Long QT in our Family Tree

“You are a link in a chain of causation that stretches before and after your life for a thousand generations.”

–Rev. Chris Michaels, founding minister of the Center for Spiritual Living, Kansas City, Mo.

Yes, I am but a link in the chain of life. As I think back in time, I believe that my life has taken a certain path based on the choices my ancestors made before me. As they departed, they left behind an energized and loving reminder embedded within my heart and soul. They have endowed within me a firm work ethic, a solid foundation of love of God and neighbor and a desire for knowledge and growth.

Our ancestors represent those who made the trek before us. We maintain our vigilance because of our ancestors’ example, determination and faith in our Lord. Knowing they walked before us, we realize that we can walk on after them.

There is also a physical connection. Not only do we look like them, but we also carry the same DNA they do/did. Passed down from parent to child, DNA (deoxyribonucleic acid) is the human hereditary material found in every cell in the body. It contains the information organisms needed to develop and reproduce. DNA is the carrier of genetic material that makes us susceptible to the similar disease processes and genetic flaws. DNA makes each individual unique. It can help you better understand YOU, your family, and your family health history, which is essential to well-being.

Genetic mutations are linked to conditions such as cancer or heart disease, often appear later in life and can cause problems when passed to future generations.

Heart disease is the most readily identifiable disease process in my family tree. Both my parents had heart disease. My mother died of aortic valve disease and my father died of coronary artery disease in his early fifties. Two grandparents died of heart disease, one on maternal side and one of paternal side.  My family history also contains the genetic disease-causing change or mutation known as Long QT Syndrome (LQTS) which is caused by abnormalities of the heart’s electrical conduction system. I am a steadfast supporter of the American Heart Association by default and by concern.

Just like there exists one common ancestor that gives family members the human trait of blue eyes, there exists a common ancestor that passed on the mutation that causes Long QT syndrome which is a genetic predisposition to an abnormal heart rhythm disorder. Long QT syndrome is passed down in families from parent to child. Every human being has two copies of each of these genes; one is inherited from their mother and one from their father. Offspring of a person with Long QT have a 50% chance of inheriting the mutation from their parent. There is a female prevalence observed in Long QT syndrome. A 2007 study involving LQTS1 patients observed that female carriers are more likely than male to transmit the genetic mutation to their offspring. Additionally, female carriers are more likely to transmit the LQTS1 gene to their daughters than to their sons.(1)

Long QT Syndrome (LQTS) may cause fast, erratic heartbeats (arrhythmia), being potentially life-threatening. It is characterized by a prolonged QT interval on an EKG.  Prolonged QT intervals increases risk for torsades des pointes which is an arrhythmia where the ventricle beats irregularly at a rapid rate, making the heart unable to pump blood effectively through the body. When the brain does not receive an adequate blood supply, the result is fainting or seizure-like activity. If the arrhythmia continues, sudden cardiac death is the result.

An EKG cycle consists of five waves denoted by the letters P, Q, R, S, T which correspond to the different phases of the heart activities. In the syndrome known as Long QT, the QT interval is prolonged, taking the heart’s electrical system longer than normal to recharge between beats. This can result in a potentially life-threatening situation.

Symptoms are provoked in a person with long QT:

  • During exercise or shortly afterwards
  • During high anxiety or stressful situations
  • During emotional excitement, especially when being startled and
  • During sleep or upon waking suddenly

Three major types of Long QT syndrome were identified in the 1990’s — KCNQ1, KCNH2 and SCN5A— which relate to the three genes and their associated proteins of cardiac potassium or sodium. The syndrome genetically identified in our family is Type 1(LQTS1) or KCNQ1 which is the most common type. This is a loss of function mutation on the gene KCNQ1 on chromosome 11p delaying the heart’s repolarization and prolonging the QT interval, with potentially life-threatening results.

Long QT syndrome is generally caused by a flawed gene affecting the heart’s electrical activity and is inherited from a parent. The greatest risk factor for provoking an LQT1 sudden cardiac death is being placed on medications that are QT dangerous. There is a website known as CREDIBLEMEDS.org https://www.crediblemeds.org/ that contains a database of QT-aggravating medications. The site is constantly being updated and serves as a needed source of information for medical providers, individuals, and family members.

In addition to QT-prolonging drugs to avoid, a person with LQTS1 should pay special attention to electrolyte and hydration replenishment, especially in the setting of vomiting and diarrheal sickness, as low body potassium is potentially QT-dangerous. If a fever results, attempts should be made to lower it.

