Cardio Genetic Testing

Question 1

What testing would I use in each of the following scenarios?

• structural heart disease w/ extracardiac manifestations
• structural heart disease w/ no extracardiac manifestations
• cardiac disease of the myocardium
• cardiac disease with EGC abnormalities/arrhythmia

Answer 1

• chromosomal (syndromes)
• chromosomal and sequencing (structural)
• cardiomyopathy sequencing
• channelopathy sequencing

Question 2

What are some of the things we look for on the family hx in cardio?

Answer 2

• CHD, heart surgeries or need for heart surgeries, pacemakers or ICD
• syncope (particularly w/ exertion), seizures, sudden death, SIDS, stillbirths, miscarriages
• unexplained drownings and/or car accidents

Question 3

What is involved in the cardiac work-up for the physical exam (before the echo is ordered)?

Answer 3

• 4 ex-BP
• pre-/post-ductal sats
• 12 or 15-lead ECG
• chest x-ray

Question 4

What cardiac features are associated w/ Turner syndrome?

Answer 4

• left-sided obstructive lesions: aortic stenosis/BAV, coarctation, HLHS
• partially anomalous pulmonary veins

Question 5

What percent of neonates w/ HLHS have a syndrome? What percent have a CMA finding of unknown significance?

Answer 5

10%, 25%

Question 6

Put the following in order from least to greatest of the survival rate based on the result of a CMA ordered for HLHS: VUS, Normal, Abnormal

Answer 6

Abnormal, Normal, VUS

Question 7

What is the risk of CHD in all live births?

Answer 7

1% (most common birth defect in live births)

Question 8

What is the recurrence risk with a sibling or parent w/ CHD? Left sided obstructive lesions? 2nd degree relative? 3rd degree relative?

Answer 8

2-5%, 8-19%, 1-2%, 1%

Question 9

What is the most common congenital heart defect?

Answer 9

BAV

Question 10

What are individuals who have BAV at risk for over time?

Answer 10

progressive aortic valve disease and aortic root aneurysm

Question 11

What is recommended for the relatives of an individual with BAV?

Answer 11

evaluation of all 1st degree relatives

Question 12

Mutations in what gene cause aortic valve disease?

Answer 12

NOTCH1

Question 13

What is the diagnostic yield of exome for infants w/ non-syndromic CHD?

Answer 13

• 2% w/ identifiable LP mutation

Question 14

Mutations in what gene account for ~11% of Shone complex cases?

Answer 14

MYH6

Question 15

Mutations in what gene account for ~2% of ToF cases?

Answer 15

FLT4

Question 16

What is the diagnostic yield for non-syndromic CHD when analyzing the non-coding regions of the genome for de novo variants?

Answer 16

8%

Question 17

What are 4 considerations of neonatal DCM?

Answer 17

• rare
• could be due to syndrome w/ mild extracardiac manifestations
• can be genetic/heritable
• can be idiopathic

Question 18

What is the diagnostic yield for genetic testing in pediatric cardiomyopathy?

Answer 18

• ARVC: ~80%
• HCM: ~70%
• RCM: ~60%
• DCM: ~30%
• LVNC: ~10%

Question 19

What are some diseases/genes associated w/ syndromic cardiomyopathy?
(2 glycogen storage, 1 lysosomal storage, 2 mito, 2 neuromuscular)

Answer 19

Glycogen storage
- HCM w/ WPW (PRKAG2)
- Pompe (GAA)
Lysosomal storage
- Fabry (GLA)
Mito
- Friedreich Ataxia (FXN)
- KSS (mtDNA deletions)
Neuromuscular
- Emery-Dreifuss (LMNA)
- Duchenne/Becker (DMD)

Question 20

What 5 genes are responsible for a lot of non-syndromic cardiomyopathy?

Answer 20

• TTN (20-30%)
• LMNA (5%)
• MYH7 (5%)
• TNNT2 (3%)
• SCN5A (3%)

Question 21

What is congenital long QT syndrome?

Answer 21

delayed repolarization

Question 22

What are 3 of the genes that are associated with long QT and what do they have in common?

Answer 22

KCNQ1, KCNH2, SCN5A –> all ion channels

Question 23

What is torsades de pointes?

Answer 23

predisposition to lethal ventricular arrhythmias

Question 24

What are the 5 cardiac channelopathies?

Answer 24

Long QT, Brugada, Short QT, CPVT, Idiopathic VF

Question 25

True or False: you need to have a strong index of suspicion prior to ordering testing for channelopathies

Answer 25

True

Question 26

What is the diagnostic yield of gene panel testing for long QT?

Answer 26

up to 75% Note: diagnostic yield depends on the channelopathy