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CARD - 1 > Congenital and Genetic Heart Disease > Flashcards

Congenital and Genetic Heart Disease Flashcards

1
Q

What are some examples of causes of congenital heart disease?

A

Copy number variation (CNV) - whole chromosome, parts of chromosomes deleted or duplicated etc. e.g. Down’s syndrome.

Single nucleotide variation (SNV) - Mendelian disorders (affect one base in the DNA).

CNV or SNV - CHARGE

Multifactorial - isolated CHD e.g. VWD

Uncertain - VACTERL

Teratogens - rubella, alcohol, anti-epileptic drugs, maternal diabetes mellitus.

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2
Q

What mutations are responsible for Down Syndrome?

A

Trisomy 21
95% maternal non-dysjunction (mat age)
3% translocation
2% mosaic

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3
Q

What heart problems are common in children with Down’s syndrome?

A

Atrio-ventricular septal defects.

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4
Q

What GI problem is common with Down’s children?

A

Duodenal atresia.

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5
Q

How can Down’s fetuses be picked up?

A

More nuchal translucency at 12 weeks. More tests to be done after to confirm.

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6
Q

What is Turner’s syndrome? What is the effect of the heart and else where?

A

45, X - one X missing.
Coarctation of aorta, short stature, gonadal dysgenesis - infertile.

Puffy hands and feet.

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7
Q

What can be a difficulty with Turner’s syndrome?

A

30% mosaic but in those with this some of the other working cells will be male and male cells in the gonads poses risk of causing gonad cancer.

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8
Q

What are the common single gene defects?

A

Noonan syndrome
Cardio-Facio-Cutaneous
Leopard syndrome
Costello syndrome

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9
Q

What is 22q11 deletion syndrome?

A

CATCH22

Cardiac malformation 
Abnormal facies
Thymic hypopalsia
Cleft palate
Hypoparathroidism
22q11 deletion.

Renal/psychiatric

Speech delay/palatal dysfunction common, very variable condition, look for additional clinical features. If 2 + features - test. Low frequency in unselected CHD (only 25% familial).

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10
Q

What psychiatric problem do adult 22q11 commonly get?

A

22% get schizophrenia.
May also get psychotic depression and other mental illness. May get mother with mental illness and child with heart problem = variable.

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11
Q

Why is 22q11 a common congenital abnormality?

A

There are the two bits of DNA of the same bases at sides of 22q11 region sometimes they stick together and loop out the 22q11 region.
Low copy number repeats, predispose to deletion and translocation (e.g. t11;22).

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12
Q

What signs would lead to you diagnosing fetal alcohol syndrome?

A 
IUGR <10th centile. 
Head < 10th centile.
Face
ADHD
3-5 units per week.
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13
Q

What can neck webbing arise from?

A

Excess nuchal folds.

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14
Q

What can be an indicator of prenatal cardiac difficulties?

A

Neck webbing.

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15
Q

What does Noonan syndrome result from? What are some features of Noonan syndrome?

A

Autosomal dominant PTPN11 mutation.

Pulmonary stenosis, short stature, neck webbing, cryptorchidism, characteristic face.

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16
Q

What is cryptorchidism?

A

Absence of one or both testes from the scrotum. Can be born with this or may develop after birth.

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17
Q

What is Cardio-Facio-Cutaneous syndrome?

A

Noonan-like, plus:

Ectodermal problems and developmental delay.

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18
Q

What is Leopards syndrome?

A

Noonan-like syndrome, plus:

Multiple lentigenes, deafness.

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19
Q

What is Costello syndrome?

A

Noonan-like, plus:

Thickened skin folds, susceptible to warts, cardiomyopathy, later cancer risk.

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20
Q

What two separate conditions did they used to think actually split 22q11 syndrome?

A 
DiGeorge syndrome (thymic hypoplasia, hypoparathyroidism, outflow tract cardiac malformation, usually sporadic)
and 
Shprintzen Syndrome (cleft palate, palatal insufficiency, outflow tract cardiac malformation, characteristic face, autosomal dominant).
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21
Q

What is the link with 22q11 syndrome and psychiatric problems?

