Long QT Syndrome pathophysiology: Difference between revisions
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The two most common types of LQTS are genetic and drug-induced. Genetic LQTS can arise from mutation to one of several genes. These mutations tend to prolong the duration of the [[ventricular action potential]] (APD), thus lengthening the QT interval. LQTS can be inherited in an [[autosomal dominant]] or an [[autosomal recessive]] fashion. The autosomal recessive forms of LQTS tend to have a more severe[[phenotype]], with some variants having associated [[syndactyly]] (LQT8) or congenital neural deafness (LQT1). A number of specific genes loci have been identified that are associated with LQTS. | The two most common types of LQTS are genetic and drug-induced. Genetic LQTS can arise from mutation to one of several genes. These mutations tend to prolong the duration of the [[ventricular action potential]] (APD), thus lengthening the QT interval. LQTS can be inherited in an [[autosomal dominant]] or an [[autosomal recessive]] fashion. The autosomal recessive forms of LQTS tend to have a more severe[[phenotype]], with some variants having associated [[syndactyly]] (LQT8) or congenital neural deafness (LQT1). A number of specific genes loci have been identified that are associated with LQTS. | ||
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Revision as of 05:12, 24 August 2012
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Long QT Syndrome Microchapters |
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Long QT Syndrome pathophysiology On the Web |
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American Roentgen Ray Society Images of Long QT Syndrome pathophysiology |
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Risk calculators and risk factors for Long QT Syndrome pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
Overview
Pathophysiology
Genetics
The two most common types of LQTS are genetic and drug-induced. Genetic LQTS can arise from mutation to one of several genes. These mutations tend to prolong the duration of the ventricular action potential (APD), thus lengthening the QT interval. LQTS can be inherited in an autosomal dominant or an autosomal recessive fashion. The autosomal recessive forms of LQTS tend to have a more severephenotype, with some variants having associated syndactyly (LQT8) or congenital neural deafness (LQT1). A number of specific genes loci have been identified that are associated with LQTS.
LQT9
This newly discovered variant is caused by mutations in the membrane structural protein, caveolin-3. Caveolins form specific membrane domains called caveolae in which among others the NaV1.5 voltage-gated sodium channel sits. Similar to LQT3, these particular mutations increase so-called 'late' sodium current which impairs cellular repolarization.
LQT10
This novel susceptibility gene for LQT is SCN4B encoding the protein NaVβ4, an auxiliary subunit to the pore-forming NaV1.5 (gene: SCN5A) subunit of the voltage-gated sodium channel of the heart. The mutation leads to a positive shift in inactivation of the sodium current, thus increasing sodium current. Only one mutation in one patient has so far been found.
Associated syndromes
A number of syndromes are associated with LQTS.
Jervell and Lange-Nielsen syndrome
The Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive form of LQTS with associated congenital deafness. It is caused specifically by mutation of the KCNE1 and KCNQ1 genes
In untreated individuals with JLNS, about 50 percent die by the age of 15 years due to ventricular arrhythmias.
Romano-Ward syndrome
Romano-Ward syndrome is an autosomal dominant form of LQTS that is notassociated with deafness.