[Tamara] Hello, welcome to Module 13.
Here, we're going to continue our discussion from last week
on some of the ethical considerations of genetic testing
and that information
and how it can be used
or even misused in some situations.
And we're going to think about this across the lifespan,
not just in terms of solely the ethical considerations,
but also what are the potential benefits
and when these tests might come up for a person.
And we're gonna think about it across the lifespan
because it really is quite different
in terms of the considerations
of the risks and benefits to a patient
when we're thinking about it at different stages of life.
Because there are different options that may be available.
It may mean different things at those different stages.
So let's take it and break it down
by stage of the life across the lifespan
and think of it that way.
So by way of introduction,
at each stage of the lifespan,
so here we're talking about prenatal or even preconception,
neonatal, pediatric, adult, geriatric,
genetic testing can impact patients differently
and can bring along
unique ethical, legal, and social implications.
Prenatal or preconception genetic testing
is typically recommended for specific diseases
known to exist in the mother or father's family history.
There are some that are also recommended
depending upon maternal age.
For example, certain aneuploidy testing,
as we talked about in an earlier module.
Neonatal screening is mandated by the state
and includes tests for genetic diseases.
These were decided
based upon a set of criteria
that each of these conditions must have met,
including that it's something
that could be easily tested for
and also something
that's either impacting the newborn immediately
or will have an early-childhood onset.
So it's not something
that would be as much a predictive test
as more of a diagnostic kind of test.
But these are all still screened.
So they would require subsequent follow-up
and clinical follow-up
in order to make a diagnosis.
Pediatric genetic testing
occurs in children demonstrating possible symptoms
of a genetic disease
like intellectual disability
or those that have sort of a set of anomalies
that haven't been classified into a particular diagnosis.
Certain genetic testing can be helpful
to identify if maybe this is associated
with a chromosomal abnormality,
like some of those we've talked about previously.
That can have a range of symptoms with them.
So it can be rather challenging to diagnose
and do actually require genetic testing for that.
Adult genetic testing
is most common in individuals
with a family history of adult-onset diseases
like cancer and Huntington's disease.
So here is where it's pretty rare
and it's generally not recommended
in the pediatric population
that, say, a child is tested for a condition
that would not have onset until adulthood
because they want to give the child the opportunity
to have autonomy
and be able to make the decision for him or herself
when they are an adult,
to be able to decide
if that's something they want to know for themselves.
So that is generally left for adult genetic testing.
Geriatric genetic testing may provide useful information
to the patient and the patient's family.
However, common age-related conditions like dementia
are not typically linked with alleles
included in most genetic tests.
So why would you do genetic testing in geriatric population?
Well, actually in some cases,
it can be informative
for their family members
more so even for themselves directly.
If a patient is diagnosed with dementia
or Alzheimer's disease,
then it may be useful
for family members to have an understanding
if there's a genetic underpinning to that.
And if so, knowing which allele that the patient has
who has, say, for example,
diagnosis of Alzheimer's disease,
will help in identifying
if their family members also have that specific allele.
So it can very much help
in interpreting the results of genetic tests within a family
to know the specific allele
that the affected family member had.
All right, so let's get started
with prenatal testing and screening.
Preconception genetic counseling
can be beneficial for those with a family history
of a specific genetic disease
or members of ethnicities or races
with high risk of certain genetic diseases.
The one in particular
that you'll probably hear about quite a bit
if you're looking into
any of these prenatal testing panels, for example,
are those in the Ashkenazi Jewish population
where there are certain genetic diseases
like Tay-Sachs disease,
which are relatively rare in the general population,
are much more common in those populations.
And thus when individuals,
especially when both the male and female
are from the same ethnic group or race
where these conditions are more common,
for them to potentially have these genetic tests done
for carrier status,
mostly to find out the risks for any children they may have
to have the disease.
But, again, it's likely specific
for conditions that are found
in a person's family history.
Preconception testing is generally carrier testing,
but the results may have direct implication
for the partner's health.
So that's something very important to keep in mind.
While you might be testing for carrier status,
it doesn't mean that it has no implication
beyond the potential impact
on future children for that person.
It may also indicate that a person has
or will have a condition presents in the future
or presently is presenting
but hadn't been recognized as that yet.
