5.7 - Genetic Testing Flashcards
1
Q
What happens in a normal pregnancy?
A
- positive pregnancy test - no longer confirmed at GP
- book into antenatal care - see midwife
- nuchal scan at 10-14 weeks gestation - different tests depending on NHS Trust e.g. nuchal translucency, combined test etc
- maternal age taken into account and risk of Down’s syndrome given - anything more than 1/150 considered high risk, anything below is low risk and no further testing done
- mid-trimester anomaly scan - 20-22 weeks gestation
- ultrasound examination is the main method for prenatal diagnosis of foetal abnormalities
2
Q
What are the aims of the nuchal scan (12 weeks)?
A
- to date the pregnancy accurately
- to diagnose multiple pregnancy
- to diagnose major foetal abnormalities
- to diagnose early miscarriage
- to assess the chance of Down’s syndrome and other chromosomal abnormalities
- takes into account maternal age, blood hormone levels, nuchal translucency thickness, nasal bone, blood flow through the foetal heart and foetal abnormalities
3
Q
What is nuchal translucency (NT)?
A
- done at 10-14 weeks
- it is the thickness of fluid at back of foetal neck
- screening test and not diagnostic
- can indicate a range of genetic syndromes
- combined with maternal blood markers and maternal age
4
Q
What can a NT increased >3mm indicate?
A
- chromosome abnormalities e.g. Down’s, Edwards, Patau, Turners –> NT and maternal age detects up to 75% of Downs syndrome with 5% false positive rate
- birth defects e.g. cardiac anomalies, pulmonary defects (diaphragmatic hernia), renal defects, abdominal wall defects
- skeletal dysplasias
5
Q
What is the aim of anomaly scan?
A
Look for structural abnormalities specifically in the heart, brain, spinal cord, face, kidney and abdomen to measure the lengths of the bones
6
Q
What other scans are available?
A
- foetal MRI if more detailed scan needed
- foetal cardiac scan offered to look at blood flow through baby heart to diagnose cardiac conditions
7
Q
When is prenatal testing offered?
A
- following abnormal findings at nuchal scan or mid-trimester scan
- following results of combined test which give an increased risk of chromosomal abnormality
- if previous pregnancy/child was affected with a condition e.g. Down’s syndrome, CF
- if parent(s) is a carrier of chromosome rearrangement or genetic condition e.g. t(13;14), DMD, Huntington’s
- if there is a family history of a genetic condition
8
Q
What are the aims of prenatal testing?
A
- to inform and prepare parents for the birth of an affected baby
- to manage the remainder of the pregnancy
- to be prepared for complications at or after birth
- to allow termination of an affected foetus - this can be after 24 weeks
- to allow in utero treatment
9
Q
How does non-invasive prenatal diagnosis (NIPD) work?
A
- non-invasive prenatal diagnosis (NIPD) works by analysing DNA fragments present in the maternal plasma during pregnancy (cell-free DNA)
- most of this DNA comes from the mother - 10-20% comes from the placenta, which is representative of the baby (cffDNA)
- cffDNA first detectable from around 4-5 weeks gestation but cannot be accurately detected on testing until around 9 weeks
- maternal blood test of 20ml of her blood (large amount)
- achondroplasia, thanatophoric dysplasia and apert syndrome can be detected from cffDNA in this blood
10
Q
How can NIPD detect dominant and recessive disorders?
A
- detects autosomal dominant single gene disorders inherited from the father e.g. NF1
- NIPD is also possible to alter management of pregnancies at risk of recessive conditions when the mother and father carry different mutations in the same gene
- if the paternal mutation has been inherited by the foetus, invasive prenatal testing can be offered to look for maternal mutation - if baby not inherited paternal mutation then we know baby won’t be affected so further tests unnecessary
- e.g. for CF - haplotyping (RHDO) can test for both maternal and paternal mutation
11
Q
How is NIPD used for foetal sexing?
A
- currently offered when there is an X-linked condition in the family e.g. DMD
- the test detects SRY gene on Y chromosome, enabling us to determine if male or female foetus
- if male, we go on to prenatal test (as they more commonly get DMD)
- if female, then no invasive test required
12
Q
What is cffDNA testing for aneuploidy (NIPT)?
A
- offered after high-risk combined screen / privately (Harmony) / via research studies
- currently tests for trisomy 13, 18 & 21 which identifies 92%, 97% & 99% of foetuses with those trisomies respectively
- done using non-invasive prenatal test (NIPT) which is not diagnostic - invasive test recommended if issue identified
13
Q
What are the limitations of NIPD and NIPT?
A
- multiple pregnancies - not possible to tell which foetus the DNA is from when carrying twins etc
- women with high BMI - relative proportion of cffDNA is reduced as they have more cell-free DNA = may need a second sample after 9 weeks
- women not prepared for implications - despite only blood test, same implications as invasive test e.g. can identify genetic problem in baby - do they want this info?
- an invasive test may still be required to confirm an abnormal result
14
Q
What are the benefits of NIPD and NIPT?
A
- the number of invasive tests carried out is likely to reduce as a result
- no increased risk of miscarriage (unlike invasive)
- less expertise is required to perform a blood test than an invasive test
- in many cases we can offer NIPD/NIPT earlier than traditional invasive testing, thereby getting a result much earlier
15
Q
What is invasive testing?
A
- offered if there is a ‘known risk’
- two types: chorionic villus sampling (CVS) where placenta tissue is taken, and amniocentesis where fluid from around developing baby is taken
- molecular, cytogenetic and biochemical tests done on these samples and ultrasound guidance used with both
- offered on an outpatient basis - come in for appointment, do test and go home same day
