Lecture 18: Testing for Genetic disorders Flashcards
Whats the difference between Prenatal diagnostic and screening tests - invasiveness/ risk, results
Diagnostic tests - test for specific chromosomal or genetic abnormality which baby
-invasive test- some risk
Screening tests - determine if the baby has increased risk of having a particular problem but does not mean the baby will get it.
- non invasive-low risk no harm baby
- not 100% specific or sensitive
What are the clinical indications for prenatal diagnostic testing for single gene disorders
- family history of serious genetic disorder
- both parents are carriers
- one have an autosomal dominant disorder
- female carrier of sex linked disorder
Why would we do prenatal screening and diagnosis
This guides family in decisions about the pregnancy - involving termination, or medical and psychological support if positive or reassurance if negative
What are the clinical indications for prenatal diagnostic testing for constitutional chromosomal disorder
- mother 30+
- having a previous child affected by a serious developmental problem
- exposure to chemical or other toxic agent
- abnormal screening test result
When and what are the 5 screening tests done prenatally for chromosomal disorders which may lead to diagnostic tests later
8-10 weeks: dates & number of babies ultrasound
9-13 weeks: trimester 1 maternal serum test for B-HCG and PAPP-A with ultrasound scan
10-13 weeks: first trimester screening using nuchal translucency ultrasound
14-18 weeks: maternal blood test alone looking at also AFP, uE3, b-hCG and inhibin A
18 weeks: detailed fetal abnormality ultrasound
What is the nuchal translucency ultrasound screening for and what other screening is it used with
NT ultrasound screens for constitutional chromosomal abnormality by measuring the space at the back of a baby’s neck.
It is used with Maternal serum testing to increase sensitivity and specificity for down syndrome
What does Maternal serum testing screen for - more likely offered for greater maternal age (not specific proteins not vital)
Looks at 3 markers - AFP, uE3 and hCG- to determine risk of chromosomal abnormalities: chromosome 13, 18 and 21 +spina bifida.
What leads to diagnostic tests for single gene disorders
From analysis of the pedigree there is risk prediction which may proceed to specific diagnostic test if requested by the family after counselling
What are the 2 types of prenatal diagnostic tests and what are the risks associated with them
The chorionic villus sampling and Amniocentesis. Risks is <1% miscarriage
When, and what is done for Chorionic villus sampling
Done at 10-12 weeks. Cells from the placenta can be taken using needle and chromosomes or DNA can be tested pretty straight away
When, and what is done for Amniocentesis
Done at 15-16 weeks. It collects amniotic fluid from a needle and grows fetal cells for 1-2 weeks before analysis.
Can give slight risk of miscarriage
How is fetal tissue analysed depending on what they are looking for
- Fluoresence in situ hybridisation (FISH) analysis using a fluorescent marker for a abnormal chromosomal number
- DNA analysis usually PCR based gene sequencing , direct mutation analysis if gene and mutation is known
- or indirect analysis using a linked or polymorphic marker
- Cytogenetic analysis
What is fetoscopy and umbilical cord blood sampling and when is it done, and risk
Done in 3rd trimester, its a direct sample of fetal cells.
Cannulation of the umbilical veins to extract a sample.
Can be used to inform of metabolic disorders or anaemia + usual chromosome and hereditary conditions but
Higher risk of miscarriage (2-10%)
What is a new Non invasive prenatal testing for down syndrome and what is
Baby’s cell free DNA is shared into the maternal blood stream so through parallel sequencing of total DNA present in the maternal plasma and alignments of this, aneuploidies can be detected and confirmed using diagnostic test.
What are the main negative issues to consider with prenatal testing
- Not comprehensive testing - things not tested for, lab errors
- Small risk to fetus
- Not moral or ethically acceptable to all
- Not all parents want to know
