Paramyotonia congenita (paramyotonia congenita) - Gen SCN4A

Paramyotonia congenita is a disorder that affects the skeletal muscles and whose clinical manifestations begin in infancy or early childhood. Affected individuals suffer episodes of myotonia that prevent muscles relax normally. Myotonia causes muscle stiffness usually occurs after exercise and muscle can be induced by cooling. This rigidity mainly affects the muscles of the face, neck, arms and hands. Unlike many other forms of myotonia, muscle stiffness associated with congenital paramyotonia it tends to worsen with repeated movements. Most people, even those without the disease feel that your muscles do not work as well when cold. This effect is dramatic in people with congenital paramyotonia. Exposure to cold causes muscle stiffness in these individuals, and prolonged exposure to cold leads to temporary episodes of mild to severe muscle weakness that can last several hours. Some older people with congenital paramyotonia develop permanent muscle weakness that can be disabling.

This process is due to mutations in the gene SCN4A (sodium voltage-gated channel alpha subunit 4), located on the long arm of chromosome 17 (17q23.3). This gene belongs to a family of genes encoding sodium channel. These channels, which transport sodium ions into cells, play a key role in the ability of a cell to generate and transmit electrical signals. Specifically, SCN4A gene encodes the synthesis of the alpha subunit of sodium channels, which are abundant in skeletal muscles. For the body to move normally, the skeletal muscles must contract and relax in a coordinated manner. Muscle contractions are caused by the flow of ions, including sodium, in skeletal muscle cells.

They have identified at least 18 SCN4A gene mutations in people with paramyotonia congenita. These mutations consist of amino acid changes in SCN4A protein, which alters the structure and function of sodium channels in skeletal muscle cells. The most common genetic changes the amino acid arginine replaced with one of several other amino acids at position 1448 of the protein. Mutations delay the closure of the SCN4A protein constituted with channels and, once the channels are closed, cause reopens too fast. These changes increase the flow of sodium ions in skeletal muscle cells. Increased flow in excess of sodium ions causes prolonged muscle contractions, which are the basis of the characteristic episodes of congenital paramyotonia.

This disease is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. In many cases, an affected person has an affected parent.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with paramyotonia congenita, by complete PCR amplification of exons SCN4A 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).