Myotonia congenita, Thomsen disease and Becker (congenital Myotonia, Thomsen disease and Becker disease) - Gen CLCN1.
Myotonia congenita is a disorder that affects the skeletal muscles, characterized by muscle stiffness and inability to relax after voluntary muscle contraction. From childhood, affected individuals have myotonia that prevents the muscle relax normally. Although it can affect any skeletal muscle, including the muscles of the face and tongue, most often it affects muscles of the lower extremities. While in some patients muscle stiffness is very slight, in other cases it may be intense enough to interfere with walking, running or other daily activities. These muscle problems are particularly noticeable during movement after a period of rest. Repeated movement can temporarily relieve muscle stiffness.
The two main types of myotonia congenita, Thomsen disease and Becker disease, distinguished by the severity of their symptoms and their inheritance patterns. Thomsen's disease is a type of autosomal dominant myotonia congenita. Signs and symptoms of Thomsen's disease begin in childhood and affect skeletal muscles. For its part, the autosomal recessive form of myotonia congenita, Becker called disease, usually occurs later in life than Thomsen's disease and causes more severe muscle stiffness, especially in males. People with Becker disease are often temporary episodes of muscle weakness, especially in the arms and hands, caused by the movement after rest periods. In addition, they can develop permanent mild muscle weakness over time. This muscle weakness is not observed in people with Thomsen disease.
The reason for these processes lies in the CLCN1 gene mutations, located on the long arm of chromosome 7 (7q35). This gene encodes an essential for normal function of skeletal muscle cells protein. For normal body movements, skeletal muscles must contract and relax in a coordinated manner. This contraction and relaxation process lies in the flow of ions into and out of the cell. Specifically, the protein encoded by the gene CLCN1 forms a channel that controls the flow of chloride ions into the muscle cells. The main function of these ions flow through the channels is to stabilize cell electric charge preventing muscle to contract abnormally.
They have identified more than 80 mutations in the gene CLCN1 in people with congenital myotonia. Most of these mutations cause autosomal recessive form of the disease known as Becker disease. Mutations in the gene CLCN1 alter the structure or function of the usual chloride channels, so altered channels can not properly regulate the flow of ions into the muscle cells. This interruption in the flow of chloride ions triggers muscle contractions longer characteristics of myotonia.
The two forms of congenital myotonia have different patterns of inheritance. Autosomal dominant inheritance Thomsen's disease involves a single altered copy of the gene in each cell is sufficient to express the disease, and in most cases, one parent says the disease. By contrast, in Becker disease, autosomal recessive, 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 myotonia congenita, by complete PCR amplification of exons CLCN1 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).