Genetics and cardiovascular disease Flashcards
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.
what does congenital heart disease mean
heart disease present at birth
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
what is the CHARGE syndrome
multiple congenital malformation syndrome - patients with it present with a variable combination of defects
what is the only congenital heart disease that is multi factorial?
isolated heart disease
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
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
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
what congenital heart problems arise from turner syndrome
coarctation of aorta
neck webbing
excess nuchal folds (normal fold of skin at back of fetal neck that occurs during pregnancy)
noonan syndrome
genetic disorder
PTPN11 gene
causes pulmonary stenosis, neck webbing, unusual facial features, short stature and heart defects.
Cardiofaciocutaneous syndrome (CFC)
rare genetic condition that typically affects the heart, facial features and skin. Developmental delay
Main defect associated with Leapord syndrome
deafness
Costello syndrome
susceptible to warts
cardiomyopathy
Later cancer risk
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)
psychiatric conditions related with 22q11 deletion
22% of adults with this gene alteraton have schizophrenia
what 2 names is the 22q11 deletion referred to as
Digeorge and Shprintzen
Features of DiGeorge Syndrome of 22q11
Thymic hypoplasia
Hypoparathyroidism
outflow tract cardiac malformation
usually sporadic
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
