Congenital heart disease

Question 1

What are the five types of congenital heart disease?

Answer 1

• copy number variation
• single gene variation
• teratogens
• uncertain
• multifactorial

Question 2

What section of congenital heart disease do chromosomal and micro deletions fall into ?

Answer 2

copy number variations

Question 3

Name some examples of chromosomal variations

Answer 3

monosomies/ trisomies

such as downs syndrome (extra 21 chromosome)

Question 4

Name tow examples of mircodeletion variations

Answer 4

22q11 deletion

williams syndrome

Question 5

How many live births does downs syndrome affect?

Answer 5

1 in 800

Question 6

what percentage of down syndrome individuals have atrio ventricular septal defects ?

Answer 6

15%

Question 7

As well as atrial ventricular septal defects, name another common problem people with downs syndrome experience

Answer 7

duodenal atresia - bowel obstruction

Question 8

How is downs syndrome screened for in the womb?

Answer 8

By nuchal translucency

• with an ultra sound probe the volume of fluid behind the neck of a foetus is measured.
• there normally is a small volume of fluid but if there is a lot of volume then this is abnormal.
• high volume of fluid doesn’t just indicate downs syndrome but other conditions as well

Question 9

What is cystic hygroma

Answer 9

lymphatic lesion anywhere on the body but commonly found behind the neck

Question 10

What percentage of foetuses and new borns with CHD are found to have abnormal chromosomes?

Answer 10

foetuses - 19%

new borns - 13%

Question 11

Name five conditions that are linked to one pathway and name the pathway.

Answer 11

Turners syndrome 
Noonans syndrome
CFC 
Leopards syndrome 
Costello syndrome 

MAPK (mitogen activated protein kinase) pathway

Question 12

Name two common characteristics associated with these five single gene variation mutations

Answer 12

neck webbing

short stature

Question 13

What causes neck webbing ?

Answer 13

excess nuchal folding

Question 14

What mutation causes turner syndrome?

Answer 14

45 X

missing a sex chromosome (X or Y chromosome)

Question 15

name two problems caused by turner syndrome

Answer 15

• aortic coarctation

- gonadal dysgenesis - progressive loss of germ cells on the developing gonads of the embryo

Question 16

state a common feature of turner syndrome in children, not including short stature and neck webbing?

Answer 16

puffy hands

Question 17

State two common problems caused from Noonans syndrome

Answer 17

pulmonary stenosis

cryptorchidism - absence of one or both teste

Question 18

Noonans syndrome,

name one common feature apart from short stature and neck webbing.

Answer 18

characteristic face

Question 19

What is the mutation that causes Noonans syndrome

Answer 19

PTPN11 (chromosome 12)

Question 20

In terms of CFC (cardio- facio- cutaneous syndrome),

Name two problems that are caused apart form neck webbing and short stature

Answer 20

• development delay

- ectodermal problems; abnormal hair, nails, skin, sweat glands, digits, cranial- facial structure

Question 21

In terms of leopard syndrome,

state six problems caused apart from neck webbing and short stature.

Answer 21

• Multiple lentigenes (brown spots)
• Pulmonary stenosis
• Abnormal genitalia
• Ocular hypertelorism (spaced apart eyes)
• Deafness
• Abnormalities with electrical signals of the heart

Question 22

In terms of Costello syndrome,

two problems that can be caused?

Answer 22

• cardiopathy

- later risk of cancer

Question 23

State two characteristics of Costello syndrome apart from neck webbing and short stature

Answer 23

• thick skin folds

- susceptible to warts

Question 24

Are these five syndromes linked by a common pathway?

Answer 24

yes, the different syndromes act at different stages of the pathway

Question 25

What is the common pathway that links these five syndromes?

Answer 25

MAPK pathway (mitogen activated protein kinase).

Question 26

Why is it important to test all genes for the different syndromes?

Answer 26

they all have similar characteristics so it can be difficult to determine which syndrome it is without genetic testing

Question 27

What are LCR? in terms of micro deletion variations

Answer 27

Low copy regions | - susceptible for deletion and translocation

Question 28

Is 22q11 syndrome common?

Answer 28

Yes very common but presentations can be very variable

Question 29

State the characteristics of 22q11 deletion

Answer 29

``` Cardiac malformation Abnormal facies Thymic hypoplasia Cleft palate Hypoparathyroidism Renal Psychiatric (22% of 22q11 patients have schizophrenia but only 2% of schizophrenic patients have 22q11 deletion) ```

Question 30

What are the two conditions that were thought to be separate in the past but are both in fact 22q11 deletion

Answer 30

Shprintzen Syndrome | DiGeorge Syndrome

Question 31

What % of 22q11 deletion is familiar ?

Answer 31

25%

Question 32

Out of Shprintzen and DiGeorge Syndrome which one is most severe?

Answer 32

DiGeorge syndrome

Question 33

In terms of Williams syndrome, | name 3 problems and 2 differences from normal caused from the mutation

Answer 33

- aortic stenosis - hypercalaemia - 5th finger clinodactyly (5th finger is bent inwards) - characteristic face - cocktail manner

Question 34

What mutation causes Williams syndrome?

Answer 34

deletion of elastin on chromosome 7

Question 35

Name 4 common teratogens that can cause mutations in foetuses.

Answer 35

- fetal alcohol syndrome - anti epileptic drugs - maternal diabetes mellitus - rubella

Question 36

State two problems caused by anti epileptic drugs during pregnancy?

Answer 36

- characteristic face | - development delay

Question 37

Teratogens causing mutations in genes and chromosomes is usually multifactorial does having a first degree relative with the mutation increase the risk of other relatives also having the mutation?

Answer 37

yes

Question 38

Which heart septal defect is associated with folate acid deficiency?

Answer 38

Ventricular septal defect

Question 39

what heart disease has increased Ca in the blood and aortic stenosis?

Answer 39

williams syndrome

Question 40

what heart disease results in thickened skin folds and patient more susceptible to warts?

Answer 40

Costello

Question 41

what heart disease results in gonadal dysgenesis and aortic coarctation?

Answer 41

Turner syndrome

Question 42

what heart disease results in deafness, ocular hypertelorism and abnormal heart electrical activity ?

Answer 42

Leopard syndrome

Question 43

what heart disease can cause children to have puffy hands?

Answer 43

Noonans

Question 44

What heart disease results in development delay and ectoderm problems?

Answer 44

CFC syndrome

Question 45

what heart disease results in cleft palate and hypoparathyroidism?

Answer 45

22q11 deletion

Question 46

what two congenital heart diseases result in pulmonary stenosis?

Answer 46

noonan and leopard syndrome