Long QT Syndrome and Its Various Types
Long QT Syndrome (LQTS) is a relatively rare heart rhythm disorder. It affects the heart’s electrical system, resulting in abnormal electrical activity in the heart that can cause potentially fatal rapid heart rates and rhythms. There are many types of inherited LQTS, and this post attempts to provide a high-level overview to answer the question, “What are the different types of Long QT Syndrome?”
The QT Interval
Essentially, the QT interval is the amount of time it takes for the heart’s ventricles, its lower chambers, to contract and pump blood, and then recover. In a heartbeat, the QT interval is the time from the beginning of the QRS complex, representing ventricular depolarization, to the end of the T wave, resulting from ventricular repolarization. Ventricular repolarization is the time it takes for the heart’s electrical system to transmit a signal through the ventricles and reset.
A long QT interval is an abnormal pattern as detected on an electrocardiogram (ECG), a simple, noninvasive test that measures electrical signals in the heart. With each heartbeat, an electrical signal travels through the heart, and an ECG can illustrate if the heart is beating at a normal rhythm and rate.
According to the Sudden Arrhythmia Death Syndromes (SADS) Foundation, LQTS is primarily diagnosed upon the detection of a prolonged QT interval on an ECG. A QTc of 470 milliseconds (ms) in males and 480 ms in females is generally considered strongly suspicious for LQTS, in the absence of medications, which prolong the QT interval or other forms of heart disease.
In people who have LQTS, the heart takes longer to repolarize or reset between beats - that is, the QT interval lasts longer than normal - and can lead to the development of dangerous rapid heart rates (arrhythmias), called torsade de pointes, which may manifest as fainting, sudden cardiac arrest, or death. Torsade de pointes is a very characteristic arrhythmia because the QRS complexes appear to be twisting around an isoelectric baseline.
Example of torsade de pointes on an ECG
Long QT Syndrome is due to an inherited genetic mutation affecting one of several cardiac ion channels. In addition, patients receiving drugs which prolong their QTc can also develop long QT intervals that predispose them to torsade de pointes. The three most common types of inherited LQTS are Types 1, 2 and 3, which have similar symptoms and complications, but different genetic causes and triggers for arrhythmia development.
Common Types of Inherited LQTS (LQTS Type 1, Type 2 & Type 3)
In Long QT Syndrome Type 1 (LQT1), a potassium ion channel coded by the KCNQ1 gene has a reduced current resulting in QT prolongation, disrupting the heart’s electrical activity. Physical exercise and emotional stress can trigger torsade de pointes.
Long QT Syndrome Type 2 (LQT2) results from reduced potassium current flowing through the hERG channel encoded by the KCNH2 gene. Emotional stress, surprise, and startling can initiate arrhythmias in people with LQT2, and common triggers include sudden, loud noises such as horns or even alarm clocks.
Long QT Syndrome Type 3 (LQT3) occurs when too much sodium flows through the heart’s ion channels due toSCN5A gene mutations. The increased sodium flow alters the cardiac cells’ proper electrical activity in the heart, and can trigger an arrhythmia. People with LQT3 often develop arrhythmias during sleep or rest, associated with a slower heart rate. Although people with LQT3 have fewer episodes of arrhythmia, those episodes are more likely to be fatal.
Long QT Syndrome Type 5
Research and related insights into Long QT Syndrome Type 5 (LQT5) is relatively new in the field, and prior to late 2019/early 2020 had been limited. Recently, new studies have been conducted to improve the community’s understanding of the clinical phenotype and genetic features associated with rare KCNE1 gene variants implicated in LQT5. Two individuals with LQT5, Marjaan Barbano and Darcy Carhill, have been featured in Thryv Therapeutics’ Shared Stories series.
Multisystem Disorders Associated with Either Prolonged QT or QTU Intervals
Far less common disorders include:
Ankyrin-B Syndrome - originally labeled LQTS Type 4 (LQT4).
Andersen-Tawil syndrome (ATS) - formerly identified as Long QT Syndrome Type 7 (LQT7) is a rare multisystem disorder characterized by a triad of clinical features including periodic paralysis, dysmorphic features, and ventricular arrhythmias.
Timothy Syndrome (TS) - formerly known as Long QT Syndrome Type 8 (LQT8), and is an extremely rare, multisystem, highly lethal arrhythmia disorder associated with extreme QT prolongation, dysmorphic facial features, congenital heart disease, immune deficiency, developmental delay, and often syndactyly.
Real Life LQTS Journeys
To see what the different types of LQTS look like in the lives of everyday people, please visit our Shared Stories series. These incredibly brave individuals have shared their symptoms, diagnoses, treatments and how LQTS influences their lives, so we can be informed and bring the LQTS community together.