So that's important for the patient to understand
as a possible outcome.
One example of that would be the sickle cell trait.
So sickle cell anemia is, as you remember,
a recessive condition.
And so if there is genetic testing for carrier status,
you might say, well, if you're a carrier for it,
you don't have any symptoms.
That is and also is not the case.
So a person who is heterozygous for sickle cell traits,
or sickle cell anemia,
they have what's called sickle cell trait,
which means while they do not have sickle cell anemia,
certainly not the symptoms
that are associated with that condition,
they do have certain health implications.
And this can include anything
just from increased risk of dehydration
and more severe effects of dehydration
and other concerning issues that might be related to that.
So the patient would need to be informed of that
as a potential outcome.
And also if the genetic test
comes back that they're a carrier,
they should be informed
of what that actually means
directly for their health as well.
Prenatal testing typically focuses on testing the fetus
for genetic disease or chromosomal abnormality.
And it also generally requires
not just a fetal sample,
but also maternal and paternal samples for comparison
so that they can better
interpret and understand the results.
And that may also give some information
to the patient or the patient's partner
that was not anticipated by the patient,
so should be explained to them prior to the testing.
Preconception results may inform or influence
future reproduction decisions,
while prenatal results may inform the decision
to carry to term
or help prepare the family
for the child's future care.
So here, again,
even within the point of prenatal and preconception,
there are differences in the implications
of the results for the patients.
And here, there are options that can be pursued.
In the case of preconception testing,
if, say, for example, there's a high likelihood
that their future child
would have a particular genetic disease,
then there are options like in vitro fertilization,
and the fertilized eggs can be tested for
which would have the particular genetic disease
and which would not.
And then those embryos
that do not have the genetic condition can be implanted.
Obviously, there's a lot of expense and time and difficulty
associated with in vitro fertilization.
So it can be a difficult decision for a couple to make,
but it is an option for those who can afford it.
So that would be one possible outcome
for those who are undergoing preconception testing.
For those who are prenatal,
you of course have the option,
the couple has the option
for considering termination of the pregnancy
or preparing themselves for a possibility
of a child with a particular condition.
And preconception and prenatal testing
can both significantly impact
the patient's emotional wellbeing and relationships.
And I'm sure you can imagine how that would be the case
and even potentially put yourself in that position
of how would it feel to have that kind of information,
either in the preconception stage
or in the prenatal stage,
the impact that can have on a person
and their psychological wellbeing.
It can certainly be very impactful,
and this is something that requires, I think,
a good amount of counseling upfront.
Preferably if they can meet with a genetic counselor
would be ideal
because they are trained,
these genetic counselors are trained specifically
to not just understand these genetic tests
and the results,
but also they're trained specifically
in knowing how to communicate these potential results
and then once the results come in
to help the patients to cope with results,
whatever they may be.
So what are some risks and cautions
associated with prenatal testing and screening?
False positives indicating,
so a false positive of course being
that the test indicates the fetus
has a genetic disease or disorder
when that is not the case,
or false negatives indicating
the fetus does not have a genetic disease or disorder
that it is actually present.
These can occur with any genetic test or screen
and must be explained as a possibility to the patient.
So regardless of what the results come back,
how the results come back,
it's never 100%.
It's never 100%.
And all screens that return a positive result
must be followed up
with other clinical diagnostics to confirm.
Some prenatal tests are invasive.
So this would include amniocentesis
or chorionic villus sampling.
They carry with them a risk to the mother and the fetus.
There's certainly a risk of miscarriage
that comes along with those
which must be considered
in balancing out the risks and benefits
of any of these types of testing procedures.
Now there's a new type of approach
that is starting to gain momentum
called cell-free fetal DNA testing.
So this is for prenatal testing.
It's a non-invasive prenatal testing,
and it is a promising approach to prenatal genetic testing,
reducing risk to the mother and fetus
from other invasive procedures.
So what happens is you basically take a blood sample
from the pregnant woman
and also taking a sample
from the father and the mother,
they can basically separate out the DNA
that's present in the mother
that must have come from the fetus.
So this is blood that was mixed in in the placenta
and is basically in the mother's bloodstream.
And this is DNA from the fetus
and not from the mother.
So it can be positively identified, separated out,
and from that they can actually do all sorts of testing.
