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myotonia congenita

MIM.255700 and MIM.160800)

Tuesday 5 August 2008

Myotonia congenita is characterized by the development of myotonia during childhood that typically improves when the individual is activating the involved muscle (“warm-up” phenomenon). There is both an autosomal-recessive (Becker, OMIM 255700) and an autosomal-dominant (Thomsen OMIM 160800) variant of the disease. Both forms are rare and clinically similar.

The few differences between the two forms are as follows: Thomsen is characterized by early onset, mild to moderate myotonia, and slight muscle hypertrophy. Becker is characterized by later onset, moderate to severe myotonia with associated transient weakness, moderate muscular hypertrophy, and in some cases permanent muscle weakness and eventual wasting. The estimated worldwide prevalence of these two forms collectively is approximately 1:100,000.

Genetic testing usually confirms the diagnosis, after the diagnosis is clinically suspected. Several mutations of the muscle chloride channel CIC-1 were described in both forms of the disease.

These mutations are thought to affect chloride-channel gating, resulting in decreased chloride conductance, and causing an electrical instability of the sarcolemma with resulting repetitive, sustained electric discharges.

The voltage-gated chloride channel (CIC-1) is encoded by the gene CLCN1 on chromosome 7q35. More than 80 mutations have been described, most of which are responsible for the recessive form of the disease. Fifteen mutations were reported to result in the autosomal-dominant form of the disease. Ten mutations were found to result in either the recessive or the dominant form.

Therapeutics

Several medications have been used to treat myotonia including mexiletine, quinine, lithium carbonate, tocainide (rarely used because of potential bone marrow suppression), procainamide, carbamazepine, phenytoin, and acetazolamide.

See also

- channelopathies