Genetics and cardiovascular disease Flashcards by Anna Coull

Causes of congenital heart disease

Copy number variation (CNV) ee.g extra, deletion etc

Single nucleotide variation (SNV)

CNV or SNV

Multifactorial

Teratogens - agent or factor which causes malformation of an embryo.

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what does congenital heart disease mean

heart disease present at birth

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what is VACTERL association?

is a disorder that affects many body systems - it’s not directly linked to genetics more likely to be caused by multiple factors

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what is the CHARGE syndrome

multiple congenital malformation syndrome - patients with it present with a variable combination of defects

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what is the only congenital heart disease that is multi factorial?

isolated heart disease

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Trisomy 21 causes which disease and what heart problems can arise from this

Down syndrome
- 95% maternal non-disjunction (mat age)

15% get atrio-ventricular septal defects

also causes duodenal atresia - increased levels of amniotic fluid during pregnancy

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what are the risk factors for a child being born with down syndrome?

maternal age and nuchal translucency - collection of fluid under the skin at the back of your baby’s neck

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what is cystic hygroma

Abnormal fluid-filled sac that results from a blockage in the lymphatic system. It is most commonly located in the neck or head area, but can be located anywhere in the body. May be found in fetus or newborn.

It is associated with congenital heart disease

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what congenital heart problems arise from turner syndrome

coarctation of aorta

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neck webbing

excess nuchal folds (normal fold of skin at back of fetal neck that occurs during pregnancy)

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noonan syndrome

genetic disorder

PTPN11 gene

causes pulmonary stenosis, neck webbing, unusual facial features, short stature and heart defects.

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Cardiofaciocutaneous syndrome (CFC)

rare genetic condition that typically affects the heart, facial features and skin. Developmental delay

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Main defect associated with Leapord syndrome

deafness

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Costello syndrome

susceptible to warts
cardiomyopathy
Later cancer risk

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22q11 deletion syndrome cause and key features

caused by specific deletion on chromosome 22

key features:- CATCH 22 = Cardiac malformation,
Abnormal facies, Thymic hypoplasia, Cleft palate, Hypoparathyroidism (decreased secretion or activity of parathyroid hormone)

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psychiatric conditions related with 22q11 deletion

22% of adults with this gene alteraton have schizophrenia

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what 2 names is the 22q11 deletion referred to as

Digeorge and Shprintzen

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Features of DiGeorge Syndrome of 22q11

Thymic hypoplasia
Hypoparathyroidism
outflow tract cardiac malformation

usually sporadic

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Features of Shprintzen syndrome of 22q11

cleft palate
outflow tract cardiac malformation
characteristic face autosomal dominant

Williams syndrome

Aortic stenosis

hypercalcemia

5th finger - clinodactyly - bone in the fifth finger is underdeveloped

Pixie looking face

Cocktail party manner- makes people extremely outgoing and irrepressibly friendly.

cause of fetal alcohol syndrome

caused by women drinking alcohol during pregnancy

key features of fetal alchohol syndrome

Intrauterine growth restriction (IUGR) is a condition where a baby’s growth slows or ceases when it is in the uterus.

underdevelopment of head

ADHD

Other than fetal alcohol syndrome give other teratogens that can cause problems with pregnancy

antiepileptic drugs
rubella
maternal diabetes mellitus

what must pregnant women not be deficient in

folate acid - it is very important for the development of a healthy foetus

difference between congenital heart disease and genetic heart disease

congenital - from birth - can be detected in fetus and newborn genetic - identified later in life - at any stage

3 main types of genetic heart disease

Cardiovascular connective tissue disease familial arrhythmias familial cardiomyopathy

example of a connective tissue disease

Marfan | Loeys-Dietz

Example of familial arrhythmias

Long QT | Brugada

Example of familial cardiomyopathy

HCM - Hypertrophic cardiomyopathy | DCM - Dilated cardiomyopathy

What is Marfan syndrome?

autosomal dominant multisystem disorder that affects connective tissue that supports and anchors organs and other structures in the body chromosome 15q21

characteristics of person with marfan's disease (4)

tall stature risk of aortic aneurysm and aortic rupture long fingers, arms and toes lens subluxation - displacement of lens in eye

how do you diagnose marfan's syndrome?

need 2 positive findings Cardiovascular system:- aortic dilatation/dissection Eyes:- ectopia lentis - displacement of lens from normal location Need a systemic score of more or equal to 7 - skeletal, skin, respiratory, dural ectasia, mitral valve prolapse Family history - unequivocally affected relative (know for definite) fibrillin 1 gene - mutation that causes syndrome - 70-90% have it with Marfan's

in which age group is it hard to diagnose Marfan's syndrome

in children

what is the optimal management of Marfan?

at least an annual clinical review Echocardiogram Beta blockers angiotensin II receptor blockers to reduce blood pressure and strain on the aorta prophyllactic aortic surgery if Sinus of Valsalva exceeds 5.5cm (bit between LV and Aorta Aortic root diameter needs to be less than 4cm in order to be safe for pregnancy

2 types of aortic root surgery for enlarged aorta

mechanical valve - lasts longer, need warfarin valve sparing procedure, patient's aort is kept but repaired or reimplanted. May need re-operation. No warfarin used

when does Marfan syndrome become life threatening

if the aorta is affected

causes of Marfan syndrome

defect in the gene that enables your body to produce a protein that helps give connective tissue its elasticity and strength.

TGF-beta and fibrillin signalling system- what is the link to Marfan's syndrome?

Normally, TGF-beta is active during fetal development but is less active in adults. Normally functioning fibrillin is like a “traffic cop” for TGF-beta, signaling it to be active when it is needed and stopping or suppressing its activity when it is not needed. But in people with Marfan syndrome, this signaling system has trouble stopping the activity of TGF-beta.

what are TGF-beta and fibrillin

fibrillin regulates growth factors | TGF-beta is a growth factor

Long QT syndrome

15 types of Long QT syndromes condition which affects repolarisation of the heart after a heartbeat. presents as abnormal ECG (prolonged QT interval) - can lead to syncope (fainting), seizure or sudden death

Each child of an affected parent with Marfan's has what chance of inheriting the disease?

50/50

Cardiovascular complications of marfan's

aortic aneurysm aortic dissection - (small tear in the innermost layer of the aorta's wall allows blood to squeeze in between the inner and outer layers of the wall) Valve malformations

Next generation sequencing

DNA is broken and amplified by PCR can read many genes at once

Cardiac genetics - what types of things do you do/look for

genetic testing can improve diagnostic accuracy and refine family management diagnosis in person being studied - looking for cardiac phenotype, carry out genetic testing family history assess relatives prevention of avoidable morbidity and mortality

what is dilated cardiomyopathy

a condition in which the heart becomes enlarged and cannot pump blood effectively

hypertrophic cardiomyopathy

thickening of the heart muscle - harder for it to pump blood

what is the GHENT criteria?

used to diagnose Marfan's syndrome need 2 positive findings Cardiovascular system -Aortic dilatation/dissection Eyes -Ectopia lentis Systemic Score ≥ 7 - Skeletal - Skin - Respiratory - Dural ectasia - Mitral valve prolapse - Myopia Family history - Unequivocally affected relative - Fibrillin 1 - Mutation known to cause MFS