Clinical Genetics 5&6 Genetic Testing, Genetics and Families Flashcards
What is the definition of genetic counselling?
What are the three main steps
To help individuals understand the nature of the genetic disorder, its transmission and the options open to them in management and family planning
- Making an accurate diagnosis
- Describing the consequences of the disorder, the probability of developing and transmitting it
- Discussing the ways in which this may be prevented and managed
Describe three things which you should be aware of when involved in genetic counselling
- Presenting all options fairly, accurately and non-coercively
- Confidentiality issues when relatives found to be at risk for a serious disease
- Appreciate the implication that genetic info can have for a person’s self-image, family relationships, social status etc
Family suggestions of how genetic counselling should be given….
- in private
- in person
- with both partners or with a supporter
- sensitivity, respect, compassion, understanding, honesty, time
- without jargon using positive sensitive language
- contact details of support groups (go on internet and get freaked out)
- follow-up meeting to answer new questions
- emotional/ psychological counselling
- Send letter to family about what was discussed ESPECIALLY risks and actual figures
What is genetic screening?
What diseases are newborns screened for in the UK
Testing a group of people to identify individuals at high risk of having or passing on a specific genetic disorder
e. g. newborn screening for GF in all babies.
e. g. carrier testing for Tay Sachs disease in Ashkenazi Jewish pop.
- PKU
- CF
- Galactosaemia
- MCADD
- Haemoglobinopathies
What is a diagnostic test?
Used to identify or rule out a specific genetic or chromosomal condition. In many cases it is used to confirm a diagnosis when a particular condition is suspected based on physical signs and symptoms
e.g. Down Syndrome - check chromosomes.
What is carrier testing?
Who is offered carrier testing?
To determine if someone carries a single copy of an altered recessive gene OR for X linked disorders if a female carries a single copy
Useful for determining risk to offspring and making reproductive decisions.
- Generally not children - will not influence their care and removes their choice of whether to undergo carrier testing or not and also whether to share info with family or not
What is a presymptomatic/ predictive test?
What is required alongside these tests?
Who is offered them?
What do you need to consider (3 questions)
Used to make a diagnosis of a late-onset disorder in someone who is at risk of developing the disorder but does not yet show the clinical features
e.g. Huntington’s Disease
Genetic counselling - need to understand how the results will impact your life esp in HD where there is no cure.
- Not children
- If it will not affect them until later adult life then wait until old enough to gain informed consent
- Will positive result accurately predict future disease and alter management?
- Will negative molecular result be definitive or do you need further tests? (Are the results accurate enough to make it worth finding out?)
- Can the result help individuals make life choices and prepare for the onset of disease?
What is the clinical indication for chromosome analysis?
Diagnosis of unknown chromosome anomaly in an individual with a pattern of mental retardation, congenital anomalies, dysmorphic features and/or aberrant growth..
Suspect e.g. Down Syndrome, Klinefelter Syndrome, miscarriage, infertility, FHx translocations, leukaemia
Children:
- Everyone with learning disability or developmental delay
- Suspected chromosomal diagnosis
- multiple cogenital anomalies
- Dysmorphic features
- Short stature
- Delayed puberty
Adults:
- Everyone with a learning disability
- Infertility (both partners)
- Parents of a stillborn baby with abnormal features if a chromosome result not available from the baby
- FHx balanced translocation
Where should you not do chromosome analysis?
- Clinically normal parents of child with a trisomy e.g. Down’s Syndrome (if the child’s chromosomes show a translocation then the parents would be contacted for a sample)
- The parents of a clinically normal stillborn baby
- Someone with a known single gene disorder eg. CF, NF unless other clinical features.
List 5 features of microarray:
- Compares individual’s DNA with control DNA sample and identifies differences between the two
- Duplications and deletions can be identified
- First line test for developmental delay, dysmorphic children etc
- Pickup rate 10-15%
- Sample needs to be in EDTA
Reason to do a genetic molecular test?
When to do a molecular test?
- Diagnosis
- Treatment
- Prognosis and management
- Presymptomatic diagnostic screening
- Genetic risk assessment
- For a firm diagnosis of a disorder in which the genetic analysis is available (CF confirmed by sweat test)
- Condition caused by readily analysed mutations in a gene (HD)
- Previously identified mutagen in relative
- High probability of a mutation being present in the individual in a known gene. H
How can you explain variation in the availability and costs of tests and the reporting time?
- Looking at single gene disorders - for some diseases the mutation is always/ usually in the same place so we can quickly test the hotspots whereas in other conditions in can be anywhere within the gene and have to do sequencing which is expensive and time consuming e.g. BRCA1.
- Some genes are small
- Other genes are enormous and it takes a long time to go through and find a mutation.
Neurofibromatosis:
What are the differences between NF I and NF 2?
- NF1 diagnosis made clinically and no gene testing because it does not affect treatment, genotype does not necessarily predict the outcome. Clinical signs evident in early life so no role for predictive testing. In some are circumstances you can do genetic risk assessment e.g. prenatal diagnosis.
- NF2 genetic testing may be necessary to make the diagnosis in individuals who show some suggestive features e.g. acoustic neuroma. Genetic testing may influence treatment and management - in UK protocol for follow-up of individuals affected with NFII because of childhood tumours.
Hurler Syndrome:
How does specific molecular diagnosis affect treatment?
Epidemiology of Hurler Syndrome:
MPS1 protein.
If mutation shows Hurler Type - treatment of choice is bone marrow transplant and needs to be done ASAP.
If mutation shows Hurler Scheie use enzyme replacement therapy (BMT doesn’t work).
Common in the travelling community.
- How do you decide who gets tested for cancer?
- What are the negatives of cancer testing?
- Name an advantage?
- Nationally agreed protocols e.g. Manchester Scoring system
- Large genes with lots of private mutations therefore testing time consuming and costly
- If a mutation is found other family members can be offered predictive testing.
