Screening for genetic conditions Flashcards
What is the goal of screening?
use screening tool designed to detect a disease or health condition in individuals who do not have any symptoms
What is the goal of a diagnostic test?
- tests or procedures to identify a disease or health condition in individuals who are showing symptoms or who score high on the screening test
- confirming an actual disease/condition
False positive on screening test
- a false alarm
- The false positive rate is the number of women who screen positive (increased risk) when they are actually carrying healthy, unaffected babies.
- if you have 100 people who are healthy, and 30 of these people incorrectly screen as having the disease when in fact they are disease-free, then the test would have a 30% false positive rate.
e.g. screen positive for covid but don’t actually have it
- can have adverse consequences:
lose time, money, person may become anxious if told they are sick
False positive results
– lead to further diagnostic testing
– Increased anxiety about possible outcomes
– Pregnancy termination (if told that child is at risk of down syndrome)
Negative results
There is still a chance that the baby may be born with a developmental disability
Detection rate of a screening test
– The detection rate of a test is also called the test’s sensitivity. It is the chance of screening positive (increased risk) when the baby is truly affected with a condition.
* the ability of the screening tool to accurately pick-up the pregnancies that are affected with the condition. if you have 100 people who are affected with a disease, and a screening test correctly identifies 95 of them as having the disease, then the test would have a 95% detection rate.
- want test to be highly sensitive to ensure that all/most cases are detected
The positive predictive value (PPV) of a screening test
- measure of the reliability of a screen positive result
- It is the chance that a positive screen is correct
– of all the women who screen positive, it is the number of women who actually have an affected pregnancy. For example, a screening test with a PPV of ½ (50%) is better than a screening test with a PPV of ¼ (25%) - With a PPV of ½ (50%), half of individuals screening at increased risk on a screening test will truly be affected with the condition. Whereas with a PPV of ¼ (25%), only one quarter of individuals screening at increased risk will truly be affected with the condition.
– A higher PPV means that fewer individuals will be caused unnecessary worry from falsely labeled at risk for the condition - as a parent want to be fully informed that test will accurately detect if their child has an illness/disease
Ideal psychometric properties of a screening test
– HIGH SENSITIVITY-pick up all cases
– HIGH SPECIFICITY-does not pick up false cases
– LOW FALSE POSITIVE RATE
– HIGH POSITIVE PREDICTIVE VALUE
Blood Test “Triple Marker Screen”
down syndrome
- an optional screening test available to all pregnant women in British Columbia when they are between 15 and 20 weeks of pregnancy. Multiple marker screening detects about 80% of pregnancies in which an open neural tube defect is present and about 60% of pregnancies in which Down syndrome is present
- blood test that screens for different elements in blood
- look at thickness of spinal column
Nuchal translucency test
down syndrome
During this test, an ultrasound is used to measure a specific area on the back of the baby’s neck. When abnormalities are present, more fluid than usual tends to collect in this neck tissue.
Non-Invasive Prenatal Testing (NIPT)
- Introduced in 2011
- $500+ — not covered in all provinces yet, or only covered for women deemed “high risk”
Main benefits of NIPT over traditional screening:
- Can be done as early as 10 weeks
- Quick results, non-invasive blood test (only take blood from mother; doesn’t involve fetus)
- Detection rate of 99.2% & false-positive rate of only 0.09%
Chorionic villus sampling (CVS)
- cells are taken from the placenta and used to analyze the fetal chromosomes.
- This test is typically performed in the first trimester, between 10 and 13 weeks of pregnancy.
- The risk of pregnancy loss (miscarriage) from a CVS is very low.
- 100% accurate
Amniocentesis
- A sample of the amniotic fluid surrounding the fetus is withdrawn through a needle inserted into the mother’s uterus.
- This sample is then used to analyze the chromosomes of the fetus.
- Doctors usually perform this test in the second trimester, after 15 weeks of pregnancy.
- This test also carries a very low risk of miscarriage.
- even more invasive
- very accurate but still some risks involved
Genetic screening for genetic conditions
a controversial topic that opens the debate about how society handles new technologies, thinks about families, or deals with human difference
Prenatal screening progress
- Technological advances means that we can now detect normal and atypical genotypes and inform parents about their fetus’ genetic status
- It is now possible to screen for developmental disabilities such as Fragile X and Down’s syndrome with very high accuracy
- not 100% percent accurate; diagnostic tests will confirm 100%
- However, we cannot tell parents about what the child’s developmental outcome will be because it is not predetermined
On what basis do we make the decision to screen for genetic conditions?
