Andersen-Tawil syndrome: Clinical presentation and predictors of symptomatic arrhythmias - Possible role of polymorphisms K897T in KCNH2 and H558R in SCN5A gene.
BACKGROUND
Andersen-Tawil syndrome (ATS) is rare channelopathy caused by KCNJ2 mutation and probably KCNJ5. It is characterized by arrhythmias, neurological symptoms, and dysmorphic features. The present study retrospectively examined the characteristics of 11 unrelated families with ATS.


METHODS
This study consisted of 11 probands positive for KCNJ2 variants and 33 family members (mean age 30.0±17.3 years, female n=31). Additional genetic screening of 3 LQTS genes (KCNQ1, KCNH2, SCN5A) was performed in 9 families. Predictors of arrhythmias [premature ventricular beats>2000/24h, biventricular and polymorphic ventricular tachycardia (VT)], syncope, and/or cardiac arrest (CA) were evaluated.


RESULTS
In KCNJ2 mutation carriers vs non-carriers (n=25 vs n=19) significant differences were observed in U-wave manifestations in V2-V4, Tpeak-Tendduration, QTUc duration (p<0.0001), dysmorphic features, and neurological symptoms. Compared to asymptomatic carriers (n=9), in those with arrhythmias and/or syncope and/or CA (n=16) micrognathia (p=0.004), periodic paralysis (p=0.019), palpitation (p=0.005), U-wave n V2-V4 (p=0.049) were more frequent; QTU (p=0.045) and Tpeak-Tend(p=0.014) were also longer (n=9). In the subgroup of carriers with syncope and/or cardiac arrest (n=10, 90% women), K897T-KCNH2 polymorphism (p=0.02), periodic paralysis (p=0.004), muscle weakness (p=0.04), palpitations (p=0.04), arrhythmias (biventricular VT, p=0.003; polymorphic VT, p=0.009) were observed more frequently. Tpeak-Tendduration was longer (p=0.007) and the percentage of patients with premature ventricular contraction >2000/24h was higher (p=0.005).


CONCLUSIONS
A higher risk of arrhythmia, syncope, and/or CA is associated with the presence of micrognathia, periodic paralysis, and prolonged Tpeak-Tendtime. Our findings suggest that K897T may contribute to the occurrence of syncope.
Department of Congenital Cardiac Defects, Institute of Cardiology, Warsaw, Poland. Electronic address: krych.michalina@gmail.com.
Michalina
M
Krych
Department of Congenital Cardiac Defects, Institute of Cardiology, Warsaw, Poland.
Elżbieta Katarzyna
EK
Biernacka
Department of Molecular Biology, Institute of Cardiology, Warsaw, Poland.
Joanna
J
Ponińska
Department of Cardiology and Internal Medicine, Specialistic Hospital, Gorlice, Poland.
Piotr
P
Kukla
First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Artur
A
Filipecki
Medical Centre Gajda-Med, Pułtusk, Poland.
Robert
R
Gajda
Department of Cardiology, Ege University School of Medicine, Izmir, Turkey.
Can
C
Hasdemir
Lankenau Institute for Medical Research, Wynnewood, PA, USA.
Charles
C
Antzelevitch
Department of Molecular Biology, Institute of Cardiology, Warsaw, Poland.
Agnieszka
A
Kosiec
Department of Molecular Biology, Institute of Cardiology, Warsaw, Poland.
Małgorzata
M
Szperl
Department of Medical Genetics, Warsaw Medical University, Poland.
Rafał
R
Płoski
First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Maria
M
Trusz-Gluza
First Department of Cardiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Katarzyna
K
Mizia-Stec
Department of Congenital Cardiac Defects, Institute of Cardiology, Warsaw, Poland.
Piotr
P
Hoffman
D000293:Adolescent; D000328:Adult; D050030:Andersen Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D000072237:ERG1 Potassium Channel / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006323:Heart Arrest / Q000150:complications / Q000235:genetics; D006801:Humans; D008297:Male; D008844:Micrognathism / Q000150:complications / Q000235:genetics; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D011110:Polymorphism, Genetic; D013575:Syncope / Q000150:complications / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000150:complications / Q000235:genetics; D018879:Ventricular Premature Complexes / Q000150:complications / Q000235:genetics; D055815:Young Adult
D000072237:ERG1 Potassium Channel; C000606913:KCNH2 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
Andersen-Tawil syndrome; Arrhythmia; K897T polymorphism; Long QT syndrome