Long QT syndromes

A disease predisposing those affected to severe cardiac arrhythmia. The term long QT syndrome refers to an abnormality found in the electrocardiograms of the patients a long QT interval caused by a prolonged... 

Congenital Long QT syndrome Human-ether-a-go-go-related protein (HERG) E-4031, astemizole, cisapride... 

In the Long QT Syndrome (LQTS), the repolarization phase of the cardiac muscle is delayed, rendering the heart vulnerable to an arrhythmia known as torsade de pointes. LQTS is associated with five genes encoding ion channels. LQTS type 3 (LQT3) results from mutations of Nav1.5, which cause persistent sodium cunent. In contrast, sodium channel mutations associated with Biugada syndrome reduce the expression level of cardiac sodium channels. 

EA, episodic ataxia LQT, long QT syndrome JLN, Jervell-Lange Nielsen syndrome BFNC, benign familial epilepsy DFNB2, deafness syndrome... 

Mutations in human Kv-channel genes have been detected that are associated with hereditary diseases ranging from heart arrythmia (long QT-syndrome) and deafness to epilepsy and ataxia (see Table 2). Typically, many Kv-channel related channelopathies are correlated with a mutant phenotype that is episodic in nature and appears as a dominant hereditary trait. 

Locus Cemleus Long-Chain Fatty Acids Long-QT Syndromes Long-Term Depression Long-Term Potentiation Loop Diuretics... 

Cavalli A, Poluzzi E, De Ponti F, Recanatini M. Toward a pharmacophore for drugs inducing the long QT syndrome insights from a CoMFA study of HERG K channel blockers. / Med Chem 2002 45 3844-53. 

Congenital long QT syndrome (MIM 192500) Mutations in genes encoding ion channels in the heart... 

Data in part from Ackerman NJ, Clapham DE Ion channels— basic science and clinical disease. N Engl J Med 1997,-336 1575. Other channelopathies include the long QT syndrome (MIM 192500) pseudoaldosteronism (Liddle syndrome, MIM 177200) persistent hyperinsulinemic hypoglycemia of infancy (MIM 601820) hereditary X-linked recessive type II nephrolithiasis of infancy (Dent syndrome, MIM 300009) and generalized myotonia, recessive (Becker disease, MIM 255700). The term "myotonia" signifies any condition in which muscles do not relax after contraction. 

Torsades de pointes may be inherited or acquired. Patients with specific genetic mutations may have the inherited long QT syndrome, in which the QT interval is prolonged, and these patients are at risk for torsades de pointes. Acquired torsades de pointes maybe caused by numerous drugs (Table 6-13) the list of drugs that are known to cause torsades de pointes continues to expand. 

The congenital form of long QT syndrome is characterized by a prolonged QT interval in the electrocardiogram and TdP [28-30]. Many patients with this syndrome... 

These outliers must be carefully considered to determine whether their high QTc value is due to chance or they have clinically silent long QT syndrome... 

Schwartz, P.J. (2006) The congenital long QT syndromes from genotype to phenotype clinical implications. Journal of Internal Medicine, 259, 39-47. 

Shimizu, W. (2005) The long QT syndrome therapeutic implications of a genetic diagnosis. Cardiovascular Research, 67, 347-356. 

Mitcheson, J.S., Chen, J., Lin, M., Culberson, C. and Sanguinetti, M.C. (2000) A structural basis for drug-induced long QT syndrome. Proceedings of the National Academy of Sciences of the United States of America, 97, 12329— 12333. 

Karagueuzian, H.S. (2000) Acquired long QT syndromes and the risk of proarrhythmia. Journal of Cardiovascular Electrophysiology, 11, 1298. 

C. R., Klemens, C.A., Gillman, B.M., Anderson, C.L., Holzem, KM., Delisle, B.P., Anson, B.D., Makielski, J.C. and January, C.T. (2006) Drug-induced long QT syndrome hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine. British Journal of Pharmacology, 149, 481 189. 

Hancox, J.C. and Mitcheson, J.S. (2006) Combined hERG channel inhibition and disruption of trafficking in drug-induced long QT syndrome by fluoxetine a case-study in cardiac safety pharmacology. British Journal of Pharmacology, 149, 457 159. 

Donger, C., Denjoy, I., Berthet, M., Neyroud, N., Cruaud, C., Bennaceur, M., Chivoret, G., Schwartz, K., Coumel, P. and Guicheney, P. (1997) KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation, 96, 2778-2781. 

Chiang, C.E. and Roden, D.M. (2000) The long QT syndromes genetic basis and clinical implications. Journal of the American College of Cardiology, 36, 1-12. 

Spectrum of mutations in long QT syndrome genes. KvLQTl, HERG, SCN5A, KCNE1, KCNE2. Circulation, 102, 1178-1185. 

---