Genetic Testing Flashcards
When does the nuchal scan take place and what happens?
10- 14 weeks gestation: booking bloods, hormone levels and scan where stenographer looks at nuchal fold (measure of baby’s neck) and take into account maternal age
Risk factor for Down’s syndrome calculated
What are the limits on risk?
Risk of 150 or higher is high, below 50 is low risk
What is the main method of pre-natal diagnosis of foetal abnormalities?
Ultrasound
All pregnant woman offered a scan at 12 weeks and anomaly scan at 20 weeks- in this scan you can see limbs and organs
What occurs in a normal pregnancy?
- Positive pregnancy test
- Book into antenatal care- see midwife
- Nuchal Scan
- Mid trimester anomaly scan
- Ultrasound at 11-14 and 20-22 weeks
What are the aims of the 12 weeks scan?
Date pregnancy accurately Diagnose multiple pregnancy Diagnose major foetal abnormalities Diagnose early miscarriage Assess risks of downs syndrome and other chromosomal abnormalities
What is nuchal translucency?
Measured at 10-14 weeks
It is the thickness of fluid at back of foetal neck
Increased more than 3mm can indicate:
-chromosomal abnormalities (NT and maternal age detects to 75% of downs syndrome)
-Birth defects (cardiac abnormalities, pulmonary, renal and abdominal wall defects)
-skeletal dysplasias
When is prenatal testing arranged?
Following abnormal findings at nuchal scan or mid trimester scan
Following result of combined test which gives increased risk of downs syndrome
If previous pregnancy affected with a condition
If parents are a carrier of chromosome rearrangement or genetic condition
Family history of genetic condition
What are aims of prenatal testing?
To inform and prepare parents for birth of affected baby
To allow in utero treatment
Manage the remainder of the pregnancy
To be prepaired for complications after birth
To allow termination of an affected foetus
What does a foetal MRI scan allow?
Allows you to look at organs more closely
What does a foetal cardiac scan allow you to do?
Allows you to see flow of blood through baby’s heart to diagnose cardiac conditions
How is testing done through cell free foetal DNA?
Non-invasive prenatal diagnosis (NIPD) works by analysing DNA fragments present in maternal plasma during pregnancy (cell free DNA)
Most DNA comes from mother
Cell free foetal DNA (cffDNA) is detectable form ~4-5 weeks gestation but cant be accurately detected until ~9 weeks
How is NIPD carried out?
At 9 weeks of gestation you take large sample of blood from mother
Testing is free for achondroplasia, thanatophoric dysplasia and aport syndrome
NIPD has been used for sexing
Sexing is offered when theres an X-linked condition in the family e.g. DMD
Test detects SRY gene on Y chromosome allowing us to enable if its a male or female foetus
If Male - go on to invasive prenatal test
If female- no invasive test required
When can NIPD be used?
Autosomal dominant single gene disorders inherited from father or arise de novo
NIPD can be used for recessive conditions where parents have different mutations- test detects paternal mutation
If the foetus has inherited paternal mutation, invasive prenatal testing can be offered
How is NIPD used for cystic fibrosis?
Haplotyping can test for both paternal and maternal mutations
How is cffDNA offered for aneuploidy?
Offered prenatal (Harmony) or via research studies- NIPT Harmony tests for T13, T18 and T21
What are limitations of NIPD and NIPT?
Multiple preganancies- not possible to tell which foetus the DNA is from is carrying multiple babies
Relative proportion of cell free foetal DNA is reduced in woman with high BMI as they have more of their own cell free DNA
Women may prepare themselves for implications of invasive test result and women must consider consequences of result
An invasive test may still be required to confirm results
What are benefits of NIPD and NIPT?
Number of invasive tests likely to be reduced
No risk of miscarriage
Less expertise is required to perform this than an invasive test
Testing occurs earlier than traditional invasive testing so result obtained quicker
What are invasive tests?
Offered if there is a known risk
There are 2 types of tests:
- chronic villus sampling- tissue from placenta
- amniocentesis- fluid from amniotic sac
You can carry out molecular, cytogenic and biochemical tests
Use US guidance
Offered on outpatient basis- come in for appointment
How does chronic villus sampling work?
Takes place at 11-14 weeks
1-2% chance of miscarriage
Transabdominal or transvaginal
Take sample of chronic villi using needle- part of developing placenta (same as DNA from foetus)
Allows patient to have earlier result than amniocentesis
How does amniocentesis work?
From 16 weeks
Take sample of amniotic fluid which contains foetal cells
What are risks of amniocentesis?
Up to 1% of miscarriage
Infection
Rh sensitisation
What tests are done with the DNA sample from invasive testing?
Test for genetic disorder in question- timing for result depends on condition
Karyotype if chromosomal abnormality is in family- result takes 2 weeks
QF-PCR for all:
- send sample to hospital lab
- look for T13, 18 and 21
- result is 24- 48 hours
What is a CGH array?
If theres concerns on a 20 week scan, gold standard is to offer CHG array
Looks for small/ large imbalances in chromosomes (picks up microdeletions and duplications)
If something is found in array we standardly test parents to see if either is a carrier
We now know there are many neurosuceptibility loci (changes in chromosomes which can cause developmental delay and other features)
What is trio exome testing?
A new test which allows us to look at exome of baby if there are significant abnormalities (e.g. heart, brain, skeletal developmental delay)
Exome is coding region of the genome. Requires taking DNA from baby (by amniocentesis) and parents
What reproductive options are there?
Conceive naturally and no prenatal testing Conceive naturally and prenatal testing Use egg/ sperm donors Adoption Choose not to have children Pre-implantation genetic diagnosis
What does egg and sperm donor involve?
No longer anonymous- children have right to contact donor when 18
Best to go through UK HFEA licence facility centre- conform to legal standards
Can privately find own donor
Some couples may consider going abroad
What are the 2 stages of adoption?
- Registration and checks
- register interest with agency
- Medical and criminal background check
- usually takes ~2 months - Assessment and approval
- have visits by social worker
- completion of prospective adopters reports, taken to adoption panel
- adoption panel reviews info and makes decision whether adoption allowed
- takes ~4 months
What is pre implantation genetic diagnosis?
Uses IVF with additional step to genetically test embryo before implantation
How does pre implantation genetic diagnosis work?
- Stimulation of ovaries
- egg collection
- Insemination
- Fertilisation
- Embryo biopsy
- Embryo testing
- Embryo transfer
- Pregnancy test
What is intracytoplasmic sperm injection (ICSI)?
Single sperm is injected into centre of each egg
Used for conditions caused by single faulty gene
How much does Pre implantation genetic diagnosis cost?
£12000 - £13000
Now nationally funded
What conditions can PGD be used for?
Used for many disorders:
- translocation carriers
- HD (huntingtons)
- DMD
- CF
What is the role of genetic councillor in prenatal testing?
Arrange and explain CVS, amniocentesis, PGD, cffDNA
Facilitate decision- making
Give results
See patients in clinic following diagnosis in utero
Arrange termination if necessary
Discuss recurrence risks and plans for future pregnancy
