Short QT syndrome pathophysiology: Difference between revisions
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Short QT syndrome types 1-3 are due to increased activity of outward potassium currents in phase 2 and 3 of the [[cardiac action potential]]. This causes a shortening of the plateau phase of the action potential (phase 2), causing a shortening of the overall [[action potential]], leading to an overall shortening of refractory periods and the [[QT interval]]. In the families afflicted by short QT syndrome, two different [[missense]] [[mutation]]s have been described in the ''human ether-a-go-go [[gene]] ([[HERG]])''. These mutations result in expression of the same amino acid change in the cardiac [[cardiac action potential|I<sub>Kr</sub> ion channel]]. This mutated I<sub>Kr</sub> has increased activity compared to the normal ion channel, and would theoretically explain the above hypothesis. Short QT syndrome types 4 and 5 are due to abnormalities in the calcium channel. | Short QT syndrome types 1-3 are due to increased activity of outward potassium currents in phase 2 and 3 of the [[cardiac action potential]]. This causes a shortening of the plateau phase of the action potential (phase 2), causing a shortening of the overall [[action potential]], leading to an overall shortening of refractory periods and the [[QT interval]]. In the families afflicted by short QT syndrome, two different [[missense]] [[mutation]]s have been described in the ''human ether-a-go-go [[gene]] ([[HERG]])''. These mutations result in expression of the same amino acid change in the cardiac [[cardiac action potential|I<sub>Kr</sub> ion channel]]. This mutated I<sub>Kr</sub> has increased activity compared to the normal ion channel, and would theoretically explain the above hypothesis. Short QT syndrome types 4 and 5 are due to abnormalities in the calcium channel. | ||
==Pathophysiology== | |||
===Genetics=== | ===Genetics=== | ||
In the families afflicted by short QT syndrome, [[mutation]]s have been described in three genes, [[KvLQT1]], the ''human ether-a-go-go [[gene]] ([[HERG]])'', and [[KCNJ2]]. Mutations in the ''[[KCNH2]]'', ''[[KCNJ2]]'', and ''[[KCNQ1]]'' genes cause short QT syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the ''[[KCNH2]]'', ''[[KCNJ2]]'', or ''[[KCNQ1]]'' gene increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of short QT syndrome. Short QT syndrome appears to have an [[autosomal dominant]] pattern of inheritance. | In the families afflicted by short QT syndrome, [[mutation]]s have been described in three genes, [[KvLQT1]], the ''human ether-a-go-go [[gene]] ([[HERG]])'', and [[KCNJ2]]. Mutations in the ''[[KCNH2]]'', ''[[KCNJ2]]'', and ''[[KCNQ1]]'' genes cause short QT syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the ''[[KCNH2]]'', ''[[KCNJ2]]'', or ''[[KCNQ1]]'' gene increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of short QT syndrome. Short QT syndrome appears to have an [[autosomal dominant]] pattern of inheritance. | ||
Revision as of 16:47, 29 July 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Short QT syndrome types 1-3 are due to increased activity of outward potassium currents in phase 2 and 3 of the cardiac action potential. This causes a shortening of the plateau phase of the action potential (phase 2), causing a shortening of the overall action potential, leading to an overall shortening of refractory periods and the QT interval. In the families afflicted by short QT syndrome, two different missense mutations have been described in the human ether-a-go-go gene (HERG). These mutations result in expression of the same amino acid change in the cardiac IKr ion channel. This mutated IKr has increased activity compared to the normal ion channel, and would theoretically explain the above hypothesis. Short QT syndrome types 4 and 5 are due to abnormalities in the calcium channel.
Pathophysiology
Genetics
In the families afflicted by short QT syndrome, mutations have been described in three genes, KvLQT1, the human ether-a-go-go gene (HERG), and KCNJ2. Mutations in the KCNH2, KCNJ2, and KCNQ1 genes cause short QT syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the KCNH2, KCNJ2, or KCNQ1 gene increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of short QT syndrome. Short QT syndrome appears to have an autosomal dominant pattern of inheritance.
Due to the autosomal dominant inheritance pattern, individuals may have family members with a history of unexplained or sudden death at a young age (even in infancy), palpitations, or atrial fibrillation. The penetrance of symptoms is high in affected family members.