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Cardiovascular > Congenital heart disease > Flashcards

Congenital heart disease Flashcards

1
Q

Congenital heart disease is the most common form of what?

A

birth defect ( approx 1 per 100)

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2
Q

Congenital heart disease may be?

A

Isolated/Non-syndromic

Syndromic

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3
Q

What factors comprise Isolated/Non-syndromic congenital heart disease?

A

No other malformations
No family history
Probably polygenic/environmental factors

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4
Q

What factors comprise Syndromic congenital heart disease?

A

Family history (approx 3-5% of cases but may be different CHD)

Not dysmorphic

No other malformations

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5
Q

There may be some people with isolated congenital heart disease, with no other abnormalities, with a family history a related or different heart problem.

True or false

A

True

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6
Q

What is a syndrome?

A

A group of symptoms which consistently occur together, or a condition characterised by a set of associated symptoms.

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7
Q

What are four causes of a syndrome?

A

Chromosomal
Genetic
Unknown/associations
Maternal factors

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8
Q

Approximately what percentage of children with a congenital heart disease experience an underlying syndrome?

A

30%

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9
Q

What represents a syndromic form of congenital heart disease?

A

Certain types of heart lesion are more frequent

E.g. Truncus Arteriosus. Tetralogy of Fallot

Any other structural abnormalities?

+/- Family history of syndrome?

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10
Q

What is the purpose of investigating whether congenital heart disease is syndromic?

A 
Prognosis and options 
Associated problems/abnormalities
Inform clinical management
Recurrence risk
Specific treatments?
Pathophysiological insights
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11
Q

What types of heart lesion are low risk of syndromic condition?

A

Transposition of the great Arteries

Total anomalous pulmonary venous drainage

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12
Q

What types of heart lesion are high risk of syndromic condition?

A

Tetralogy of Fallot

Ventricular septal defect

Truncus arteriosus

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13
Q

What is the current Pregnancy Screening in the UK?

A

11-13 weeks – Combined test to give a risk for trisomy 21 , 13 and 18

Nuchal translucency measurement,
PAPP-A and beta HCG levels
combined with maternal age

20 week fetal anomaly scan with 4 chamber view of the heart

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14
Q

What is increased Nuchal Translucency (NT) associated with?

A

Downs Syndrome

Chromosomal abnormalities

Congenital Heart Disease (any)

Other genetic (syndromes)

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15
Q

Chance of adverse outcome increases with increasing nuchal thickness

True or false

A

True

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16
Q

What forms of genomic variation is found in congenital heart disease?

A

Whole chromosomal abnormalities

Copy number variants

Insertions and duplications

Single nucleotide variants

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17
Q

What percentage of all children with a congenital heart disease have a chromosomal abnormality?

What do these include?

What percentage deviate from this condition?

A

10.8%

trisomy 21 (62%) 
trisomy 18 (15%) 
trisomy 13 (6.4%)

1.6%

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18
Q

What percentage of children with downs syndrome/ trisomy 21 have a congenital heart disease?

What is the most common heart defect?

What are other heart defects?

A

40-50%

atrioventricular septal defect, or AV canal defects (45%)

ventricular septal defects (35%),
secundum atrial septal defects (8%),
patent ductus arteriosus (7%).
tetralogy of Fallot (4%)

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19
Q

There is an increased risk presented of down syndrome with combined antenatal tests/clues.

What do these include?

What are non genetic tests?

A

Maternal age- INCREASED

serum free β-human chorionic gonadotrophin
(free β-hCG) - INCREASED

Pregnancy associated plasma protein A
(PAPP-A) - DECREASED

NIPT result
Absent nasal bone
Short femurs

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20
Q

What is Edwards syndrome caused by?

A

Trisomy 18 defect

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21
Q

What type of congenital heart defects are presented in trisomy 18?

and clues on antenatal scan

A

Type of lesion: VSD with Aortic override, unusual AV valves , DORV, …’dysmorphic’ heart

Small baby with small head
Increased risk on combined test
‘strawberry’ shaped skull
Rocker bottom feet
exomphalos
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22
Q

What is Patau’s syndrome caused by?

A

Trisomy 13 defect

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23
Q

What are types of congenital heart defects in trisomy 13 and clues on antenatal scan?

