Genetics and Cardiovascular disease Flashcards
What are copy number variants?
Changes in number of whole or parts of chromosomes
Name a trisomy associated with CHD?
Downs syndrome (trisomy 21) - AV septal defects and duodenal atresia
Name a monosomy associated with CHD?
Turners (45, x) - coarctation of aorta, AS, bicuspid aortic valve
Name some micro deletions associated with CHD
22q11 deletion - cardiac malformation
Williams syndrom - supravalvular AS
Name some single gene defects that cause CHD
Noonan/Cardio-facio-cutaneous syndrome Marfans Leopord syndrome Costello syndrome Holt-Oram Fanconi CHARGE
Name some teratogens known to cause CHD
Rubella
Alcohol
Anti-epileptic drugs
Maternal DM
What causes trisomy 21?
Mostly maternal non-disjunction (95%)
Translocation (3%)
Mosaic (2%)
What is nuchal translucency used for?
Collection of fluid under skin at back of babies neck, measured with ultrasound at around 12 weeks.
This is increased in babies with Downs and those with CHD
How do we test for Downs syndrome in babies?
Nuchal translucency
Blood tests for hCG and PAPP-A
All increased in downs, and if positive they are sent for amniocentesis or chorionic villus sampling
What is associated with CHD and abnormal chromosomes in newborns?
Cystic hygroma - congenital multiloculated lympathic lesions, usually located in left posterior triangle of neck and armpits
Name signs of Turners syndrome
Short stature Wide set nipples Broad chest Low set ears Gonadal dysgenesis Reproductive sterility Puffy hands and feet due to lymphedema CHD - coarctation, AS, bicuspid AV
What is somatic mosaicism?
It describes the presence of two or more populations of cells with different genotypes in one individual, which may only affect a portion of the body and is not transmitted to progeny
What is neck webbing?
Caused by excessive nuchal folds and cystic hygroma during development
What CHDs can cause neck webbing?
Turners Noonan syndrome Cardio-facio-cutaneous syndrome Leopord syndrome Costello syndrome
Name 3 Noonan like syndromes
Cardio-facial-cutaneous syndrome - plus ectodermal problems and developmental delay
Leopord syndrome - plus multiple lentigenes and deafness
Costello syndrome - plus thickened skin folds, susceptible to warts, cardiomyopathy and cancer risk later in life
Describe the physical characteristics of Noonans syndrome
Pulmonary stenosis
Short
Neck webbing
Cryptorchidism (loss of one or more testes)
Characteristic face (wide eyes, deep philtre, short broad nose)
What gene is responsible for Noonan syndrome, and Noonan like syndromes?
PTPN11 mutation in chromosome 12, autosomal dominant, causing mutations in MAPK pathway
What are the signs for 22q11.2 deletion syndrome?
CATCH 22
Cardiac malformation Abnormal facies e.g. floppy ears, bulbous nose, cleft lip, long face, hooded eyelids Thymic hypoplasia Cleft palate Hypoparathyroidism 22q11 deletion
also have asymmetric crying face
How can 22q11.2 deletion syndrome present later in life?
Renal impairment
Psychiatric - schizophrenia, depression, bipolar
What 2 syndromes are referred to as 22q11.2 deletion syndrome?
DiGeorge syndrome
- thymic hypoplasia
- hypoparathyroidism
- outflow tract cardiac malformation
- usually sporadic
Shprintzen syndrome
- cleft palate/palatal insufficiency
- outflow tract cardiac malformation
- characteristic face
- autosomal dominant
Describe the signs of Williams syndrome
Supravalvular aortic stenosis Murmurs and narrowing of vessels Hypercalcaemia 5th finger clinodactyly "Elfin" face - broad forehead, short nose, full cheeks, widely spaced teeth, long philtrum Mild to moderate intellectual disability Cocktail party manner/behaviour Failure to thrive Poor muscle tone
What causes Williams syndrome?
Deletion of elastin gene and neighbouring genes on chromosome 7
