Cardio Genetic Testing Flashcards
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
- chromosomal (syndromes)
- chromosomal and sequencing (structural)
- cardiomyopathy sequencing
- channelopathy sequencing
What are some of the things we look for on the family hx in cardio?
- 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
What is involved in the cardiac work-up for the physical exam (before the echo is ordered)?
- 4 ex-BP
- pre-/post-ductal sats
- 12 or 15-lead ECG
- chest x-ray
What cardiac features are associated w/ Turner syndrome?
- left-sided obstructive lesions: aortic stenosis/BAV, coarctation, HLHS
- partially anomalous pulmonary veins
What percent of neonates w/ HLHS have a syndrome? What percent have a CMA finding of unknown significance?
10%, 25%
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
Abnormal, Normal, VUS
What is the risk of CHD in all live births?
1% (most common birth defect in live births)
What is the recurrence risk with a sibling or parent w/ CHD? Left sided obstructive lesions? 2nd degree relative? 3rd degree relative?
2-5%, 8-19%, 1-2%, 1%
What is the most common congenital heart defect?
BAV
What are individuals who have BAV at risk for over time?
progressive aortic valve disease and aortic root aneurysm
What is recommended for the relatives of an individual with BAV?
evaluation of all 1st degree relatives
Mutations in what gene cause aortic valve disease?
NOTCH1
What is the diagnostic yield of exome for infants w/ non-syndromic CHD?
- 2% w/ identifiable LP mutation
Mutations in what gene account for ~11% of Shone complex cases?
MYH6
Mutations in what gene account for ~2% of ToF cases?
FLT4
What is the diagnostic yield for non-syndromic CHD when analyzing the non-coding regions of the genome for de novo variants?
8%
What are 4 considerations of neonatal DCM?
- rare
- could be due to syndrome w/ mild extracardiac manifestations
- can be genetic/heritable
- can be idiopathic
What is the diagnostic yield for genetic testing in pediatric cardiomyopathy?
- ARVC: ~80%
- HCM: ~70%
- RCM: ~60%
- DCM: ~30%
- LVNC: ~10%
What are some diseases/genes associated w/ syndromic cardiomyopathy?
(2 glycogen storage, 1 lysosomal storage, 2 mito, 2 neuromuscular)
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)
What 5 genes are responsible for a lot of non-syndromic cardiomyopathy?
- TTN (20-30%)
- LMNA (5%)
- MYH7 (5%)
- TNNT2 (3%)
- SCN5A (3%)
What is congenital long QT syndrome?
delayed repolarization
What are 3 of the genes that are associated with long QT and what do they have in common?
KCNQ1, KCNH2, SCN5A –> all ion channels
What is torsades de pointes?
predisposition to lethal ventricular arrhythmias
What are the 5 cardiac channelopathies?
Long QT, Brugada, Short QT, CPVT, Idiopathic VF
True or False: you need to have a strong index of suspicion prior to ordering testing for channelopathies
True
What is the diagnostic yield of gene panel testing for long QT?
up to 75%
Note: diagnostic yield depends on the channelopathy
