Genetics of Cardiovascular Disease

Question 1

What is the chromosomal abnormality of Down syndrome?

Answer 1

Trisomy 21

Question 2

Cardiac abnormalities associated with down syndrome

Answer 2

AVSD

Question 3

Other congenital abnormalities with Down syndrome

Answer 3

AVSD

Duodenal atresia

Question 4

What do down syndrome babies have more of?

Answer 4

Nuchal translucency

Question 5

What % of foetuses with CHD have abnormal chromosomes?

Answer 5

13%

Question 6

What is the genetic abnormality of turners syndrome?

Answer 6

45X

Question 7

What CHD can turner syndrome result in?

Answer 7

Coarctation of aorta

Question 8

What abnormalities are associated with turner syndrome?

Answer 8

Coarctation of aorta
Short stature
Gonadal dysgenesis
Lymphoedema of hands and feet

Question 9

What gender gets turners syndrome?

Answer 9

Girls only

Question 10

What is there a risk of in turners syndrome?

Answer 10

Gonadal cancer

Question 11

What can neck webbing possibly be an indicator of?

Answer 11

Prenatal cardiac difficulties

Question 12

What causes neck webbing?

Answer 12

Excess nuchal folds

Question 13

Syndromes associated with neck webbing

Answer 13

Turners
Noonans
CFC
Leopard
Costello

Question 14

Abnormalities of noonan syndrome

Answer 14

Pulmonary stenosis
Short stature
Neck webbing
Cryptorchidism 
Characteristic face

Question 15

What is cryptorchidism?

Answer 15

One or both of the testes fail to descend from the abdomen into the scrotum

Question 16

What is the genetics of noonan syndrome?

Answer 16

PTPN11 gene (chromosome 12)
Autosomal dominant

Question 17

What gender gets noonan syndrome?

Answer 17

Both boys and girls

Question 18

What does CFC stand for?

Answer 18

Cardio-facio-cutaneous

Question 19

What abnormalities are found in CFC?

Answer 19

Noonan like
Ectodermal problems
Developmental delay

Question 20

What gender gets CFC?

Answer 20

Boys and girls

Question 21

What abnormalities are found leopard syndrome?

Answer 21

Noonan like
Multiple lentigines (small pigmented spots on skin)
Deafness

Question 22

Presentation of Costello syndrome

Answer 22

Noonan syndrome
Thickened skin folds
Susceptibility to warts
CARDIOMYOPATHY
Late cancer risk

Question 23

What is the pneumonic to remember the presentation of 22q11 deletion syndrome?

Answer 23

CATCH 22

• cardiac malformation
• abnormal facies
• thymic dysplasia
• cleft palate
• 22q11 deletion (renal, psychiatric (schizophrenia), floppy overfolded ears, small mouth, bulging tip of nose, speech delay, very variable)

Question 24

What syndromes does 22q11 deletion syndrome emcompass?

Answer 24

Both DiGeorge syndrome and Velocardiofacial (Shpritzen) syndrome

Question 25

Features of DiGeorge syndrome

Answer 25

Thymic hypoplasia Hypoparathyroidism Outflow tract cardiac malformation Sporadic

Question 26

Features of shprintzen syndrome

Answer 26

Cleft palate/palatal insufficiency Outflow tract cardiac malformation Characteristic face AD

Question 27

Cardiac manifestations of Williams syndrome

Answer 27

Aortic stenosis (supravalvular)

Question 28

Abnormalities of Williams syndrome

Answer 28

``` Aortic stenosis Hypercalcaemia 5th finger clinodactyly Characteristic face Cocktail party manner ```

Question 29

Genetics of Williams syndrome

Answer 29

Deletion of elastin on chromosome 7 Deletion of contiguous genes LIM kinase

Question 30

Inheritance of marfans syndrome

Answer 30

AD

Question 31

Genetics of marfans syndrome

Answer 31

Fibrillin 1 gene | Chromosome 15q21

Question 32

Presentation of marfans syndrome

Answer 32

``` Tall stature Long fingers AORITC DISSECTION Ectopia lentis Scoliosis ```

Question 33

What is ectopia lentis?

Answer 33

Lens of the eye slips out of place and can cause visual problems

Question 34

Another name for long QT syndrome

Answer 34

Romano-Ward syndrome

Question 35

Features of long QT syndrome

Answer 35

``` Syncope Seizure Sudden death ECG - prolonged QTc interval Repolarisation anomalies (T/U waves) Paroxysmal polymorphic VT ```

Question 36

Features of brugada syndrome

Answer 36

``` RBBB QTc normal ST elevation V1-V3 Episodic VT/VF Rest and sleep M > F ```

Question 37

Presentation of hypertrophic cardiomyopathy

Answer 37

Sudden death

Question 38

Who is sudden death of hypertrophic cardiomyopathy common in?

Answer 38

< 14 y/o | Symptomatic

Question 39

Features of dilated cardiomyopathy

Answer 39

History or presyncope or syncope Tachy or brady arrhythmia ECG investigation

Question 40

What genetic tests should be carried out with dilated cardiomyopathy?

Answer 40

LMNA SCN5A Dystrophin Sacromere genes

Question 41

Causes of congenital heart disease

Answer 41

``` Chromosomal Microdeletions Single gene Teratogens Viral Isolated (multifactorial) ```

Question 42

Features of teratogens

Answer 42

``` IUGR < 10th centile Head < 10th centile SN hearing loss Long filtrium Increased space between eyes Visuomotor difficulties Fine motor difficulties ADHD ```

Question 43

Examples of teratogens

Answer 43

Alcohol Antiepileptic drugs Rubella Maternal DM

Question 44

What is VSD associated with in the mother?

Answer 44

Folate deficiency

Question 45

Clinical diagnosis of marfans syndrome

Answer 45

``` 2 system findings must be +ve CVS - aortic dilatation/dissection Eyes - ectopia lentis Systemic score >7 - skeletal - skin - resp - dural ectasia - MVP - myopia FH Fibrillin 1 mutation ```

Question 46

What are the systemic scores for skeletal features of marfans?

Answer 46

``` ULSR and SHR Scoliosis/kyphosis Pectus deformity Thumb and wrists Foot / ankle Reduced elbow extension < 170 ```

Question 47

What are some other systemic score features for marfans?

Answer 47

``` Myopia > 3 dioptres MVP Pneumothorax Dura Striae Face Protrusio Acetabuli ```

Question 48

What additional tests should be done in marfans?

Answer 48

ECHO mandatory ! | MRI/Pelvic X ray if need

Question 49

What % of marfans patients have the fibrillin 1 mutation?

Answer 49

70-90%

Question 50

What is cascade screening?

Answer 50

3 generation FH ECGs for 1st degree relatives 2nd degree special cases

Question 51

Management of marfans disease

Answer 51

``` Annual clinical review ECHO Beta blockers ARBs Prophylactic aortic surgery if sinus Valsalva exceeds 5.5cm ```

Question 52

What heart sounds are classically associated with a VSD?

Answer 52

``` Pansystolic murmur Lower left sternal border Heaving apex beat Split S2 Sings of pulmonary HTN RHF ```