ABSTRACT
Congenital long QT syndrome (LQTS) is a primary cardiac channelopathy. Genetic testing has not only diagnostic but also prognostic and therapeutic implications. At present, 15 genes have been associated with the disease, with most mutations located in 3 major LQTS-susceptibility genes. During a routine genetic screening for KCNQ1, KCNH2 and SCN5A genes in index cases with LQTS, seven novel variants in KCNH2 and SCN5A genes were found. Genotype-phenotype correlations were analysed in these patients and their families. An open reading frame and splice site analysis of the exons was conducted using next-generation sequencing. In novel variants, phenotypes of carriers and their affected relatives were analysed. In 39 unrelated patients, 40 pathogenic/putative pathogenic mutations were found. Thirty-three of them, predominantly missense, were reported previously: 11 were in the KCNQ, 17 in the KCNH2 and 5 in the SCN5A gene. Seven novel missense variants were found in eight families. Among them, four variants were in typical for LQTS location. Two variants in the KCNH2 gene (p.D803Y and p.D46F) and one in the SCN5A gene (G1391R) were in amino acid (AA) position which up to present has not been reported in LQTS. Phenotype analysis showed the life-threatening course of the disease in index cases with a history of sudden cardiac death in six families. Mutation carriers presented with ECG abnormalities and some of them received beta-blocker therapy. We report three novel variants (KCNQ1 p.46, KCNH2 p.D803Y, SCN5A p.G1391R) which have never been reported for this AA location in LQTS; the phenotype-genotype correlation suggests their pathogenicity.
Subject(s)
Genetic Association Studies , Long QT Syndrome/genetics , Adult , DNA Mutational Analysis , ERG1 Potassium Channel/genetics , Female , Genetic Testing , Heterozygote , Humans , KCNQ1 Potassium Channel/genetics , Long QT Syndrome/congenital , Male , Mutation, Missense , NAV1.5 Voltage-Gated Sodium Channel/genetics , Pedigree , Phenotype , Poland , Young AdultABSTRACT
Transcatheter pulmonary valve implantation (TPVI) is a relatively new method of treating patients with significant pulmonary regurgitation or pulmonary stenosis, or both, after reconstruction of the right ventricular outflow tract. It is an attractive alternative to conduit replacement in this group of patients, who are typically young and active. This report includes 4 young women who after successful TPVI became pregnant and gave birth. Transthoracic echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance imaging were performed in all patients. The results suggest that pregnancy and delivery after successful TPVI is safe when the appropriate precautions have been taken.
Subject(s)
Pulmonary Valve Insufficiency/surgery , Pulmonary Valve Stenosis/surgery , Pulmonary Valve/surgery , Adult , Cardiac Catheterization/methods , Echocardiography , Exercise Test , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging, Cine , Postoperative Period , Pregnancy , Pregnancy Outcome , Pulmonary Valve/diagnostic imaging , Pulmonary Valve Insufficiency/diagnosis , Pulmonary Valve Stenosis/diagnosis , Treatment OutcomeABSTRACT
BACKGROUND: The aim of the study was to determine, whether electrocardiogram (ECG) screening could reduce the risk of sudden cardiac death in patients with hearing loss through the early diagnosis of Jervell and Lange-Nielsen syndrome and the introduction of the therapy. METHODS: One thousand and eighty patients with hearing loss (aged 21.8 ± 19.9 years) underwent ECG. Additionally, all subjects were asked to complete a 3-question survey. Those who met, at least, one of the high-risk criteria underwent further cardiac assessment and genetic testing. RESULTS: QTc assessment was possible in 1,027 patients. Mean QTc measured 422.8 ± 23.7 ms in 313 women, 414.9 ± 27.7 ms in 273 men and 421.1 ± 21.5 ms in 441 children (individuals younger than 14 years). Abnormal QTc was found in 13 (4.1%) women, 20 (7.3%) men, and 72 (16.3%) children. In the studied group, no recessive mutation of KNCQ1 or KCNE1 was found. In 6 patients, other mutations were found: in KCNQ1 (n = 1), in KCNH2 (n = 3) and in SCN5A (n = 1), which were pathogenic for long-QT-syndromes (LQTS), and 2 mutations of unknown clinical significance in SCN5A. Overall, out of these 6 patients LQTS was diagnosed in 3 asymptomatic patients, but with abnormal QTc and in 2 patients with normal QTc, but who were previously treated for epilepsy. CONCLUSIONS: Jervell and Lange-Nielsen syndrome is a very rare condition even in a population with hearing loss. In this population, the prevalence of prolonged QT interval is increased over the general population. Further investigations are necessary.
