Genetics of CV Disease Flashcards
What is Long QT syndrome?
Loss of function mutations in VG Na and K channels
Characterized by prolonged QT interval
Stress triggers:
Syncope - torsade de pointes
Sudden death - ventricular fibrillatyion
What is LQT1?
Mutations in KCNQ1 - reduced K current
Exercise more likely to trigger cardiac event than in either LQT2 or 3
What is LQT2?
Mutation in KCNH2 gene - reduced K current
Symptoms triggered by stress and rest
Arrhythmic events more likely to be triggered by sudden loud noises
What is LQT3?
Mutation in SCN5A gene - increased Na current
Syncope or cardiac arrest more likely to happen during sleep or inactivity
High lethality
What are two possible mechanisms for prolonged QT?
Increased inward currents through maintained sodium channel activity
Decreased outward currents through K channels
What is the first choice treatment for prolonged QT?
Beta-blockers
What is short QT syndrome?
Shorter than normal QT (<340ms)
Caused by GoF mutations in K channels, results in increased efflux of K during repolarization
Symptoms: Dizziness, atrial or ventricular fib., Sudden death
What is Brugada syndrome?
Characterized by RBBB and ST segment elevation in right precordial leads
Majority fast sodium channel LoF mutations
Describe the genetics of Atrial Fibrillation
GoF K channel mutations increases rate of phases 2 and 3
LoF K channel - leads to longer AP and possibly early afterdepolarizations
Uneven distribution of Connexin 40
What is hypertrophic cardiomyopathy?
One part of the heart is thicker than others
Most common monogenic in origin
Predominant gene mutations are those involved in the muscle contraction mechanism - cause cells to grow thick and result in myofibril disarray
What is the clinical spectrum of hypertrophic cardiomyopathy?
Asymptomatic to heart failure, exercise intolerance and chest pain
Patients show symptoms with advancing age
Increased risk for sudden cardiac death
What is dilated cardiomyopathy?
Left ventricular enlargement, reduced EF
Mutations of genes that make up the sarcomere
Muscle cells stretch and become thinner