The medication of choice and standard of care for Long QT syndrome has been beta-blockers. They have shown to reduce the recurrence of fainting spells and mortality in patients with LQTS1.

Because Long QT syndrome is an inherited condition, it can exist in many individuals in a family. It is important to know if you carry the mutation. If the test shows a positive result, medical attention, advice, and treatment is available. It is simple to talk to your physician about the possibility of having this genetic mutation. Both you and the care provider should consider the risks and benefits as you determine if genetic testing is appropriate.

Some individuals are reluctant to get the genetic test for Long QT when they receive the news that they may have inherited the defective gene.  If LQTS1-causative variant mutation is identified in your family, it is essential that you and your family members get tested. It is a scary thought as a parent, not knowing you have Long QT syndrome, and that you could pass on a gene that could potentially cause your child’s death. A genetic test for Long QT syndrome is simple and available and recommended to confirm a suspected diagnosis.

You could become pregnant and have an increased risk of stillbirth. LQTS-precipitated sudden deaths continue to claim otherwise healthy infants, children, adolescents, and adults at a high rate. You would choose to be tested because LQTS can be diagnosed early, and sudden death could be prevented. Early diagnosis of LQTS have been shown to prevent symptoms and increase life expectancy. A screening EKG is recommended in childhood for first degree relatives with Long QT syndrome. Learning about the genetic fate of their children should be impetus to get genetic testing.

When I study genealogy, I see my family history coming alive. There are family secrets to uncover and mysteries to solve. Everyone desires to know their genetic ethnicity and to trace how the pieces came together. I will always wonder which one of my ancestors passed the KCNQ1 gene down to us.

Neither my mother nor my father was living at the time of the positive result for the genetic confirmation of the KCNQ1 causative mutation. Therefore, no testing was able to be completed.

It was speculated by the cardiologist that the likelihood of maternal inheritance was increased due to both a maternal grandmother and mother with a history of a stillbirth. There is data available in research studies at Mayo Clinic in Rochester, MN demonstrating stillbirths are higher in mothers with long QT syndrome than the fathers with long QT syndrome.

In addition, the cardiologist was able to review an EKG of my father’s, which showed a reasonable QTc interval of 350 to 390 msec. It was felt to be a reasonable calculation. It was noted at that time that the T-waves looked normal. Studies have shown that the morphology of the T wave is an additional marker for diagnosis. Based on that specific electrocardiogram and the fact that I have more than one sibling with LQTS1 mutation, it would cause him to suspect that my mother was positive. Yet the existence of Long QT on my paternal side has not been entirely ruled out.(2)

I can see that my gnarly tree saw many parents bury their baby there at St. Anthony’s Cemetery. I can imagine my tree reaching out its rambling branches as a sign of comfort to the mourning mother and father. These were my ancestors. Stillbirth is such an empty word. The term itself is defined as a baby born without any signs of life. The heartbreak must be unimaginable.

Although many stillbirths were once classified as “cord accidents”, I wonder how many parents were given that diagnosis when there was nothing else to say. Were they merely giving parents what they needed to know: “WHY did this happen?” Were adequate studies done at the time of the birth/death to truly have a feasible diagnosis?  A thorough evaluation of a stillbirth should include a fetal autopsy, histologic exam of the placenta and the umbilical cord as well as a genetic evaluation. Was such an evaluation carried out in the early1900’s or even in the 1950’s?

Current studies demonstrate that nuchal cord (cord around the infant’s neck) is not a reasonable cause for an infant’s death. Many babies are, indeed, born with a nuchal cord with no effects. The study concluded that neither a single nor a multiple cord nuchal cord increases the incidence of fetal death.(3)

In a recent international study, “Fetal LQTS Consortium. Mothers with Long QT syndrome are at increased risk for fetal death: findings from a multicenter international study”, researchers set out to determine if there is an increased risk for fetal death among mothers diagnosed with long QT syndrome. The RESULTS were stated as follows:

  • “Most offspring (80%; 118/148) were liveborn at term; 66% of offspring (73/110) had long QT syndrome. Newborn infants of mothers with long QT syndrome were delivered earlier and, when the data were controlled for gestational age, weighed less than newborn infants of long QT syndrome fathers.
  • Fetal arrhythmias were observed rarely, but stillbirths (fetal death at >20 weeks gestation) were 8 times more frequent in long QT syndrome (4% vs approximately 0.5%); miscarriages (fetal death at ≤20 weeks gestation) were 2 times that of the general population (16% vs 8%).
  • The likelihood of fetal death was significantly greater with maternal vs paternal long QT syndrome (24.4% vs 3.4%; P=.036). Only 10% of all fetal deaths underwent postmortem long QT syndrome testing; 2 of 3 cases were positive for the family long QT syndrome genotype.”(4

