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Flashcards in Genetics of Cardiovascular Disease Deck (88):
1

What are some causes of congenital heart disease?

Copy number variation (CNV)

Single nucleotide variation (SNV)

Multifactorial

Teratogens

2

What does CNV stand for?

Copy number variation

3

What does SNV stand for?

Single nucleotide variation

4

What are examples of copy number variations?

Whole chromosome (trisomy, monosomy)

Part of a chromosome (22q11 deletion, Williams)

5

What is an example of single nucleotide variation?

Mendelian disorder (Noonan/CFC, Marfan)

6

What are examples of teratogens?

Rebella

Alcohol

Anti-epileptic drugs

7

What causes down syndrome?

Trisomy 21 (usually due to maternal non-dysjunction)

8

What percentage of people with down syndrome have atrioventricular septal defects?

15%

9

How does the risk that a pregnancy has down syndrome increase?

With maternal age

10

What does CHD stand for?

Coronary heart disease

11

What causes Turner's syndrome?

45, X (only affects females)

12

What are some characteristics of Turner's syndrome?

Coarctation of aorta

Short stature

Gonadal dysgenesis

Puffy hands

13

What is neck webbing?

Excess nuchal folds

An indicator of prenatal cardiac difficulties

14

What is neck webbing an indicator of?

Prenatal cardiac difficulties

15

What genetic diseases is neck webbing present in?

Turner's syndrome

Noonan syndrome

CFC syndrome

Leopard syndrome

Costello syndrome

16

What are characteristics of Noonan syndrome?

Pulmonary stenosis

Short stature

Neck webbing

Cryptochidism

Characteristic face

PTPN 11 gene (chromosome 12)

17

What does MAPK pathway stand for?

Mitogen activated protein kinase pathway

18

What is the MAPK pathway?

Chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus

19

What are characteristics of 22q11 deletion syndrome?

Cardiac malformations

Abnormal facies

Thymic hypolasia

Cleft palate

Hypoparathyroidism

22q11 deletion

Encompasses both DiGeorge and Velocardiofacial syndrome

20

What is 22q11 deletion syndrome a combination of?

DiGeorge and Velocardiofacial syndrome

21

What are characteristics of DiGeorge syndrome?

Thymic hypoplasia

Hypoparthyroidism

Outflow tract cardiac malformation

22

What are characteristics of Velocardiofacial syndrome?

Cleft palate

Outflow tract cardiac malformation

Characteristic face

23

What kind of inheritance does Velocardiofacial syndrome show?

Autosomal dominant

24

What are characteristics of Williams syndrome?

Aortic stenosis

Hypercalcaemia

5th finger clinodactyly

Characteristic face

Cocktail party manner

Delection of elastin on chromosome 7

Deletion of contiguous genes

25

What causes Williams syndrome?

Deletion of elastin on chromosome 7 and contiguous genes

26

What is foetal alcohol syndrome?

Diagnostic term to describe the impacts on the braina dn body of people prenatally exposed to alcohol during pregnancy

27

What is a diagnostic term used to describe the impacts on the braina dn body of people prenatally exposed to alcohol during pregnancy?

Foetal alcohol syndrome

28

What model does multifactorial inheritance use?

Threshold model

29

What are some examples of simple congenital heart diseases?

Lesion

Aortic stenosis

Patent ductus arteriosus

Coarctation

Atrial septal defect

Ventricular septal defect

Pulmonary stenosis

Tetralogy of Fallot

30

What is ventricular septal defect associated with?

Folate deficiency

31

What is folate deficiency associated with?

Ventricular septal defect

32

What is folate?

Vitamin B12

33

What are different categories of cardiac genetic disease?

Cardiovascular connective tissue disease

Familial arrhythmias

Familial cardiomyopathy

34

What are examples of cardiovascular connective tissues diseases that are genetic?

Marfan

Loeys-Dietz

Ehlers Danlos

FTAA

35

What are examples of familial arrhythmias?

Long QT

Brugda

CPVT

36

What are examples of familial cardiomyopathy?

Hypertrophic cardiomyopathy (HCM)

Dilated cardiomyopathy (DCM)

37

What does HCM stand for?

Hypertrophic cardiomyopathy

38

What does DCM stand for?

Dilated cardiomyopathy

39

What kind of inheritance does Marfan syndrome show?

Autosomal dominant

40

What causes Marfan syndrome?

Fibrillin 1 gene which is located chromosome 15q21

41

What does diagnosis of Marfan require?

2 positive findings of the following:

Aortic dilation/dissection (cardiovascular)
Ectopia lentis (eyes)
Systemic score more than or equal to 7 (includes skeletal, skin, respiratory, dural ectasia, mitral valve prolapse and myopia)
Family history
Fibrillin 1 mutation

42

What do people with Marfan syndrome generally look like?

Tall and thin

43

When should you do a genetic test for Marfan syndrome?

In a suspected case when a positive result would change the diagnosis (such as case with only a single major feature)

44

Explain the biochemistry of Marfan syndrome?

