Paramyotonia Congenita

Paramyotonia congenita is an autosomal dominant sodium channelopathy (SCN4A) with cold induced muscle stiffness that worsens with repeated activity ("paradoxical" myotonia), and episodes of weakness. Prevalence is about 1 in 100,000.

Pathophysiology. Impaired fast inactivation of the skeletal muscle sodium channel keeps the muscle membrane depolarised, giving myotonia, then paralysis when depolarisation is prolonged. Potassium intake worsens attacks.

Onset is in infancy or childhood, with stiffness of the face, hands and limbs on exposure to cold, which increases with exercise. Weakness may last minutes to days after cold exposure or exercise. Eyelid myotonia and tongue stiffness are common. Some have attacks of hyperkalaemic type paralysis. Weakness may become permanent in later life.

Electromyography shows myotonic discharges that disappear with cooling and are replaced by reduced insertional activity during weakness. Cold exercise testing shows a marked drop in compound muscle action potential. Genetic testing of SCN4A confirms the diagnosis. Serum potassium can be normal or raised during attacks.

Differential diagnosis.

• Myotonia congenita and potassium aggravated myotonia.
• Hyperkalaemic periodic paralysis and myotonic dystrophy.
• Cold related disorders such as Raynaud phenomenon.

Prevention. Avoid cold, heavy exertion, fasting and potassium rich foods. Wear warm clothes and gloves.

Drug therapy.

• Mexiletine 150 mg orally twice daily, increased to 200 mg three times daily (maximum 600 mg daily), with ECG monitoring and liver tests. Mexiletine is usually the most effective.
• Alternatives: carbamazepine 100 to 400 mg twice daily, lamotrigine 100 to 200 mg daily, or acetazolamide 125 to 250 mg twice daily.

Attacks of weakness. Mild: carbohydrate and light movement. Severe hyperkalaemia: salbutamol inhaler, glucose with insulin, calcium gluconate 10% 10 mL IV if there are ECG changes.

Anaesthesia. Avoid suxamethonium, and maintain warmth during surgery.

Monitoring. Yearly review of symptoms, strength, potassium and ECG on mexiletine.

Referral and escalation. Refer to neurology and genetics.

Special groups. Children: mexiletine dosing by weight (2 to 5 mg/kg three times daily) with cardiology input.