INTRODUCTION: Progress in molecular genetics contributed to the discovery of 
pathophysiologic mechanisms of hereditary diseases as well as better diagnostics 
and efficient therapy. Several defective ge- nes have been discovered on 
different chromosomes (3,4,7,11 and 21 pair of chromosomes), and also their 
relationship with some types of LQTS (long QT syndrome). Gene dysfunction leads 
to the dysfunction of ion channels, which consequently causes prolonged duration 
of repolarization in cardiac muscle. These changes are manifested on 
electrocardiogram with prolonged duration of QT interval (over 0.44 sec.). 
Familial forms of LQTS are inherited as autosomal dominant (Roman Ward syndrome) 
and autosomal recessive (Jervell Lange-Neilsen syndrome). The final form of LQTS 
is defined even with hearing loss. Clinical survey: malignant ventricular 
arrhythmia, syncope and sudden death. MOLECULAR ARCHITECTURE OF VOLTAGE-GATED 
ION CHANNELS: Duration of voltage-gated ion can be regulated by Na and K 
channels. Cardiac action potential plateau is an indicator of the balance of 
inward and outward ionic currents. During this process of voltage-gated 
potential two currents are activated: depolarized inward current (it happens in 
the Na channels) and repolarized outward current (it happens in the K channels). 
Na channels are polypeptides incorporated in cell membrane. Their main function 
is to control excitability in myocardial cell. They consist of two subunits: 
alpha and beta. Class Ib of anty-arrhythmics (Lidocaine, Mexiletine and 
Tocainide) as well as Diphenylhydantoin blocks Na channels in the state of 
inactivation, in fact, during the depolarization of the cell. For controlling 
the cardiac voltage-gated potential the most important are voltage-sensitive K 
channels. For appearance of K ions delayed refraction of K channels (Kv) is of 
importance. Depending on the velocity of activation, Kv are divided into two 
groups: channels with rapid activation (Kvr) and channels with slow activation 
(Kvs). By activation of these delayed rectification channels (Kv) beta agonists 
shorten the action potential of the heart.
GENETIC ASPECTS OF LQTS: Five loci which are connected with Romano Ward's 
familial form of LQTS have been described up to now. Specific mutant gene is 
responsible for function of K channels and it is located on short branch (part) 
of the 11-th pair of chromosome 11p15.5 (KVLQT-LQT1), long branch of the 7-th 
pair of chromosomes 7q35-36 (K- HERG-LQT2), as well as on the 21-st pair of 
chromosome (KCNE1-LQT5). Defective gene which is responsible for the function of 
Na channels is located on the short branch of chromosome 3p21-24 (SCN5A-LQT3). 
The gene which is located on the long branch of the 4-th pair of chromosome 
4q25-27 (LQT4) has not been examined sufficiently. Persons with Jevell 
Lange-Neilsen syndrome inherit pathological allele from both parents (KvLQT1 or 
LQT5-minK).
CONNECTION BETWEEN ION CHANNELS AND GENE MUTATION: Among all genes which are 
responsible for LQTS the most examined one is the so-called HERG gene located on 
the 7-th pair of chromosome (LQT2). Mutation of this gene leads to reduction in 
strength of outward K currents or to the dysfunction of K channel proteins. 
Mutant gene causes so-called missense mutation, in fact wrong change of amino 
acid in the protein chain. Among all described LQTS the most frequent and the 
most malignant form is LQT1. In 99% cases psychophysical stress can cause 
arrhythmia, syncope or sudden death. LQT3 and LQT5 are very rare.
CONCLUSION: Genetic screening in LQTS patients provides discovery of risk 
population which demands anti-arrhythmic therapy with beta-blockers. A lot of 
arguments speak in favour of genetic screening in cases with LQTS. It is 
considered that if the diagnosis is known, genetic testing is not necessary, but 
it is useful. Moreover, it is obligatory in symptomatic cases as well as in 
those with suspected diagnosis of LQTS.