Central core disease

Goknur Haliloglu MD (Dr. Haliloglu of Hacettepe Children's Hospital in Ankara, Turkey, has no relevant financial relationships to disclose.)
Haluk Topaloglu MD (Dr. Topaloglu of Hacettepe Children's Hospital in Ankara, Turkey, has no relevant financial relationships to disclose.)
Harvey B Sarnat MD FRCPC MS, editor. (

Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.

Originally released September 18, 1994; last updated January 22, 2017; expires January 22, 2020

This article includes discussion of central core disease, CCD, and core myopathies. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Congenital myopathies represent a clinically and genetically heterogeneous group of neuromuscular diseases with characteristic, but not always specific, histopathological features, often presenting with stable and/or slowly progressive truncal and proximal weakness. It is often not possible to have a diagnosis on clinical ground alone. Additional extraocular, respiratory, distal involvement, scoliosis, and distal laxity may provide clues.

The “core myopathies” are the most common form of congenital myopathy and are most commonly associated with Ryanodine 1 gene (RYR1) mutations. RYR1 mutations have been described as the predominant genetic cause of nondystrophic neuromuscular disorders, with a wide clinical spectrum and genetic background, associated with dominantly central core disease, and subgroups of recessively inherited multi-minicore myopathy (MmD), centronuclear myopathy (CNM), and congenital fibre type disproportion. Malignant hyperthermia susceptibility (MHS) trait is a dominantly inherited allelic trait and is described as a pharmacogenetic predisposition to severe and potentially life-threatening reaction in response to halogenated anesthetic agents and depolarizing muscle relaxants.

Dominantly inherited RYR1-related central core disease is characterized by mild to moderate muscle weakness presenting from infancy to childhood. Congenital hip dislocation, scoliosis, generalized joint laxity are common. In contrast to the recessive forms with a more severe clinical phenotype, there is no extraocular muscle involvement. Bulbar, respiratory, and cardiac involvement is uncommon. Myalgia may be prominent. Central core disease tends to be stable over long periods with a possible progression in adulthood, and due to intrafamilial variability, there may be a delay in diagnosis.

Recessive core disease may be associated with tissue-specific silencing of the normal allele, an interesting epigenetic phenomenon.

RYR1-related malignant hyperthermia susceptibility is allelic to central core disease, and some patients with central core disease may also be malignant hyperthermia susceptible. Malignant hyperthermia susceptibility-related RYR1 mutations have also been described as a common cause of induced and episodic phenotypes such as exertional rhabdomyolysis or periodic paralysis presenting throughout life. Late-onset presentations in the adulthood period highlight relevance of the congenital myopathies for adult neuromuscular practice.

Key points


• Central core disease is a relatively common congenital myopathy.


• Most cases of central core disease are dominantly inherited.


• Recessive central core disease is less common and often more severe, and it presents at a younger age.


• No clear phenotype-genotype correlation has yet emerged in patients with recessive central core disease.


• Most cases of central core disease are due to mutations in the gene for ryanodine, a skeletal muscle calcium channel receptor.


• RYR1-related malignant hyperthermia susceptibility trait is an allelic condition to central core disease.


RYR1 mutations may present in the adulthood period as induced and episodic phenotypes such as exertional rhabdomyolysis and periodic paralysis.

Historical note and terminology

In 1956, Shy and Magee described "a new congenital nonprogressive myopathy" characterized by a distinctive microscopic appearance on skeletal muscle biopsy (Shy and Magee 1956). Two years later, this disorder was named “central core disease” (Greenfield et al 1958), the name it has carried ever since.

In their report, Shy and Magee described 5 patients in 3 generations within a single family. All were hypotonic at birth, had delayed onset of walking, and had proximal muscle weakness that was worse in the legs. Their disability remained static with increasing age. Muscle biopsy revealed muscle fibers with central areas of clearing (Shy and Magee 1956). Dubowitz and Pearse subsequently demonstrated an absence of oxidative enzyme and phosphorylase reactivity in the cores seen on muscle biopsy in these patients (Dubowitz and Pearse 1960).

Shy and Magee's original publication was significant for much more than the fact that it described a new disease (Shy and Magee 1956). This publication represented the first recognition of the congenital myopathies, the diagnosis of which was based on the distinct structural or histochemical changes in biopsied skeletal muscle, as a distinct group of diseases.

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.