CV Genetics

Question 1

What is pleitropy?

Answer 1

When one genetic mutation effects multiple traits/phenotypes

Question 2

What is genetic heterogeniety?

Answer 2

When one disease can be caused by multiple genetic mutations

Question 3

Wht is variable expressivity?

Answer 3

Individuals have variable expression of diseases

Question 4

What is RWS?

Answer 4

A genetic disorder that causes LQTS w/ no deafness

AD; 50% penetrance, genetic heterogeniety (10 genes)

Question 5

Most common RWS mutation

Answer 5

KCNQ1 >60% of cases; has highest incidence of cardiac events

Question 6

Which RWS mutation has symptoms triggered by sleep?

Answer 6

SCN5A; Na channel mutation

Question 7

RWS Treatment

Answer 7

Beta-blockers
Pacemakers
ICD

Question 8

Jervel and Lange-Nielson Syndrome

Answer 8

AR; congenital LQTS w/ bilateral sensorineural deafness

Question 9

Jervell and Lange-Nielson Syndrome mutations

Answer 9

KCNQ1 = 90% (LQTS type 1)
KCNE1 = 10% (LQTS type 5)

Question 10

Jervell and Lange-Nielson Syndrome mortality/complications

Answer 10

• Increased risk of SIDS

- >50% of untreated die before 15 years old

Question 11

Current LQTS genetic testing detection rate

Answer 11

75%; 25% of LQTS do not have a detectable gene mutation

Question 12

Does a negative genetic test rule out LQTS?

Answer 12

No

Question 13

What is Brugada syndrome

Answer 13

Disorder characterized by ST-segment elevation in leads V1-V3

Syncope, SIDS, SUNDS

Question 14

Major genetic mutation in Brugada

Answer 14

SCN5A gene; alpha subunit of Na channel

Question 15

What is catecholaminergic polymorphic ventricular tachycardia (CPVT)

Answer 15

Bidirectional polymorphic ventricular tachycardia, can become VFib

-Exercise or emotional trigger causes syncope

Question 16

CPVT mutation

Answer 16

RYR2 (ryanodine receptor channel) = AD inheritance

CASQ2 (calsequesterin of SR) = AR inheritance

Question 17

HCM inheritance

Answer 17

AD inheritance

• 50-60% with a famhx have sarcomere gene mutation
• 20-30% without a famhx have a sarcomere gene mutation

Question 18

HCM mutated genes

Answer 18

MYH17 - myosin head; classic

MYBPC3; later age of onset

TNNT2; mild or absent LVH, higher risk of arrhythmias and SCD

Question 19

What two diseases resemble HCM

Answer 19

Danon disease

Fabry disease

Question 20

Which HCM mutation has highest risk of arrhythmias

Answer 20

TNNT2

Question 21

What is the primary indication of cardiac transplantation

Answer 21

DCM

Question 22

What is idiopathic DCM

Answer 22

All acquired causes excluded, except genetic causes

Question 23

DCM detection rate

Answer 23

30%; high genetic heterogeneity; 20 genes, most are AD

Question 24

LMNA mutation

Answer 24

DCM; prominent conduction disease

Pleiotrophic gene; involved in other diseases

Question 25

When is screening recommended for cardiomyopathy

Answer 25

• Asymptomatic first degree relatives

- Relatives known to carry the mutations

Question 26

HCM screening

Answer 26

Positive or negative:

• yearly during puberty
• Every 3 years until 30
• Every 5 years after 30 (if negative, only when symptomatic)

Question 27

DCM screening

Answer 27

Positive mutation:

• yearly during childhood
• every 1-3 years during adulthood

Negative mutation:
-every 3-5 years

Question 28

Familial hypercholesterolemia levels

Answer 28

Untreated adults:
-LDL > 190 mg/dL or TC > 310

Untreated children:
-LDL >160, TC >230

Homozygous mutation:
TC > 500

Question 29

Familial hypercholesterolemia mutations

Answer 29

LDL-R = most common
ApoB
PCSK9 = least common

HeFH = AD
HoFH = AR