Last updated:
6/16/2025
Years published: 2021, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, Ana Isabel Moreno-Manuel and José Jalife, MD, PhD, Senior Investigator, Director, Arrhythmia Research Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain for the preparation of this report.
Summary
Short QT syndrome (SQTS) is a rare but potentially life-threatening condition that affects the way the heart’s electrical system works. SQTS is named for its most important feature, a very short QT interval seen on an electrocardiogram (ECG), a test that measures the heart’s electrical activity. The QT interval represents the time it takes for the heart’s lower chambers (ventricles) to contract and then recover before the next beat. In people with SQTS, this process happens too fast, increasing the risk of serious heart rhythm problems and sudden cardiac death.
SQTS can cause dangerous heart rhythms including atrial fibrillation, ventricular tachycardia and ventricular fibrillation. These can occur suddenly, sometimes without any warning signs. In some people, the first symptom of SQTS may be sudden cardiac arrest.
SQTS is considered channelopathy, a condition caused by changes (variants) in genes that control ion channels. Ion channels are tiny structures in cells that allow charged particles like potassium, calcium and sodium to move in and out. These movements are what make the heart beats.
SQTS can be inherited, usually in an autosomal dominant pattern. This means that if one parent carries the gene variant, there’s a 50 percent chance their child will inherit it. But the condition shows low penetrance, which means not everyone who inherits the variant will show symptoms.
Implantable cardioverter defibrillators (ICDs) are the main treatment for people with symptoms and at risk for sudden cardiac death, especially those who have already had cardiac arrest or sustained ventricular arrhythmias.
Introduction
Although doctors had suspected that a very short QT interval might be linked to sudden cardiac death, the condition was not officially recognized as a distinct syndrome until the year 2000. In 2004, Dr. Ramon Brugada and his team studied families who had experienced sudden deaths and found that some had a specific variant in a gene called KCNH2. This gene helps produce a protein that forms potassium channels. Since then, scientists have discovered that SQTS can be caused by variants in several different genes. Because of this, researchers have been working to include these genes in genetic testing panels. The goal is to diagnose SQTS earlier and more accurately, especially in families with a history of heart rhythm problems or sudden deaths.
Symptoms of SQTS can vary broadly, even among people in the same family. Some people have no symptoms while others may experience life-threatening arrhythmias that may appear at rest or during exercise with no apparent initiating cause. The reported signs and symptoms include:
In some people, SQTS may also be linked with epilepsy or behavior problems resembling autism, likely because the same ion channels affected in the heart are also found in brain cells. However, these associations are still being researched.
The median age of onset is 30 years, though it ranges widely from a few months to 60 years of age.
All the above signs of the syndrome are associated with a QTc interval briefer than 0.34 seconds in people with structurally normal hearts. The precise link between the electrical abnormality and the severity of the syndrome has not been established.
SQTS is considered a channelopathy, a condition caused by changes (variants) in genes that control ion channels. Ion channels are tiny structures in cells that allow charged particles like potassium, calcium and sodium to move in and out. These movements are what make the heart beats.
There are currently eight identified genetic types (called genotypes) of SQTS caused by variants in different genes:
However, gene variants are found in less than half of the people diagnosed with SQTS. Secondary causes of SQT, including electrolyte imbalances, drug-induced effects, or other genetic conditions (e.g., primary carnitine deficiency) should be taken into consideration as other possible diagnoses in people with SQT.
SQTS can be inherited, usually in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females. SQTS shows low penetrance, which means not everyone who inherits a gene variant will show symptoms.
Many people with SQTS likely go undiagnosed or misdiagnosed, and therefore, estimating SQTS incidence and prevalence are difficult due to limited data. Some have estimated the SQTS prevalence at less than 1 in 10,000. Although it is very rare, recent data suggest that SQTS may affect between 0.02% and 0.1% of the adult population. It is more common in males than in females. It has been suggested that SQTS shows a peak incidence during the first year of life and another peak in late adulthood. So far, around 250 cases have been reported in the medical literature. A higher risk in certain ethnic groups has not been reported in the literature.
Short QT syndrome (SQTS) has this specific name because on the electrocardiogram (ECG) its main characteristic is the presence of an abnormally short QT interval. The ECG is widely used by cardiologists to diagnose heart rhythm and conduction problems associated with cardiovascular conditions. Every time the heart beats, electrical currents flow through it and the ECG records the changes in voltage associated with such currents versus time. By placing electrodes at specific locations of the body surface and connecting them to an ECG machine, an expert can identify a wide variety of cardiac alterations, including abnormal heart rate and rhythm.
Normally on ECG, each beat is composed of specific voltage waves, labelled P, Q, R, S and T, and organized as complexes, segments and intervals with known amplitudes and durations. They indicate the local excitation and recovery as the electrical wave moves from the atria to the ventricles of the heart. The P wave represents the excitation (depolarization) of the atria; the QRS complex represents the depolarization of the ventricles, and the T wave indicates the recovery (repolarization) from ventricular excitation. The time interval between the onset of the QRS and the end of the T wave is the QT interval.
The QT interval shows how long it takes the heart’s lower chambers (the ventricles) to recover between beats. When this interval is too short it can signal SQTS. More specifically, the focus is on a corrected version of the QT interval called the QTc (corrected QT). If the QTc is less than 340 milliseconds it strongly points toward a diagnosis of SQTS. Even if the QTc falls between 320 and 360 milliseconds, it might still qualify as SQTS, especially if there are symptoms like unexplained fainting (syncope) or other warning signs.
To help estimate how likely it is that someone has SQTS, doctors sometimes use a system called the Schwartz Score. This score gives points based on a person’s symptoms, family history, ECG results and genetic testing.
For example, points are given if a person has:
If the total score is 4 or more, there’s a high chance of having SQTS. A score of 3 suggests a moderate chance and 0 to 2 means a low chance.
Besides the ECG and Schwartz Score, doctors may use implantable loop recorders to monitor heart rhythms over time. This is especially helpful for younger adults who may not show symptoms right away.
Genetic testing can sometimes confirm the diagnosis, especially in families where sudden unexplained deaths have occurred. However, it’s important to understand that not all genetic causes are currently known. Many people may show clear signs of SQTS but test negative for known gene variants. That’s why genetic testing is helpful but not always definitive.
According to medical guidelines, genetic testing should still be considered, especially if someone in the family has already been diagnosed. The test usually looks at certain genes: KCNH2, KCNQ1, KCNJ2, CACNA1C and CACNB2b. Sometimes other genes like CACNA2D1, SCN5A and SLC4A3 are also checked. If a variant is found in one of these genes, other family members should be tested so they can be diagnosed early.
Treatment
There are no standardized protocols for the treatment of SQTS. A team of specialists including cardiologists and other healthcare professionals should determine the treatment plan.
The main treatment for people with symptoms and at risk for sudden cardiac death, especially those who have already had cardiac arrest or sustained ventricular arrhythmias are implantable cardioverter defibrillators (ICDs). ICDs detect abnormal rhythms and can deliver a shock to restore normal heartbeat.
People who may qualify for an ICD include:
Medications are sometimes used when an ICD is not possible, especially in younger people. The most effective drug is quinidine which helps normalize the QT interval by blocking certain potassium channels. Hydroquinidine, a similar drug, can also be used, though it’s not yet clear how well it prevents cardiac events.
Amiodarone and sotalol, while they usually lengthen the QT interval, have not been shown to work in SQTS, especially in people with SQT1. This is likely because the specific ion channel gene variants involved in SQTS make these drugs less effective.
Currently, drug treatment focuses mainly on SQTS1 and more research is needed to find medications tailored to the other genetic subtypes.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Cardiac Electrophysiology: From Cell to Bedside, 7th ed. Zipes DP, Jalife J, editors. 2017. Elsevier Saunders, Philadelphia, PA.
JOURNAL ARTICLES
Boulmpou A, Giannopoulos A, Papadopoulos C, et al. The Uncommon Phenomenon of Short QT Syndrome: A Scoping Review of the Literature. J Pers Med. 2025;15(3):105. Published 2025 Mar 8. doi:10.3390/jpm15030105
Nehme RD, Sinno L, Shouman W & cols. Cardiac Channelopathies: Clinical Diagnosis and Promising Therapeutics. J Am Heart Assoc. 2025 May 6;14(9):e040072. doi: 10.1161/JAHA.124.040072. Epub 2025 Apr 25. PMID: 40281647.
