Cardio <3 Flashcards
Non-genetic risk factors to cardiomyopathy
hypertension, DM, thyroid disease, chemo exposure, obesity, long term alochol misuse, illicit drug use
What is hypertrophic cardiomyopathy
left ventricular outflow tract obstruction and mitral valve regurgitation, diastolic dysfunction
Syndromic causes of HCM
Fabry disease
Pompe disease
RASopathies (i.e. Noonan)
Non-syndromic, genetic
causes of HCM
most common genes: MYBPC3 (50%)
MYH7 (33%)
MOI: AD
Fabry disease
Gene: GLA
MOI: X-linked
phenotype: periodic pain crisis, angiokeratomas, hyperhidrosis, ocular abnormalities, kidney disease
Heart: HCM
Pompe disease
Gene: GAA
MOI: AR
Phenotype: poor feeding, macroglossia, motor delay / muscle weakness, respiratory difficulties
Heart: HCM
Noonan
RASopathies
Gene: most common PTPN11
MOI: AD
Phenotype: characteristic facial features, short stature, developmental delay, webbed neck
Heart: HCM
Cardiac amyloidosis (amyloid cardiomyopathy)
Disease caused by the buildup of abnormal proteins in the heart. *Symptoms include fatigue, weakness, shortness of breath, dizziness, swelling of abdomen and legs.
Gene: TTR
MOI: AD
Dilated Cardiomyopathy is characterized by
Left ventricular enlargement
Systolic dysfunction (EF < 50%)
Syndromic associations of DCM
Duchene and Becker muscular atrophy
Carvajal syndrome
Barth syndrome
Non-syndromic, genetic causes of DCM
MOI: typically AD
Genes:
TTN ~15-20% Truncating variants
LMNA ~6%
MYH7 ~4%
Others… FLNC, BAG3, TNNT2, RBM20, SCN5I, DES, PLN, … + more
Duchene and Becker muscular atrophy
heart: DCM
Gene: DMD
MOI: X-linked
Features:
Muscle weakness
Elevated CK
Loss of ambulation in males
Carvajal syndrome
heart: DCM
Gene: DSP
MOI: AR
Features:
Wooly hair
Palmoplantar keratoderma
Barth syndrome
Heart: DCM
Gene: TAFAZZIN
MOI: X-linked
Features:
neuropathy
Muscle weakness
Growth delay
infantile/early childhood onset
Arrythmogenic cardiomyopathy
Prevalence: ~1 in 1000
Accounts for ~11% of young adult sudden cardiac death cases
Average age of dx: 31 (but variable)
Genetic causes of arrythmogenic cardiomyopathy
MOI: typically AD
More common causes
Associated with desmosomal proteins
PKP2 , DSP, DSC2, DSG2, JUP, TMEM43
Less common: CTNNA3, DES, LMNA, PLN, RYR2, TGFB3, TTN
characteristics of restrictive cardiomyopathy
Myocardial stiffness w/ normal/mildly increased wall thickness
Generally diastolic dysfunction, but normal/mildly reduced EF
Causes of restrictive cardiomyopathy
Infiltrative disorders (amyloidosis, hemochromatosis, others)
Inflammatory disorders (sarcoidosis, scleroderma)
Treatment-related cardiotoxicity (radiation therapy)
Genes overlapping with those related to HCM and/or DCM I.e. TTR,
Still unexplained
Characteristics of left-ventricular non-compaction
Abnormal muscle leads to risk for arrhythmia, thromboembolism, LV dysfunction
Prevalence: ~2-10%
Genetic testing for left-ventricular non-compaction
Genetic testing should be guided by cardiomyopathy or other cardiovascular phenotype
If asymptomatic and otherwise normal heart structure/function then genetic testing not recommended, no specific family screening recommendations
Screening tools for cardio
ECG/EKG
Holter (wearable ECG)
Exercise treadmill test
Echo
Sudden cardiac death accounts for _% of mortality in the general population
20%
Phenotype of Brugada syndrome
Ventricular arrhythmias & sudden death
Symptoms seen in adulthood; sudden death mean age is 40y if untreated. Peds onset is rare
More prevalent in males
Brugada syndrome gene
SCN5A (30%)
Phenotype for Catecholamiergic polymorphic ventricular tachycardia
exercise and high emotions stress = tachycardia and syncope
Syncope episodes start around 7y - 12y
Incorrect dx of epilepsy due to seizure like activity during syncope
Treatment for Catecholamiergic polymorphic ventricular tachycardia
beta blockers
genes for Catecholamiergic polymorphic ventricular tachycardia
GENES:
AD: RYR2, CALM
AR: CASQ2, TRDN
Phenotype for Long QT syndrome
Phenotype: syncope + arrhythmias with prolonged QT interval = LQTS phenotype
Arrhythmia episode leads to faithing (looks like seizure)… leading cause of SCD if left untreated under the age of 35
Syndromes associated with Long-QT
Jervell-Lange-Neilson : profound sensorineural hearing loss
Timothy Type B: Hand/foot deformities and neurodevelopmental
Andersen-Tawil (Type 7): Muscle weakness, dysmorphism
Genes associated to Long QT
KCNQ1, KCNH2, SCN5A KCNE1, KCNE2
phenotype for early onset atrial fibrillation
Irregular heartbeat- can be too fast, too slow, or mixed
Increases risk for stroke, heart failure
Genes for early onset atrial fibrillation
KCNQ1
SCN5A
LAMIN A/C
phenotype for familial hypercholesterolemia
very high total cholesterol and LDL, xanthomas, corneal arc
Incidence: 1 in 250
90% are undiagnosed
genes associated to familial hypercholesterolemia
LDLR, APOE, PCSK9
Treatment for familial hypercholesterolemia
statins as early as 8-10y
