Genetics Testing Flashcards
Prenatal Tests
- Scanning - Ultrasound, MRI
- Non-invasive
- Invasive - Chorionic villus sampling (CVS), Amnioncentesis
- Scanning - Ultrasound , MRI
· Ultrasound is the main method of diagnosing foetal abnormalities -
All pregnant women should be offered routine ultrasound scans at 11-14 weeks and again at 20-22 weeks.
Nuchal scan – 10-14 weeks gestation. Different tests dependent upon NHS Trust e.g. nuchal translucency, combined test etc.
Mid-trimester anomaly scan
Foetal MRI
Foetal cardia scan
- Non-invasive
- Maternal blood test
2. cffDNA - cell free foetal DNA
- Invasive
Offered if there is a ‘known risk’
- Chorionic villus sampling (CVS)
- Amniocentesis
- Molecular, cytogenetic and biochemical tests
- Ultrasound guidance
- Outpatient basis
Progression of a normal pregnancy
Positive pregnancy test – no longer confirmed at GP
Book into antenatal care – see midwife
Nuchal scan – 10-14 weeks gestation. Different tests dependent upon NHS Trust e.g. nuchal translucency, combined test etc.
Mid-trimester anomaly scan
Ultrasound examination is the main method for prenatal diagnosis of foetal abnormalities. All pregnant women should be offered routine ultrasound scans at 11-14 weeks and again at 20-22 weeks.
What are the aims of the 12 weeks scan?
- To date the pregnancy accurately.
- To diagnose multiple pregnancy.
- To diagnose major foetal abnormalities.
- To diagnose early miscarriage.
- To assess the risks of Down Syndrome and other chromosomal abnormalities.
Taking into account the maternal age, blood hormone levels, nuchal translucency thickness*, nasal bone, blood flow through the fetal heart and fetal abnormalities.
Nuchal Translucency test
10-14 weeks
Thickness of fluid at back of fetal neck
Increased > 3mm can indicate:
- Chromosome abnormalities (e.g. Downs, Edwards, Patau, Turners) :
NT + maternal age detects up to 75% of Down syndrome with 5% false positive rate - Birth defects:
1. Cardiac anomalies
2. Pulmonary defects (diaphragmatic hernia) 3. Renal defects
4. Abdominal wall defects - Skeletal dysplasias
There are many genetic syndromes seen with increased NT
When is prenatal testing arranged?
- Following abnormal findings at nuchal scan or mid-trimester scan
- Following results of combined test which give an increased risk of Down Syndrome
- If previous pregnancy affected with a condition e.g. DS, CF
- If parent(s) carrier of chromosome rearrangement/abnormality or genetic condition, e.g. t(13;14), DMD, HD.
- Family history of genetic condition
Aims of prenatal testing
- To inform and prepare parents for the birth of an affected baby/To be prepared for complications at or after birth
- To allow in utero treatment
- Manage the remainder of the pregnancy
- To allow termination of an affected foetus
Maternal Serum screening
Tests maternal serum markers in the blood to detect increased risk of fetal trisomy 21, trisomy 18 and/or neural tube defects
- 1st trimester maternal serum screening (with nuchal translucency measurement): 11-14 weeks [hCG, PAPP A]
- 2nd trimester maternal serum screening (triple screen): 16-20 weeks [AFP, uE3, hCG]
- Nuchal translucency measurement: 11-14 weeks
- Other variations combining 1st and 2nd trimester screening results available privately
Cell-free foetal DNA (cffDNA)
Non-invasive prenatal diagnosis (NIPD) works by analysing the DNA fragments present in the maternal plasma during pregnancy (cell-free DNA).
Most of this DNA comes from the mother
10%-20% of it comes from the placenta, which is representative of the unborn baby (cell-free fetal DNA).
Cell-free fetal DNA (cffDNA) is first detectable from about 4 -5 weeks’ gestation, but cannot accurately be detected on testing until around 9 weeks
Non Invasive Prenatal Diagnosis (NIPD) in the NHS
Maternal blood test at around 9 weeks of pregnancy :
- Achondroplasia - testing is free
- Thanatophoric dysplasia - testing is free
- Apert syndrome - testing is free
SEXING:
Currently offered when there is a X-linked condition in the family e.g. DMD
- Test detects SRY gene on Y chromosome, enabling us to determine if male or female fetus
If male then go on to prenatal test
If female, no invasive test required
NIPD offered privately in NHS
Autosomal dominant single gene disorders inherited from the father or arise de novo
NF1
NIPD is also possible to alter management of pregnancies at risk of recessive conditions when the mother and father carry different altered genes.
- If the paternal alteration has been inherited by the foetus, invasive prenatal testing can be offered to find the maternal gene
- Cystic fibrosis – haplotyping (RHDO) can test for both maternal and paternal mutation
cffDNA testing for aneuploidy (NIPT)
Offered privately (Harmony) or via research studies
Harmony currently test for T13, T18, T21 and this identifies:
99% of fetuses with trisomy 21
97% of fetuses with trisomy 18
92% of fetuses with trisomy 13.
Is this accurate enough to make a decision?
Limitations of NIPD and NIPT
- Multiple pregnancies - It is not possible to tell which fetus the DNA is from when carrying twins/triplets etc. - so only used with singleton pregnancies
- The relative proportion of cell-free fetal DNA is reduced in women with a high BMI as they have more of their own cell-free DNA.
- Although it is just a blood test, it has the same implications as an invasive test.
- Women may prepare themselves more for the implications of an invasive test result
- Women must consider the consequences of the results. Do they want this information?
An invasive test may still be required to confirm an abnormal result.
