthesia Clinic, Skåne University Hospital/Lund, SE-221 85 Lund, Sweden. Tel: +46 46 17 10 00, email: gunilla.islander@skane.se.

Associate Professor Christopher Lindberg, Neuromuscular Centre, Sahlgrenska University Hospital/Sahlgrenska, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 10 00, email: christopher.lindberg@vgregion.se.

Senior Physician Björn Lindvall, Muscle Centre, Örebro University Hospital, SE-701 85 Örebro, Sweden. Tel: +46 19 602 10 00, email: bjorn.lindvall@orebroll.se.

Associate Professor Göran Solders, Neurology Clinic, Huddinge, Karolinska University Hospital, SE-141 86 Stockholm, Sweden. Tel: +46 8 585 800 00, email: goran.solders@karolinska.se.

Courses, exchanges of experience, recreation


Organizations for the disabled/patient associations

NHR, The Swedish Association for Persons with Neurological Disabilities, St Eriksgatan 44, Stockholm. Sweden. Mailing address: Box 49084, SE-100 28 Stockholm, Sweden. Tel: +46 8 677 70 10, fax: +46 8 24 13 15, email: nhr@nhr.se, www.nhr.se.

RBU, The Swedish National Association for Disabled Children and Young People, St Eriksgatan 44, Stockholm. Mailing address: Box 8026, SE-104 20 Stockholm, Sweden. Tel: +46 8 677 73 00, fax: +46 8 677 73 09, email: info@rbu.se, www.rbu.se.

Courses, exchanges of experience for personnel


Research and development (R&D)

Research into the clinical expression of the disease and its association with different mutations is underway in France, England, Germany, Sweden and Australia.

Information material

An information leaflet on central core disease that summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2004-126-1177.) Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.


Broman M, Islander G, Müller CR, Ranklev-Twetman E. Malignant hyperthermia and central core disease causative mutations in Swedish patients. Acta Anaesthesiol Scand 2007; 51: 50-53.

Denborough MA, Dennett X, Andersson RM. Central-core disease and malignant hyperpyrexia. Br Med J 1973; 1: 272-273.

Dirksen RT, Avila G. Altered ryanodine receptor function in central core disease: leaky or uncoupled Ca2+ release channels? Trends Cardiovasc Med 2002; 12: 189-197.

Frank JP, Harati Y, Butler IJ, Nelson TE, Scott CI. Central core disease and malignant hyperthermia syndrome. Ann Neurol 1980; 7: 11-17.

Gamble JG, Rinsky LA, Lee JH. Orthopedic aspects of central core disease. J Bone Joint Surg 1988; 70: 1061-1066.

Greenfields JG, Cornman T, Shy GM. The prognostic value of muscle biopsy in the “floppy infant”. Brain 1958; 81: 461-464.

Jungbluth H, Muntoni F, Ferreiro A. 150th ENMC international workshop: core myopathies, 9-11th March 2007, Naarden, the Netherlands. Neuromuscul Disord 2008; 18: 989-986.

Kossugue PM, Paim JF, Navarro MM, Silva HC, Pavanello RC, Gurgel-Gianetti J et al. Central core disease due to recessive mutations in RYR1 gene: is it more common than described? Muscle Nerve 2007; 35: 670-674.

Loke J, MacLennan DH. Malignant hyperthermia and central core disease: disorders of Ca2+ release channels. Am J Med 1998; 104: 470-486.

McArthy TV, Quane KA, Lynch PJ. Ryanodine receptor mutations in malignant hyperthermia and central core disease. Human Mutat 2000; 15: 410-417.

Robinson RL, Brooks C, Brown SL, Ellis FR, Halsall PJ, Quinnell RJ et al. RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes. Hum Mutat 2002; 20: 88-97.

Romero NB, Monnier N, Viollet L, Cortey A, Chevallay M, Leroy JP et al. Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia. Brain 2003; 126: 2341-2349.

Quinlivan RM, Müller CR, Davis M, Laing NG, Evans GA, Dwyer J et al. Central core disease: clinical, pathological, and genetic features. Arch Dis Child 2003; 88: 1051-1055.

Shuaib A, Paasuke RT, Brownell AK. Central core disease. Clinical features in 13 patients. Medicine 1987; 66: 389-96.

Shy GM, Magree KR. New congenital non-progressive myopathy. Brain 1956; 79: 610-21.

Vukcevic M, Broman M, Islander G, Bodelsson M, Ranklev-Twetman E, Müller CR et al. Functional properities of RYR1 mutations identified in Swedish patients with malignant hyperthermia and central core disease. Anesth Analg 2010; 111: 185-190.

Wu S, Ibarra MC, Malicdan MC, Murayama K, Ichihara Y, Kikuchi H et al. Central core disease is due to RYR1 mutations in more than 90% of patients. Brain 2006; 129: 1470-1480.

Zhou H, Yamaguchi N, Xu L, Wang Y, Sewry C, Jungbluth H et al. Characterization of recessive RYR1 mutations in core myopathies. Hum Mol Genet 2006; 15: 2791-2803.

Database references

OMIM (Online Mendelian Inheritance in Man)
Search: central core disease

GeneReviews (University of Washington)
www.genetests.org (find GeneReviews, then Titles)
Search: central core disease

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Associate Professor Christopher Lindberg, Sahlgrenska University Hospital/Sahlgrenska in Gothenburg.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2011-12-29
Version: 3.0
Publication date of the Swedish version: 2011-10-05

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.


About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.