Genetic testing Flashcards
In a normal pregnancy what are the regular scans and when do they take place?
Nuchal scan – 10-14 weeks’ gestation
Mid-trimester anomaly scan - 20-22 weeks’ gestation
What are the aims of the nuchal scan in a pregnancy?
To date the pregnancy accurately
To diagnose multiple pregnancy
To diagnose major fetal abnormalities
To diagnose early miscarriage
To assess the chance of Down syndrome and other chromosomal abnormalities
How do you interpret nuchal translucency?
Thickness of fluid at back of fetal neck
Increased > 3mm can indicate:
Chromosome abnormalities e.g. Down syndrome, Edwards, Patau, Turners
Combined with maternal blood markers and maternal age
When is prenatal testing offered?
Following abnormal findings at nuchal scan or mid-trimester scan
Following results of combined test which give an increased risk of a chromosome abnormality
If previous pregnancy or child affected with a condition e.g. Down syndrome, cystic fibrosis
If parent(s) carrier of chromosome rearrangement or genetic condition, e.g. t(13;14), DMD, HD.
If there is a family history of genetic condition
What is the aim of the anomaly scan in normal pregnancy?
Look for structural anomalies specifically in the heart, brain, spinal cord, face, kidney and abdomen and to measure the lengths of the bones
What are the aims of pre-natal testing
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 fetus
What is NIPD(Non-invasive prenatal diagnosis)
Non-invasive prenatal diagnosis 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 baby (cell-free fetal DNA).
Accurately detected on testing at around 9 weeks
What gene is used for NIPD sexing?
SRY on y gene
What are the next steps if a baby is at suspicion of having an X-linked gene after sexing
If male > go on to prenatal test
If female > no invasive test required unless manifesting females in family
When is NIPT for aneuploidy offered?
After high risk combined screen
What does NIPT for aneuploidy currently test for?
T13, T18, T21
-NOT DIAGNOSTIC
In what cases are NIPD and NIPT limited?
Multiple pregnancies
Women with a high BMI
Women not always appropriately counselled about implications
An invasive test may still be required to confirm an abnormal result
What are the benefits for NIPD and NIPT
The number of invasive tests carried out is likely to reduce as a result
There is no increased risk of miscarriage
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 earlier
When are invasive tests offered and what are they?
Offered if there is a ‘known risk’
Two types
Chorionic villus sampling (CVS)
Amniocentesis
Molecular, cytogenetic and biochemical testing can be done on these samples
How is chorionic villus sampling performed and what are the risks?
12-14 weeks
Transabdominal or transvaginal
Takes sample of chorionic villi – part of developing placenta – same DNA as fetus
-
Risks
0.5% risk of miscarriage
Infection
Rhesus sensitisation
How is amniocentesis performed and what are the risks
From 15 weeks
Takes sample of amniotic fluid which contains fetal cells
-
Risks
0.5% risk of miscarriage
Infection
Rhesus sensitisation
What tests are performed for a pre-natal genetic sample?
Test for the monogenic disorder in question
Timing for results dependent upon condition
Karyotype if chromosomal abnormality in family
Results 2 weeks (dependent upon the cells growing)
QF-PCR for all:
Looks for T13, 18 & 21 (plus sex chromosomes if sex chromosome disorder suspected)
Result within 3 days
What is a CGH array used for and how does it function?
If there are concerns on 20-week scan the gold standard is to offer CGH array
Looks for small/large imbalances in chromosomes (picks up microdeletions and microduplications)
If something is found on array we standardly test parents to see if either is a carrier. This can help with interpretation.
How does a pre-implantation genetic diagnosis work?
Uses IVF with an additional step to genetically test the embryo before implantation
PGD is particularly used by people who do not want TOP
What test is most favourable when looking for specific regions of damage on the body
Prenatal exome R21
Consider where fetus has significant anomalies e.g. heart, brain, skeletal, dysmorphic features
Often this test is happening at 20+ weeks of pregnancy
Exome is the coding region of the genome. Take DNA from fetus and parents.
At what developmental stage is an embryo biopsy conducted?
At the blastocyst stage
What available options are there for a known reproductive risk?
Conceive naturally, no prenatal testing
Conceive naturally, have prenatal testing
Pre-implantation genetic diagnosis (PGD)
Use of egg and/or sperm donors
Adoption
Choose not to have children
Give some reasons why patients might have PGD(Pre implantation genetic diagnosis) and what legal limitations are placed upon it?
Translocation
HD
DMD
CF
-
Funded for 3 cycles only
An HEFA license is required for each genetic condition
What is the eligibility criteria for PGD?
Female is under 39
BMI between 19-30
Both partners are non-smokers
No living unaffected children from the relationship
Known risk of having a serious genetic defect
What is the role of genetic counselling in pre-natal testing
Arrange/explain CVS/amniocentesis
Facilitate decisions
Give results
Arrange termination
See patients following a diagnosis
Discuss/plan future pregnancies
