Genetic and Environmental Factors In Development of Heart Disease ✅ Flashcards
Do all congenital heart disease cases have an identifiable cause?
No, only a small percentage do
What are the possible identifiable causes of congenital heart disease?
- Primary genetic factors
- Environmental factors
- Genetic-environmental interactions (multi-factorial)
What % of CHD with an identifiable cause is caused by primary genetic factors?
10%
What are the potential primary genetic factors causing CHD?
- Chromosomal abnormalities
- Single gene abnormalities
What syndromes are associated with cardiac lesions?
- Down’s syndrome
- Turners syndrome
- Noonan’s syndrome
- William’s syndrome
- DiGeorge syndrome
- CHARGE
- VACTERL
- Edward’s syndrome
- Patau syndrome
- Marfan’s syndrome
- Erlers-Danlos syndrome
- Tuberous sclerosis
What is the genetic abnormality in Down’s syndrome?
Trisomy 21
What % of children with Down’s syndrome have CHD?
Up to 50%
What are the most common CHD in children with Down’s syndrome?
VSD most common, followed by AVSD.
Pulmonary vascular disease develops early
What is the genetic abnormality in Turner’s syndrome?
XO
What CHDs are found in Turner’s syndrome?
- Bicuspid aortic valve
- Coarctation of the aorta
What % of children with Turner’s syndrome have a bicuspid aortic valve?
33%
What is the genetic abnormality in Noonan’s syndrome?
PTPN11 gene on chromosome 12
What CHDs are found in Noonan’s syndrome?
- Pulmonary stenosis
- ASD
- Hypertrophic cardiomyopathy
What is the genetic abnormality in William’s syndrome?
Deletion of genes from the long arm of chromosome 7
What CHDs are found in William’s syndrome?
- Supravalvular aortic stenosis
- Branch pulmonary artery stenosis
What is the genetic abnormality in DiGeorge syndrome?
22q11.2 deletion
What CHDs are found in DiGeorge syndrome?
- Aortic arch abnormalities
- Truncus arteriosus
- Pulmonary atresia
- Tetralogy of Fallot
- Familial VSD
What is the genetic abnormality in CHARGE syndrome?
CHD7 gene on chromosome 8
What CHDs are found in CHARGE syndrome?
- Tetralogy of Fallot
- VSD
- AVSD
- Double outlet right ventricle
What is the abnormality in VACTERL?
Abnormalities in structures derived from the embryonic mesoderm (no known genetic or chromosomal cause)
What CHDs are found in VACTERL?
- Tetralogy of Fallot
- VSD
- Coarctation of the aorta
- PDA
What is the genetic abnormality in Edwards syndrome?
Trisomy 18
What CHDs are found in Edwards syndrome?
- VSD
- ASD
- PDA
- Coarctation of the aorta
- Bicuspis aortic valve
- Double outlet right ventricle
What is the genetic abnormality in Patau syndrome?
Trisomy 13
What CHDs are found in Patau syndrome?
- VSD
- ASD
- PDA
- Coarctation of the aorta
- Bicuspid aortic valve
- Double outlet right ventricle
What is the genetic abnormality in Marfans synrome?
FBN1 gene encoding connective protein fibrillin-1 on chromosome 5
What CHDs are found in Marfan’s syndrome?
- Aortic aneurysm
- Aortic regurgitation
- Mitral regurgitation
What is the genetic abnormality in Ehlers-Danlos syndrome?
Defect in synthesis of type I or III collagen
What CHDs are found in Ehlers-Danlos syndrome?
Aortic root dilatation
What is the genetic abnormality in tuberous sclerosis?
TSC1 on chromosome 9 or TSC2 on chromosome 16, which code for tumour suppressor genes hamartin and tuberin respectively
What is the inheritance pattern of tuberous sclerosis?
Autosomal dominant
What cardiac disease is found in tuberous sclerosis?
Cardiac rhabdomyoma
What prenatal environmental factors can lead to CHD?
- Diabetes mellitus
- Maternal phenylketonuria
- SLE
- Rubella
- Alcohol
- Aspirin
- Lithium
- Coxsackie B infection
- Diphenylhydantoin
What CHD might maternal diabetes mellitus lead to?
- LVOT (left ventricular outflow tract) obstruction
- Hypertrophic cardiomyopathy
- TGA (transposition of great arteries)
- VSD
What CHD might maternal phenylketonuria lead to?
- VSD
- ASD
- PDA
- Coarctation of the aorta
What CHD might maternal SLE lead to?
- Heart block
- Pericarditis
- Endomyocardial fibrosis
What CHD might prenatal rubella lead to?
- PDA
- Branch pulmonary stenosis
What CHD might prenatal exposure to alcohol lead to?
- Pulmonary stenosis
- VSD
- ASD
- Tetralogy of Fallot
What CHD might prenatal exposure to aspirin lead to?
- PPHN (persistent pulmonary hypertension of the newborn)
What CHD might prenatal exposure to lithium lead to?
- Ebstein abnormality
What CHD might prenatal Coxsackie B infection lead to?
- Myocarditis
What CHD might prenatal exposure to diphenylhydantoin lead to?
- Aortic stenosis
- Pulmonary stenosis
What % of CHD with an identifiable cause is caused by environmental factors?
3-5%
What % of CHD with an identifiable cause is caused by genetic-environmental interactions (multifactorial)?
85%
What is the recurrence risk of cardiovascular anomalies?
Varies, from 1-4% and is higher with more common lesions e.g. VSD
What happens to the recurrence risk of cardiovascular anomalies with two affected first-degree relatives?
The risk is tripled
