Genetic and Environmental Factors In Development of Heart Disease ✅

Question 1

Do all congenital heart disease cases have an identifiable cause?

Answer 1

No, only a small percentage do

Question 2

What are the possible identifiable causes of congenital heart disease?

Answer 2

• Primary genetic factors
• Environmental factors
• Genetic-environmental interactions (multi-factorial)

Question 3

What % of CHD with an identifiable cause is caused by primary genetic factors?

Answer 3

10%

Question 4

What are the potential primary genetic factors causing CHD?

Answer 4

• Chromosomal abnormalities

- Single gene abnormalities

Question 5

What syndromes are associated with cardiac lesions?

Answer 5

• 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

Question 6

What is the genetic abnormality in Down’s syndrome?

Answer 6

Trisomy 21

Question 7

What % of children with Down’s syndrome have CHD?

Answer 7

Up to 50%

Question 8

What are the most common CHD in children with Down’s syndrome?

Answer 8

VSD most common, followed by AVSD.

Pulmonary vascular disease develops early

Question 9

What is the genetic abnormality in Turner’s syndrome?

Answer 9

XO

Question 10

What CHDs are found in Turner’s syndrome?

Answer 10

• Bicuspid aortic valve

- Coarctation of the aorta

Question 11

What % of children with Turner’s syndrome have a bicuspid aortic valve?

Answer 11

33%

Question 12

What is the genetic abnormality in Noonan’s syndrome?

Answer 12

PTPN11 gene on chromosome 12

Question 13

What CHDs are found in Noonan’s syndrome?

Answer 13

• Pulmonary stenosis
• ASD
• Hypertrophic cardiomyopathy

Question 14

What is the genetic abnormality in William’s syndrome?

Answer 14

Deletion of genes from the long arm of chromosome 7

Question 15

What CHDs are found in William’s syndrome?

Answer 15

• Supravalvular aortic stenosis

- Branch pulmonary artery stenosis

Question 16

What is the genetic abnormality in DiGeorge syndrome?

Answer 16

22q11.2 deletion

Question 17

What CHDs are found in DiGeorge syndrome?

Answer 17

• Aortic arch abnormalities
• Truncus arteriosus
• Pulmonary atresia
• Tetralogy of Fallot
• Familial VSD

Question 18

What is the genetic abnormality in CHARGE syndrome?

Answer 18

CHD7 gene on chromosome 8

Question 19

What CHDs are found in CHARGE syndrome?

Answer 19

• Tetralogy of Fallot
• VSD
• AVSD
• Double outlet right ventricle

Question 20

What is the abnormality in VACTERL?

Answer 20

Abnormalities in structures derived from the embryonic mesoderm (no known genetic or chromosomal cause)

Question 21

What CHDs are found in VACTERL?

Answer 21

• Tetralogy of Fallot
• VSD
• Coarctation of the aorta
• PDA

Question 22

What is the genetic abnormality in Edwards syndrome?

Answer 22

Trisomy 18

Question 23

What CHDs are found in Edwards syndrome?

Answer 23

• VSD
• ASD
• PDA
• Coarctation of the aorta
• Bicuspis aortic valve
• Double outlet right ventricle

Question 24

What is the genetic abnormality in Patau syndrome?

Answer 24

Trisomy 13

Question 25

What CHDs are found in Patau syndrome?

Answer 25

- VSD - ASD - PDA - Coarctation of the aorta - Bicuspid aortic valve - Double outlet right ventricle

Question 26

What is the genetic abnormality in Marfans synrome?

Answer 26

FBN1 gene encoding connective protein fibrillin-1 on chromosome 5

Question 27

What CHDs are found in Marfan's syndrome?

Answer 27

- Aortic aneurysm - Aortic regurgitation - Mitral regurgitation

Question 28

What is the genetic abnormality in Ehlers-Danlos syndrome?

Answer 28

Defect in synthesis of type I or III collagen

Question 29

What CHDs are found in Ehlers-Danlos syndrome?

Answer 29

Aortic root dilatation

Question 30

What is the genetic abnormality in tuberous sclerosis?

Answer 30

TSC1 on chromosome 9 or TSC2 on chromosome 16, which code for tumour suppressor genes hamartin and tuberin respectively

Question 31

What is the inheritance pattern of tuberous sclerosis?

Answer 31

Autosomal dominant

Question 32

What cardiac disease is found in tuberous sclerosis?

Answer 32

Cardiac rhabdomyoma

Question 33

What prenatal environmental factors can lead to CHD?

Answer 33

- Diabetes mellitus - Maternal phenylketonuria - SLE - Rubella - Alcohol - Aspirin - Lithium - Coxsackie B infection - Diphenylhydantoin

Question 34

What CHD might maternal diabetes mellitus lead to?

Answer 34

- LVOT (left ventricular outflow tract) obstruction - Hypertrophic cardiomyopathy - TGA (transposition of great arteries) - VSD

Question 35

What CHD might maternal phenylketonuria lead to?

Answer 35

- VSD - ASD - PDA - Coarctation of the aorta

Question 36

What CHD might maternal SLE lead to?

Answer 36

- Heart block - Pericarditis - Endomyocardial fibrosis

Question 37

What CHD might prenatal rubella lead to?

Answer 37

- PDA | - Branch pulmonary stenosis

Question 38

What CHD might prenatal exposure to alcohol lead to?

Answer 38

- Pulmonary stenosis - VSD - ASD - Tetralogy of Fallot

Question 39

What CHD might prenatal exposure to aspirin lead to?

Answer 39

- PPHN (persistent pulmonary hypertension of the newborn)

Question 40

What CHD might prenatal exposure to lithium lead to?

Answer 40

- Ebstein abnormality

Question 41

What CHD might prenatal Coxsackie B infection lead to?

Answer 41

- Myocarditis

Question 42

What CHD might prenatal exposure to diphenylhydantoin lead to?

Answer 42

- Aortic stenosis | - Pulmonary stenosis

Question 43

What % of CHD with an identifiable cause is caused by environmental factors?

Answer 43

3-5%

Question 44

What % of CHD with an identifiable cause is caused by genetic-environmental interactions (multifactorial)?

Answer 44

85%

Question 45

What is the recurrence risk of cardiovascular anomalies?

Answer 45

Varies, from 1-4% and is higher with more common lesions e.g. VSD

Question 46

What happens to the recurrence risk of cardiovascular anomalies with two affected first-degree relatives?

Answer 46

The risk is tripled