A

2% schizo patients had 22q11 deletion.
22% 22q11 deletion patients had schizo.
Of 40 adults with 22qDS - 25% schizo, 13% depressed, 2.5% bipolar.

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22
Q

What are the features of Williams Syndrome?

A

Aortic stenosis (supravalvar), hypercalcemia, 5th finger clinodactyly (curvature), characteristic face, cocktail party manner.

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23
Q

What causes Williams Syndrome?

A

Deletion of (ELN) gene for elastin on chromosome 7. Deletion of contiguous genes. Loss of LIM kinase 1 (intracellular signalling and brain development enzyme).

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24
Q

What other teratogens may cause a features similar to fetal alcohol syndrome?

A

Antiepiletic drugs, rubella and maternal diabetes mellitus.

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25
Q

What affects do alcohol/antiepiletic drugs/rubella have on the baby?

A

Hearing loss, visuomotor difficulties, fine motor difficulties.

26
Q

Why is it easier to tell the effect of maternal diabetes mellitus from the other teratogens?

A

Should know if mother has diabetes.

Affects way lower limbs and spinal cord form, unlike other teratogens.

27
Q

Why do the teratogens have a similar effect on the baby?

A

They all affect methylation, switching of genes on and off.

28
Q

What drugs can cause fatal anticonvulsant syndromes?

A

Valproate, phenytoin, carbamazepine.

29
Q

What are some common characteristics of metal anticonvulsant syndromes?

A

Characteristic faces, malformation patterns, developmental delay, common and specific features.

30
Q

How are the risks of getting a congenital heart disease increased if you have family history of congenital heart disease?

A

Risks are increased. Especially if mother has congenital defect. If father has - risk increased, and if sibling has - risk decreased but least so.

31
Q

VSD is associated with deficiency of what?

A

Folate. If previous child has VSD then mother is put of folic acid supplementation during the next pregnancy. Given irregardless of whether it is CHD or due to affected MTHFR gene (resp. for producing folate).

32
Q

What are three groups of genetic cardiac disease?

A

Cardiovascular connective tissue disease
Familial arrhythmias
Familial cardiomyopathy

33
Q

Give examples of cardiovascular connective tissue damage.

A

Marfan, Loeys-Dietz, Ehlers Danlos, FTAA.

34
Q

Give examples of familial arrhythmias.

A

Long QT, Brugada, CPVT, ARVC.

35
Q

Give examples of familial cardiomyopathies.

A

HCM, DCM.

36
Q

What is Marfan Syndrome?

A

Autosomal dominant, multisystem, connective tissue disorder.

37
Q

What mutation causes Marfan syndrome?

A

Fibrillin 1 gene mutation, chromosome 15 (15q21).

38
Q

What is a syndrome related to Marfan?

A

TGFbeta2 (and 1) - on chromosome 3p22 (9q33).

39
Q

What is the Ghent criteria used for?

A 
To clinically diagnose Marfan. 
Must have 2 positive findings of:
CV system - aortic dilatation/dissection
Eyes - ectopia lentis
Systemic score of 7+
(skeletal, skin, resp, dural ectasia, mitral valve prolapse, myopia)
40
Q

What is the Ghent criteria used for?

A

To clinically diagnose Marfan.
Must have 2 positive findings of:
CV system - aortic dilatation/dissection
Eyes - ectopia lentis
Systemic score of 7+
(skeletal, skin, resp, dural ectasia, mitral valve prolapse, myopia)
Family history (unequivocally affected relative)
Fibrillin 1 (mutation known to cause MFS).
2 systemic findings must be +ve.

41
Q

What is ectopia lentis?

A

Lens dislocation in the eye leading to serious vision problems. Can actually see lens slipping out of place when the eye is moved.

42
Q

Give examples of skeletal features which may add to the Ghent systemic score.

A

Arm span that exceeds height (1).
Scoliosis/kyphosis (1).
Pectus deformity (2/1).
Double jointed thumb (1), can fit hand round wrist (1), if both = 3.
Abnormal foot/ankle angles(2/1).
Reduced elbow extension (1)(<170 degrees).

