Jitka Kadlecová

The homozygous KCNQ1 gene mutation associated with recessive Romano-Ward syndrome.

In a 7‐year‐old boy with normal hearing suffering from repeated syncope an extremely prolonged QTc interval (up to 700 ms) was found. The mother was completely asymptomatic and the father had an intermittently borderline QTc interval (maximum 470 ms) but no symptoms. In the proband a mutation analysis of KCNQ1 gene revealed a homozygous 1893insC mutation. The parents were heterozygous for this mutation. There was no consanguineous marriage in the family. The clinical relevance of these findings is that apparently normal individuals may have a latent reduction of repolarizing currents, a “reduced repolarization reserve,” because they are carriers of latent ion channel genes mutations.

Mutation Analysis Ion Channel Genes Ventricular Fibrillation Survivors with Coronary Artery Disease

Background: Observations from population‐based studies demonstrated a strong genetic component of sudden cardiac death. The aim of this study was to test the hypothesis that ion channel genes mutations are more common in ventricular fibrillation (VF) survivors with coronary artery disease (CAD) compared to controls.

A new homozygous mutation of the KCNQ1 gene associated with both Romano-Ward and incomplete Jervell Lange-Nielsen syndromes in two sisters

The mutations in the KCNQ1 gene (GenBank accession no. AF000571) encoding the subunit of the KCNQ1 channel can cause 2 different diseases: Romano-Ward syndrome (RWS), traditionally described as a combination of repeated syncope episodes and a prolonged QT interval, and the less frequent Jervell and Lange-Nielsen syndrome (JLNS), also associated (except for the abovementioned symptoms) with congenital bilateral deafness.1 The first one is usually associated with the heterozygous gene mutation, the latter one with the homozygous mutation. The disease prevalence is estimated at close to 1 in 2,500 live births, and JLNS has been reported to affect about 3 in 1 million individuals, which represents less than 1% of all long-QT syndrome (LQTS) patients.

Clinical characteristics of 30 Czech families with long QT syndrome and KCNQ1 and KCNH2 gene mutations: importance of exercise testing

BACKGROUND Classic symptoms of long QT syndrome (LQTS) include prolongation of QT interval on electrocardiograph, syncope, and cardiac arrest due to a distinctive form of polymorphic ventricular tachycardia, known as Torsade de Pointes. We assessed occurrence of LQTS signs in individuals from 30 Czech families with mutations in KCNQ1 and KCNH2 genes. METHODS AND RESULTS One hundred five individuals from 30 Czech families with LQTS were genotyped for KCNQ1 and KCNH2. The occurrence of typical LQTS signs (pathologic prolongation of QT interval; syncope; cardiac arrest; Torsade de Pointes) was clinically assessed by exercise test with QT interval analysis. Family history of sudden cardiac death was taken. Statistical analysis was performed to determine correlation of clinical results and mutation status. KCNQ1 gene mutations were found in 23 families, and KCNH2 gene mutations in eight families. Only 46 (70%) of the 66 mutation carriers had at least two of the typical LQTS signs. The others were minimally or asymptomatic. From 39 noncarrier individuals, only 1 fulfilled the clinical criteria of LQTS diagnosis, another 4 had an intermediate probability of diagnosis. The exercise test had 92% sensitivity and 93% specificity for LQTS diagnosis. CONCLUSIONS Incidence of classical signs of LQTS was not high in Czech carriers of KCNQ1 and KCNH2 mutations. Therefore, proper diagnosis relies on detection of symptoms at presentation. The exercise test may be beneficial owing to its high sensitivity and specificity for LQTS diagnosis.

Clinical Characteristics and Mutational Analysis of the RyR2 Gene in Seven Czech Families with Catecholaminergic Polymorphic Ventricular Tachycardia

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare hereditary arrhythmia. The onset of clinical symptoms usually occurs during childhood, and is typically related to exercise. The aim of our study was to describe the clinical characteristics of seven Czech families with CPVT and the results of mutational analysis of the RyR2 gene in these families.