Episodic, reversible weakness or paralysis known as periodic paralysis is associated with transient alterations in serum potassium levels, usually hypokalemia but occasionally hyperkalemia. All familial forms of periodic paralysis are caused by mutations in genes encoding voltage-gated ion channels in muscle: sodium, calcium, and potassium (see Table 603-1). During attacks, myofibers are electrically inexcitable, although the contractile apparatus can respond normally to calcium. The disorder is inherited as an autosomal dominant trait. It is precipitated in some patients by a heavy carbohydrate meal, insulin, epinephrine including that induced by emotional stress, hyperaldosteronism or hyperthyroidism, administration of amphotericin B, or ingestion of licorice. The defective genes are at the 17q13.1-13.3 locus in hyperkalemic periodic paralysis, the same as in paramyotonia congenita, and at the 1q31-32 locus in hypokalemic periodic paralysis.

Attacks often begin in infancy, particularly in the hyperkalemic form, and the disease is nearly always symptomatic by 10 yr of age, affecting both sexes equally. Late childhood or adolescence is the more typical age of onset of the hypokalemic form, Andersen-Tawil syndrome (see later) and paramyotonia congenita. Periodic paralysis is an episodic event; patients are unable to move after awakening and gradually recover muscle strength during the next few minutes or hours. Muscles that remain active in sleep, such as the diaphragm and cardiac muscle, are not affected. Patients are normal between attacks, but in adult life the attacks become more frequent, and the disorder causes progressive myopathy with permanent weakness even between attacks. The usual frequency of attacks in childhood is once a week. The differential diagnosis includes thyrotoxic periodic paralysis, myotonia congenita, and paramyotonia congenita. A triad of periodic paralysis, potentially fatal cardiac ventricular ectopy (due to a defect in Kir2.1 channels for terminal repolarization), and characteristic physical features is known as Andersen-Tawil syndrome.

Alterations in serum potassium level occur only during acute episodes and are accompanied by T-wave changes in the electrocardiogram. Hypokalemia may be due to alterations in calcium gradients. The creatine kinase (CK) level may be mildly elevated at those times. Plasma phosphate levels often decrease during symptomatic periods. Muscle biopsy findings are often normal between attacks, but during an attack a vacuolar myopathy is demonstrated. Pathologic changes in the periodic paralyses are similar whether the disease is due to a sodium or a potassium channel defect, suggesting that they might result from the recurrent paralytic state rather than the specific channelopathy. The vacuoles are dilated sarcoplasmic reticulum and invaginations of the extracellular space into the cytoplasm, and they may be filled with glycogen. Hypoglycemia does not occur. Loci for the majority of periodic paralyses have been demonstrated and the genes at least partially characterized, but many patients with the same clinical phenotype exhibit no mutations in the identified genes.