Central Core Disease

Central Core Disease

National Organization for Rare Disorders, Inc.


It is possible that the main title of the report Central Core Disease is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • CCD
  • CCO
  • Muscle Core Disease
  • Muscular Central Core Disease
  • Myopathy, Central Fibrillar
  • Shy-Magee Syndrome
  • Central Core Disease of Muscle
  • Myopathy, Central Core

Disorder Subdivisions

  • None

General Discussion

Central core disease (CCD) is a rare genetic neuromuscular disorder that is classified as a congenital myopathy, meaning that it is a muscle disorder (myopathy) that is present at birth (congenital). Affected infants have diminished muscle tone (hypotonia) resulting in abnormal "floppiness", muscle weakness, and a variety of skeletal abnormalities such as side-to-side curvature of the spine (scoliosis). Muscle weakness normally affects the proximal muscles, which are those muscles closest to the center of the body such as the muscles of the shoulder, pelvis and upper arms and legs. Affected infants may experience delays in acquiring motor milestones such as crawling or walking. Some individuals with CCD may be susceptible to developing malignant hyperthermia, a condition in which individuals develop adverse reactions to certain anesthetic drugs. CCD may be very mild or may cause serious complications. Most cases are inherited as autosomal dominant trait and associated with nonprogressive muscle disease and a favorable prognosis. Some cases are inherited as autosomal recessive traits and are more likely to be associated with severe complications.

The disorder derives its name from characteristic, abnormal areas within the centers of muscle fibers. These abnormal "central cores" are detected during microscopic examination of small samples of muscle tissue (muscle biopsy). Such study may reveal characteristic findings such as a lack of mitochondria, the parts of the cells that release energy, or absence of the sarcoplasmic retiuculum, an internal membrane of muscle fibers.


The specific symptoms and their severity may vary greatly from case to case. Some individuals may develop very mild muscle disease that may go unnoticed; others may develop serious muscle disease that can delay motor milestones or cause serious breathing (respiratory) difficulties. In most cases, muscle weakness in CCD is not progressive or only progresses very slowly.

Infants with CCD typically have diminished muscle tone (hypotonia), resulting in abnormal "floppiness". Weakness of the proximal muscles occurs early during infancy. The proximal muscles are those muscles closest to the center of the body such as the muscles of the shoulder, pelvis and upper arms and legs. In CCD, the hip-girdle area is especially affected by muscle weakness. In some cases, muscle cramps or stiffness may occur especially upon exertion. Muscles weakness may cause delays in acquiring milestones that require the coordination and development of muscles (motor milestones) such as crawling, standing and walking. Intelligence is unaffected.

Certain facial muscle may be affected in individuals with CCD. In rare cases, individuals may develop wasting of facial muscles. Mild facial muscle involvement may not be noticeable, except for the inability to bury the eyelashes. In classic, autosomal dominant CCD, the muscles around the eyes are not affected, an important finding that distinguishes CCD from other congenital myopathies. In the autosomal recessive form of CCD, these muscles may be affected.

A variety of skeletal abnormalities often occur in individuals with CCD including abnormal side-to-side curvature of the spine (scoliosis) and congenital dislocation of the hip, a condition in which the hip joint is too shallow causing the upper bone of the leg (femur) to pop out of the joint. These skeletal findings may be present at birth. Additional skeletal symptoms may occur including front-to-back curvature of the spine (kyphosis), dislocation of the kneecap (patella), clubfoot (talipes equinovarus), flattening of the arch of the foot (flatfoot or pes panus), and an abnormally high arch of the foot (pes cavus). Abnormal tightening of certain joints, resulting in restricted or stiff movements (contractures) may occur in rare cases. The Achilles tendon is most common site for contracture.

Some cases of CCD may present with severe symptoms at birth or early during infancy. Severe symptoms associated with CCD may be caused by a prolonged decrease or absence of movements by the fetus (fetal akinesia sequence). Such symptoms include profoundly diminished muscle tone (hypotonia or floppiness), reduced mobility of many joints of the body due to the overgrowth (proliferation) of fibrous tissue in the joints (arthrogryposis multiplex congenital), and breathing (respiratory) difficulties that may require a mechanical device to assist breathing. In some cases of severe CCD, affected infants may not be able to walk independently. Severe cases of CCD are more likely to be inherited as autosomal recessive traits.

Individuals with CCD have susceptibility to developing malignant hyperthermia, an autosomal dominant genetic disorder in which affected individuals are susceptible to adverse reactions to certain anesthetic drugs. The drugs that trigger malignant hyperthermia are the volatile inhalation gases including sevoflurane, desflurane, isoflurane, halothane, enflurane, methoxyflurane and depolarizing muscle relaxants such a succinylcholine. The characteristics of a malignant hyperthermia episode are variable and include muscle rigidity, high blood pressure (hypertension), increased levels of carbon monoxide in the blood or exhaled gas, a rapid irregular heart rate, rapid deep breathing, blue skin, acidity of the blood and muscle damage. Body temperature can rise rapidly (hyperthermia), but sometimes only occurs late in an episode. When an episode is not recognized and treated, internal bleeding, brain damage, skeletal muscle degeneration (rhabdomyolysis), and kidney and heart failure can result.


In most cases, central core disease is inherited an autosomal dominant trait. Some cases are inherited as an autosomal recessive trait and are usually associated with more severe symptoms.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.

