Inherited Arrhythmias

Inherited Arrhythmias

There are several groups of inherited arrhythmias, with each having several genotypes. Important ones are:

1. Long QT Syndrome
2. Brugada Syndrome
3. Catecholaminergic Polymorphic Ventricular Tachycardia
4. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
5. Short QT Syndrome
6. Familial Atrial Fibrillation
7. Sinus Node Disease and
8. Progressive Cardiac Conduction Defect

Congenital Long QT Syndromes

1. LQT1: KCNQ1 (Alpha sub unit) Decrease in IKs (Slow component of delayed rectifier potassium current)
2. LQT2: HERG (Alpha sub unit) Decrease in IKr (Rapid component of delayed rectifier potassium current)
3. LQT3: SCN5A Increase in Late INa (Late sodium current)
4. LQT4: Ankyrin-B Anchoring protein which anchors ion channel to plasmalemma and sarcolemma
5. LQT5: KCNE1(minK) (Beta sub unit) Decrease in IKs
6. LQT7: KCNJ2 (Andersen syndrome) Associated with dysmorphic features and potassium sensitive periodic paralysis
7. LQT6 KCNE2 (MiRP1)(Beta sub unit) Decrease in IKrLQT7: KCNJ2 (Andersen syndrome)
8. LQT8: CACNA1c (Timothy syndrome) Associated congenital heart disease and syndactyly
9. LQT9: CAV3  (caveolin 3 – SIDS) Caveolin is the protein the caveolae (invaginations of the plasma membrane)
10. LQT10: SCNB4 (Beta subunit of sodium channel)
11. LQT11: AKAP9 (A-kinase anchor protein 9)
12. LQT12: SNTA1 (alpha-1 syntrophin)

Homozygous state in congenital long QT syndrome causes defective endolymph secretion in the inner ear and deafness, and is called Jervell-Lange-Nielsen Syndrome

1. JLN1 KCNQ1 (homozygous defect of alpha subunit) Decrease in IKs
2. JLN2 KCNE1(minK) (homozygous defect of beta sub unit) Decrease in IKs

Congenital Short QT syndromes

1. SQT1: Brugada et al – HERG (KCNH2)  Gain in function of Iks
2. SQT2: Bellocq et al – KCNQ1 (KvLQT1) Gain in function of Ikr
3. SQT3: Priori et al – KCNJ2 Gain in function of Ik1

Other causes for shortening of QT interval have to be excluded before diagnosing short QT syndrome, like:

1. Tachycardia
2. Hyperthermia
3. Hypercalcemia and
4. Digoxin

Clinical manifestations of short QT syndrome includes:

1. Short refractory periods
2. Inducible Ventricular Fibrillation at EP study
3. Family history of sudden death and
4. Atrial fibrillation

Brugada Syndrome

Most important mutations in SCN5A gene
Autosomal dominant, incomplete penetrance
5 to 66 per 10,000, male predominance
ST elevation in precordial leads, polymorphic ventricular tachycardia
Cardiac arrest, syncope and family history

Arrhythmogenic Right Ventricular Dysplasia now known as Arrhythmogenic Cariomyopathy as left ventricluar involvement has also been described. Features include: 

Regional or 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