Table 3

Examples of congenital cardiac arrhythmias

GeneProteinIon channel affectedDysfunctionImpact on heart physiologyPotential therapies
LQTS
 LQT1KCNQ1KvLQT1 (Kv7.1)IKs-α SULoss of functionProlongation and dispersion of refractoriness, EADs, VT, TdP, syncope, VF, sudden deathCorrect electrolyte imbalance, β-ADR blockers (first choice therapy), ICDs, Left cardiac sympathetic denervation, see ref. 36
Mexiletine, flecainide, ranolazine (late Na block for LQT3 syndrome)
 LQT2KCNH2hERG (Kv11.1)IKr-α SULoss of function
 LQT3SCN5ANav1.5INa-α SUGain of function
 LQT4ANK2Ankyrin-BNa/K ATPase, NCXLoss of functionSinus node dysfunction, bradycardia, delayed conduction, AF, QT prolongation
 LQT5KCNE1minKIKs-β SULoss of function
 LQT6KCNE2MiRP1IKr-β SULoss of function
 LQT7 (Andersen–Tawil syndrome)KCNJ2Kir2.1IK1Loss of functionProminent U wave, ventricular ectopic beats, polymorphic VT, bidirectional VT
 LQT8 (Timothy syndrome)CACNA1CCav1.2ICaL-α SUGain of functionImpaired ICaL inactivation, QT prolongation, congenital heart diseases, 2 : 1 AV block, TdP, VF
 LQT9CAV3Caveolin-3InaGain of functionLQT3-like phenotype
 LQT10SCN4BNav1.5INa-β SUGain of function2 : 1 AV block, QT prolongation
 LQT11AKAP9Yotiao/A-kinase-anchoring proteinIKsGain of function
 LQT12SNTN1α1-SyntrophinInaGain of functionLQT3-like phenotype
 LQT13 (Andersen–Tawil syndrome)KCNJ5Kir3.4IK(ATP)Loss of functionRecurrent palpitations, syncope, AT, AF
Brugada syndrome
SCN5ANav1.5INa-α SULoss of functionShortening of refractoriness, contractility impairment, VT, VF, sudden deathICDs
Quinidine, isoproterenol
Radiofrequency catheter ablation
SQTS
KCNQ1KvLQT1IKs-α SUGain of functionShortening of refractoriness, re-entries, VT, sudden death
KCNH2hERGIKr-α SUGain of function
KCNJ2Kir2.1IK1Gain of function
CDPVT
 Bidirectional and polymorphic VT triggered by adrenergic stimuliRYR2Ryanodine receptorGain of functionDiastolic calcium release from SR, DADs, VTRyR2 and CamKII blockers in development
CASQ2CalsequestrinGain of function
Idiopathic sick sinus syndrome
HCN4IfLoss of functionsinus bradycardia, sinus arrest, chronotropic incompetence
SCN5ANav1.5INaLoss of functionAtrial inexcitability
Familial atrial fibrillation
KCNH2hERGIKr-α SUGain of functionShortening of refractoriness, re-entry pathways, tissue remodellingSpecific atrial ion channel blockers in development, ranolazine,
KCNE2MiRP1IKr-β SUGain of function
KCNQ1KvLQT1IKs-α SUGain of function
KCNJ2Kir2.1IK1Gain of function
  • For details, see ref 36.

  • ADR, adrenoceptor; AF, atrial fibrillation/flutter; AV, atrioventricular; CDPVT, catecholamine-dependent polymorphic ventricular tachycardia; DAD, delayed afterdepolarisations; EAD, early afterdepolarisations; JLN, Jervell and Lange-Nielsen; LQTS, long QT syndrome; PVCs, premature ventricular contractions; SCD, sudden cardiac death; SQTS, Short QT syndrome; SR, sarcoplasmic reticulum; SU, subunit; TdP, Torsade de Pointes; VT, ventricular tachycardia, VF, ventricular fibrillation.