Congenital Myopathies

Central core disease/malignant hyperthermia susceptibilty

What is central core disease (CCD)?

Central core disease is one of the inherited myopathies, a group of diseases that causes problems with the tone and contraction of skeletal muscles. The disease is named for damaged areas within muscle cells (the "cores"), where the filament proteins are disorganized and mitochondria (the tiny energy-producing factories that power muscle contraction) are missing. The impact of these "cores" on disease severity is still unclear.

What are the symptoms of CCD?

CCD causes poor muscle tone (hypotonia) and persistent muscle weakness in infants. In rare cases, toddlers with the disease fail to walk at all, but usually they’re just late in reaching motor milestones.

Older children and adults typically experience mild disabilities that worsen slowly with time, if at all. Due to chronic muscle weakness, many people develop skeletal deformities, including joint dislocations and scoliosis, or curvature of the spine that can compress vital internal organs.

People with this disease should be cautious about surgery because they face an especially high risk of malignant hyperthermia, a potentially fatal reaction to certain anesthetic drugs (See the Medical Management section).

What causes CCD?

Central core disease appears to have multiple origins, but it’s commonly caused by specific mutations in the ryanodine receptor (RYR1) gene. Certain variants in the RyR1 gene disrupts the normal flow of calcium ions through pores in cell membranes The defect causes leakage of calcium, which appears to damage muscle cells and abnormalities in muscle contraction. It is autosomal dominant, meaning it is produced by a defective gene contributed by one parent. In rare cases, it can be autosomal recessive, or produced by defective genes contributed by both parents. See Causes/Inheritance.

Multi-minicore disease is linked to pathogenic variants of several genes, including selenoprotein N(SELENON), RYR1 and titin (TTN).

What is the progression of CCD?

CCD is congenital, meaning its onset is at or near birth. It progresses slowly, if at all.

What is the status of research on CCD?

MDA-supported researchers have identified numerous genetic mutations that can result in CCD and in malignant hyperthermia susceptibility. Using animal models, researchers are investigating how these genetic mutations cause the formless "cores" that characterize this disease. For more, see Research.

To read more about central core disease, please see the Spring 2010 report In Focus: Central Core Disease.