43
Q

What are some other things that may add to the Ghent systemic score?

A 
Myopia > 3 dioptres (1). 
MVP (1). 
Pneumothorax (2). 
Dura (2). 
Striae (1). 
Face (1). 
Protrusio acetabuli (2).
44
Q

How high must the systemic score be to diagnose Marfan?

A 
7+ = Marfan 
5+ = do MASS if at least 1 skeletal.
45
Q

What must you do with EVERY Marfan patient? What other test might you do?

A

Echocardiography - check for any heart problems.
Undertake MRI and/or pelvic X-ray where diagnosis would change if positive (dural ectasia affects about 92% of Marfan patients).

46
Q

What considerations must you take when suspecting Marfans in children?

A

A lot of the symptoms will not come on until later (e.g. striae and aortic stenosis…) so its harder to diagnose and need to have a higher index of suspicion (can’t expect them to have everything).

47
Q

When should you do genetic testing for Marfans?

A

When a positive result would change the diagnosis. So, basically if you can’t diagnose on clinical features alone.

48
Q

How do TGFbeta and fibrillin interact?

A

They are both secreted into the ECM and interact in vitro. Incorporation of fibrin into microfibrils results in proteolytic release of TGFbeta.

49
Q

What is the role of TGFbeta?

A

TGFbeta signalling affects cell proliferation, differentiation and apoptosis.

50
Q

Transgenic mice deficient in fibrillin show what features? What can resolve these features in these mice?

A

Have excess TGFbeta signalling and Marfan features.

TGFbeta antibodies or the TGFbeta antagonist Losartan rescue the Marfan phenotype.

51
Q

What are some Marfan-like syndromes?

A

loeys-Dietz syndrome
Marfan syndrome type 2
Familial thoracic aortic aneurysms
MASS phenotype

52
Q

What are some features of Loeys-Dietz syndrome?

A

Arterial dissection, tortuosity, bifid uvula/cleft palate, hypertelorism, skin and skeletal findings.

53
Q

How does Marfan syndrome type 2 differ from Marfan syndrome?

A

It’s non-ocular.

54
Q

What genes are known to cause familial thoracic aortic aneurysms?

A

11q, 5q - genes unknown.

3p22, 16p13, 10q22-24

55
Q

What features might someone with a MASS phenotype experience?

A

Myopia, mitral valve prolapse, mild aortic dilatation, striae, minor skeletal involvement.

56
Q

What is involved in optimal management of Marfan?

A

At least annual clinical review.
Echocardiogram, beta blockers, angiotensin II receptor blockers, prophylactic aortic surgery is sinus of valsalva exceeds 5.5cm or 5% growth per year. Monitor aortic root frequently in pregnancy if diam exceeds 4cm.

57
Q

To slow the rate of dilatation what should be considered in all Marfan patients?

A

Beta-blocker therapy despite the fact the response is heterogeneous.
Angiotensin 2 receptor blockers also slow rate of dilatation.

58
Q

What are the different ways to go about aortic root surgery?

A

May replace the valve with mechanical valve which can mean it will last longer, lower chance of needing to re-intervene. If not may need to re-operate to replace the valve later on, but won’t need to patient on warfarin.

59
Q

What is sudden unexpected death?

A

Between 1 year and 40 years with no cause shown at post-morteum. Assumed to be arrhythmic.

60
Q

What is Romano-Ward syndrome?

A

A major variant of long QT syndrome. It is a condition that causes disruption of the normal heart rhythm. ECG shows prolonged QTc interval (myocytes taking longer to recover), depolarisation anomalies (T/U waves), paroxysmal polymorphic VT (Torsade de Pointes). Can cause syncope, ‘seizure’, sudden death with emotion/exercise/drugs.

61
Q

What is Jervell Lange-Neilson syndrome?

A

As above + congenital sensorineural deafness (2 mutations, same cardiac features + deafness).

CARD - 1 (28 decks)

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