Congenital Heart Disease andGenetic Heart Disease Flashcards
What are the causes of congenital heart disease?
Chromosomal (trisomies / monosomies)
Microdeletions (22q11 deletion, Williams)
Single gene (Noonan/CFC, Marfan)
CNV or SNV (Copy number variation / Single nucleotide variation)
Teratogens
Other
Multifactorial
What does CNV stand for?
Copy number variation (CNVs)
Sections of the genome are repeated and the number of repeats in the genome varies between individuals in the human population.
What does SNV stand for?
Single nucleotide variation
A variation in a single nucleotide without any limitations of frequency
What are the congenital heart defects associated with Down syndrome? (trisomy 21)
Atrioventricular septal defects
What is the main risk factor attached to bearing a child with down syndrome?
Maternal age
What is used to determine the presence of down syndrome?
Nuchal scan - detect cardiovascular abnormalities
Increased nuchal translucency associated with pathology
What is the percentage of fetuses/newborns with CHD have abnormalities with chromosomes?
19% of fetuses
13% of newborns
What heart defects is Turner syndrome associated with? (45,X)
Coarctication of the aorta
(Short stature, puffy hands, gonadal dysgenesis)
What causes neck webbing?
Excess nuchal folds
What syndromes are associated with neck webbing?
Turner syndrome
Noonan syndrome
CFC syndrome
Leopard syndrome
Costello syndrome
What is the effect of noonan syndrome on circulation?
Pulmonary valvular stenosis (50–60%)
Septal defects: atrial (10–25%) or ventricular (5–20%)
Hypertrophic cardiomyopathy (12–35%)
Also causes (short stature, neck webbing, cryptorchidism (he absence of one or both testes from the scrotum), characteristic face)
What gene is responsible for noonan syndrome?
PTPN11 mutation
What are the noonan like syndromes?
lCardio-Facio-Cutaneous (CFC)
lLeopard syndrome
lCostello syndrome
What pathway are Leopard, Noonan, CFC and Costello syndrome all associated with?
Associated with mutations in the MAPK pathway (Mitogen activated Protein Kinase)
What does CATCH 22 refer to?
Cardiac malformation
Abnormal facies
Thymic hypoplasia
Cleft palate
Hyperthyroidism
22q11 deletion
What is the most common microdeletion syndrome?
22q11 deletion syndrome
What conditions does 22q11 deletion syndrome encompass?
DiGeorge and velocardiofacial syndrome (Shprintzen)
What are the sings/symptoms associated with DiGeorge syndrome?
Thymic hypoplasia
Hypoparathyroidism
Outflow tract cardiac malformation
What are the signs/symptoms associated with Velocardiofacial syndrome?
lCleft palate/palatal insufficiency
lOutflow tract cardiac malformation
lCharacteristic face
lAutosomal dominant
What percentage of 22q11 deletion syndrome is familial?
about 25%
What is the common mental problema associated with 22q11 deletion syndrome?
What are LRC’s and how do they predispose 22q11 to deletion and translocation?
LCR’s are highly homologous sequence elements within the eukaryotic genome.
Misalignment of LCRs during non-allelic homologous recombination (NAHR) is an important mechanism underlying the chromosomal microdeletion disorders.
(Non-allelic homologous recombination (NAHR) is a form of homologous recombination that occurs between two lengths of DNA that have high sequence similarity, but are not alleles. It usually occurs between sequences of DNA that have been previously duplicated through evolution, and therefore have low copy repeats)
What are the heart problems associated with Williams syndrome?
Aortic stenosis (supraclavicular)
Hypercalcaemia
What causes Williams syndrome?
Deletion of elastin on chromosome 7
Deletion of contiguous genes (deletion or duplication that removes several genes lying in close proximity to one another on the chromosome)
List some teratogens
Alcohol
Antiepileptic drugs
Rubella (congenital rubella syndrome - causes heart defects among many other things)
Maternal Diabetes Mellitus
Who is the biggest factor on whether or not you will get a congenital heart disease?
Mother - if mother is affected the risk is much higher than sibling or father
What is VSD associated with?
Folate deficiency