Genetics & Cardiovascular Disease Flashcards
What is Trisomy 21?
What causes it?
Down’s syndrome
Additional chromosome 21 (i.e. 3 of chromosome 21)
What are the congenital defects associated with Down’s syndrome?
- AVSD (artio-ventricular septal defects)
- duodenal atresia
What is duodenal atresia?
- congenital absence or complete closure of a portion of the lumen of the duodenum.
- increases levels of amniotic fluid during pregnancy (polyhydramnios) and intestinal obstruction in newborn babies.
What is nuchal translucancy?
What does it indicate?
- sonographic appearance of a collection of fluid under the skin behind the fetal neck in the first-trimester of pregnancy.
- indicative of chromosomal abnormality
What is a cystic hygroma?
- fluid-filled sac that results from a blockage in the lymphatic system
- commonly located in the neck or head area.
What is (45, X)?
Who is affected by this syndrome?
Turner’s syndrome
females only
What are the congenital defects associated with Turner’s syndrome?
(5)
- short stature
- neck webbing (excess nuchal folds)
- coarctation of the aorta
- gonadal dysgenesis
- puffy hands
What are the congenital defects often associated with Noonan’s syndrome?
(5)
- pulmonary stenosis (CHD)
- short stature
- mild unusual facial features
- neck webbing
- cryptorchidism (failure of testicle descent)
What are some of the congenital abnormalities associated with 22q11 syndrome?
(5)
CATCH
Congenital abnormalities Abnormal facial features Thymic hypoplasia (under developed) Cleft palate Hypothyroidism
22q11 deletion syndrome encompasses both ________ and _________ syndromes.
DiGeorge
Shprintzen
What are the characteristic features and congenital abnormalities associated with William’s syndrome?
(5)
- aortic stenosis
- characteristic face
- clinodactyly (5th finger/toe)
- cocktail party syndrome
- hypercalcaemia
Give example of some teratogens which can lead to congenital heart disease.
(4)
- alcohol (fetal alcohol syndrome)
- antiepileptic drugs
- rubella
- maternal DM
Explain the multifactorial threshold model (in terms of the bell curve distribution).
- the shaded under the curve to the right of the threshold line represents population affected by congenital defects
- the curve for first-degree relatives is shifted to the right thus the shaded area to the right of the threshold also increases, more chance of congenital abnormality.
A child of an affected ________ is at risk of inheriting aortic stenosis.
mother
What is folate deficiency associated with?
VSD
Outline some genetic cardiac disease which cause connective tissue disease?
(3)
- Marfan’s syndrome
- Ehlers Danlos
- Loeys-Dietz
What pattern of inheritance does Marfan’s syndrome have?
autosomal dominant - affected individual has one copy of a mutant gene and one normal gene on a pair of autosomal chromosomes.
What causes Marfan’s syndrome?
mutation in FBN1 gene, a gene that makes fibrillin which results in abnormal connective tissue.
What are the physical characteristics of a person with Marfan’s sydnrome?
(5)
- affects males and females
- tall and thin
- long arms, legs, fingers and toes
- flexible joints
- scoliosis
What are the congenital abnormalities associated with Marfan’s syndrome?
- heart: mitral valve prolapse
- aorta: aortic aneurysm
- other affected areas: bone, eyes and lungs
Diagnosis of Marfan’s syndrome requires two positive findings from a set criteria.
What is in this criteria?
- FHx (with/without)
- aortic dissection/dilation
- ectopia lentitis (malposition of the eye’s crystalline lens from its normal location)
- FBN1 mutation
- Systemic score (skeletal, skin, respiratory, dural ectasia, mitral valve prolapse, myotpia_
When should you do a genetic test (FBN1) in a suspected index case?
When a positive result would change the diagnosis:
- cases with a single major feature (aortic or eye) or;
- systemic score of 7 (and no more), or positive FHx.
i.e. borderline patients
How is Marfan’s syndrome managed clinically?
- annual review/echocardiogram
- beta-blockers or;
- CCBs or ARBs
What surgical intervention may be recommended for patients with Marfan’s?
(2)
- prophylactic aortic surgery (aortic repair)
- heart valve repair (e.g. mitral valve repair)
What are some differential diagnosis to Marfan’s?
2
- Loeys-Dietz syndrome
- Ehlers-Danlos syndrome (stretchy skin)
What is long QT syndrome?
condition (often genetic) which affects the repolarisation of the heart
What are symptoms of long QT syndrome?
- congenital sensorineural deafness
- arrhythmias (Torsades de Pointes)
- presyncope (light headedness, faint)
What are the complications of long QT syndrome?
- epilepsy
- cardiac arrest/SCD
How is long QT syndrome managed/treated?
- avoiding strenuous exercise
- sufficient K supplement
- beta-blockers
- ICD (implantable cardioverter-defibrillators)
What are common familial cardiomyopthies?
- hypertrophic cardiomyopathy
- dilated cardiomyopathy
Dilated cardiomyopathy has many causes other than genetics which should be excluded. What are they?
(7)
- hypertension/DM
- alcohol abuse (SHx)
- cardiotoxic drugs (DHx)
- MSK disease
- IHD/CAD]
- valvular disease
- haemochromatosis (Fe storage in tissues)
What might be included in genetic tests investigating possible familial cardiomyopathy?
(5)
- SCN5A
- titin
- LMNA
- dystrophin
- sarcomere genes
What is a proband?
The first affected family member who seeks medical attention for a genetic disorder.
What are the main things to consider/investigate when a person presents with possible congenital disease?
(5)
- genetic testing
- detailed FHx
- assess relatives
- cascade screening (a mechanism for identifying people at risk for a genetic condition by a process of systematic family tracing)
- prevention
