LQT2: Difference between revisions
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Revision as of 21:49, 8 October 2012
Long QT Syndrome Microchapters |
Diagnosis |
---|
Treatment |
Case Studies |
LQT2 On the Web |
American Roentgen Ray Society Images of LQT2 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
Overview
LQT2 is the second most common subtype of mutations within long QT syndrome, occurring in 35-45% of LQTS patients. This subtype has been known to come to the attention of the cardiologist as a result of a cardiac event during the post-partum period or after being triggered by an alarm clock. The LQT2 mutation involves the HERG gene on chromosome 7, which regulates the channel responsible for the potassium rectifying current, which terminates the cardiac action potential. Most drugs that cause acquired long QT syndrome, do so by blocking the potassium rectifying current via the HERG gene. These drugs include antiarrhythmic drugs, certain non-sedating antihistamines, macrolide antibiotics, certain psychotropic medications, and certain gastric motility agents.
LQT2 Subtype
Type | OMIM | Mutation | Notes |
LQT2 | 152427 | alpha subunit of the rapid delayed rectifier potassium channel (HERG + MiRP1) | Current through this channel is known as IKr. This phenotype is also probably caused by a reduction in repolarizing current. |
Genetics and Pathophysiology
This form of long QT syndrome most likely involves mutations of the human ether-a-go-go related gene (HERG) on chromosome 7. The HERG gene (also known as KCNH2) is part of the rapid component of the potassium rectifying current (IKr). (The IKr current is mainly responsible for the termination of the cardiac action potential, and therefore the length of the QT interval.) The normally functioning HERG gene allows protection against early after depolarizations (EADs).
There is a possibility, that like in LQT1 mutations, the location of the mutation may have a differing impact on the individual who is affected. A study of 201 patients showed that persons with mutations in the pore region had a greater risk of cardiac events and sudden cardiac death, and that these manifestations occurred earlier than in persons with mutations in the non-pore regions [1].
Acquired LQTS with Medications
In some patients, drug associated LQTS appears to be due to a congenital form of LQTS which is clinically latent until until the patient is exposed to a drug, or another factor which may bring forth the manifestations of long QT syndrome. Most drugs that cause long QT syndrome do so by blocking the IKr current via the HERG gene. This causes rapid closure of the potassium channels and an abnormal rise in IKr. Similar to LQT1 this also causes results in a delayed ventricular repolarization and a lengthened QT interval.These include erythromycin, terfenadine, and ketoconazole. The HERG channel is very sensitive to unintended drug binding due to two aromatic amino acids, the tyrosine at position 652 and the phenylalanine at position 656. These amino acid residues are poised so drug binding to them will block the channel from conducting current. Other potassium channels do not have these residues in these positions and are therefore not as prone to blockage.
Drug Class | Examples |
Antiarrhythmics | amiodarone, procainamide, quinidine, sotalol, disopyramide, ibutilide, dofetilide |
Antibiotics|bgcolor="Beige"| azithromycin, | |
Side effects | Drug intolerance: an undesirable pharmacologic effect that can occur at low doses, and is not caused by underlying abnormalities in metabolism or drug excretion. |
Drug interactions | Drug idiosyncrasy: an abnormal, unexpected effect, usually caused by underlying abnormalities in drug metabolism or excretion |
References
- ↑ Moss AJ, Zareba W, Kaufman ES, Gartman E, Peterson DR, Benhorin J; et al. (2002). "Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel". Circulation. 105 (7): 794–9. PMID 11854117.