Furthermore, studies suggest that approximately 10% of sudden infant death syndrome (SIDS) may be explained by long QT syndrome. When effective treatment of Long QT syndrome is initiated, the mortality rate decreases from 50% to under 2%.(5)

Surely, genetic testing for long QT is imperative in a family with a history of a confirmed diagnosis of long QT. Pre-conception and early pregnancy counselling, along with management of pregnancy and postpartum are available for mothers with Long QT syndrome. We should remember that deaths can be prevented due to early diagnosis, necessary precautions, and treatment.

There is promising research on the horizon in the treatment of Long QT syndrome by Mayo Clinic. An article, published in Circulation, April 2021, titled “Suppression-Replacement KCNQ1 Gene Therapy for Type 1 Long QT Syndrome” discusses the fact that researchers have shown “potential therapeutic effectiveness in two in vitro model systems” that used beating heart cells reengineered from blood samples of patients with the KCNQ1 gene. Both my daughter and I are enrolled as part of the Mayo Clinic study: Genetic Modifier and Reengineered Heart Cell Study.(6)

Gene therapy is a promising approach for treatment of a variety of genetic diseases where new functional genes are created in a laboratory and then delivered to specific cells in the body as potential treatment.

No one knows where this journey in life will take us. We are but a link in the chain of family, bonding those in front of us with those behind us. We are all responsible for each other. I share this knowledge so others will know our story, learn, and save lives.

Knowledge shared = Knowledge 2

Sending blessings to you on your life journey.

Please Remember: Take care of your heart.

  1. Imboden M et al. Female predominance and transmission distortion in the long-QT syndrome. N Engl J Med 2006 Dec 28; 355:2744-51.
  2. Schwartz, P. J., Crotti, L., & Insolia, R. (2012). Long-QT syndrome: from genetics to management. Circulation. Arrhythmia and electrophysiology5(4), 868–877. https://doi.org/10.1161/CIRCEP.111.962019
  3. Carey JC, Rayburn WF. Nuchal cord encirclements and risk of stillbirth. Int J Gynaecol Obstet 2000;69:173 – 4.
  4. Cuneo BF, Kaizer AM, Clur SA, Swan H, Herberg U, Winbo A, Rydberg A, Haugaa K, Etheridge S, Ackerman MJ, Dagradi F, Killen SAS, Wacker-Gussmann A, Benson DW, Wilde AAM, Pan Z, Lam A, Spazzolini C, Horigome H, Schwartz PJ; Fetal LQTS Consortium. Mothers with long QT syndrome are at increased risk for fetal death: findings from a multicenter international study. Am J Obstet Gynecol. 2020 Mar;222(3):263.e1-263.e11. doi: 10.1016/j.ajog.2019.09.004. Epub 2019 Sep 11. PMID: 31520628
  5. Simma A, Potapow A, Brandstetter S, Michel H, Melter M, Seelbach-Göbel B, Apfelbacher C, Kabesch M, Gerling S: Electrocardiographic Screening in the First Days of Life for Diagnosing Long QT Syndrome: Findings from a Birth Cohort Study in Germany. Neonatology 2020;117:756-763. doi: 10.1159/000511572
  6. Steven M. Dotzler, BA, C.S. John Kim, PhD, William A.C. Gendron, BS, Wei Zhou, MD, Dan Ye, MD, J. Martijn Bos, MD, PhD, David J. Tester, BS, Michael A. Barry, PhD, Michael J. Ackerman, MD, PhD: Suppression-Replacement KCNQ1 Gene Therapy for Type 1 Long QT Syndrome. Circulation. 2021; 143:1411 – 1425.

6 Comments on “Long QT in our Family Tree”

  1. Wow, I love your writings. I think I knew most of what you’ve written today about long qt but I’m again amazed at your details put in interesting ways ESP relating it to your family. I’m thinking how much you love research and studying. Have you ever thought about starting on your PhD? You would love it and you almost Have the thesis started! Just for yourself. Of course you are already doing the genealogy study. We won’t have time to discuss these things today. 😄

    >

  2. This blog took me abit to read & a whole lot longer to understand. It was fascinating & I could feel your intense assurance that genetic testing for LQTS is so very important. Thank you for a stimulating read. You have really written a wonderful blog.

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