Stanford Center for Inherited Cardiovascular Disease

Long QT Syndrome In Depth

Background

Long QT ECG 2

The long QT syndrome is a disorder that is characterized by a finding on the electrocardiogram that represents abnormal electrical flow in the heart. The two ways one can develop this condition are either from medications that interfere with the ion channels, which are proteins in the heart cells responsible for normal electrical conduction, or from genetic mutations in these ion channels. Patients with long QT syndrome run the risk of “Torsades de Pointes”, which is a condition where the heart beats too quickly and irregularly to maintain normal blood flow.

The genetic form of long QT syndrome is rare, occurring in approximately one out of 2,000 people, but is an important cause of sudden death in children, adolescents and young adults. The number of patients who suffer from long QT syndrome due to medication use is difficult to estimate, however, developing “Torsades de Pointes” from the use of these medications is unusual. A list of medications that can prolong the QT is kept at www.longqtdrugs.com. Patients who develop long QT from these medications may have a genetic predisposition.

Diagnosis

The diagnosis of long QT syndrome can be difficult to make. Most patients do not suffer any symptoms until their first episode of Torsades de Pointes, which can cause dizziness, syncope (passing out) or even death. These episodes typically occur during exercise, but can occur with emotional stress or other situations where there is a surge in adrenaline.

The diagnosis of long QT hinges on the electrocardiogram. There is an interval, or measurement, called the QT in each beat that represents the time between when electricity in the heart first begins to flow, and when the cells are electrically ready for the next beat. The difficulty behind this diagnosis is that the QT interval can be difficult to measure on the electrocardiogram, and can be different from one day to the next in the same patient. There are scores that rely on the QT interval, age and gender; however, it is very difficult to predict who is at risk of Torsades de Pointes. Generally speaking, those with very long QT intervals are at greatest risk.

There is currently no “cure” for the long QT syndrome. However, medications such as beta blockers, in the right patients, can significantly reduce the risk of syncope or sudden death. In patients who have recurrent bouts of syncope, despite medications, implantable cardiac defibrillators are often recommended and can nearly eliminate the risk of dying suddenly from Torsades de Pointes. Patients with long QT syndrome are asked not to play competitive sports and to avoid taking medications, noted above, that can make the condition worse. These patients, however, can lead otherwise normal, productive lives.

Genetics of Long QT Syndrome

The long QT syndrome can be caused by a mutation in one of over ten genes that have been identified. The vast majority of the genes involved are potassium and sodium channels, specifically KCNQ1, HERG and SCN5A. The syndromes are numbered, for example LQT1, LQT2 and LQT3, depending on the gene that is mutated. Most of the long QT syndrome genetic mutations are inherited in a dominant manner, meaning that only one copy of the mutation is sufficient to cause the disease. However, in a small percentage of patients, particularly those who also have inherited forms of deafness, the syndrome is inherited in a recessive manner, meaning that the patient must have two copies of the mutation, one mutation inherited from each parent.

There are currently commercially available genetic tests to identify mutations in the five most common genes of long QT syndrome, however, these tests currently identify the mutation in only 75% of patients. This means that a genetic test that is “negative” does not completely exclude the disease. In addition, there are patients with genetic mutations who never develop the disease, meaning that a “positive” test does not automatically mean that a person will develop the disease. Some mutations are more severe than others, and knowing which mutation one has may help with the management of the patient, although much degree of personalized medicine is still experimental.

Genetic testing is most useful when one member of a family has been clinically diagnosed with long QT syndrome. If the mutation causing the disease in that person is identified, then the family members can be tested for the disease with genetic screening. We recommend genetic counseling before genetic tests are ordered to discuss the implications of the testing itself and the potential results.

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