Prenatal Testing Flashcards
What is the most common autosomal chromosome defect at birth?
Trisomy 21
Before genetic carrier screening, what is important to ask?
Family history
With recessive conditions, often no family history
When is carrier screening best performed?
Pre-conception
When is carrier screening often performed?
During pregnancy
What is the relationship between maternal age and risk of Down syndrome?
Risk of having affected baby increases with maternal age
However, young maternal age also carries risk
How can the majority of neural tube defects be prevented?
Taking folate supplements before and during pregnancy
To whom are screening tests offered?
All pregnant women
To whom are diagnostic tests offered?
Women who are at increased risk of having child with birth defect
What does prenatal screening identify?
Subset of women, from general population, at increased risk of having child with birth defect
Are prenatal screening tests definitive?
No, need to be followed up be followed up by specific diagnostic procedure
What is first trimester combined screening?
Non-invasive prenatal testing/screening (NIPT/S)
Test for
- Trisomy 21
- Trisomy 18
What is second trimester screening?
Test for
- Trisomy 21
- Trisomy 18
- Neural tube defects
What happens in first trimester combined screening?
Blood taken at 9-13 weeks - 2 biochemical analytes measured Ultrasound performed at 11-13 weeks - Nuchal translucency measured - Crown rump length Other factors; eg: maternal age Algorithm calculates risk figure
What is nuchal translucency?
Increased width of nuchal translucency associated with chromosomal abnormalities
- Especially trisomy 21
All babies have certain amount
Many resolve over time
What are the risk cut-offs in first trimester combined screening?
Trisomy 21: 1 in 300
Trisomy 18: 1 in 175
What happens in second trimester maternal serum screening?
Blood taken at 14-20 weeks
- 4 biochemical analytes measured
Other factors; eg: maternal age
What are the risk cut-offs in second trimester maternal serum screening?
Trisomy 21: 1 in 250
Trisomy 18: 1 in 200
How is NIPT/S done?
Uses cell-free foetal DNA in maternal blood
Massively parallel sequencing
Compare individual sequenced chromosome against reference for analysis
Detection of aneuploidy; eg: trisomy 21
What are the two foetal sampling procedures used?
Chorionic villus sampling (CVS)
Amniocentesis
Describe CVS
From 11 weeks gestation usually
Placental tissue
Ultrasound
Invasive
Risk of miscarriage 1% above background risk
If termination of pregnancy requested, dilatation and curettage under general anaesthetic (<16 weeks)
Describe amniocentesis
15-16 weeks gestation usually
20mL of amniotic fluid containing sloughed off foetal cells removed
Ultrasound
Invasive
Risk of miscarriage 0.5% above background risk
If termination of pregnancy requested, by prostaglandin induction of labour (>16 weeks)
what is fluorescence in situ hybridisation (FISH)?
DNA probe specific for something; eg: chromosome 21 Put probe on Measure fluorescence Count number of chromosomes Increasingly used Turn around time of 24-48 hours
What is FISH used to test for?
Trisomy - 13 - 18 - 21 XX and XY testing
What is the gold standard for detecting chromosomal abnormalities?
Karyotyping
What is karyotyping?
Looking in more detail at chromosomes
Take dividing cells > burst cells > stain > line up chromosome pairs > count them
What is a balanced translocation?
Reciprocal translocation between 2 chromosomes
No net gain/loss of function
May not result in abnormal phenotype
What is a Robertsonian translocation?
Translocation between 2 acrocentric chromosomes
- 13
- 14
- 15
- 21
- 22
How can an unbalanced translocation lead to trisomy 21 and therefore Down syndrome?
Balanced translocation between chromosomes 14 and 21 > carrier status
Unbalanced translocation between chromosomes 14 and 21 > trisomy 21
- Extra 21 on a copy of chromosome 14
How can Down syndrome be inherited?
Chromosomes in 1 possible gamete who is carrier of balanced translocation translocation + chromosomes in gamete from non-carrier parent
Embryo is trisomic for chromosome 21: Down syndrome
What are microarrays or DNA chips, and what can they be used for?
Can look at single nucleotide polymorphisms (SNPs)
Can look at larger changes - number of chromosomes and copy number variations (CNVs)
How do chromosomal microarrays (CMAs) work?
Patient sample labelled with red fluorescent dye + normal control sample labelled with green fluorescent dye Mix together and apply to slide Hybridisation Microarray scanner Can measure deletion and duplications
When should prenatal molecular karyotyping be performed?
Foetal abnormality identified on ultrasound scan
Nuchal translucency measurement >3.5 mm
Banded (classical cytogenetic) karyotype identifies complex change
Family member has microdeletion syndrome and pregnancy at risk
What is pre-implantation genetic diagnosis (PGD)?
Requires IVF
1-2 cells from dividing zygote at 8 cell stage
Can do DNA testing if parents known carriers, FISH, and chromosomal microarrays
Unaffected embryos implanted
