The Importance of Long QT Syndrome Research

April 17, 2002 was a day of record breaking heat in New York State. The day is very clear in my mind for several reasons; it was my last birthday in my 20s, I had just bought my first house (and was taking the week to paint as I had not planned on the heat), and my niece was rushed to the hospital after an episode of "fainting". She was diagnosed with Long QT syndrome, something I had never heard of but was to learn quite a bit about.

What is Long QT Syndrome (LQTS)?

LQTS occurs due to a disruption in the heart's ion channels regulating the electrical system in the heart. Symptoms of LQTS are fainting, seizures and cardiac arrest.

It is important to note that as many as 50% of patients are asymptomatic and often the first symptom is sudden cardiac death.

LQTS can be genetic, or acquired, and is a leading cause of sudden cardiac death in people under age forty.

Researchers have identified three major LQTS genes and 10 minor LQTS-susceptibility genes which account for nearly 80% of the affected population¹, but its genetic component is still not completely understood. While my family has had genetic testing done, and we are able to trace who is at risk based on family histories of sudden cardiac death, the gene associated with our LQTS has not yet been identified.

Broader Impacts of LQTS

Beyond its human cost, LQTS may be affecting the development of new drugs; "attenuation of the QT interval is one of most common reasons of US Food and Drug Administration black box warnings or medications being halted in development because of the risk of sudden cardiac death²." Without better understanding of the mechanisms behind LQTS, it is impossible to completely assess its impact on the drug discovery and development pipeline.

Animal Models of LQTS

Relevant animal models are critical to understanding how to modulate LQTS and find cures for the disease. "Mouse models of long QT syndrome" offers is an excellent primer on the basics of the disease and relevant mouse models to investigate therapeutics and understand disease mechanisms.

References:

1. Tester, DJ., and Ackerman, MJ. "Genetics of long QT syndrome." Methodist DeBakey cardiovascular journal. 10.1 (2014): 29.

2. Bos, JM and Pereira, NL. "Unraveling the Puzzle of the Role of Heritability in the Variability of the QT Interval Using Exome Array Analysis" Circ Genom Precis Med. 2018; 11:e002007.