Long QT Syndrome classification: Difference between revisions
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===LQT1=== | |||
LQT1 is the most common type of long QT syndrome, making up about 40 to 55 percent of all cases. The LQT1 [[gene]] is {{gene|KCNQ1}} which has been isolated to[[chromosome]]11p15.5. KCNQ1 codes for the voltage-gated potassium channel [[KvLQT1]]that is highly expressed in the heart. It is believed that the product of the KCNQ1 gene produces an alpha subunit that interacts with other proteins (particularly the minK beta subunit) to create the I<sub>Ks</sub> ion channel, which is responsible for the delayed potassium rectifier current of the [[cardiac action potential]]. | |||
Mutations to the KCNQ1 gene can be inherited in an [[autosomal dominant]] or an[[autosomal recessive]] pattern in the same family. In the autosomal recessive mutation of this gene,[[homozygous]] mutations in KVLQT1 leads to severe prolongation of the QT interval (due to near-complete loss of the I<sub>Ks</sub> ion channel), and is associated with increased risk of ventricular arrhythmias and congenital deafness. This variant of LQT1 is known as the [[Jervell and Lange-Nielsen syndrome]]. | |||
Most individuals with LQT1 show paradoxical prolongation of the QT interval with infusion of [[epinephrine]]. This can also unmark latent carriers of the LQT1 gene. | |||
Many [[missense mutation]]s of the LQT1 gene have been identified. These are often associated with a high risk percentage of symptomatic carriers and sudden death. | |||
===Drug=== | |||
Drug induced LQT is usually a result of treatment by [[Antiarrhythmic agent|anti-arrhythmic]] drugs such as [[amiodarone]] or a number of other drugs that have been reported to cause this problem (e.g. [[cisapride]]). Some[[anti-psychotic]] drugs, such as [[Haloperidol]] and [[Ziprasidone]], have a prolonged QT interval as a rare side effect. Genetic mutations may make one more susceptible to drug induced LQT. | Drug induced LQT is usually a result of treatment by [[Antiarrhythmic agent|anti-arrhythmic]] drugs such as [[amiodarone]] or a number of other drugs that have been reported to cause this problem (e.g. [[cisapride]]). Some[[anti-psychotic]] drugs, such as [[Haloperidol]] and [[Ziprasidone]], have a prolonged QT interval as a rare side effect. Genetic mutations may make one more susceptible to drug induced LQT. | ||
Revision as of 05:05, 24 August 2012
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Long QT Syndrome Microchapters |
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Long QT Syndrome classification On the Web |
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Risk calculators and risk factors for Long QT Syndrome classification |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
Overview
Classification
The two most common types of LQTS are genetic and drug-induced. Genetic LQTS can arise from mutation to one of several genes. Following is a list of the most common mutations:
| Type | OMIM | Mutation | Notes |
| LQT1 | 192500 | alpha subunit of the slow delayed rectifier potassium channel (KvLQT1 or KCNQ1) | The current through the heteromeric channel (KvLQT1 + minK) is known as IKs. These mutations often cause LQT by reducing the amount of repolarizing current that is required to terminate the action potential, leading to an increase in the action potential duration (APD). These mutations tend to be the most common yet least severe. |
| 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. |
| LQT3 | 603830 | alpha subunit of the sodium channel (SCN5A) | Current through this channel is commonly referred to as INa. Depolarizing current through the channel late in the action potential is thought to prolong APD. The late current is due to failure of the channel to remain inactivated and hence enter a bursting mode in which significant current can enter when it should not. These mutations are more lethal but less common. |
| LQT4 | 600919 | anchor protein Ankyrin B | LQT4 is very rare. Ankyrin B anchors the ion channels in the cell. |
| LQT5 | 176261 | beta subunit MinK (or KCNE1) which coassembles withKvLQT1 | - |
| LQT6 | 603796 | beta subunit MiRP1 (or KCNE2) which coassembles with HERG | - |
| LQT7 | 170390 | potassium channel KCNJ2 (or Kir2.1) | The current through this channel and KCNJ12 (Kir2.2) is called IK1. LQT7 leads to Andersen-Tawil syndrome. |
| LQT8 | 601005 | alpha subunit of the calcium channel Cav1.2 encoded by the gene CACNA1c. | Leads to Timothy's syndrome. |
| LQT9 | Caveolin 3 | ||
| LQT10 | SCN4B |
LQT1
LQT1 is the most common type of long QT syndrome, making up about 40 to 55 percent of all cases. The LQT1 gene is KCNQ1 which has been isolated tochromosome11p15.5. KCNQ1 codes for the voltage-gated potassium channel KvLQT1that is highly expressed in the heart. It is believed that the product of the KCNQ1 gene produces an alpha subunit that interacts with other proteins (particularly the minK beta subunit) to create the IKs ion channel, which is responsible for the delayed potassium rectifier current of the cardiac action potential.
Mutations to the KCNQ1 gene can be inherited in an autosomal dominant or anautosomal recessive pattern in the same family. In the autosomal recessive mutation of this gene,homozygous mutations in KVLQT1 leads to severe prolongation of the QT interval (due to near-complete loss of the IKs ion channel), and is associated with increased risk of ventricular arrhythmias and congenital deafness. This variant of LQT1 is known as the Jervell and Lange-Nielsen syndrome.
Most individuals with LQT1 show paradoxical prolongation of the QT interval with infusion of epinephrine. This can also unmark latent carriers of the LQT1 gene.
Many missense mutations of the LQT1 gene have been identified. These are often associated with a high risk percentage of symptomatic carriers and sudden death.
Drug
Drug induced LQT is usually a result of treatment by anti-arrhythmic drugs such as amiodarone or a number of other drugs that have been reported to cause this problem (e.g. cisapride). Someanti-psychotic drugs, such as Haloperidol and Ziprasidone, have a prolonged QT interval as a rare side effect. Genetic mutations may make one more susceptible to drug induced LQT.