genetics testing Flashcards
order of a normal p
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 fetal abnormalities. All pregnant women should be offered routine ultrasound scans at 11-14 weeks and again at 20-22 weeks.
why is nuchal scan importnat
determine risk of genetic condition
hormone tested
measure back of baby neck
risk figure for down syndrome( 1 in 150 is higher is high risk)
Aims of the 12 week scan
To date the pregnancy accurately. To diagnose multiple pregnancy. To diagnose major fetal abnormalities. To diagnose early miscarriage. To assess the risks of Down Syndrome and other chromosomal abnormalities.
what do you take into account
Taking into account the maternal age, blood hormone levels, nuchal translucency thickness, nasal bone, blood flow through the fetal heart and fetal abnormalities.
Increased Nuchal Translucency (NT) of > 3mm can indicate:
Chromosome abnormalities
Birth defects: -
Skeletal dysplasias
what is Nuchal Translucency (NT)
Thickness of fluid at back of fetal neck
how is an increase in Thickness of fluid at back of fetal neck
shown
larger gap between surface and neck
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 or genetic condition, e.g. t(13;14), DMD, HD.
FH of genetic condition
Aims of Prenatal Testing
To inform and prepare parents for the birth of an affected baby
To allow in utero treatment
Manage the remainder of the pregnancy
To be prepared for complications at or after birth
To allow termination of an affected fetus
for a more detailed scan what can be offered
feotal mri
see organs more clearly
how to diagnose heart conditions
featol cradiac scan
look at baby blood flow through heart
can genetic testing be done through
Cell-free fetal DNA (cffDNA)
where is it
floughting aroound mother blood
why in blood
from the placenta
when is it first detectable
from about 4 -5 weeks’ gestation
when is it accuratyly detected
9 weeks
what is cfdna
short dna fragments
NIPD
non invasive pre nateal diagnoses
done through dna
what can it test NIPD for
Achondroplasia - testing is free
Thanatophoric dysplasia - testing is free
Apert syndrome- testing is free
what other catergy
and what it tests for
xing
Currently offered when there is a X-linked condition in the family
Test detects SRY gene on Y chromosome, enabling us to determine if male or female fetus
if male
prenatal testing
female
no invasive test
cffDNA testing for Aneuploidy
NIPT
non duagnistic but a test
Limitations of NIPD and NIPT
Multiple pregnancies - It is not possible to tell which fetus the DNA is from when carrying twins/triplets etc.
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.
Benefits of 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 much earlier.
when is Invasive Tests
if a known risk
what are teh Invasive Tests
Chorionic villus sampling (CVS)
Amniocentesis
what is CVS
tissue from the placenta
what is Amniocentesis
fluid from around developing baby
when does CVS happen
11-14 weeks
what is the risk of misccarige
1-2 percent
how is it done
Transabdominal
or transv
what sample do you take
Takes sample of chorionic villi – part of developing placenta – same DNA as fetus
what is a good thing abourt cvs
Allows patient to have an earlier result than amnio - important for many patients re. TOP decision
when is Amniocentesis done
From 16 weeks
what sample is taken
Takes sample of amniotic fluid which contains fetal cells
what is the risk of miscarriage
up to 1 percent
other risks (2)
Infection
Rh sensitisation
What tests are done with the DNA sample?
Test for the genetic disorder in question
Karyotype if chromosomal abnormality in family
what happens to all the samples
QF-PCR for all:
what does QF-PCR look for
for chromosmes 13, 18 & 21
maybe s chromosome if s chromosme disorder is suspected
when is CGH array done
If there are concerns on 20 week scan the gold standard is to offer CGH array
what does it look for
Looks for small/large imbalances in chromosomes (picks up microdeletions and duplications)
are parents tested
If something found on array we standardly test parents to see if either is a carrier. This can help with interpretation
what is teh function of trio exome
looks at exome of baby if there are significant anomalies
what is an exome
is the coding region of the genome
is dna taken from both fetis and parents
yes
why parenst
to confirm whether they are carriers
when would it happen
~20 weeks
what are the options of if there is a known reeproduction risk
Conceive naturally, no prenatal testing Conceive naturally, have prenatal testing Use of egg and/or sperm donors Adoption Choose not to have children Pre-implantation genetic diagnosis (PGD)
what is the 2 stages of adoption
Registration and checks
Assessment and approval
what is Pre-implantation genetic diagnosis
Uses IVF with an additional step to genetically test the embryo before implantation
PGD is particularly used by people who do not want TOP
(termination of fetus)
The process of PGD (8)
Stimulation of the ovaries Egg collection Insemination Fertilisation 5. Embryo biopsy 6. Embryo testing 7. Embryo transfer 8. Pregnancy test
what is intracytoplasmic s injection ICSI
single s injected to the centre of each egg
what stage is teh single cell taken away
for genetic condition testing
blastocysts
You receive a referral for Becky, who is 17 and is 12 weeks pregnant. Her brother died two months ago from Duchenne Muscular Dystrophy.
- ) What information do you need?
- ) What are her options?
- ) What psychosocial issues might you anticipate?
1) if her brother had a confirmed genetic diagnosis
is it from the mother or from a new mutation
test becky for if she is a carrier for
2) tests preg, invasive test
do gender test, if boy then invasive
termination
3) guilt, if she wants a baby with same genetic condition as her borther
You receive a referral for Madeleine. She is 41 and has had 2 previous terminations for Down Syndrome. She is 6 weeks pregnant.
- ) What information do you need?
- ) What are her options?
- ) What psychosocial issues might you anticipate?
1) confirm diagnosis
check that doen syndorme is casused by a full extra 21 chromosome- if yes then it may be age related risk
2) Invasive test or NIPT
3) nervous,
You receive a referral for Mary. Mary’s husband carries a balanced translocation between chromosomes 1 and 12. This translocation has a 1% liveborn risk and an increased miscarriage risk. She has had 7 miscarriages and is now 11 weeks pregnant.
- ) What information do you need?
- ) What are her options?
- ) What psychosocial issues might you anticipate?
1) confrim partners translocatoin
2) tests
continue or invasive test
3) Maybe nerbous for invasive test
Barbara has a son who has global developmental delay, ASD, dysmorphic features. He is age 4 and has no speech. She is 5 weeks pregnant
1) What information do you need?
2) What are her options?
3) What psychosocial issues do you anticipate?
1) son comes in for genetic review, may have a CDH array
see if genetic diagnosis
2) test in preg for conditions
3) guilt
