This is a second form of congenital myotonia, inherited as an autosomal recessive trait. Like the dominant Thomsen form, it is caused by an allelic mutation of the gene encoding the chloride ion channel of the muscle fiber membrane. The clinical features of the dominant and recessive types are similar except that myotonia in the recessive type does not become manifest until 10 to 14 years of age, or even later, and tends to be more severe in the dominantly inherited variety. The myotonia appears first in the lower limbs and spreads to the trunk, arms, and face. Hypertrophy is invariably present. There may be associated mild distal weakness and atrophy; this was found in the forearms in 28 percent of Becker’s 148 patients and in the sternocleidomastoids in 19 percent. Dorsiflexion of the feet was limited and fibrous contractures were common. Weakness may also be present in the proximal leg and arm muscles. The most troublesome aspect of the disease is the transient weakness that follows initial muscle contraction after a period of inactivity. Progression of the disease continues to about 30 years of age, and according to Sun and Streib, the course of the illness thereafter remains unchanged. In contrast to Thomsen disease, the creatine kinase (CK) may be elevated. Testicular atrophy, cardiac abnormality, frontal baldness, and cataracts—the features that characterize myotonic dystrophy—are conspicuously absent.
The main diseases in this category are hyperkalemic periodic paralysis and paramyotonia congenita. The derivative disorders normokalemic periodic paralysis, acetazolamide-responsive myotonia, myotonia fluctuans, and myotonia permanens are variants of hyperkalemic periodic paralysis. All of them are caused by mutations in the gene encoding the alpha subunit of the membrane-bound voltage-gated sodium channel in skeletal muscle (SCN4A).
The essential features of this disease are episodic generalized weakness of fairly rapid onset and a rise in serum potassium during attacks. Weakness appearing after a period of rest that follows exercise is particularly characteristic. This type of periodic paralysis was first described and distinguished from the more common (hypokalemic) form by Tyler and colleagues in 1951. Five years later, Gamstorp described 2 additional families with the disorder and named it adynamia episodica hereditaria. As further examples were reported, it was noted that in many of them there were minor degrees of myotonia, which brought the condition into relation with paramyotonia congenita (see further on). Hyperkalemic periodic paralysis is associated with a defect in the alpha subunit of the sodium channel gene (Fontaine et al, 1990). It is now appreciated that there are distinct variants of hyperkalemic periodic paralysis that are genetically distinct. All are associated with membrane hyperexcitability because of delays in sodium channel inactivation following membrane depolarization, as discussed later.