Preimplantation Genetic Testing for Long QT Syndrome

by | Feb 12, 2019
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Because the heart muscle is controlled by the automatic (involuntary) nervous system, we often take our heartbeat for granted. The characteristic, steady rhythm that sounds like “lub, dub…lub, dub…lub,dub” is controlled by our body’s very own coordinated electrical system. When that system has a problem, it’s possible for the heart’s rhythm to change, which is called an arrhythmia.  

Millions of people experience arrhythmia at some point in their lives.  Most of these episodes are harmless, and occur in people without heart disease. But in some, the arrhythmia can be life-threatening.  It is estimated that sudden cardiac death occurs in about 3 out of 100,000 men and women under the age of 40 in North America, and that at least half of these unexplained cases are caused by a hereditary arrhythmia syndrome. One of these hereditary heart conditions is long QT syndrome (LQTS).         

What is LQTS?

Long QT syndrome, which affects 1 in every 2,500 live births, gets its name because episodes are caused by a delay in the time it takes for the electrical system to recharge after each heartbeat, called the QT interval. The QT interval can be measured via an electrocardiogram (ECG or EKG). People with LQTS can experience episodes where their heart rhythm becomes erratic and chaotic, which can lead to symptoms. If the rhythm remains erratic for too long, the episode can be life-threatening.

There are typically no other clues that would indicate to healthcare providers that someone is at risk for this condition, since the disorder only affects the heart (with an exception of one rare type of LQTS, which is also associated with congenital deafness).  “Most patients find out they are at risk for LQTS either by having a personal history consistent with LQTS, such as syncope (fainting), a prolonged QT interval on testing such as an EKG, or experiencing a sudden cardiac arrest,” says Amy Sturm, a licensed genetic counselor, Professor and Director of the MyCode Genomic Screening and Counseling and Cardiovascular Genomic Counseling Programs at Geisinger. “Patients may also find out they are at risk for LQTS due to a positive family history of LQTS, a family member or members with positive genetic testing for LQTS, sudden death, sudden cardiac arrest, and/or syncope.”

Fainting spells are one of the most common symptoms of LQTS, and usually occur out of the blue. A syncope episode among individuals without the disorder is typically preceded with a warning sign, like feeling lightheaded or having heart palpitations.

Congenital or inherited LQTS means that a person inherited the disorder from a parent, in contrast to acquired LQTS that is developed over time by taking certain medications or having other medical conditions. Those with inherited LQTS typically have a 50% chance of passing on the disease to their children, which is called autosomal dominant inheritance. Not all individuals who have inherited LQTS will develop symptoms, and those that do can exhibit mild to severe symptoms, even within the same family. Cardiac symptoms are most common from the preteen years through the 20s, although they can occur from infancy through middle age. Also, it is currently thought that up to 12% of sudden infant death syndrome (SIDS) is caused by LQTS.

How is congenital/inherited LQTS diagnosed?

The diagnosis can be made by a cardiologist or a healthcare professional specializing in genetics, by observing a long QT interval on an EKG and/or by finding a variant that’s known to cause the disease (also called a mutation) in one of the 15 associated genes. Not all patients with LQTS will have an abnormal EKG or have mutation detected on a gene test. Thus, some doctors may order a non-exercise stress test, which involves using adrenaline to stimulate the heart and then monitor the heart’s electrical activity.

“LQTS is a genetic, inherited condition, so it can be helpful for patients to meet with a genetic counselor to learn more about their risks, the chance that they could have children with LQTS, and/or the chance that their current children could have inherited LQTS,” says Sturm. “Genetic counselors, who have specialized training in both genetics and psychology, can also help patients adjust to a new diagnosis of LQTS, find resources, and determine the best way to share risk information with at-risk family members.  In addition, genetic counselors can discuss the benefits and limitations of genetic testing for LQTS, and help patients understand their genetic testing options, as well as their genetic testing results and how to best implement them into their overall care plan.”

What is the treatment for LQTS?

A beta blocker is a commonly prescribed medication that is used to lower blood pressure, and is used as a preventative strategy. Some patients are resistant to beta blockers, and require surgically inserted device such as an implantable cardioverter-defibrillators (ICD). Avoidance of certain drugs, intense exercise and stress are also preventative measures.

Genetic testing is important to guide treatment for the patient since some mutations can lead to more severe risk of sudden cardiac death. “I had a female patient in her late 20s who had a cardiac arrest during the night shift at work,” says Sturm. Luckily, the emergency medical team arrived quickly and was able to save her life with a defibrillator. During the initial patient consultation, Sturm recalls that the patient did not report a personal or family history of fainting spells or sudden cardiac death (SCD), “but when the family did more digging via Ancestry.com and other means, they found a distant family history of sudden death.” It was later discovered she had family members who tested positive for the same mutation that caused LQTS in Sturm’s patient, which is known to predispose individuals to a higher risk of SCD. Thus, her clinical care team used that information to recommended an ICD.

Because pregnancy can add extra stress on the heart, women with LQTS who wish to become pregnant are best cared for by using a team of healthcare professionals experienced with managing pregnancies complicated by an inherited heart disease.   

Is preimplantation genetic testing (PGT) available for LQTS?

Yes, PGT (also referred to as PGT-M or PGD) is available for LQTS as long as the mutation in one of the known genes has been identified so that the laboratory will be able to develop the test to screen the embryos. Performing PGT for this condition is a common request for fertility clinics that provide this service, and has been performed successfully for many couples.

“All patients with LQTS who are of childbearing age should be provided with all of their reproductive options, including PGT-M/PGD,” says Sturm. “It is best for individuals with LQTS to learn about their reproductive risks and options prior to becoming pregnant if at all possible, as this gives individuals and couples the information they need to make informed decisions regarding their reproductive health.”

For more information about hereditary arrhythmia syndromes including LQTS, check out Sudden Arrhythmia Death Syndromes (SADS) Foundation.

Leslie is a board-certified clinical genetic counselor and former Program Manager for the preimplantation genetic testing (PGT) program of the ORM Genomics team and former Project Manager for SharingHealthyGenes.com. She completed her Bachelor’s degree at DePauw University and her Master’s degree in Genetic Counseling at the University of Texas Graduate School of Biomedical Sciences at Houston. Since graduating in 2000, she has worked as a clinical genetic counselor in several specialties including prenatal, pediatric and cancer genetics and has been very involved with the National Society of Genetic Counselors.

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