Congenital long qt syndrome


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The long QT syndrome (LQTS) is a rare inherited heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsades de pointes (TDP, a form of irregular heartbeat that originates from the ventricles). These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation. Episodes may be provoked by various stimuli, depending on the subtype of the condition.The condition is so named because of the appearances of the electrocardiogram (ECG/EKG), on which there is prolongation of the QT interval. In some individuals the QT prolongation occurs only after the administration of certain medications.

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Congenital long qt syndrome

  1. 1. A sharp brain also stops working in presence of a beauty Congenital Long QT Syndrome Ramachandra
  2. 2. Tell me a story about The first documented case of Long QT syndrome was described in Leipzig by Meissner in 1856, where a deaf girl died after her teacher yelled at her. When the parents were told about her death, they told that her older brother who also was deaf died after a terrible fright. This was several decades before the ECG was invented, but is likely the first described case of Jervell and Lange-Nielsen syndrome. In 1957, the first case documented by ECG was described by Anton Jervell and Fred Lange-Nielsen, working in Tønsberg, Norway. Italian pediatrician Cesarino Romano, in 1963 and Irish pediatrician Owen Conor Ward, in 1964 separately described the more common variant of Long QT syndrome with normal hearing, later called Romano-Ward syndrome. The establishment of the International Long-QT Syndrome Registry in 1979 allowed numerous pedigrees to be evaluated in a comprehensive manner. This helped in detecting many of the numerous genes involved. On September 29, 2006, Konowalchuk announced his retirement after a regular examination detected Long QT Syndrome
  3. 3. Define
  4. 4. Manifested LongQTs Positive 12 Lead ECG Man:QTc ≥ 450ms Women ≥QTc 460ms Screening :QTc ≥ 470msec(M) & QTc ≥ 480msec(Female) Giudicessi JR, Ackerman MJ. Determinants of incomplete penetrance Giudicessi JR, Ackerman MJ. Determinants of incomplete penetrance and variable expressivity in heritable cardiac arrhythmia syndromes. and variable expressivity in heritable cardiac arrhythmia syndromes. Transl Res 2013;161:1-14 Transl Res 2013;161:1-14 Morita H, Wu J, Zipes DP. The QT syndromes: long and short. Lancet Morita H, Wu J, Zipes DP. The QT syndromes: long and short. Lancet 2008;372: 750-63 2008;372: 750-63
  5. 5. Concealed LongQTS 10%-40% of genotype-positive individuals do not display any objective evidence of a QT abnormality
  6. 6. Attributes of congenital LongQT Genetically heterogeneous Heritable Repolarisation abnormality Phenotype of QT prolongation on 12-ECG Increased risk of potentially life-threatening cardiac arrhythmias Treatable
  7. 7. At the molecular level • Mutations in15 distinct genes for encoding ion channel pore-forming a-subunits and accessory β-subunits central to the electromechanical function
  8. 8. Inheritance-Prototypes Autosomal dominant – Romano-Ward syndrome (RWS)  Autosomal recessive -Jervell and Lange-Nielsen syndrome (JLNS)
  9. 9. Phenotypes Only cardiac: RWS Cardiac and ear: JLNS Multi organ: Timothy syndrome (TS)
  10. 10. Key Errors: Loss or Gain Activation and inactivation process of α/β sub units of the following channels Inward depolarizing currents(INa⁺/ICa²) -Enhance  outward repolarisation currents(Ikr/Iks/Ik1) - Diminished
  11. 11. LongQT Projection
  12. 12. Major LQTS–Susceptibility Genes KCNQ1 (LQT1)  KCNH2 (LQT2) SCN5A (LQT3)  most common causes 60%-75%
  13. 13. KCNQ1 AD JLNS Kv7.1pore-forming α-subunit Iks Physiological QT shortening with rise in HR Endocochlear K current Heterozygous loss-of- function most prevalent LQTS subtype
  14. 14. KCNQ1 .....Contd physical and emotional stress Defective IKs fails to adopt with β-adrenergic stimulation i.e. QT prolongs in place of shortening:Fatal LongQT
  15. 15. About them
  16. 16. Minorities • At least 10 mutations • 5% of LongQT
  17. 17. Multisystem Long-QT Syndrome  Ankyrin-B  Anderson-Tawil  Timothy syndrome  Recurrent Infantile Cardiac Arrest Syndromes
  18. 18. Genetic Modifiers of Long QT Syndrome Disease Severity
  19. 19. Schwartz et al • • • • • • 2009 Population-based ECG Molecular screening 44,456 Italian Phenotypes of Congenital LQTS = 1/ 2000 Pathogenic LQTS genotype=1/80
  20. 20. T- morphology
  21. 21. Diagnosis • Personal/family Hx • LongQTS-triggered syncope/seizure/SCD • Provoke like accident/drownings/emotional/sleep/rest • ECG: QTc>450msec(M) & >460msec (F)
  22. 22. Schwartz score ≥3.5:high (P)
  23. 23. Bazett’s QTc =QT/√RR
  24. 24. Rare variants
  25. 25. Risk Stratification :Geno+Pheno
  26. 26. Mutation reports
  27. 27. Management
  28. 28. M-FACT score
  29. 29. External Link
  30. 30. Stop imagination....learned a lot
  31. 31. Have nice time