Campuzano O, Fernandez-Falgueras A, Lemus X, et al. Short QT Syndrome: A Comprehensive Genetic Interpretation and Clinical Translation of Rare Variants. J Clin Med. 2019;8(7):1035. Published 2019 Jul 16. doi:10.3390/jcm8071035
Campuzano O, Sarquella-Brugada G, Cesar S, Arbelo E, Brugada J, Brugada R. Recent Advances in Short QT Syndrome. Front Cardiovasc Med. 2018;5:149. Published 2018 Oct 29. doi:10.3389/fcvm.2018.00149
Fernández-Falgueras A, Sarquella-Brugada G, Brugada J, Brugada R, Campuzano O. Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances. Biology (Basel). 2017;6(1):7. Published 2017 Jan 29. doi:10.3390/biology6010007
Mazzanti A, Maragna R, Vacanti G, et al. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. J Am Coll Cardiol. 2017;70(24):3010-3015. doi:10.1016/j.jacc.2017.10.025
Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36(41):2793-2867. doi:10.1093/eurheartj/ehv316
Mazzanti A, O’Rourke S, Ng K, et al. The usual suspects in sudden cardiac death of the young: a focus on inherited arrhythmogenic diseases. Expert Rev Cardiovasc Ther. 2014;12(4):499-519. doi:10.1586/14779072.2014.894884
Tristani-Firouzi M. The Long and Short of It: Insights Into the Short QT Syndrome. J Am Coll Cardiol. 2014;63(13):1309-1310. doi:10.1016/j.jacc.2013.11.021
Tülümen E, Giustetto C, Wolpert C, et al. PQ segment depression in patients with short QT syndrome: a novel marker for diagnosing short QT syndrome?. Heart Rhythm. 2014;11(6):1024-1030. doi:10.1016/j.hrthm.2014.02.024 \
Miyamoto A, Hayashi H, Yoshino T, et al. Clinical and electrocardiographic characteristics of patients with short QT interval in a large hospital-based population. Heart Rhythm. 2012;9(1):66-74. doi:10.1016/j.hrthm.2011.08.016
Giustetto C, Schimpf R, Mazzanti A, et al. Long-term follow-up of patients with short QT syndrome. J Am Coll Cardiol. 2011;58(6):587-595. doi:10.1016/j.jacc.2011.03.038
Bjerregaard P, Nallapaneni H, Gussak I. Short QT interval in clinical practice. J Electrocardiol. 2010;43(5):390-395. doi:10.1016/j.jelectrocard.2010.06.004
Holbrook M, Malik M, Shah RR, Valentin JP. Drug induced shortening of the QT/QTc interval: an emerging safety issue warranting further modelling and evaluation in drug research and development?. J Pharmacol Toxicol Methods. 2009;59(1):21-28. doi:10.1016/j.vascn.2008.09.001
Kobza R, Roos M, Niggli B, et al. Prevalence of long and short QT in a young population of 41,767 predominantly male Swiss conscripts. Heart Rhythm. 2009;6(5):652-657. doi:10.1016/j.hrthm.2009.01.009
Funada A, Hayashi K, Ino H, et al. Assessment of QT intervals and prevalence of short QT syndrome in Japan. Clin Cardiol. 2008;31(6):270-274. doi:10.1002/clc.20208
Schimpf R, Borggrefe M, Wolpert C. Clinical and molecular genetics of the short QT syndrome. Curr Opin Cardiol. 2008;23(3):192-198. doi:10.1097/HCO.0b013e3282fbf756
Anttonen O, Junttila MJ, Rissanen H, Reunanen A, Viitasalo M, Huikuri HV. Prevalence and prognostic significance of short QT interval in a middle-aged Finnish population. Circulation. 2007;116(7):714-720. doi:10.1161/CIRCULATIONAHA.106.676551
Gussak I, Bjerregaard P. Short QT syndrome–5 years of progress. J Electrocardiol. 2005;38(4):375-377. doi:10.1016/j.jelectrocard.2005.06.012
Priori SG, Pandit SV, Rivolta I, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res. 2005;96(7):800-807. doi:10.1161/01.RES.0000162101.76263.8c
Viskin S, Zeltser D, Ish-Shalom M, et al. Is idiopathic ventricular fibrillation a short QT syndrome? Comparison of QT intervals of patients with idiopathic ventricular fibrillation and healthy controls. Heart Rhythm. 2004;1(5):587-591. doi:10.1016/j.hrthm.2004.07.010
Bellocq C, van Ginneken AC, Bezzina CR, et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation. 2004;109(20):2394-2397. doi:10.1161/01.CIR.0000130409.72142.FE
Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation. 2004;109(1):30-35. doi:10.1161/01.CIR.0000109482.92774.3A
Gaita F, Giustetto C, Bianchi F, et al. Short QT Syndrome: a familial cause of sudden death. Circulation. 2003;108(8):965-970. doi:10.1161/01.CIR.0000085071.28695.C4
Gussak I, Brugada P, Brugada J, et al. Idiopathic short QT interval: a new clinical syndrome?. Cardiology. 2000;94(2):99-102. doi:10.1159/000047299
Nierenberg DW. Spironolactone and metabolic acidosis. Ann Intern Med. 1979;91(2):321-322. doi:10.7326/0003-4819-91-2-321_3
INTERNET
Online Mendelian Inheritance in Man (OMIM). Johns Hopkins University. Short QT Syndrome 1; SQT1. Entry No: 609620. Last Edited: 01/03/2024. Available at: https://www.omim.org/entry/609620. Accessed May 27, 2025.
Online Mendelian Inheritance in Man (OMIM). Johns Hopkins University. Short QT Syndrome 2; SQT2. Entry No: 609621. Last Edited: 02/09/2017. Available at: https://www.omim.org/entry/609621. Accessed May 27, 2025.
Online Mendelian Inheritance in Man (OMIM). Johns Hopkins University. Short QT Syndrome 3; SQT3. Entry No: 609622. Last Edited: 01/02/2024. Available at: https://www.omim.org/entry/609622. Accessed May 27, 2025.
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