• Long QT syndrome 1 – OMIM#192500 gene
  • Long QT syndrome 5 – OMIM#613695 gene
  • Long QT syndrome 8 – OMIM#618447 gene. Also includes: Brugada syndrome 3; Timothy syndrome; CACNAC1- related syndromes
  • Short QT syndrome 3 – OMIM#609622 – KCNJ2 gene. Also includes: Andersen syndrome; Familial atrial fibrillation 9

Catecholaminergic polymorphic ventricular tachycardia (CPVT)


1. The Disease:

Sudden infant death syndrome (SIDS) is always a devastating and unexpected occurrence. SIDS is the leading cause of death in the first 6 months after birth in the industrialized world. Around 10-20% of SIDS cases have been proposed as being caused by genetic variants in either ion channel or ion channel-associated proteins. SIDS may hereby be the initial symptom of rare primary electric channelopathies such as long QT, short QT and Brugada syndrome, as well as catecholaminergic polymorphic ventricular tachycardia. Alterations in any of these currents, and in the availability of intracellular free calcium, leaves the myocardium vulnerable to polymorphic ventricular tachycardia or ventricular fibrillation. Each channelopathy has its own electrocardiogram (ECG) signature, typical mode of presentation, and most commonly related gene.

2. The symptoms:

Long QT syndrome and CPVT typically present with cardiac events syncope-like or cardiac arrest during or immediately after exercise in young individuals. They are commonly misdiagnosed as seizure disorders. Lack of early signs or symptoms does not exclude the diagnosis.

  • Approximately 50% of untreated individuals with a pathogenic variantin one of the genes associated with LQTS have symptoms, usually one to a few syncopal events. While cardiac events may occur from infancy through middle age, they are most common from the preteen years through the 20s.
  • Some types of LQTS are associated with a phenotypeextending beyond cardiac arrhythmia. In addition to the prolonged QT interval, associations include muscle weakness and facial dysmorphism in Andersen-Tawil syndrome (LQTS type 7 see specific entry); hand/foot, facial, and neurodevelopmental features in Timothy syndrome (LQTS type 8 see specific entry); and profound sensorineural hearing loss in Jervell and Lange-Nielson syndrome (see specific entry).

3. Actions to take in case of early diagnosis

  • Infants with a positive genetic test [having 1 pathogenic variant in heterozygosis in one of these genes – CACNA1C, RYR2, CALM1, CALM2, CALM3, TECRL and ANK2] or [having 1 or 2 variants (heterozygosis or homozygosis) in one of these genes – KCNQ1, KCNE1 or KCNJ2] or 1 biallelic variant in the CASQ2 and TRDN genes], should continue breastfeeding.
  • The diagnosis is based on genetic results, familial history, clinical signs, ECG and rhythm holter.
  • GC are a lifelong group of conditions that requires lifetime management and regular follow-up with a paediatrician specialist in cardiology, geneticist, and a multidisciplinary approach to care.
  • The most import would be the cardiac surveillance and serial exams to evaluate cardiac rhythm evolution and the necessity for pharmacological treatment. Beta blockers are the mainstay of treatment for long QT syndrome and CPVT, and flecainide is remarkably effective in CPVT.
  • Prevention of secondary complications: Special precautions during anaesthesia are necessary because of the increased risk for cardiac arrhythmia.
  • Agents/circumstances to avoid: Drugs that cause further prolongation of the QT interval; activities known to precipitate syncopal events in persons with long QT syndrome and CPVT.
  • Treatment for Jervell and Lange-Nielsen syndrome manifestations: cochlear implantation to treat hearing loss; beta-adrenergic blockers for long QT interval (only partially effective); implantable cardioverter defibrillators (ICDs) for those with a history of cardiac arrest and/or failure to respond to other treatments; ensure availability of automated external defibrillators where appropriate; standard treatment for those with iron-deficiency anaemia.
  • Training for family members in cardiopulmonary resuscitation; use of an ID bracelet explaining the diagnosis; notifying local emergency medical services of high-risk persons with channelopathy.
  • Genetic counselling is highly recommended for family planning and evaluation of at-risk first-degree family members.

4. For more information: