Cardio <3

Question 1

Non-genetic risk factors to cardiomyopathy

Answer 1

hypertension, DM, thyroid disease, chemo exposure, obesity, long term alochol misuse, illicit drug use

Question 2

What is hypertrophic cardiomyopathy

Answer 2

left ventricular outflow tract obstruction and mitral valve regurgitation, diastolic dysfunction

Question 3

Syndromic causes of HCM

Answer 3

Fabry disease
Pompe disease
RASopathies (i.e. Noonan)

Question 4

Non-syndromic, genetic
causes of HCM

Answer 4

most common genes: MYBPC3 (50%)
MYH7 (33%)
MOI: AD

Question 5

Fabry disease

Answer 5

Gene: GLA
MOI: X-linked
phenotype: periodic pain crisis, angiokeratomas, hyperhidrosis, ocular abnormalities, kidney disease
Heart: HCM

Question 6

Pompe disease

Answer 6

Gene: GAA
MOI: AR
Phenotype: poor feeding, macroglossia, motor delay / muscle weakness, respiratory difficulties
Heart: HCM

Question 7

Noonan

Answer 7

RASopathies
Gene: most common PTPN11
MOI: AD
Phenotype: characteristic facial features, short stature, developmental delay, webbed neck
Heart: HCM

Question 8

Cardiac amyloidosis (amyloid cardiomyopathy)

Answer 8

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

Question 9

Dilated Cardiomyopathy is characterized by

Answer 9

Left ventricular enlargement
Systolic dysfunction (EF < 50%)

Question 10

Syndromic associations of DCM

Answer 10

Duchene and Becker muscular atrophy
Carvajal syndrome
Barth syndrome

Question 11

Non-syndromic, genetic causes of DCM

Answer 11

MOI: typically AD
Genes:
TTN ~15-20% Truncating variants
LMNA ~6%
MYH7 ~4%
Others… FLNC, BAG3, TNNT2, RBM20, SCN5I, DES, PLN, … + more

Question 12

Duchene and Becker muscular atrophy

Answer 12

heart: DCM
Gene: DMD
MOI: X-linked
Features:
Muscle weakness
Elevated CK
Loss of ambulation in males

Question 13

Carvajal syndrome

Answer 13

heart: DCM
Gene: DSP
MOI: AR
Features:
Wooly hair
Palmoplantar keratoderma

Question 14

Barth syndrome

Answer 14

Heart: DCM
Gene: TAFAZZIN
MOI: X-linked
Features:
neuropathy
Muscle weakness
Growth delay
infantile/early childhood onset

Question 15

Arrythmogenic cardiomyopathy

Answer 15

Prevalence: ~1 in 1000
Accounts for ~11% of young adult sudden cardiac death cases
Average age of dx: 31 (but variable)

Question 16

Genetic causes of arrythmogenic cardiomyopathy

Answer 16

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

Question 17

characteristics of restrictive cardiomyopathy

Answer 17

Myocardial stiffness w/ normal/mildly increased wall thickness
Generally diastolic dysfunction, but normal/mildly reduced EF

Question 18

Causes of restrictive cardiomyopathy

Answer 18

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

Question 19

Characteristics of left-ventricular non-compaction

Answer 19

Abnormal muscle leads to risk for arrhythmia, thromboembolism, LV dysfunction
Prevalence: ~2-10%

Question 20

Genetic testing for left-ventricular non-compaction

Answer 20

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

Question 21

Screening tools for cardio

Answer 21

ECG/EKG
Holter (wearable ECG)
Exercise treadmill test
Echo

Question 22

Sudden cardiac death accounts for _% of mortality in the general population

Answer 22

20%

Question 23

Phenotype of Brugada syndrome

Answer 23

Ventricular arrhythmias & sudden death
Symptoms seen in adulthood; sudden death mean age is 40y if untreated. Peds onset is rare
More prevalent in males

Question 24

Brugada syndrome gene

Answer 24

SCN5A (30%)

Question 25

Phenotype for Catecholamiergic polymorphic ventricular tachycardia

Answer 25

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

Question 26

Treatment for Catecholamiergic polymorphic ventricular tachycardia

Answer 26

beta blockers

Question 27

genes for Catecholamiergic polymorphic ventricular tachycardia

Answer 27

GENES:
AD: RYR2, CALM
AR: CASQ2, TRDN

Question 28

Phenotype for Long QT syndrome

Answer 28

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

Question 29

Syndromes associated with Long-QT

Answer 29

Jervell-Lange-Neilson : profound sensorineural hearing loss
Timothy Type B: Hand/foot deformities and neurodevelopmental
Andersen-Tawil (Type 7): Muscle weakness, dysmorphism

Question 30

Genes associated to Long QT

Answer 30

KCNQ1, KCNH2, SCN5A KCNE1, KCNE2

Question 31

phenotype for early onset atrial fibrillation

Answer 31

Irregular heartbeat- can be too fast, too slow, or mixed
Increases risk for stroke, heart failure

Question 32

Genes for early onset atrial fibrillation

Answer 32

KCNQ1
SCN5A
LAMIN A/C

Question 33

phenotype for familial hypercholesterolemia

Answer 33

very high total cholesterol and LDL, xanthomas, corneal arc
Incidence: 1 in 250
90% are undiagnosed

Question 34

genes associated to familial hypercholesterolemia

Answer 34

LDLR, APOE, PCSK9

Question 35

Treatment for familial hypercholesterolemia

Answer 35

statins as early as 8-10y