A

VSDs, AVSD,

Increased risk on combined test

Polydactyly

Holoprosencephaly

Cleft lip

Small baby with small head

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24
Q

What are trisomy 13 and 18 increased risk with combined test include?

A

Maternal age INCREASED
serum free β-human chorionic gonadotrophin
(free β-hCG) DECREASED
pregnancy associated plasma protein A
(PAPP-A) DECREASED
Nuchal translucency INCREASED

25
Q

What genetic defect leads to turner syndrome?

A

Karyotype 45,X0 ( or variations/mosaicism)

26
Q

> 90% of women with a baby with turner syndrome miscarry due to what?

A

Fetal hydrops

27
Q

What are antennal clues of turner syndrome?

A

Markedly increased nuchal translucency (>5mm)
Renal anomalies – horseshoe kidney
Pedal oedema of hands & feet ( 3rd trimester)
Fetal hydrops

28
Q

What is the prevalence of cardiac malformations in babies with Turner syndrome?

What is the most common heart defect?

What are other heart defects?

A

approx 30%.

mostly left heart outflow tract obstructions

bicuspid aortic valve (16%)  
coarctation of the aorta (11%). 
aortic valve disease (3.2%) 
hypoplastic left heart 
partial anomalous pulmonary venous drainage had the highest relative risk.
29
Q

Trisomies/monosomies are rarely inherited

True or false

A

True

30
Q

Chromosomal abnormalities are not related to maternal age

True or false

A

False

Related to maternal age

31
Q

Any other chromosomal imbalance – important to check both parents as will affect recurrence risk

True or false

A

True

32
Q

Approximately 10% of babies congenital heart disease harbour a copy number variant for which the cause is unknown

What are the most common?

A

1q21.1,
7q11.23,
8p23.1,
11q25, 1
5q11.2, and
22q11.2.

33
Q

What test be used to detect small deletions or duplications?

A

Microarray

34
Q

Congenital heart disease is reported in approximately what percentage of babies with DiGeorge syndrome (22q11 microdeletion)?

What are the known cono-truncal’/left outflow tract heart defects?

A

80%.

tetralogy of Fallot, 
pulmonary atresia with ventricular septal defect,
truncus arteriosus/common arterial trunk
interrupted aortic arch, 
isolated anomalies of the aortic arch, 
ventricular septal defect.
35
Q

22q11 Deletions were found in:

A

Approx 1 in 2 of patients (50.0%) with interrupted aortic arch
Approx 1 in 3 ( 33%) of patients with common arterial trunk
Approx 1 in 6 (15%) of patients with tetralogy of Fallot

36
Q

What are clinical features of 22q11 microdeletion 1 in 4000 livebirths?

A

Immunodeficiency

Nasal Speech

Learning difficulties

Short stature

Cleft Palate/ Pierre Robin sequence

Kidney abnormalities

Hypocalcaemia

Psychiatric abnormalities

(30% develop schizophrenia-like psychoses)

37
Q

What is Williams Syndrome caused by?

A

Microdeletion 7q11.23

38
Q

How do you test for 22q11 microdeletion?

A

Can not see on normal chromosome analysis (karyotype)

FISH
but now superseded by

Array CGH

Soon…….NIPT.

39
Q

Congenital heart disease is experienced by 80% of babies with Williams Syndrome.

What does this include?

A

75% supravalvular aortic stenosis

25% supravalvular pulmonary stenosis

40
Q

What are characteristic features of Williams syndrome?

A

Characteristic Facial features
Developmental delay
Overfriendly personality
Hypercalcaemia (15%)

41
Q

Jin SC, Homsy J, Zaidi S, et al. Contribution of rare inherited and de novo variants in 2871 congenital heart disease probands. Nat Genet 2017 found what?

A

ONLY 8% of CHD had de novo variants (after excluding chromosomal and CNVs)
~3% of isolated CHD
~28% with both neurodevelopmental and extra-cardiac congenital anomalies

rare inherited mutations in 1.8%

42
Q

Autosomal Dominant…

A

Manifest in HETEROZYGOUS form

Multiple generations affected (vertical transmission)

Male to male transmission

50% risk to offspring

Reduced Penetrance

43
Q

What are Autosomal Dominant conditions associated with Congenital Heart Disease e.g?

How may these appear?

