Historically, only the most severe cases of LQTS were detected and reported, suggesting that the condition was extremely rare.[9]Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J. 1957 Jul;54(1):59-68.
http://www.ncbi.nlm.nih.gov/pubmed/13435203?tool=bestpractice.com
However, it is currently estimated that at least 1 in 2000 to 1 in 2500 people worldwide are affected with congenital LQTS, although its observed prevalence has increased as awareness and screening for the condition has improved.[4]Wallace E, Howard L, Liu M, et al. Long QT syndrome: genetics and future perspective. Pediatr Cardiol. 2019 Oct;40(7):1419-30.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785594
http://www.ncbi.nlm.nih.gov/pubmed/31440766?tool=bestpractice.com
[5]Wilde AAM, Semsarian C, Márquez MF, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases. Europace. 2022 Sep 1;24(8):1307-67.
https://www.doi.org/10.1093/europace/euac030
http://www.ncbi.nlm.nih.gov/pubmed/35373836?tool=bestpractice.com
[11]Schwartz PJ, Stramba-Badiale M, Crotti L, et al. Prevalence of the congenital long-QT syndrome. Circulation. 2009 Nov 3;120(18):1761-7.
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.109.863209?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
http://www.ncbi.nlm.nih.gov/pubmed/19841298?tool=bestpractice.com
Untreated LQTS has an annual rate of sudden cardiac death of <0.5% in asymptomatic patients, which rises to approximately 5% in patients who have a history of syncope.[2]Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Oct 21;43(40):3997-4126.
https://www.doi.org/10.1093/eurheartj/ehac262
http://www.ncbi.nlm.nih.gov/pubmed/36017572?tool=bestpractice.com
LQTS is thought to be responsible for approximately 3000 sudden deaths in the US annually.[11]Schwartz PJ, Stramba-Badiale M, Crotti L, et al. Prevalence of the congenital long-QT syndrome. Circulation. 2009 Nov 3;120(18):1761-7.
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.109.863209?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
http://www.ncbi.nlm.nih.gov/pubmed/19841298?tool=bestpractice.com
[12]Schwartz PJ, Priori SG, Napolitano C. How really rare are rare diseases?: The intriguing case of independent compound mutations in the long QT syndrome. J Cardiovasc Electrophysiol. 2003 Oct;14(10):1120-21.
http://www.ncbi.nlm.nih.gov/pubmed/14521668?tool=bestpractice.com
[13]Modell SM, Lehmann MH. The long QT syndrome family of cardiac ion channelopathies: a HuGE review. Genet Med. 2006 Mar;8(3):143-55.
http://www.ncbi.nlm.nih.gov/pubmed/16540748?tool=bestpractice.com
[14]Vincent GM. The long-QT syndrome - bedside to bench to bedside. N Engl J Med. 2003 May 8;348(19):1837-8.
http://www.ncbi.nlm.nih.gov/pubmed/12736277?tool=bestpractice.com
The 10-year mortality rate in untreated, symptomatic index cases is approximately 50%.[5]Wilde AAM, Semsarian C, Márquez MF, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases. Europace. 2022 Sep 1;24(8):1307-67.
https://www.doi.org/10.1093/europace/euac030
http://www.ncbi.nlm.nih.gov/pubmed/35373836?tool=bestpractice.com
The mean age of patients at presentation is 14 years.[2]Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Oct 21;43(40):3997-4126.
https://www.doi.org/10.1093/eurheartj/ehac262
http://www.ncbi.nlm.nih.gov/pubmed/36017572?tool=bestpractice.com
Few data are available to suggest worldwide racial or ethnic variation in prevalence, but this has not been widely studied. LQTS is more commonly diagnosed in women, which may be a spurious observation resulting from the higher upper limit for the corrected QT interval (QTc) in postpubertal females than in males (460 ms and 450 ms, respectively), although one report suggests a slightly higher incidence in women on the basis of genetics.[15]Imboden M, Swan H, Denjoy I, et al. Female predominance and transmission distortion in the long-QT syndrome. N Engl J Med. 2006 Dec 28;355(26):2744-51.
http://www.nejm.org/doi/full/10.1056/NEJMoa042786#t=article
http://www.ncbi.nlm.nih.gov/pubmed/17192539?tool=bestpractice.com
About 70% to 85% of patients with LQTS have an identifiable genetic mutation.[2]Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Oct 21;43(40):3997-4126.
https://www.doi.org/10.1093/eurheartj/ehac262
http://www.ncbi.nlm.nih.gov/pubmed/36017572?tool=bestpractice.com
[5]Wilde AAM, Semsarian C, Márquez MF, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases. Europace. 2022 Sep 1;24(8):1307-67.
https://www.doi.org/10.1093/europace/euac030
http://www.ncbi.nlm.nih.gov/pubmed/35373836?tool=bestpractice.com
The LQT1, LQT2, and LQT3 subtypes of the condition constitute over 90% of cases for which a gene can be identified, with LQT4 to LQT15 accounting for the remainder. KCNQ1 mutations, which lead to LQT1, account for up to 35% to 45% of genotyped patients and are the most commonly identified mutations in these patients, followed by KCNH2 mutations, which lead to LQT2.[16]Moss AJ. Long QT syndrome. JAMA. 2003 Apr 23-30;289(16):2041-4.
http://www.ncbi.nlm.nih.gov/pubmed/12709446?tool=bestpractice.com
Romano-Ward syndrome is the most common form of LQTS and has an autosomal dominant form of inheritance, as opposed to the Jervell and Lange-Nielsen syndrome, which is a rare autosomal recessive form of LQTS.[8]Roden DM. Clinical practice. Long-QT syndrome. N Engl J Med. 2008 Jan 10;358(2):169-76.
http://www.ncbi.nlm.nih.gov/pubmed/18184962?tool=bestpractice.com
The overall incidence and prevalence of acquired LQTS is not known and is difficult to estimate. In one retrospective review of hospital admissions, 0.7% of patients had a corrected QT interval >500 ms.[17]Yu H, Zhang L, Liu J, et al. Acquired long QT syndrome in hospitalized patients. Heart Rhythm. 2017 Jul;14(7):974-8.
http://www.ncbi.nlm.nih.gov/pubmed/28323171?tool=bestpractice.com
In another case-control study from a cohort of hospitalised cancer patients, 1.5% had a corrected QT interval >500 ms.[18]Lin Y, Yu H, Liu F, et al. Hospitalized cancer patients with acquired long QT syndrome-a matched case-control study. Cardiooncology. 2020;6:3.
https://www.doi.org/10.1186/s40959-020-0057-2
http://www.ncbi.nlm.nih.gov/pubmed/32154029?tool=bestpractice.com