Long QT syndrome (LQTS) is one of the leading causes of sudden cardiac death. It is a rare arrhythmia, or irregular heart rhythm. When the heart beats, the electrical impulses that cause it to contract must follow a precise pathway through the heart. Any interruption in these impulses can cause an arrhythmia. LQTS can be inherited or may be caused by blood electrolyte imbalances or drug use.
The hollow center of the heart is divided into four sections, called chambers. The two upper chambers in the heart are called atria. The two lower chambers in the heart are called ventricles. Normal heart rhythm is very regular, with minimal changes. Atrial contraction is always followed by ventricular contraction in the normal heart. Arrhythmias occur when this rhythm becomes irregular, too fast, too slow, or when the frequency of the atrial and ventricular beats are different.
LQTS is a heart rhythm disorder that may cause fast, chaotic heartbeats. This electrical disturbance can be seen on an electrocardiogram (ECG). Rapid heartbeats in LQTS may lead to fainting. In some cases, the heart's rhythm may beat so erratically that it can cause sudden death. People with LQTS may experience an arrhythmia called torsade de pointes, which is a very fast, abnormal heart rhythm. When this rhythm occurs, no blood is pumped out from the heart, and the brain quickly becomes deprived of oxygen. Torsade de pointes can lead to brain damage and ultimately death.
After a heartbeat, the heart's electrical system recharges itself in preparation for the next heartbeat. This is called repolarization. In LQTS, however, the heart takes longer than normal to recharge between beats. The QT interval is the time that it takes for depolarization and repolarization of the ventricles of the heart. In LQTS, the duration of repolarization is longer than normal.
Some people are born with a genetic mutation that puts them at risk for LQTS. There are many different types of inherited LQTS that are caused by different genetic mutations. LQTS may also be caused by use of certain drugs. There are more than 50 medications that may cause LQTS. Medical conditions, such as congenital heart defects, may also cause LQTS. Arrhythmias in individuals with LQTS are often associated with exercise or excitement.
Treatment for LQTS may include limiting physical activity, avoiding certain medications, or taking medications to prevent arrhythmia, such as beta-blockers. Some people with LQTS also need an implantable device, such as a pacemaker, to control the heart's rhythm and to prevent cardiac arrest.
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types of the disease
Acquired long QT syndrome: More than 50 medications, many of them common, can lengthen the QT interval in otherwise healthy people. Use of these drugs may cause a form of long QT syndrome (LQTS) known as drug-induced or acquired LQTS. Medications that can lengthen the QT interval and upset heart rhythm include certain antibiotics, antidepressants, antifungals, antihistamines, antipsychotics, diuretics, heart medications, cholesterol-lowering drugs, and diabetes medications. People who develop drug-induced LQTS may also have some subtle genetic defects in their hearts that make them more susceptible to disruptions in heart rhythm caused by using these drugs.
Inherited long QT syndrome: At least 12 genes associated with LQTS have been identified thus far, and hundreds of mutations within these genes have been identified. Mutations in three of these genes account for about 75% of LQTS.
Romano-Ward syndrome: Romano-Ward syndrome is a form of inherited LQTS that follows an autosomal dominant pattern of inheritance. Romano-Ward syndrome affects about one in 2,500 people.
Jervell and Lange-Nielsen syndrome: Jervell and Lange-Nielsen syndrome (JLNS) is a form of inherited LQTS that follows an autosomal recessive pattern of inheritance. JLNS is associated with deafness that is congenital (present at birth). It is caused by defects in the KCNE1 and KCNQ1 genes. Symptoms of this rare form of LQTS usually occur earlier in life and are more severe than in Romano-Ward syndrome. JLNS is generally suspected in children who are born deaf and who have inherited LQTS.
LQT1: LQT1 is the most common type of LQTS. In LQT1, the KCNQ1 gene is defective. This gene provides instructions for making the potassium channel in the heart. Mutations to the KCNQ1 gene can be inherited in an autosomal dominant or an autosomal recessive manner, even within the same family. People with this type of LQTS have high rates of fainting but a lower risk of sudden death than other forms. Jervell and Lange-Nielsen syndrome is one form of LQT1.
LQT2: LQT2 is the second-most common form of LQTS. This type most likely involves mutations of the HERG gene, which is partially responsible for the time that it takes to complete one heartbeat and therefore the length of the QT interval.
LQT3: LQT3 is caused by mutations in the gene that provides instructions for making part of the sodium channel in the heart (SCN5A). A large number of mutations have been characterized as leading to LQT3. Mutations in SCN5A can also cause Brugada syndrome, which causes unexpected cardiac death; cardiac conduction disease, which causes heart failure due to a blocked heart; and dilated cardiomyopathy, which causes a weakened and enlarged heart.
LQT5: LQT5 is an uncommon form of the disease that follows an autosomal dominant pattern of inheritance. LQT5 is caused by mutations in the KCNE1 gene, which provides instructions for making a component of the heart potassium channel. It can lead to JLNS.
LQT6: LQT6 is an uncommon form of the disease that follows an autosomal dominant pattern of inheritance. It involves mutations in the KCNE2 gene, which provides instructions for making a component of the heart potassium channel.
LQT7: LQT7, which is also called Andersen-Tawil syndrome, is an autosomal dominant form of LQTS that is associated with skeletal deformities and paralysis. LQT7 is caused by a mutation in the KCNJ2 gene, which provides instructions for making a component of the heart potassium channel.
LQT8: LQT8, which is also called Timothy's syndrome, is caused by mutations in the calcium channel gene CACNA1c. Patients with Timothy's syndrome have many clinical manifestations including congenital heart disease, autism, syndactyly (fusion of the fingers or toes), and immune deficiency.
LQT9: LQT9 is caused by mutations in the membrane structural protein caveolin-3, which is important in the heart sodium channel. Similar to LQT3, these particular mutations increase late sodium currents and impair cardiac repolarization.
LQT10: LQT10 is caused by a defect in the SCN4B gene. The mutation leads to a positive shift in inactivation of the sodium current, thus increasing sodium current. Thus far, only one mutation in one patient has been found for this type of LQTS.