Genetic testing Flashcards
What tests/diagnosis are done between 11 and 14 weeks of pregnancy?
- dating the pregnancy
- Diagnosing multiple pregnancies
- Diagnosing major foetal abnormalities
- Diagnose early miscarriage
- assess risk of genetic conditions (downs) through nuchal translucency
What test is done between 20 and 22 weeks of pregnancy?
What does this examine?
Mid trimester anomaly scan
- gives a detailed look at bones, heart, brain, spinal chord, face and kidneys
- Looks for 11 rare conditions
What non-invasive tests can be carried out between 20-22 weeks?
Maternal blood test
Cell free foetal DNA (cffDNA)
What invasive tests can be carried out in pregnancy and when?
Chronic villus sampling 11-14 weeks
Amniocentesis 16+ weeks
What is a nuchal translucency test and what does it check for?
Nuchal translucency is a collection of fluid at the back of the foetal neck between 10-14 weeks
Increased >3mm can indicate chromosomal abnormalities (Downs, Edwards, Patau)
detects birth defects - cardiac anomalies, pulmonary defects, renal defects, abdominal wall defects
Skeletal dysplasia
screening not diagnostic
What is prenatal testing arranged following?
Abnormal findings at nuchal/mid-trimester scans
in women with high risk of Down’s syndrome or a previous history of genetic disease (including previous pregnancies)
following results of combined test which give an increased risk of down syndrome
If parents carrier of chromosome rearrangement or genetic condition
What are four aims of prenatal testing?
To inform/prepare parents for the birth of an affected baby/complications after birth
To allow possible in utero treatment
To aid in managing the remainder of the pregnancy
To allow termination of an affected fetus
What is tested for in maternal serum screening?
NIPT test - maternal blood test
Tests maternal serum markers in the blood to detect increases risk of fetal trisomy 21/18 and neural tube defects- markers will leap from placenta into the maternal blood
Achondroplasia, thanatophoric dysplasia, apert syndrome testing is free
What is cell-free foetal DNA?
Analyses placental DNA in maternal plasma - small amount of foetal DNA from placental leaks into maternal plasma
can be detected at 4-5 weeks but more accurate at 9 weeks
Not reliable if you have had previous pregnancies
What is chorionic villus sampling? What is the benefit and disadvantage of it?
Sample taken by a needle either transabdominally/vaginally of chorionic villi as it has the same DNA as foetus (part of placenta)
Allows for earlier results than amnio for abortion, but 1-2% risk of miscarriage and also risk of infection so only done where there is a known risk
What is amniocentesis?
Sample cells taken from amniotic fluid contain foetal cells as at 18-20 weeks the DNA is present in amniotic fluid
Risk of Rh sensitisation- mother can attack the foetus as if it was a blood clot so further treatment must be given
Infection
When is sexing done using placental dna?
When there is an X-linked condition in the family
Detects SRY on y chromosome to determine whether it is a male so that prenatal testing can be done
What is a CGH array?
Offered when there are concerns on the 20 week scan
Looks for chromosomal imbalances to pick up diseases (picks up micro deletions duplications)
May require testing of parents to interpret as some imbalances are normal
What is the trio exome?
Full genetic sequencing, offered where previous pregnancies have has significant anomalies
Exome is the coding region of the genomes - dna taken from parents and child
What are the limitations of NIPD and NIPT?
- multiple pregnancies mean you cant tell which foetus the DNA is from even if one of the pregnancies have been terminated
- the relative proportion of ccfDNA is reduced in women with a high BMI as they have more of their own
- invasive tests may still be needed to confirm diagnosis
What are the benefits to NIPD and NITP?
- Number of invasive tests carried out is likely to reduce as a result
- no increased risk of miscarriage
- less expertise is required to take a blood test
- usually offered earlier than invasive options
When there is a known reproductive risk what options are offered ?
Conceive naturally (with or without prenatal testing)
Adoption
Egg/sperm donors
Pre-implantation genetic diagnosis (IVF)
What are the rules and regulations on egg/sperm donation?
Not anonymous - children can contact donor at 18
Usually go through UK HFEA licensed fertility centres
What are the two stages of adoption?
Registration and checks (2months) -medical and criminal
Assessment and approval (4 months) - home visits, panel review and decision made
What is pre-implantation genetic diagnosis?
Uses IVF with an additional step to genetically test the embryo before implantation
Used by those who don’t want to TOP
number of cycles allowed is very varied
What are the steps of PGD?
- Stimulation of the ovaries
- Egg collection
- Insemination
- Fertilisation
- Embryo biopsy
- Embryo testing
- Embryo transfer
- Pregnancy test
What is the PGD referral criteria ?
Female partner is under age 39
Both partners are non-smokers
Known risk of having a child affected by a ‘serious’ genetic condition (at least 10%)
Female partner has hormone levels that suggest she will respond to treatment
An accurate genetic test is available
A licence is required from the HFEA for each genetic condition or indication
Eligible couples are usually funded for three rounds of PGD.
What is the role of a genetic councillor in prenatal testing?
Arrange and explain CVS, amniocentesis, PGD, cffDNA
Facilitate decision making
Give results
See patients in clinic following a diagnosis in utero
Arrange termination of necessary
Discuss recurrence risks and plans for future pregnancies
Explain the timeline of when testing is done throughout pregnancy.
Start with ccfDNA at around nine weeks
Do a nuchal scan 2 weeks later as well as some other tests ie serum markers
20 week scan down (mid semester scan)
If anything is picked up do some non-invasive tests (
And if more problems detected do invasive tests
If you do not want invasive tests you can carry out further usually private testing (CGH array/trio exome)
