Congenital long qt syndrome
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Transcript of Congenital long qt syndrome
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Congenital Long QT Syndrome
Ramachandra
A sharp brain also stops working in presence of a beauty
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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
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Define
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Manifested LongQTs
Positive 12 Lead ECGMan:QTc ≥ 450msWomen ≥QTc 460msScreening :QTc ≥ 470msec(M) & QTc ≥
480msec(Female)Giudicessi JR, Ackerman MJ. Determinants of incomplete penetrance and variable expressivity in heritable cardiac arrhythmia syndromes. Transl Res 2013;161:1-14 Morita H, Wu J, Zipes DP. The QT syndromes: long and short. Lancet 2008;372: 750-63
Giudicessi JR, Ackerman MJ. Determinants of incomplete penetrance and variable expressivity in heritable cardiac arrhythmia syndromes. Transl Res 2013;161:1-14 Morita H, Wu J, Zipes DP. The QT syndromes: long and short. Lancet 2008;372: 750-63
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Concealed LongQTS
10%-40% of genotype-positive individuals do not display any objective
evidence of a QT abnormality
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Attributes of congenital LongQT
Genetically heterogeneousHeritable Repolarisation abnormalityPhenotype of QT prolongation on 12-ECGIncreased risk of potentially life-threatening
cardiac arrhythmiasTreatable
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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
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Inheritance-Prototypes
Autosomal dominant– Romano-Ward syndrome (RWS)
Autosomal recessive -Jervell and Lange-Nielsen syndrome (JLNS)
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Phenotypes
Only cardiac: RWSCardiac and ear: JLNSMulti organ: Timothy syndrome (TS)
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Key Errors: Loss or Gain
Activation and inactivation process of α/β sub units of the following channelsInward depolarizing currents(INa⁺/ICa²) -Enhance outward repolarisation currents(Ikr/Iks/Ik1) - Diminished
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LongQT Projection
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Major LQTS–Susceptibility Genes
KCNQ1 (LQT1) KCNH2 (LQT2)SCN5A (LQT3)
most common causes 60%-75%
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KCNQ1
ADJLNS Kv7.1pore-forming α-subunitIksPhysiological QT shortening with rise in HREndocochlear K currentHeterozygous loss-of- function most prevalent LQTS subtype
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KCNQ1 .....Contd
physical and emotional stressDefective IKs fails to adopt with β-adrenergic
stimulation i.e. QT prolongs in place of shortening:Fatal LongQT
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About them
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Minorities
• At least 10 mutations• 5% of LongQT
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Multisystem Long-QT Syndrome
Ankyrin-B Anderson-Tawil Timothy syndrome Recurrent Infantile Cardiac Arrest Syndromes
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Genetic Modifiers of Long QT Syndrome Disease Severity
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Schwartz et al
• 2009 • Population-based ECG• Molecular screening• 44,456 Italian• Phenotypes of Congenital LQTS = 1/ 2000• Pathogenic LQTS genotype=1/80
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T- morphology
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Diagnosis
• Personal/family Hx• LongQTS-triggered syncope/seizure/SCD• Provoke like
accident/drownings/emotional/sleep/rest• ECG: QTc>450msec(M) & >460msec (F)
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Schwartz score ≥3.5:high (P)
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Bazett’s QTc =QT/√RR
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Rare variants
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Risk Stratification :Geno+Pheno
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Mutation reports
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Management
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M-FACT score
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External Link
http://www.youtube.com/watch?v=_QElcK_fpV8
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Stop imagination....learned a lot
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Have nice time