Clinical Genetics and Pregnancy 2 Flashcards
(20 cards)
Purpose of aCGH?
Used for chromosome deletions / duplications
NOTE - cannot be used for balanced rearrangements; instead, chromosome analysis should be used
Purpose of Next Generation Sequencing?
Sequence many genes before pulling out the gene of interest
Difference between polymorphisms and mutations?
An individual will have millions of polymorphisms, the majority of which have no effect on the gene
The change must affect protein production in order to cause disease
Mutations are a cause of disease
Disadvantage of next generation sequencing?
Finds lots of polymorphisms
Major principle of any DNA analysis test?
Require clinical information and must have a diagnosis in mind, i.e: must know which genes to look at
Main antenatal USS appointments?
Booking scan (usually at 10-12 weeks)
Detailed scan at 20 weeks, in order to look for specific anomalies:
• Cardiac (12-20 weeks)
• Microcephaly (usually seen after 22 weeks)
• Short limbs (usually seen after 22 weeks)
• Brain malformations
NOTE - a minor scan abnormality may still be an indicator of severe disease
Providing information on the prognosis to parents?
Contact patient support group
Explain clinical findings on USS
Communicate the uncertainty that may be present
Communicate results of genetic testing
Looking at this family tree, what is the risk that the new child is affected? (EXAMS)
ADD IMAGE
As the gender of the child is unknown, 1/4 risk
If the child is found to be male, the risk increases to 1/2; if found to be female, the risk is eliminated
ADD IMAGE
Explain inheritance of autosomal dominant diseases
A disease seen in all generations of the family, as there is a 50% risk of an affected child, if a parent is affected; males and females are equally likely to be affected
The severity of the disease can be variable, i.e: in some cases, an individual with the mutation may not show signs of the disease
Explain inheritance of automsomal recessive diseases
Often, only 1 generation is affected, as the risk of an affected child, if the parents are carriers, is 1/4
The likelihood increases in consanguineous families
Testing for Down’s syndrome?
On USS, the nuchal thickness is measured; if this is increased, non-invasive prenatal testing (NIPT) can be used
Explain DNA testing in pregnancy
Usually PCR-based, with results being available in 2-3 days
Chorionic villus biopsy can be used at 11.5+ weeks
Amniocentesis at 16+ weeks
In the case of the above family tree, what is the best genetic Mx?
Non-invasive foetal sexing should be used initially, to determine gender:
• If female - reassure
• If male - chorionic villus biopsy
Advantages of foetal pathology (post-mortem)?
Often the only way of establishing a diagnosis
It obtains important info for the parents
Confirms the prenatal findings
Secondary options are not as good and inc. limited post-mortem, external examination and a foetal post-mortem MRI
What is pre-implantation genetic diagnosis (PGD)?
Performing a genetic test on an embryo (created via ICSI), before re-implanting one with the correct genotype
i.e: embryos are created using ICSI and only the genetically healthy embryo is inserted
Centres must be licensed, by the HFEA, to practice PGD and each new conditions must be licensed by the HFEA
Disadvantages of PGD?
Expensive and invasive
Overall, there is a 30% take home baby rate per cycle, making it emotionally difficult; this is due to limitations on the embryos that can be used: • Poor quality embryos • Biopsy fails or not DNA result • Affected embryos • Failure to grow
DNA analysis is less reliable than prenatal testing, as there is only analysis of a single cell
Risk of multiple pregnancy, as for any IVF procedure
Advantages of PGD?
Pregnancy is less likely to be affected from the outset
Lower likelihood of requiring TOP
Situations where PGD might be considered?
Parental chromosome abnormality, e.g: Robertsonian translocation or reciprocal translocation
X-linked disorders, i.e: can re-implant female embryos
Other single gene disorders, e.g: spinal muscular atrophy, CF, Huntington’s disease
When is the input of a clinical geneticist required during pregnancy?
If there is a FH of disease that may affect the pregnancy, either the foetus or mother
When there is an unexpected finding in pregnancy, either on USS or on genetic testing
When a previous pregnancy / child has malformations
When is genetic input most helpful for a woman / couple?
If possible, at the pregnancy planning stage, as pre-conceptual counselling can be given
