Andersen-Tawil Syndrome

Andersen-Tawil syndrome is a rare autosomal dominant potassium channelopathy (KCNJ2 in about 60%) with a triad of periodic paralysis, ventricular arrhythmia with prolonged QU interval, and dysmorphic features. Prevalence is about 1 in 1,000,000.

Pathophysiology. Loss of function of the inward rectifier potassium channel Kir2.1 prolongs repolarisation in skeletal and cardiac muscle and affects bone development.

Episodic weakness (hypokalaemic, hyperkalaemic or normokalaemic) often after rest following exercise, palpitation, syncope and ventricular arrhythmia (bidirectional ventricular tachycardia, torsades de pointes). Dysmorphic features: short stature, low set ears, hypertelorism, micrognathia, fifth finger clinodactyly, syndactyly and scoliosis. Cognitive and behavioural features occur. Penetrance is variable.

Red flags.

• Syncope, palpitation or collapse.
• Family history of sudden cardiac death.

ECG shows prominent U waves, prolonged QU interval and ventricular ectopy. Holter monitoring detects arrhythmia. Check potassium during an attack. Genetic testing of KCNJ2 confirms the diagnosis. The long exercise test shows decrement of compound muscle action potential. Echocardiography excludes structural disease.

Differential diagnosis.

• Hypokalaemic periodic paralysis, thyrotoxic periodic paralysis.
• Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia.
• Gitelman syndrome and primary hyperaldosteronism.

Cardiac risk is the priority.

Arrhythmia. Beta blockers (nadolol 40 to 80 mg daily or propranolol) with flecainide 50 to 100 mg twice daily (maximum 300 mg daily) in selected patients, under cardiology supervision. Implantable defibrillator for survivors of cardiac arrest or syncope with ventricular tachycardia. Avoid QT-prolonging drugs and correct potassium and magnesium.

Periodic paralysis. Acetazolamide 125 to 250 mg twice daily, increased to 1000 mg daily, or dichlorphenamide 50 mg twice daily. Treat hypokalaemic attacks with oral potassium 20 to 40 mmol, with ECG monitoring. Avoid triggers (carbohydrate load, rest after exercise).

Other care. Orthopaedic care of scoliosis, genetic counselling and cascade testing.

Monitoring. Yearly ECG, Holter monitoring, potassium and echocardiography.

Referral and escalation. Refer to cardiology and neurology.

Special groups. In pregnancy, continue beta blockers and plan delivery in a specialist unit.