Genetic Testing Flashcards
What happens in the normal pregnancy
Positive pregnancy test - no longer confirmed at GP
Book in antenatal care - where you give birth
Nuchal scan - e.g. nuchal translucency, combined test
Anomaly scan at 20 weeks
What happens during a nuchal scan
12 weeks of pregnancy
Genetic risk
Blood done
Scan - nuchal fold, measurement at the baby’s neck
What is the aim of the 12 week scan
Date pregnancy
Diagnose multiple pregnancy
Major fetal abnormalities
Early miscarraige
Asses the risk of down syndrome
Take into account maternal age, blood hormone, nuchal translucency thickness, nasal bone, blood flow and fetal abnormalities
What is nuchal Translucency
Thickness of fluid at back of fetal neck
Increased >3mm can indicate chromosome problem
Chromosome abnormalities (downs)
Birth defects: cardiac anomalies, pulmonary, renal
Skeletal dysplasias
Is NT screening test or diagnostic test
NT is a screening test
When is prenatal testing arranged
Abnormal findings at nuchal scan or mid trimester scan
Results of combined test which give increased risk of Down Syndrome
Previous pregnancy affected, DS, CF
Parent is carrier of chromosome, DMD, HD
Family history of genetic condition
Aims of Prenatal Testing
Inform and prepare parents
In utero treatment
Manage remainder of pregnancy
Prepared for complications of birth
Termination
What other fetal scans can you do
Fetal MRI - look at organs clearly
Fetal cardiac scan - flow of blood
What is cell-free fetal DNA
Floating around mother’s blood
DNA from baby placenta shed into mother’s bloodstream
Detectable from 4-5 but accurately detected at 9 weeks
Non invasive
What test for NIPD (non invasive prenatal diagnosis)
20ml
Achondroplasia, thanatophoric dysplasia, apert syndrome
Male and Female fetus SRY gene on Y chromosome
DMD may have to be organised if boy
What are NIPD offered privately via NHS
Autosomal dominant single gene disorders inherited from the father
Test will detect paternal mutation - if inherited go on to do invasive
CF - can test for maternal and paternal
cffDNA testing for Aneuploidy (NIPT)
Aneuploidy - extra chromsome 21, 18, 13
Offered privately
Non invasive test
Limitations of NIPD and NIPT
Multiple pregnancies
Cell free fetal DNA reduced in women with higher BMI - second sample may be needed
Do women want the information
An invasive test may still be required to confirm an abnormal result
Benefits of NIPD and NIPT
Number of invasive test
No increased risk of miscarriage
Less expertise
Offer NIPD earlier than traditional invasive testing
What are the invasive test
Chorionic villus sampling (CVS)
Amniocentesis
Molecular, cytogenetic and biochemical tests
Ultrasound guidance
What happens in Chorionic Villus Sampling
11-14 weeks
1-2% risk of miscarriage
Transabdominal or transvaginal
Sample of chorionic villi - part of developing placenta - same DNA as fetus
Allows patient to have earlier result that amnio - TOP decision
What happens in amniocentesis
From 16 weeks
Sample of amniotic fluid
1% risk of miscarriage
Infection
Rh sensitisation
What tests are done with the DNA sample
Test for genetic disorder in quesiton - CF
Karyotype if chromosomal abnormality in family - 2 week results
QF-PCR - t13, 18 and 21 which are reported in 24-48
What is the CGH array
Small/arge imbalances in chromosomes
Concerns on 20 week scan
If something is found, we test parents - interpretation
Neurosusceptibility
What is trio exome
Considered when fetus in previous pregnancy had significant anomalies
Exome region of DNA look - take DNA from baby and parents
May not prduce answer the parents are hoping for
Reproductive options
Conceive naturally with or without prenatal testing
Egg and sperm donors
Adoption
Pre-implantation genetic diagnosis
Facts about egg and sperm donation
No longer anonymous, children conceived have right to contact donor when 18
Go through UK HFEA licensed fertility centre - legal standards
Privately find donor
Go abroad
Adoption
Registration and checks - interest, medical and criminal background, 2 months
Assessment and approval - home visits by social worker, prospective adopters report given to panel, panel review information, 4 months
What happens during preimplantation genetic diagnosis
Uses IVF which geneticlaly test embryo before implantation
People who don’t want TOP
Process of PGD
Stimulation of ovaries - hyperstimulation
Egg collection
Insemination
Fertilisation
Embryo biopsy - blastocyte stage, one cell taken away
Embryo testing
Embryo transfer
Pregnancy test
What is the process of intracytoplasmic sperm injection
Single sperm injected into centre of each egg
no contamination of other sperms
Where is PGD avaliable
UCH
Guys hospital
13000,12000
What is PGD used for
Translocation carriers
HD
DMD
CF
What is the eligibility criteria for PGD
Female under 39
BMI of 19-30
Non smokers
Living together over a year
No living unaffected children
Know risk of having a child affected by genetic condition (10%)
Femal partner hormone levels will respond to treatment
Accurate genetic test is available
No welfare concerns for unborn child
Licence required from HFEA
Funded for three rounds of PGD
Role of genetic counselling
Arrange CVS, amniocentesis, PGD, cffDNA
Facilitate decision-making
Give results
See patients in clinic
Arrange termination
Discuess recurrence risks and plans for future pregnancies
How do you facilitate decision making
Previous experience, family situation, religion, personal beliefs, psychosocial situation, balancing miscarriage risk with genetic risk, dealing with indecision
