Short QT syndrome (SQTS) is a rare heart condition characterized by an abnormally short QT interval on an electrocardiogram (ECG), which reflects the electrical activity of the heart. This shortened QT interval indicates that the heart’s electrical system is repolarizing faster than normal, which can disrupt the heart’s rhythm and increase the risk of dangerous arrhythmias, including atrial fibrillation and sudden cardiac death.
The primary cause of short QT syndrome lies in **genetic mutations affecting ion channels in the heart**, particularly those that regulate potassium flow. These mutations are typically **gain-of-function variants**, meaning they increase the activity of certain potassium channels, speeding up the repolarization phase of the cardiac cycle. The main genes involved include:
– **KCNH2**: Encodes a potassium channel responsible for the rapid delayed rectifier current (IKr). Gain-of-function mutations here cause Short QT Syndrome Type 1.
– **KCNQ1**: Encodes a potassium channel responsible for the slow delayed rectifier current (IKs). Gain-of-function mutations cause Short QT Syndrome Type 2.
– **KCNJ2**: Encodes an inward rectifier potassium channel. Mutations here are linked to Short QT Syndrome Type 3.
These genetic changes alter the normal function of potassium channels, leading to an **accelerated repolarization of the heart muscle cells**. This means the heart cells reset their electrical state too quickly after each beat, shortening the QT interval on the ECG.
Besides potassium channel mutations, other ion channels can be involved, such as sodium channels (encoded by SCN5A) and calcium handling proteins, but potassium channel mutations are the most common cause of SQTS.
The abnormal electrical activity caused by these mutations creates a substrate for **arrhythmias** because the heart’s electrical signals can become erratic or reentrant circuits can form. This increases the risk of:
– **Atrial fibrillation**, which is an irregular and often rapid heart rhythm originating in the atria.
– **Ventricular arrhythmias**, which are more dangerous and can lead to sudden cardiac death if untreated.
While SQTS is primarily inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene can cause the syndrome, it is very rare and often diagnosed in young individuals or those with a family history of sudden cardiac death.
In some cases, short QT intervals can be seen transiently due to other conditions, such as electrolyte imbalances or certain medications, but these are not true SQTS. True SQTS is a genetic channelopathy.
Additionally, inflammatory heart conditions like myocarditis or cardiac sarcoidosis can sometimes cause arrhythmias, but they do not typically cause the characteristic short QT interval seen in SQTS.
In summary, short QT syndrome is caused by inherited gain-of-function mutations in potassium channel genes that accelerate cardiac repolarization, leading to a shortened QT interval and increased risk of life-threatening arrhythmias.
