Long QT Syndrome

Types

There are two types of long QT syndrome, acquired LQTS and inherited LQTS.

Acquired Long QT Syndrome

Many external factors (medications, abnormal electrolyte balance, medical conditions) can prolong the QT interval in the heart's rhythm and cause acquired LQTS.

It is important to distinguish inherited LQTS from acquired LQTS for several reasons:

• Acquired LQTS usually affects just one person, not multiple family members.
• Acquired LQTS is not passed on to the next generation.
• Acquired LQTS may be reversed after identifying the factor that is responsible for it, depending on the cause.

Medications

Medications are the most common cause of acquired long QT syndrome. Approximately 50 medications approved by the Food and Drug Administration have a possible side effect of prolonging the QT interval.

Medications that may cause acquired long QT syndrome include:

• Antibiotics
• Antidepressants
• Antifungals
• Antihistamines
• Diuretics
• Heart medications
• Lipid-lowering medications
• Oral hypoglycemics (for diabetes)
• Psychotropic medications

It is important that people with inherited LQTS do not take any medications known to have the side effect of prolonging the QT interval unless their physician has specifically recommended it. The possible risks and benefits of the medication must be weighed carefully.

Inherited Long QT Syndrome

Inherited LQTS occurs when a change or defect develops in one or more of the genes that program the ion channels of the heart. The ion channels are "electrical tunnels" that control the flow of ions and produce the electrical activity in the heart.

A LQTS gene defect can occur spontaneously (a spontaneous germline mutation or "lightning bolt"). People who have a "lightning bolt" mutation have a 50-50 chance of passing on the mutation to their children. However, no other family members (parents, aunts, uncles, siblings, etc.) are at risk.

For most people with LQTS, it is likely that the genetic abnormality has been passed on from previous generations of the family. It may affect several family members. Often the syndrome has been undiagnosed, so the frequency with which it appears is unknown. This means that all relatives need to be evaluated carefully for LQTS when the inherited form is diagnosed.

To date, researchers have identified 12 types of genetic defects involved in long QT syndrome. Within those 12 types, researchers have found hundreds of mutations. However, 65 to 75 percent of all inherited LQTS can be explained by defects in the three most common types of long QT syndrome genes, identified as LQT1, LQT2 and LQT3.

Additionally, scientists have been investigating a possible link between sudden infant death syndrome (SIDS) and long QT syndrome. Some researchers believe that approximately 10 percent to 15 percent of babies with SIDS had a genetic defect or mutation for LQTS.

Importance of dentifying the Gene Defect

Discovering the type of gene defect responsible for LQTS is important because:

• Finding the type of genetic defect can help determine whether other family members are also at risk for long QT syndrome. Finding the mutation is like finding a needle in a haystack. There are several "haystacks" in which Mayo's LQTS Genomics Laboratory knows to look for the mutation.
• Certain treatments work better for certain types of gene defects. For example, beta-blockers seem to be more effective in LQT1 than in LQT3.
• Triggers for symptoms may vary, depending on the specific genetic defect. For example, if swimming is a trigger, it almost always points to an LQT1 genetic defect, whereas sound triggers (doorbells, alarm clocks, ringing phones) tend to occur more often in people with LQT2.

Clinical genetic testing is available to determine the specific gene that causes LQTS.

Triggers for Inherited LQTS

Although the triggers of inherited long QT syndrome depend on the gene defect present, certain things seem to increase the chance for abnormal rhythms.

• Intense physical activity (e.g., swimming or running)
• Strong emotions (crying, stressful situations)
• Noises that startle (doorbell, phone ringing, alarm clock)
• Sleep (most common in LQT3, which accounts for approximately 5 percent of people with LQTS)
• Certain medications

Medication triggers

Besides the long list of medications that may prolong the QT interval, some medications also may trigger fast heart rhythms in people who have inherited long QT syndrome.

• Appetite suppressants
• Bronchodilators
• Catecholamines
• Certain common antibiotics (e.g., erythromycin)
• Decongestants
• Uterine relaxants
• Vasoconstrictors

If possible, people with inherited long QT syndrome should avoid these medications. Generally, these medications do not trigger fast heart rhythms in people with acquired LQTS.