The pattern of inheritance is autosomal dominant as noted, with an onset usually in infancy and childhood. Characteristically, attacks of weakness occur before breakfast and later in the day, particularly when resting following exercise. In the latter case, the weakness appears after 20 to 30 min of becoming sedentary. The patient notes difficulty that begins in the legs, thighs, and lower back and spreads to the hands, forearms, and shoulders over minutes or more. Only in the severest attacks are the neck and cranial muscles involved; respiratory muscles are usually spared. As the muscles become inexcitable, tendon reflexes are diminished or lost. Attacks usually last 15 to 60 min, and recovery can be hastened by mild exercise. After an attack, mild weakness may persist for a day or 2. In severe cases, the attacks may occur every day; during late adolescence and the adult years, when the patient becomes more sedentary, the attacks may diminish and even cease entirely. In certain muscle groups, if myotonia coexists, it is difficult to separate the effects of weakness from those of myotonia. Indeed, when an attack of paresis is prevented by continuous movement, firm, painful lumps may form in the calf muscles. Usually, however, the presence of myotonia can only be detected electromyographically. Some patients with repeated attacks may be left with a permanent weakness and wasting of the proximal limb muscles.
During the attack of weakness serum K rises, often, but not always, up to 5 to 6 mmol/L. This is associated with increased amplitude of T waves in the electrocardiogram (ECG) and a fall in the serum Na level (because of entry of Na into muscle). With increased urinary excretion of K, the serum K falls and the attack terminates. Between attacks serum K is usually normal or only slightly elevated.
The attacks of paralysis are virtually alike in all clinical variants of the disease. In the paramyotonic form discussed below, the attacks are associated with paradoxical myotonia (myotonia induced by exercise and also by cold).
The provocative test, undertaken under careful supervision when the patient is functioning normally, consists of the oral administration of 2 g of KCl in a sugar-free liquid repeated every 2 h for 4 doses, if that many are necessary to provoke an attack. The test is given in the fasting state, ideally just after exercise. The weakness typically has a latency of 1 to 2 h after the administration of K. The patient must be carefully monitored by ECG and frequent serum estimations of serum potassium. The test should never be undertaken in the presence of an attack of weakness, or when there is reduced renal function, or in those with diabetes requiring insulin.
The treatment of this syndrome is the same as that for paramyotonia congenita, described further on.
Normokalemic periodic paralysis This form of episodic paralysis resembles the hyperkalemic form in practically all respects except that serum potassium does not increase out of the normal range, even during the most severe attacks. However, some patients with normokalemic periodic paralysis are sensitive to potassium loading (Poskanzer and Kerr); other kindreds are not (Meyers et al). The disorder is also transmitted as an autosomal dominant trait and the basic defect has proved to stem from the same mutation as that of hyperkalemic periodic paralysis of which it may be considered a variant.