Right now, it is being used
to test for aneuploidies
and may be more effective
and actually more accurate
than some other types of genetic testing
in the prenatal setting.
And certainly carries with it far fewer risks
given that it's just simply a blood draw
as opposed to an amniocentesis.
So this is gaining in popularity.
I would not say it is mainstream at this point,
but certainly I think it is headed in that direction,
and given more time and clinical support,
I do actually believe this will be heading into common use
in, say, the next five years or so.
So moving on to newborn screening
and genetic testing.
Newborn screening is mandated by the state.
In Vermont, parents have a right
to refuse screening for any reason.
Screening looks for both protein abnormalities
and genetic abnormalities or diseases.
The way the list of diseases is set
for what is actually assessed in newborn screening
is influenced by the Wilson and Jungner
classic screening criteria,
which include that the conditions
present serious health problems,
have accepted treatment, can be diagnosed,
have recognizable, latent, or early-onset symptoms.
So it would only be something that would come up,
either present already or soon after the child is born.
Have a suitable test
acceptable to the population,
have a well-understood natural history for the condition,
agreed policy who is treated for the condition,
the cost of testing and treatment is balanced,
and the case finding is continuous.
So meeting these criteria,
the state of Vermont has some 30 odd different conditions
that are tested for
as standard practice in newborn screening.
So what are we looking to in the future
of newborn screening?
Well, with whole-genome sequencing
becoming readily available and cost-effective,
the possibility of newborn genome sequencing becomes real.
Now, I want you to think about that.
What does that actually mean?
What am I saying here?
What I'm saying is it's not science fiction
to imagine that at least in the near future
we'll have the possibility
to have basically at the time a baby is born
the normal heel prick.
So blood is drawn.
That not only could it be scanned
for these different enzyme tests, protein assays
that are commonly done in newborn screening,
they could also actually sequence
the newborn's entire genome.
Sequence the whole genome and then have it on file.
Okay, well, what do you do with that information?
How is that information stored?
How do we interpret it?
These are all very important questions.
Now, certainly here it's important to balance
that risk versus benefit.
As of today, what would be the benefits
of having whole-genome sequencing for every newborn?
Honestly, I don't think those would outweigh the risks
at this point,
given that we don't have enough information
to be able to carefully and accurately interpret
all of that information
coming from a whole-genome sequencing.
That's not to say we're not on the path to that
because certainly that could be the case.
There may be certain genetic conditions
where we could easily and definitively
check from a whole-genome sequencing.
But then what do you do with the rest of that information?
Is it stored?
Is it kept basically under lock and key
until the child is of age
to decide if he or she wants to know that information?
Who provides consent?
Would it be the parents
at the time that the child is born?
And would it be for all information
or only for information
that would be relevant to diseases
that may present during childhood
before the child would be of age
to autonomously be able to decide
whether or not they want that information themselves?
So many, many, many ethical questions come up
when we start talking about this.
But it's important to start thinking about these right now,
even though, yes, it's true,
we're not doing whole-genome sequencing on newborns today.
But that's not to say it won't happen,
and that's not to say it's a bad thing.
It's simply to say
that there are ethical considerations
which we need to address
and start thinking about today
so that in the future we can be prepared
for what might come
and be prepared to utilize these technologies
in a beneficial way
that minimizes the risk and harm
while really maximizing the benefit
to the individual and to society as well.
So that's just some food for thought
on the future of newborn screening
and where that might be headed.
So moving on now up the lifecycle
to the pediatric setting.
Pediatric genetic testing recommendations.
And these are coming from the American Academy of Pediatrics
and have provided their specific recommendations
in the extended form
and the reading folder for this week too.
Children presenting with symptoms
consistent with genetic disease
may, with parental consent,
undergo genetic testing to aid in diagnosis.
The American Academy of Pediatrics
recommends the principal factor
in making the decision for genetic testing
is whether it is in the best interest of the child.
Because really it is preferred
to, when possible, delay genetic testing
to a time when the child has grown up to an adult
and has the capacity to make an informed decision
for his or herself.
Predictive genetic testing
is only recommended for those diseases
with onset or possible intervention during childhood
with parental consent
and, when possible, with child assent as well.
