Inherited Arrhythmias
Long QT Syndrome (LQTS 1-12)
Brugada Syndrome (BrS 1,2)
Catecholaminergic Polymorphic VT (CPVT 1,2)
Arrhythmogenic Right Ventricular Cardiomyopathy
Short QT Syndrome (SQTS 1-3)
Familial Atrial Fibrillation (FAF 1-4)
Sinus Node Disease (HCN4, SCN5A)
Progressive Cardiac Conduction Defect
Congenital Long QT Syndromes
LQT1: KCNQ1 (Alpha sub unit) Decrease in IKs (Slow component of delayed rectifier potassium current)
LQT2: HERG (Alpha sub unit) Decrease in IKr (Rapid component of delayed rectifier potassium current)
LQT3: SCN5A Increase in Late INa (Late sodium current)
LQT4: Ankyrin-B Anchoring protein which anchors ion channel to plasmalemma and sarcolemma
LQT5: KCNE1(minK) (Beta sub unit) Decrease in IKs
LQT7: KCNJ2 (Andersen syndrome) Associated with dysmorphic features and potassium sensitive periodic paralysis
LQT6 KCNE2 (MiRP1)(Beta sub unit) Decrease in IKrLQT7: KCNJ2 (Andersen syndrome)
LQT8: CACNA1c (Timothy syndrome) Associated congenital heart disease and syndactyly
LQT9: CAV3 (caveolin 3 – SIDS) Caveolin is the protein the caveolae (invaginations of the plasma membrane)
LQT10: SCNB4 (Beta subunit of sodium channel)
LQT11: AKAP9 (A-kinase anchor protein 9)
LQT12: SNTA1 (alpha-1 syntrophin)
Jervell-Lange-Nielsen Syndrome: Homozygous state causes defective endolymph secretion in the inner ear and deafness
JLN1 KCNQ1 (homozygous defect of alpha subunit) Decrease in IKs
JLN2 KCNE1(minK) (homozygous defect of beta sub unit) Decrease in IKs
Congenital Short QT syndromes
SQT1: Brugada et al – HERG (KCNH2) Gain in function of Iks
SQT2: Bellocq et al – KCNQ1 (KvLQT1) Gain in function of Ikr
SQT3: Priori et al – KCNJ2 Gain in function of Ik1
Other causes for shortening of QT interval
Tachycardia
Hyperthermia
Hypercalcemia
Digoxin
SQTS: Clinical Manifestations
Short refractory periods
Inducible VF at EP study
Family history of sudden death
Atrial fibrillation
Brugada Syndrome
Mutation in SCN5A / GPD1-L
Autosomal dominant, incomplete penetrance
5 to 66 per 10,000, male predominance
ST elevation in precordial leads, polymorphic VT
Cardiac arrest, syncope, family history
Arrhythmogenic Right Ventricular Dysplasia
Regional / global fibro-fatty replacement of myocardium
1:1000 to 1:10 000 incidence
Syncope, sustained VT, cardiac arrest
Familial in 30%
Autosomal dominant, incomplete penetrance
Epsilon wave on ECG
T wave inversion in anterior leads