A

Noonan syndrome
Holt Oram syndrome
Alagille Syndrome

May be inherited OR de novo

44
Q

How many Noonan syndrome causative genes are known? What does this lead to?

A

Several genes >23 so testing in pregnancy can be difficult

45
Q

What are characteristics of Noonan syndrome?

A

Short stature
Learning difficulties
Webbed neck ( markedly increased nuchal translucency)

46
Q

What congenital heart defects are noted in Noonan syndrome?

A 
Pulmonary stenosis (2nd/3rd trimester)
Atrial septal defect
Tetralogy of Fallot
Hypertrophic Cardiomyopathy (3rd trimester)
47
Q

There is clinical overlap between Noonan syndrome and which other rasopathies?

A

Cardio-facio-cutaneous syndrome
Costello syndrome
(Neurofibromatosis type 1)

48
Q

What genes are affected in the rasopathies

A 
H-RAS
K-RAS
SOS1
Neurofibromin 
BRAF
RAF-1
MEK 1/2
SHP2
49
Q

What are antennal clues of Noonan syndrome?

Risk increases with what? …

Who should be looked at and why?

A

Markedly increased nuchal translucency often >5mm and persists (Vigneswaran et al., 2017)
Type of heart lesion (often in 3rd trimester)
Polyhydramnios
Pleural effusions/Fetal hydrops/agenesis ductus venosus
Hydronephrosis
Relative macrocephaly
Short femurs

Paternal age

Parents, they may be affected

50
Q

Who should be looked in relation to Tuberous Sclerosis and why?

What are antennal clues of Tuberous Sclerosis?

A

Look carefully at parents- highly variable (BUT 50% de novo)

MULTIPLE cardiac rhabdos- nearly always TS
But beware – they may become multiple OR they may look single but on post mortem they are found to be multiple

Tubers on brain – 3rd trimester only mainly seen on fetal MRI.
Genetic testing is improving so now helpful two genes TSC1 and TSC2
50% risk of seizures/autism/ severe ID

51
Q

What are three features of Holt Oram syndrome?

A

ASD/AVSD/TOF

Radial ray defect

+/- family history

52
Q

Differential diagnosis of CHD with radial ray defect

A 
Bilateral
Holt Oram syndome ( dominant and de novo)
TAR syndrome ( recessive)
Fanconi anaemia (recessive)
VACTERL association

Unilateral
Trisomy 18 ( sporadic)
Fetal valproate syndrome
Cornelia de Lange

53
Q

Autosomal Recessive….

A

Manifest in HOMOZYGOUS/ COMPOUND HETEROZYGOUS form

Carriers not affected

Usually one generation affected (horizontal transmission)

May be consanguinity
e.g. cousin marriages

54
Q

What are Autosomal Recessive conditions associated with Congenital Heart Disease?

A

Ellis Van Creveld syndrome
AVSD
ASD

55
Q

What are clues of Ellis Van Creveld syndrome?

A

Short long bones
Narrow thorax
Polydactyly

56
Q

What are Non-Genetic causes/Tetratogens of congenital heart disease?

A

Fetal alcohol
Maternal diabetes
Maternal drugs e.g.anticonvulsants esp. Sodium valproate,
IVF/ICSI

57
Q

What are antennal clues of Fetal Alcohol Syndrome?

A 
Growth retardation including microcephaly
Brain malformations
Agenesis of the corpus callosum 
Limb defects
Cardiac abnormalities

Maternal history!!

58
Q

In Fetal Valproate Syndrome what risk is there of multiple congenital malformations ?

A

10.7%

dose-dependent increased risk

Four fold increased risk of CHD
Mainly Septal defects and valvular problems
No consistent type of defect

59
Q

What are specific genes for non-syndromic CHD?

A

NKX2.5 - ASD, atrioventricular block, ventricular septal defect (VSD), Ebstein anomaly, and tetralogy of Fallot (TOF).

GATA4, a transcription factor - ASD, VSD, and pulmonary stenosis.

TBX1 - TOF, patent ductus arteriosus, and interrupted aortic arch

TBX20 - ASD, VSD, valve defects, and impaired chamber growth.

MYH6, which codes for an alpha myosin heavy chain (ASD)

Notch 1 - valve formation (bicuspid aortic valve and aortic stenosis)

Cardiovascular (19 decks)

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