Adult onset predictive disease testing
is not generally deemed to be
in the best interest of the child
because, first of all,
what are you gonna do with that information?
If if it's something like Huntington's disease, for example,
which doesn't have onset
until a person is in their thirties or forties,
what would a child
at the age of 5 or 6 or 10 or even 15
do with that information?
It would be preferred to allow the child to develop,
again, to the point when they're an adult,
when they can make that decision for themselves.
Carrier status testing
is also generally not pursued in children,
as it's only relevant for family planning
for the individual.
And that's when that's the case.
So when we were talking about the sickle cell anemia
versus sickle cell trait,
so individuals who are technically carriers
for sickle cell anemia
have what's called sickle cell trait,
and they may have some specific health concerns themselves.
And so it may be beneficial
for a child to be tested for that,
if they're, for example,
going to, say, be on a sports team
or a situation
where they're going to potentially face dehydration
and the issues that may come along with that.
So genetic testing in that scenario
might be considered not for carrier status in particular
in terms of making reproductive decisions,
but for the health of the child at the time.
All right, so moving on to adult population genetic testing.
Genetic diseases with adult onset
may be tested for in the adult population
and those who have a family history
and have decided to do so.
So those who are well-informed
of what the test will and will not show
or may or may not show
and have a plan, have an understanding of,
okay, well, what are you going to do
if the results are positive,
if the results are negative,
if the results are inconclusive?
Huntington's disease is an autosomal-dominant
neurodegenerative disease
a patient may choose to be tested for
if one of his or her parents or grandparents
had Huntington's disease.
There are other ethical considerations here as well.
As I mentioned, talking through all the possible results
and what the patient would do with each of those results.
This is, again, something that falls nicely
in the realm of genetic counselors where they're available
and can talk to a patient before testing.
Because that way they can come up with a plan,
come up with an understanding of what they're going to do,
and it won't be such a surprise or shock
one way or the other
depending upon how the results come out.
And for something like Huntington's disease,
it's possible that, say, you have a person
who is 18 or 19 years old, so an adult,
and let's say he is,
I think I gave this example,
I may have given this example last week as well,
but this is actually a real example as well.
He knows that his grandfather had Huntington disease,
on his mother's side,
but his mother's never been tested for it.
And his mother is, say, 35 years old.
So she would just be at the stage
where she might start being symptomatic
but may not be diagnosed yet,
and so she doesn't want to know.
Well, if the son gets tested who's now an adult
and if he finds out he does have Huntington's disease,
then that means necessarily his mother
also has Huntington's disease.
She must.
Because it's a dominant disorder.
So that gives him some information about his mother
that she did not necessarily consent to.
So there are many ethical considerations.
So in talking to the patient
and talking through each of those
and discussing what is he going to do
if the results come back positive,
the results come back negative,
if the results come back inconclusive
can help to generate a plan
and can take away some of the anxiety
and uncertainty around it
for the patient
and make things go a bit smoother.
Cancer predisposition testing may be recommended
for those with a family history of cancer
or red flags of heritable cancer,
and carrier status may be tested
in those planning to have children
or those who are sexually active
and are interested in better understanding
their carrier status.
In the geriatric population,
Alzheimer's disease,
age-related macular degeneration, and cancer
are common age-related diseases
with a demonstrated genetic component.
But at the same time,
there also are spontaneous cases,
many spontaneous cases of these diseases.
As an individual ages,
the chance that this is happening
more because of a patient being older
as opposed to it being something
that has a strong genetic component increases.
So Alzheimer's disease genetic testing
is restricted to select alleles
demonstrated to contribute to early onset.
So that would be Alzheimer's disease
starting between 60 and 65 years old,
not late-onset Alzheimer's disease.
So if a patient comes in and says
their 85-year-old grandmother
was diagnosed with Alzheimer's disease,
it's important of course to note that
in their family history.
But it's also very, very important to note the age
of the family member at the age of diagnosis.
So that way it can be a little clearer
if it was maybe more related to age as opposed to genetics.
And while genetic testing may not improve clinical care
for a patient already diagnosed with the disease,
it can inform the relatives of the patient
that they may be at increased risk.
And this also helps in the interpretation
of genetic testing for family members.