Less commonly, CCD may appear to occur spontaneously for unknown reasons (sporadically) in the absence of any apparent family history of the disorder.

Investigators have determined that CCD is caused by mutations of the ryanodine receptor (RYR1) gene located on the long arm (q) of chromosome 19 (19q13.1). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further subdivided into many bands that are numbered. For example, "chromosome 19q13.1" refers to band 13.1 on the long arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

The RYR1 gene regulates production of a protein (known as a calcium-release channel) that plays an essential role in calcium regulation in skeletal (voluntary) muscle. Certain changes (mutations) of the RYR1 gene are thought to result in abnormalities in the normal flow of electrically charged particles known as calcium ions through pores in cell membranes (calcium channels), potentially leading to impaired maturation of skeletal muscle, abnormalities in muscle contraction, and other symptoms and findings associated with the disorder. Investigators suggest that most cases of CCD may be due to certain RYR1 gene mutations. In addition, mutations in the same gene appear to be responsible for over 50 percent of cases in which people have susceptibility to malignant hyperthermia (allelic disorder). (For further information on malignant hyperthermia, please use "hyperthermia" as your search term in the Rare Disease Database.)

Affected Populations

Central core disease affects males and females in equal numbers. The exact incidence and prevalence of CCD is unknown. CCD is believed to be the most common form of congenital myopathy, which as a group occurs in 6 out of every 100,000 live births.

The disorder was originally described in 1956 (Shy GM, Magee KR) in five members in three successive generations of a family. However, the disease entity was not termed "central core disease" until later.

Standard Therapies


Central core disease (CCD) may be diagnosed based upon a thorough clinical evaluation, detection of characteristic physical findings, patient and family history, and specialized tests. The disorder may sometimes be diagnosed during the first years of life; however, not infrequently, it may not be recognized until later during childhood, adolescence, or adulthood, such as due to certain associated musculoskeletal abnormalities (see "Symptoms").

Diagnostic studies may include blood tests, electromyography (EMG), nerve conduction velocity studies, muscle biopsies, and/or other tests. In those with CCD, blood studies typically reveal normal or slightly increased levels of the enzyme creatine kinase in the fluid portion of the blood (except during a malignant hyperthermic crisis). EMG is a test that records electrical activity in skeletal (voluntary) muscles at rest and during muscle contraction. Reports indicate that EMG results may be almost normal in those with CCD, particularly in younger children; however, the recorded electrical activity developed in certain muscle fibers during activity (motor unit action potential) may be of unusually short duration and low amplitude. During a nerve conduction velocity study, motor and sensory nerves are electrically stimulated to assess a nerve's ability and speed in conducting nerve impulses. Evidence indicates that the results of such a study are usually normal in those with CCD.

Small samples of muscle tissue are also removed and examined microscopically with the use of special stains (histochemistry). In cases of CCD, such microscopic evaluation typically reveals dense, ill-defined areas within the central portion of muscle fibers ("central cores") that contain myofibril material. (Muscle fibers are the thread-like muscle cells within skeletal muscle comprised of slender, usually highly organized strands known as myofibrils.) These altered regions or central cores within muscle fibers may appear to lack enzyme activity, contrasting with normal activities in surrounding fibers. (Enzymes are proteins that accelerate particular chemical activities in the body.) In addition, absence of certain cellular structures known as mitochondria may be confirmed with an electron microscope, which uses electron beams rather than visible light for increased magnification. Mitochondria are the rod-like structures (organelles) outside the nuclei of cells that serve as a primary source of cellular energy due to their complex, continual chemical reactions. As a result, they are important to the proper functioning of muscle cells, including those of skeletal muscle.

Additional diagnostic studies may also be recommended to help confirm the diagnosis and detect and/or characterize particular abnormalities that may be associated with the disorder. For example, advanced imaging techniques may be conducted to characterize certain skeletal abnormalities.


The treatment of central core disease (CCD) is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; specialists who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues in children (pediatric orthopedists); physicians who specialize in physical medicine and rehabilitation (physiatrists); physical therapists; occupational therapists; and/or other health care professionals.

Specific therapies for the treatment of CCD are symptomatic and supportive. In cases of "floppiness" during infancy, disease management may require careful attention to posture, the use of appropriate adaptive seating with careful trunk and head support, and other measures. In addition, for infants with extremely severe weakness, tube-feeding may be required to ensure proper caloric and nutritional intake.

In some cases, various orthopedic techniques, such as the use of special braces, other devices, and/or surgical measures, may be recommended to help prevent and/or treat certain musculoskeletal abnormalities potentially associated with the disorder. Family-centered, early intervention services may also be advised, such as physical and occupational therapy, including assistance with seating and mobility devices; instruction for parents on properly handling, exercising, and stretching certain muscles; and/or other measures as appropriate.

Because individuals with CCD may be at risk for malignant hyperthermia when exposed to certain general anesthetics or muscle relaxants, this risk must be taken into consideration by surgeons, anesthesiologists, dentists, and other health care workers when making decisions concerning surgery, the use of particular anesthetics, and the administration of certain medications. Any surgical procedure, including dental surgery, must be performed in a setting that is well monitored by anesthesiologists with necessary precautions to help prevent or appropriately manage a possible malignant hyperthermic event.

Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:




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