Week 3: Cardiogenetics Flashcards
Tell me about arrhythmogenic right ventricular cardiomyopathy (ARVC)
-Cardiac muscle is progressively replaced by scar tissue and fatty deposits
-Predominantly impact right ventricle but can extend to the left
-Disrupts the heart’s electrical signals
-Symptoms: asymptomatic, palpitations, syncope, sudden cardiac arrest, death
-11% of young adult cardiac death due to ARVC
-Onset 12-50yo, avg 30yo
-Decreased penetrance, intrafamilial variability
-Typically caused by variants in desmosomal genes, AD mostly few AR, rarely de novo
Tell me about restrictive cardiomyopathy (RCM)
-RARE
-Cardiac muscle of left ventricle is stiff and ridgid=impaired ventricular filling
-Definition is more functional than structural
-Very poor prognosis especially in kids, often need transplant
-Typically due to secondary causes (aquired) or idiopathic (unknown), occasionally genetic (isolated & syndromic)
-Lowest genetic testing yield of all cardiomyopathy
-Most common genes: MYH7 and TNNI3
-If acquired= treat underlying cause
-If idiopathic= transplant
Tell me about left ventricular non-compaction (LVNC)
-Characterized by prominent left ventricular trabeculations with deep intertrabecular recess and thinning of compact epicardium
-Can be seen in isolation or with other cardiomyopathy (DCM, HCM, RCM)
-Many individuals with LVNC don’t have evidence of impaired cardiac function. Controversial because is it just excess trabeculations or coupled with other cardiomyopathy
-Genetic, syndromic, nonsyndromic
-Barth syndrome
-Genetic testing not recommended if individual is asymptomatic and has otherwise normal heart structure
-Most common gene is LBD3
Tell me about long QT syndrome
-Cardiac electrophysiological disorder characterized by increased timing of QT interval which causes T-wave abnormalities
-Key feature: syncope caused by torsade de pointes (TdP) (tornado!!) related to emotion, audio stimulation, exercise, sleep
-Other key feature is death: unexplained accidents, in sleep
-Other less common features: seizures, hearing loss, neurodev delays, dysmorphic features
-3 subtypes all with different triggers, penetrance rates, and cardiac event incidences
-AD, reduced penetrance
-Main genes: KCNQ1, KCNH2, SCN5A
What’s it called when the heart beats too slow?
Bradycardia
What’s it called when the heart beats too fast?
Tachycardia
Tell me about A-fib
-Most common type of heart arrhythmia
-Symptoms: palpitations, dizziness, fainting, shortness of breath
-Many nongenetic causes
-Should have a genetic concern when there is no clear cause, pt is young
Tell me about Brugada syndrome
-Arrhythmia syndrome characterized by cardiac conduction abnormalities
-High risk for ventricular arrhythmias
-Characteristic EKG
-Can present with fainting, cardiac arrest while sleeping or resting
-Symptom onset typically 30-40s but can be anytime
-Most have clinical diagnosis, genetics confirms
-Management: ICDs, avoid cocaine, fevers, electrolyte disturbance, meds
-Genetics: several AD genes (except XL KCNE5)
Tell me about catecholaminergic polymorphic ventricular tachycardia (CPVT)
-Characterized by episodes of syncope during exercise or acute emotion in individuals without structural cardiac abnormalities (caused by onset of ventricular tachycardia)
-Mean onset 7-9yo (may explain some cases of SIDS)
-Resting EKG is normal
-Cardiac arrest occurs in 30% of affected individuals
-AD: CALM1, RYR2
-AR: CASQ2, TRDN
-RYR2 associated with SIDS
-Management: beta blockers, ICD, surgery, avoid certain meds and competitive sports
Tell me about hypertrophic cardiomyopathy (HCM)
-Wall of left ventricles become thicker than normal
-Makes walls stiff and harder to pump blood out=less blood out to body
-Often onset before 35yo
-Nonsyndromic (disease of sarcomere) or syndromic (Fabry, Fredreich ataxia, Pompe, Noonan, etc)
-Core sarcomeric genes: MYH7, MYBPC3, MYL2, MYL3, TNNT2, TNNI3, TNNC1, TPM1, ACTC1
-GT yield 30-60%
-Management: lifestyle, meds, septal reduction, rhythm management, transplant
Tell me about dilated cardiomyopathy (DCM)
-Left ventricle dilates like a balloon causing the walls to stretch and become thinner
-Walls of LV are not able to pump as efficiently causing systolic dysfunction
-Incidence: 1/250
-Onset typically 4th-6th decade of life
-If onset in childhood, concerned for genetic/primary cause because young and less time for acquired exposures
-Syndromic causes DCM: Barth syndrome, Duchenne and Becker MD, HFE hemochromatosis, mito disorders, etc
-Genetics: over 50 genes, most common TTN and LMNA
-Management: unaffected carriers screen with echo and ECG, treat underlying secondary causes, meds, ICD, transplant
True or false: knowing the causative gene for DCM always changes management recommendations
False! Except for LMNA, knowing gene doesn’t usually change management
LMNA= earlier management and ICD placement because highly penetrant!
True or false: GT should be offered to every patient with nonischemic DCM
True!
Tell me about familial hypercholesterolemia
-Severely elevated total and LDL cholesterol levels
-Xanthomas, arcus cornealis (cholesterol deposits on outer edge of cornea), phx pemature CAD, phx vascular disease, fhx early MI
-Genetics: hetero and homozygous forms (homozygous often childhood onset and more severe) but both inherited AD (two path variants=severe FH)
-Most common genes: LDLR, APOB, PCSK9
