<unk>  is a genetic disorder caused by mutations in genes responsible for producing certain ion channels within heart cells. It appears to be inherited in an autosomal dominant pattern. Some genetic variants cause an increased flow of potassium out of the cell, while others reduce the flow of calcium into the cell. The common effect of all these variants is to<unk> en the cardiac action potential, reflected on the surface ECG as a<unk> ening of the<unk>  interval. A list of genes in which variants have been associated with<unk>  can be found in the table below. Type OMIM Gene Notes SQT1 KCNH2 Also known as hERG, encodes the potassium channel KV11.1 responsible for the delayed rectifier potassium current IKr SQT2 KCNQ1 Encodes the potassium channel responsible for the delayed rectifier potassium current IKs SQT3 KCNJ2 Encodes the potassium channel Kir2.1 responsible for the inward rectifying potassium current IK1 SQT4 CACNA1C Encodes the alpha subunit of the L-type calcium channel carrying ICa(L) SQT5 CACNA2D1 Encodes the alpha2/delta subunit of the L-type calcium channel carrying ICa(L) SQT6 SLC4A3 Encodes a bicarbonate / chloride exchanger Mechanism The overall effect of each of the genetic variants associated with<unk>  is to<unk> en the cardiac action potential, which in turn increases the risk of developing abnormal heart rhythms including atrial fibrillation and ventricular fibrillation. During the normal rhythm of the heart, or sinus rhythm, smooth waves of electrical activity pass regularly through the cardiac muscle. In contrast, during atrial or ventricular fibrillation, waves of electrical activation spiral through the cardiac muscle chaotically in a mass of disorganised, broken wavelets. The consequence of fibrillation is that the chambers of the heart affected by the disorganised electrical activation lose their pumping ability – fibrillation of the cardiac atria in atrial fibrillation leads to an irregular pulse, and fibrillation of the cardiac ventricles in ventricular fibrillation renders the heart unable to pump blood at all. There are several possible mechanisms by which<unk>  action potentials might promote fibrillation. The link between these mechanisms is how the duration of the action potential influences how frequently a heart muscle cell can be excited. A<unk> er action potential generally allow a heart muscle cell to be excited more frequently – the refractory period is<unk> er. The first mechanism, referred to as the dispersion of repolarisation, occurs because the action potential<unk> ening seen in this condition occurs to a greater extent in some layers of the heart wall than in others. This means that at certain points in the cardiac cycle, some layers of the heart wall will have fully repolarised, and are therefore ready to contract again, while other regions are only partially repolarised and therefore are still within their refractory period and not yet able to be re-excited. If a triggering impulse arrives at this critical point in the cardiac cycle, the wavefront of electrical activation will conduct in some regions but block in others, potentially leading to wavebreak and re-entrant arrhythmias. The second mechanism relates to the increased number of fibrillatory wavelets that can simultaneously exist if the action potential decreases, in a concept known as the arrhythmia wavelength. During fibrillation, the chaotic wavelets rotate, or re-enter, within the muscle of the heart, continually extinguishing and reforming. The volume of tissue in which each wavelet can complete a re-entrant circuit is dependent on the refractory period of the tissue and the speed at which the waves of depolarisation traverse move – the conduction velocity. The product of the conduction velocity and refractory period is known as the wavelength. In tissue with a lower wavelength a wavelet can re-enter within a smaller volume of tissue. A<unk> er refractory period therefore allows more wavelets to exist within a given volume of tissue, reducing the chance of all wavelets simultaneously extinguishing and terminating the arrhythmia.
Short QT syndrome
Long QT syndrome
Opitz G/BBB syndrome
Brugada syndrome
Familial atrial fibrillation
Aicardi–Goutières syndrome
Phidippides cardiomyopathy
Pacak–Zhuang syndrome