- Medical practicioner
– no medical remedy - may suggest to terminate pregnancy since there is no cure
- Social values
– freedom of choice, protecting rights of the child - Parental burden
– physical pain, social stigma - parents have to make decisions about their unborn child and have to live with those decisions
- Research evidence
– evidence on prevalence, severity, accuracy of screening techniques
Who should be involved in decision to screen for genetic conditions?
- We need to hear from all stakeholders
– Genetic conditions impact individuals but also society as a whole and we need to balance individual rights and social benefit - costs involved when trying to provide care to individual’s w disabilities
- Disability Advocates argue for:
– “a wider discussion which includes what are available options, treatment, what the outlook is, where one can make predictions about that for an individual condition, that presents the family with a range of options that are not focused solely on avoidance of the genetic disease” - important for parents to see the bigger picture of what life can be like with the condition, not just avoiding it or getting rid of it
- The inclusion of disabled voices in debates
– “disabled people, not doctors, are the real experts on disability, because of their personal
experience of living with impairments”
Paternalism
- e.g., professionals know what’s best
- don’t always have the whole picture; lack the lived experience
- Social consequences of decisions such as, for example, increased discrimination against disabled people and the gender balance of the population
How do we provide screening information?
- In a democratic society only the parents have the right and the burden of deciding whether to continue the pregnancy
- This highlights the importance accurate and balanced information from professionals
- Counsellor is needed with a dual focus on the medical but also functional aspects of genetic conditions and family life with genetic disabilities.
- what living w disability could look like; talking to people who have it
- Consumers need to be informed about the accuracy and margin of error of prenatal tests to a greater extent than they currently are
Once we’ve screened what do we do with the information?
- Stipulate more explicitly the conditions for which screening would be prohibited (e.g., for sex selection)
- parents used to not be told sex of baby to prevent pregnancy termination
Are we providing informed choices?
- Difficulties of opting out of the process; persuasive pressures on choice through the very offer/mandate of screening tests
- Lack of time to properly discuss options with patients
- Social communication and language used; many aspects of disability are socially constructed
- valuing high IQ over low IQ; both are different from the norm but one is more highly valued
- Societal attitudes towards disability; media representations
Possible benefits of identifying a genetic cause for intellectual disability
- Confirm the diagnosis and etiology of the ID
- Repair abnormalities on fetus
- for certain conditions that could cause death
- Provide explanation to parents of why child
- is the way they are; prepare for arrival and what will be necessary (e.g. surgeries)
- Prepare for the arrival of the child
- Provide accurate recurrence risks
- whether there is a risk of having another child w the same disability
- May reduce the need for termination
- if parents understand more about the disability and what is available to them
Genetic screening decisions based on course of condition: Duchenne muscular dystrophy (DMD)
- is caused by a defective gene for dystrophin (protein in the muscles). Muscles become weak.
- Symptoms usually appear before age 6 and may appear as early as infancy. Most are unable to walk by the age of 12 and with good care may live 30 years old.
- The sons of females who are carriers of the disease (women with a defective gene, but no symptoms themselves) each have a 50% chance of having the disease. The daughters each have a 50% chance of being carriers.
- For Duchenne muscular dystrophy the demand is high and many parents of either affected boys or where there is a family history of Duchenne muscular dystrophy request prenatal testing and termination of an affected pregnancy.
Genetic screening decisions based on course of condition: Huntington’s Disease (HD)
- an inherited brain disorder leads to degeneration of nerve cells. Mutant huntington protein causes parts of the brain to die.
- As the brain cells die, symptoms appear (physical, cognitive and emotional).
- each child of a parent with HD has a 50% chance of inheriting the disease and is said to be “at-risk”.
- Symptoms appear at 30-40 yrs
- Only 9-15 % of those who know they are at risk of developing Huntington’s disease actually come forward to have a predictive test and very few contemplate prenatal testing
- may be bc there is a better quality of life (symptoms appear later in life, treatment options)
Is genetic screening encouraging eugenics?
- In response to roll out of Non-invasive prenatal testing (NIPT)
- ‘eugenic anti-disabled discrimination’
the unique value she brings to our
family and the positive impact she has on others around her
- There appears to be a medical culture in some hospitals in the UK with an evident bias against disabled babies in the womb.
- Without reforming this culture, the widespread availability of NIPT is likely to see a further increase in eugenic abortions on those babies with Down’s syndrome
Pro-life agenda uses Down syndrome
- Eugenics argument is used to support the prolife position.
If abortion of Down syndrome babies is wrong then why not all forms of abortion?
- decision is based on the baby’s characteristics rather than the mother’s reasons (e.g. not being ready to have a baby)
