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.

1. A sharp brain also stops working in presence of a beauty
Congenital Long QT Syndrome
Ramachandra

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. Define

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. Concealed LongQTS
10%-40% of genotype-positive
individuals do not display any objective
evidence of a QT abnormality

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. 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. Inheritance-Prototypes
Autosomal dominant
– Romano-Ward syndrome (RWS)
 Autosomal recessive
-Jervell and Lange-Nielsen syndrome (JLNS)

9. Phenotypes
Only cardiac: RWS
Cardiac and ear: JLNS
Multi organ: Timothy syndrome (TS)

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

12. LongQT Projection

13. Major LQTS–Susceptibility Genes
KCNQ1 (LQT1)
 KCNH2 (LQT2)
SCN5A (LQT3)
 most common causes
60%-75%

14. 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

15. 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

16. About them

17. Minorities
• At least 10 mutations
• 5% of LongQT

18. Multisystem Long-QT Syndrome
 Ankyrin-B
 Anderson-Tawil
 Timothy syndrome
 Recurrent Infantile Cardiac Arrest Syndromes

19. Genetic Modifiers of Long QT Syndrome Disease Severity

20. Schwartz et al
•
•
•
•
•
•
2009
Population-based ECG
Molecular screening
44,456 Italian
Phenotypes of Congenital LQTS = 1/ 2000
Pathogenic LQTS genotype=1/80

21. T- morphology

22. Diagnosis
• Personal/family Hx
• LongQTS-triggered syncope/seizure/SCD
• Provoke like
accident/drownings/emotional/sleep/rest
• ECG: QTc>450msec(M) & >460msec (F)

23. Schwartz score ≥3.5:high (P)

24. Bazett’s QTc =QT/√RR

25. Rare variants

26. Risk Stratification :Geno+Pheno

27. Mutation reports

28. Management

29. M-FACT score

30. External Link
http://www.youtube.com/watch?v=_QElcK_fpV8

31. Stop imagination....learned a lot

32. Have nice time