KCNH2 mutation c.3099_3112del causes congenital long QT syndrome type 2 with gender differences

Abstract Introduction: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. Methods and results: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. Conclusions: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.

Descripción de dos familias con síndrome de QT largo / Description of 2 families with long QT syndrome

Resumen El síndrome de QT largo representa un grupo de desórdenes electrofisiológicos cardiacos, caracterizados por la prolongación del intervalo QT, que se asocian a muerte súbita, taquicardias ventriculares y síncope. Se presenta el caso de dos familias con la descripción clínica de los afectados, el estudio genético y el respectivo manejo, y se hace una breve actualización de la literatura sobre el síndrome de QT largo.

Abstract Long QT syndrome represents a group of electrophysiologic disorders characterized by a prolongation in the QT interval that are associated with sudden death, ventricular tachycardia and syncope. We present 2 families describing the clinical presentation, the genetic study and their respective treatment also there is a brief review about long QT syndrome.

Stressful Work Involvement and Inherited Long QT-Syndrome.

Aims: The long QT syndrome (LQTS) is an inherited cardiac disorder which predisposes the mutation carrier to ventricular arrhythmias that can lead to sudden death. The objective of the study was to study whether stressful work involvement (i.e. worrying about work and job dissatisfaction) is related to arrhythmic risk in LQTS. Study design: Cross-sectional study. Place and Duration of Study: The study took place in Finland in 2006 for the LQTS mutation carriers and 2007 for the general Finnish population. Methodology: The study subjects included 164 symptomatic and 229 asymptomatic LQTS mutation carriers from the Finnish LQTS registry and 1368 comparison subjects randomly derived from the population-based sample, Young Finns Study (YFS). Stressful work involvement was measured with questions derived from the Framingham type A scale. Results: Upon assessment of the stressful work involvement, symptomatic LQTS mutation carriers scored higher than asymptomatic LQTS mutation carriers (1.51 vs. 1.40, p=0.003, η²=0.022) and the general Finnish population (1.51 vs. 1.39, p<0.001, η²=0.012), while asymptomatic LQTS mutation carriers did not differ from the general Finnish population in the corresponding scores (1.40 vs. 1.39, p=0.374, η²<0.001). Conclusion: The results confirm the suggestion that perceived stress, in terms of stressful work involvement, may increase the likelihood of arrhythmic events in LQTS mutation carriers. Thus, individual stress proneness may be a risk factor for LQT symptoms, which should be taken into account in counseling LQTS patients. There is previous evidence that stress proneness can be modified by behavioral therapy.

Long QT Syndrome - A case report.

Long QT syndrome (LQTS) is an uncommon disease due to genetic defect and responsible for polymorphic VT (torsade-de pointes-TdP) and sudden cardiac death. A case of 25 year-old woman with palpitation, severe headache and recurrent syncopal episode since 16 year-old is reported. The ECG showed bigeminy ventricular premaure contraction (VPC) , prolonged QTc interval and abnormal T wave. Peripartal cardiomyopathy was diagnosed recently after the first delivery. In July 2002, she was hospitalized due to recurrent syncope, seizure proceeded by TdP and VF. On admission she need several times DC shock and temporary pacemaker with relatively high rate. Beta-blocker and implantation of dual chamber permanent pacemaker finally could control the malignant arrhythmias. During follow-up for 4 months, she was doing well and no syncopal episode occurred.

The structure and function of KCNQ1 channel / 中国药理学通报

The paper concluded systematically the progress of study on KCNQ1 in recent years.Firstly,the structure of ? subunit or ? subunit and its interaction between each other were explained in the paper.Secondly,the physiological function of complex KCNQ1/KCNE was interviewed,such as many kinds of inherited cardiac arrhythmias induced by mutation of KCNQ1 or KCNE and secretion of KCNQ1 in different epithelial cells.Eventually,the paper introduced the study of antagonists and agonists on KCNQ1 channel.