1) TGF beta and fibrillin are both secreted into the extracellular matrix and interact in vitro

2) Incorporation of fibrillin into microfibrils results in the proteolytic release of TGF beta

3) TGF beta signalling affects cell proliferation, differentiation and apoptosis

45

What does TGF beta stand for?

Transforming growth factor beta

46

What is proteolytic?

Breakdown of proteins into smaller polypeptides or amino acids

47

What does the management of Marfan syndrome involve?

Annual clinical reviews which includes:

Echocardiogram
Beta blockers
Angiotensin II receptor blockers
Prophylactic aortic surgery if sinus or Valsalva exceeds 5.5cm or 5% frowth per year
Monitor aortic root frequently in pregnancy if diameter exceeds 4cm

48

What are examples of Marfan like syndromes?

Loeys'diets syndrome

Familial thoracic aortic aneurysm

MASS phenotype

49

What are characteristics of Loeys-diets syndrome?

Arterial dissection

Tortuosity

Hypertelorism

Skin and skeletal findings

50

What are characteristics of MASS phenotype?

Myopia

Mitral valve prolapse

Mild aortic dilation

Striae

Minor skeletal involvement

51

What is sudden unexpected death syndrome?

Sudden arrhythmic death of adults or children, usually during sleep

52

What age group usually die from sudden unexpected death syndrome?

Beteen 1 year and 40 years

53

What are the typical causes of sudden unexpected death syndrome?

Arrthymic

Inherited heart disease

Ion channelopathy (most are long QT syndrome)

54

What is long QT syndrome?

Condition that affects repolarisation of the heart after a beat

55

56

What are symptoms of long QT syndrome?

Syncope

Seizure

Sudden death

57

What are exacerbating factors for long QT syndrome?

Emotion

Exercise

Drugs

58

What does the ECG for long QT syndrome show?

Prolonged QT interval

Repolarisation anomalies (T/U waves)

59

What are some mutations that suggest precipitants of arrhythmia?

KCNQ1

KCNH2

SCN5A

60

What is the precipitant of arrhythmia for KCNQ1 mutation?

Exercise

61

What is the precipitant of arrhythmia for KCNH2 mutation?

Noise/arousal

62

What is the precipitant of arrhythmia for SCN5A mutation?

Sleep/bradycardia

63

What is Brugada syndrome?

Condition that disrupts normal rhythm of the heart

64

What are the different types of Brugada syndrome?

Type 1

Type 2

Type 3

65

What is seen in Brugada syndrome?

Prolonged PR interval

Enlarge left ventricle

66

Who usually suffers from Brugada syndrome?

Young men, especially of far Eastern origin

67

What mutation if Brugada syndrome due to?

SCN5A and 11 other genes

68

What is the management of Brugada syndrome?

Avoid fever, excess alcohol and overeatin

Implantable cardioverter defibrillator (ICD)

69

What does AVC stand for?

Atrioventricular canal defect

70

What is atrioventricular canal defect?

Hole between the chambers of the heart

71

What is atrioventricular canal defect diagnosed by?

Echocardiogram or MRI

72

What does the ECG for atrioventricular canal defect show?

Epsilon waves

T wave inversion

73

What does histology for atrioventricular canal defect show?

Fatty infiltration of right ventricle

74

What is hypertrophic cardiomyopathy?

Heart muscles (myocardium) becomes abnormally thick

75

What is it called when the heart muscles (myocardium) becomes abnormally thick?

Hypertrophic cardiomyopathy

76

What is the prevalence of hypertrophic cardiomyopathy?

1/500

77

What is the presentation of hypertrophic cardiomyopathy?

Variable

78

What is the mortality of hypertrophic cardiomyopathy?

6% per year diagnosed in childhood

2.5% per year diagnosed in adult life

0.5% per year diagnosed in screening

79

What is dilated cardiomyopathy?

Heart becomes enlarged and cannot pump blood effectively

80

What is it called when the heart becomes enlarged and cannot pump blood effectively?

Dilated cardiomyopathy

81

What should be done before diagnosing dilated cardiomyopathy?

Exclude:

 

Ischaemic heart disease (angiography)

Hypertension

Skeletal muscle disease (neurology/genetic evaluation)

Alcohol abuse (history and biochemical evidence)

Exposure to cardiotoxic (history)

Haemochromatosis

82

What may genetic testing for dilated cardiomyopathy include?

Titin

LMNA

SCN5A

Dystrophin

Sarcomere genes

83

What is the largest gene in the genome?

Titan with 363 exons and 38138 amino acids

84

What are different kinds of genetic sequencing?

Sanger sequencing

Next generation sequencing (can read many genes at once)

85

What is the difference between Sanger and next generation sequencing?

Next generation sequencing can read many genes at once

86

What is genomics?

Branch of molecular biology concerned with the structure, function evolution and mapping of genomes

87

What is the branch of molecular biology converned with the structure, function, evolution and mapping of genomes?

Genomics

88

What is genetic cardiology conditions diagnosed by?

Cardiac phenotype and genetic history

Family history

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