Multiminicore, disease ...; Multiminicore myopathy (Multiminicore disease) - Genes Sepn1 and RYR1.

Multiminicore disease is a process that mainly affects skeletal muscles causing muscle weakness and related health problems ranging from mild to potentially fatal. They have identified at least four forms of disease differ in their signs and symptoms.

The most common form, the classical form is characterized by the manifestation of muscle weakness in infancy or early childhood. This weakness is most noticeable in the axial muscles and is less intense in the muscles of the arm and leg. The disease causes hardening of the muscles of the thorax and spine. When combined with the weakness of the muscles needed for breathing, this rigidity causes serious or potentially fatal respiratory problems. In addition, almost all affected children develop scoliosis worsens steadily over time.

Other less common forms of the disease have different patterns of signs and symptoms. All of them represent about 25% of all cases. Atypical forms of the disease tend to be milder and result in little or no problem of respiratory type. The moderately, with the participation of hand, causes muscle weakness and laxity of joints, especially in the arms and hands. Another way multiminicore disease, known as prenatally with arthrogryposis, characterized by stiffness, arthrogryposis, distinctive facial features and other birth defects. Paralysis of the eye muscles (external ophthalmoplegia) is a primary characteristic of other atypical disease multiminicore. This form of the disease also causes muscle weakness and feeding difficulties that occur in the first year of life.

Many people with the disease multiminicore have a higher risk of developing malignant hyperthermia, severe to certain drugs used during surgery and other invasive procedures reaction. Malignant hyperthermia occurs in response to some anesthetic gas and a particular type of muscle relaxant. If given these drugs, people at risk of malignant hyperthermia may have muscle rigidity, rhabdomyolysis, high fever, acidosis and tachycardia. Complications of malignant hyperthermia can be fatal if not treated immediately. Multiminicore disease owes its name to small and disorganized areas called minicores, found in muscle fibers of many individuals affected. These abnormal regions can only be seen under a microscope. Although the presence of minicores can help doctors diagnose the disease, it is unclear how they relate to muscle weakness and other characteristics of this disorder.

This process is due to mutations in the RYR1 gene, located on the long arm of chromosome 19 (19q13.2) and Sepn1, located on the short arm of chromosome 1 (1p36.13). In some affected families, the genetic cause of the disease has not been identified. Mutations in different genes to Sepn1 and RYR1 may be the reason for the disease in these families.

And severe classical form of the disease is often due to mutations in the Sepn1 gene encoding protein selenoprotein N1. Although their function is unknown, it is believed that this protein may play a role in myogenesis before birth. It may also be important for normal muscle function after birth, although concentrations in adult tissue are less. This protein contains a region that allows you probably bind calcium. At least 17 mutations have been identified in the Sepn1 gene in people with the classic form of the disease. Many of these genetic changes result in coding an abnormally short version of the selenoprotein N1. Other amino acid change mutations in critical regions of the protein, altering its function. It is unclear how mutations in the gene Sepn1 lead to muscle weakness and other characteristics of the disease.

Often, atypical disease multiminicore are due to changes involving the RYR1 gene. Mutations in the RYR1 gene are also associated with increased risk for malignant hyperthermia. This gene encodes the protein ryanodine receptor 1, which plays an essential role in skeletal muscles. 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. In response to certain signals, the ryanodine receptor protein forms a channel 1 that releases calcium ions inside muscle cells. The resulting increase in the concentration of calcium ions inside muscle cells stimulates the muscle fibers to contract. Mutations in the RYR1 gene change the structure and function of the protein ryanodine receptor 1. Some mutations can cause problems with the control channel RYR1, while other mutations appear to change the shape of the channel such that calcium ions they can not flow through it properly. An interruption in the transport of calcium ions alters muscle contraction, resulting in the characteristic muscle weakness disease multiminicore.

This 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 multiminicore, by complete PCR amplification of the exons of Sepn1 and RYR1, respectively, and subsequent sequencing genes.

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).