Ion channel disease associated with congeintal dysmorphies, ventricular arrhytmias and periodic paralysis: Andersen–Tawil syndrome
Borbás János1, Erdős Barbara1, Katona Márta2, Környei László3, Ördög Balázs4
1Szegedi Tudományegyetem, II. sz. Belgyógyászati Klinika és Kardiológiai Központ, Szeged
2Szegedi Tudományegyetem, Gyermekgyógyászati Klinika, Szeged
3Gottsegen György Országos Kardiológiai Intézet, Budapest
4Szegedi Tudományegyetem, Farmakológiai és Farmakoterápiai Intézet, Szeged
Andersen-Tawil syndrome (ATS) is a rare and unique genetic disorder considered as one of the subtypes of long QT syndrome (LQT7) and characterized by a triad of clinical manifestations including periodic paralysis, ventricular arrhythmias and dysmorphic features. From the genetic and molecular point of view, ATS is inherited as an autosomal dominant trait and is caused by mutations affecting the KCNJ2 gene. KCNJ2 gene encodes the Kir2.1 protein, which is the main pore-forming unit of the inward rectifier potassium channel conducting the IK1 ionic current.
Cardiac involvement in ATS includes typical ECG manifestations represented by mild QT prolongation, prominent U waves, premature ventricular beats, as well as bidirectional ventricular tachycardia. Non-cardiac manifestation of ATS include cranial, facial and skeletal muscle anomalies such as low-set ears, deep-set eyes, hypertelorism, broad forehead, broad nasal bridge, micrognathia, as well as short stature. Periodic paralysis is a frequent non-cardiac symptom, and sometimes cognitive abnormalities may occur.
The diagnosis of the disease is based on the identification of typical signs of ATS which is complemented by genetic testing. Due to the widespread organ manifestation of the disease treatment requires multidisciplinary approach. Keeping potassium level in the “high normal” range reduces the occurrence of periodic paralysis and arrhythmias. Carboanhydrase inhibitors may reduce the symptoms of periodic paralysis. Flecainide therapy seems to be the most effective for reducing the arrhythmia burden of the disease and may prevent tachycardia induced cardiomyopathy. Despite of the pronounced arrhythmia burden implantable cardioverter defibrillator (ICD) is indicated clearly only as secondary prevention after aborted sudden cardiac death. Symptomatic disease refractory of drug treatment or development of left ventricular dysfunction may also indicate ICD implantation after careful consideration.