Andersen–Tawil syndrome, also called Andersen syndrome and long QT syndrome 7, is a rare genetic disorder affecting several parts of the body. The three predominant features of Andersen–Tawil syndrome include disturbances of the electrical function of the heart characterised by an abnormality seen on an electrocardiogram (a long QT interval) and a tendency to abnormal heart rhythms, physical characteristics including low-set ears and a small lower jaw, and intermittent periods of muscle weakness known as hypokalaemic periodic paralysis.
Andersen–Tawil syndrome is inherited in an autosomal dominant pattern. It is caused in most cases by a mutation in the KCNJ2 gene which encodes an ion channel that transports potassium out of cardiac muscle cells. The arrhythmias seen in the condition can be treated with flecainide or beta-blockers, but an implantable defibrillator may sometimes be required. Periodic paralysis can be treated with carbonic anhydrase inhibitors such as acetazolamide. The condition is very rare and is estimated to affect one person in every million. The three groups of features seen in this condition were first described in 1971 by Ellen Andersen, and significant contributions to its understanding were made by Rabi Tawil.
Signs and symptoms
Andersen–Tawil Syndrome classically comprises three groups of features: abnormal electrical function of the heart, hypokalemic periodic paralysis, and characteristic physical features, although some of those affected will not exhibit all aspects of the condition.
left|thumb|[[Electrocardiography|Electrocardiogram showing bidirectional Ventricular Tachycardia in a 9-year-old female with Andersen–Tawil syndrome]]
Andersen–Tawil syndrome affects the heart by prolonging the QT interval, a measure of how long it takes the heart to relax after each heart beat. This, as in other forms of long QT syndrome, can lead to abnormal heart rhythms such as ventricular ectopy or ventricular tachycardia causing palpitations. In type 2 Andersen–Tawil, accounting for about 40% of cases, a KCNJ2 mutation is not identified. Mutations in a related gene encoding a similar potassium ion channel, KCNJ5, have been identified in some of those with type 2 Andersen–Tawil, but in many cases a genetic mutation is not found. The main ion current responsible for maintaining this polarity is /<sub>K1</sub>, and a decrease in this current leads to less polarity at rest, or a depolarised resting membrane potential. When these cells contract, positively charged ions such as sodium and calcium enter the cell through ion channels, depolarising or reversing this polarity. After a contraction has taken place, the cell restores its polarity (or repolarises) by allowing positively charged ions such as potassium to leave the cell, restoring the membrane to its relaxed, polarised state.
thumb|Mechanisms underlying early afterdepolarisations (EADs) and delayed afterdepolarisations (DADs) responsible for the arrhythmias seen in Andersen–Tawil syndrome
The prolonged action potentials can lead to arrhythmias through several potential mechanisms. The frequent ventricular ectopy and bidirectional VT typical of Andersen–Tawil syndrome are initiated by a triggering beat in the form of an afterdepolarisation. Early afterdepolarisations, occurring before the cell has fully repolarised, arise due to reactivation of calcium and sodium channels that would normally be inactivated until the next heartbeat is due. Under the right conditions, reactivation of these currents can cause further depolarisation of the cell, facilitated by the sodium-calcium exchanger. The frequent ventricular ectopy and bidirectional ventricular tachycardia seen in Andersen–Tawil syndrome can also occur in catecholaminergic polymorphic ventricular tachycardia.
Treatment
As a genetic condition, Andersen–Tawil syndrome cannot be cured. However, many of symptoms of Andersen–Tawil such as blackouts due to abnormal heart rhythms or periodic paralysis can be successfully treated with medication or implantable devices. The rarity of the condition means that many of these treatments are based on consensus opinion as there are too few patients to conduct adequately powered clinical trials. Drugs which reduce blood levels of potassium such as diuretics like furosemide and bendroflumethiazide should also be avoided as these can worsen the tendency to periodic paralysis and arrhythmias. The condition is estimated to affect one person in every 1,000,000. and Rabi Tawil who made significant contributions to the understanding of the condition in 1994.
References
- This article incorporates public domain text from the United States National Library of Medicine