Central core disease ... (Central core disease) - Gen RYR1.  

The central core disease is a disorder that affects skeletal muscles. This disease causes muscle weakness ranging from almost imperceptible to very serious.

Most people have mild muscle weakness does not worsen over time. This weakness affects the proximal muscles, particularly the muscles of the thighs and hips. In childhood, muscle weakness may delay the development of motor skills such as sitting, standing and walking. In severe cases, affected children have hypotonia and severe breathing problems or life threatening. The disease is also associated with skeletal abnormalities such as scoliosis, hip dislocation and contractures that restrict the movement of certain joints. Many people affected are at increased risk of developing malignant hyperthermia, which occurs in response to some anesthetic gases used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk of malignant hyperthermia may develop muscle stiffness, breakdown of muscle fibers, high fever, acidosis and rapid heart rate. Complications of malignant hyperthermia can be fatal if not treated immediately.

This process is due to mutations in the RYR1 gene, located on the long arm of chromosome 19 (19q13.1). This gene encodes the receptor protein ryanodine-1. This protein plays an essential role in skeletal muscles. In order for the body to move normally, these muscles must contract and relax in a coordinated manner. Muscle contractions are caused by the flow of ions in muscle cells. When muscles are at rest, the calcium ions are stored in the sarcoplasmic reticulum within each muscle cell. In response to certain signals, the channel releases calcium ions from the sarcoplasmic reticulum into the cytoplasm. The resulting increase in the concentration of calcium ions inside muscle cells stimulates the muscle fibers, allowing the body to move.

There are more than 40 mutations in the gene RYR1 causing the central core disease (CCD). Most of these mutations affect amino acids in critical regions of the protein ryanodine receptor-1. These mutations change the structure of the ryanodine receptor-1, allowing calcium ions seeping abnormally through the channel or alter the channel capacity to release stored calcium ions at the correct time. This interruption in the transport of calcium ions prevents muscles from contracting normally, leading to muscle weakness characteristic of the disease.

The central core disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the alteration. In some cases, an affected person inherits the mutation from an affected parent. Other cases may be the result of new mutations in the gene. These cases occur in people with no history of disease in your family.

Less frequently, the disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with disease of the central core, by the complete PCR amplification of the exons of the RYR1 gene and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).