Thomsen And Becker Disease

A rare, genetic, skeletal muscle channelopathy characterized by slow muscle relaxation after contraction (myotonia).

Epidemiology

Worldwide prevalence is estimated at 1/100,000.

Clinical description

Onset occurs early in life, usually in the first two decades, with myotonia potentially affecting every muscle after contraction, most frequently lower limb and hand muscles. Myotonia usually improves with exercise (e.g. after warm-up). Myotonia congenita may be inherited as an autosomal dominant (Thomsen disease) or recessive (Becker's disease) inheritance, with a more severe and earlier phenotype in recessively inherited disease.

Etiology

Disease is caused by loss of function mutations in the gene encoding the chloride channel, CLCN1 (7q34), that plays a role in muscle cell repolarization.

Diagnostic methods

The clinical diagnosis can easily be confirmed by electromyography (EMG), which reveals myotonic discharges in association with hyperexcitation of the muscle fiber membrane. EMG testing under exercise and cold stress allows detailed characterization of the myotonia and helps orientate the molecular diagnosis. Identification of mutations in the chloride channel gene can be considered as diagnostic.

Differential diagnosis

Steinert myotonic dystrophy, proximal myotonic myopathy and sodium channel channelopathies should be always considered in the differential diagnosis. Steinert myotonic dystrophy and proximal myotonic myopathy represent the most relevant differential diagnosis; these diseases present with fixed muscle weakness and wasting, and multisystem involvement, which are usually not associated to Thomsen and Becker disease, and occasionally may present with only myotonia. In addition, some degree of weakness may be observed in Thomsen and Becker disease, especially in later disease stages. Sodium muscle channelopathies may present with myotonia, which may be very similar to that reported in Thomsen and Becker disease or characterized by worsening with exercise, the so-called ''paradoxical myotonia'' (paramyotonia congenita).

Genetic counseling

The mode of transmission may be autosomal dominant (Thomsen myotonia) or autosomal recessive (Becker myotonia). Although some clinical and EMG clues may help distinguish Thomsen from Becker disease, genetic counselling should be proposed and the results of the molecular analysis should be interpreted with care as the same mutations have been associated with both dominant and recessive modes of transmission depending on the family studied.

Management and treatment

Treatment revolves around sodium channel blocking agents such as mexiletine hydrochloride (indication approved in Europe), carbamazepine, phenytoin, ranolazine or lamotrigine.

Prognosis

Myotonia congenital prognosis is relatively good, with normal life expectancy. Becker disease is considered more severe than Thomsen disease.