Myotonia congenita

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Overview
Myotonia congenita is a genetic, neuromuscular disorder characterized by the slow relaxation of the muscles. Symptoms may include muscle stiffness and hypertrophy (enlargement). The disorder is caused by a genetic mutation involving the chloride channel of the muscles. The muscle stiffness, which particularly occurs in the leg muscles, may be enhanced by cold and inactivity, and is often relieved by exercise.

Types
Historically two forms of myotonia congenita have been classified. The less severe form has been termed Thomsen myotonia congenita and is inherited in a dominant fashion; the more severe form has been termed Becker myotonia congenita and is inherited in a recessive fashion. More recently, as the individual mutations that give rise to this condition have been identified, these classifications are less widely used. The onset of the myotonia congenita is typically before the age of 20; most cases of myotonia congenita are nonprogressive and relatively nonlimiting.

It is important to note that involuntary twitches in skeletal muscle may not be caused by myotonia congenita as a far more common cause is fasciculation arising from benign fasciculation syndrome.

Goats of the "fainting goat" breed all suffer from this condition.

Genetics
Mutations in the CLCN1 gene cause myotonia congenita. The CLCN1 gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contraction and relaxation are controlled by the flow of ions into and out of muscle cells. Specifically, the protein produced from the CLCN1 gene forms a channel that controls the flow of negatively charged chloride ions into these cells. The main function of this channel is to stabilize the cells' electrical charge, which prevents muscles from contracting abnormally.

Mutations in the CLCN1 gene alter the usual structure or function of chloride channels. The altered channels cannot properly regulate ion flow, reducing the movement of chloride ions into skeletal muscle cells. This disruption in chloride ion flow triggers prolonged muscle contractions, which are the hallmark of myotonia.

The two forms of myotonia congenita have different patterns of inheritance. Thomsen disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

Becker disease is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene, but do not show signs and symptoms of the disorder.

Because several CLCN1 mutations can cause either Becker disease or Thomsen disease, doctors usually rely on characteristic signs and symptoms to distinguish the two forms of myotonia congenita.

Treatment
Some cases of myotonia congenita do not require treatment. If necessary, however, symptoms of the disorder may be relieved with quinine, phenytoin, and mexiletine and other anticonvulsant drugs. Physical therapy and other rehabilitative measures may also be used to help muscle function. Genetic counseling is available.