So if there's a record of the specific allele,
which mutation is found in the family
that's been associated
with Alzheimer's disease, for example,
if a person is tested for the disease
and it comes back that they share that same allele,
then it's much easier to interpret those results
as, in fact, contributing to Alzheimer's disease
potentially in that person.
As opposed to what happens,
actually not uncommonly, in genetic testing
where we the results come back
and indicate it is inconclusive.
Well, if you have already a family history of it,
you've identified
in certain family members that have the disease
which alleles they have,
then you can match that up
to whether or not the other family members
have those specific alleles.
It just makes it much easier to understand the implications
of the genetic test results.
And that leads us to VUSs.
So variants of unknown significance.
Well, this is a tough one to explain
because you can imagine
a patient has talked through
and thought about genetic testing.
They've gone through the experience
of really making that decision for themselves.
And then they think,
"Well, at least I'll know.
"At least I will know
"if I have this or if I don't have this."
Well, unfortunately that's not always the case.
That's not always the case.
So sometimes the results come back,
and they indicate
that a person has a variant of unknown significance.
And what does that mean?
It's really difficult to interpret those results.
Unfortunately, it basically is inconclusive.
It neither says a patient does not have the disease
nor does it say they do have it
or the increased likelihood of the disease.
So unfortunately that can be disturbing
for the patient as well.
That can be kind of traumatic for them
'cause they come in
thinking they're going to get an answer.
"Even if it's positive result for this disease,
"I want to know."
But they come back and they get this kind of result.
It can be challenging to know what to do next.
So basically it's indicating a patient has an allele
for a gene that has not been demonstrated conclusively
to have either a positive or negative impact on disease.
The result can be confusing and frustrating
for a patient who is anticipating an answer,
and future research may link that variant
to a specific risk,
but as of today,
there's no clear way to interpret those results.
So I think it's important upfront to inform the patient
that that is a possible result.
It could be positive, it could be negative,
it could be inconclusive.
So then the real question is,
is it a good idea to do genetic testing?
Well, let's take a look
at some of the reported outcomes in patients
following genetic testing.
So they're following up on patients
after they have undergone genetic testing.
And these are just a few examples, the BRCA1/2.
In general, there's temporary stress relieved,
which is relieved long-term.
So, for example, a person undergoes the BRCA1/2 test
and it comes back positive
that in fact they do have the BRCA1/2 alleles
that make them
increase their likelihood
of developing breast or ovarian cancer.
While there is temporary stress that a patient endures,
long term, that stress is relieved.
And this commonly results in increased surveillance
and general improvement to health
in most patients in the long term.
In Alzheimer's disease,
there's neutral to slightly positive impact
on psychological health long-term
in knowing either way, actually,
if they have the APOE allele
that puts them at risk
for early-onset Alzheimer's disease or not.
In Huntington's disease,
short-term 7 to 10 days post-results,
the impact worsens depression scores
for those who test positive.
However, depression scores improve long-term
in the 6-to-12-month frame
for those who test positive and negative.
Regardless of what the results come back as,
the patients feel better in the long term.
And knowing, in general,
that's obviously not the case for every specific patient,
but when looked at on average,
it does seem to be beneficial
for a patient to know,
at least in these specific conditions.
So it's important, I think, to consider
both the short-term and long-term impact
that genetic test results can have.
Because, again, remembering that genetic testing
is unique in that it is a lifelong result.
So we do need to consider
both short-term and long-term implications.
That being said,
I think it's also important to consider
all possible outcomes from a test,
both negative, positive, and unknown,
and unknown being inconclusive,
and their impact on the approach you would take
to the patient's care,
positive or negative lifestyle changes
that the patient may take,
the patient's psychological and emotional welfare,
and the patient's family or social group
and how they may interact with them
and how that might be affected by genetic test results,
patient's understanding of his or her health and wellbeing.
So would that be beneficial or detrimental to the patient?
Patient's healthcare coverage and employment.
Now, keeping in mind the extent and limitations of GINA
that we talked about last week.
So what will you, the patient's healthcare team
and/or the patient do differently
in response to each of all possible test results?
And this was mentioned and discussed well this past week
in the discussion board
where exactly that query was raised.
And I think it's so appropriate
to think through basically what would you do differently?
What would the patient do differently?
How would the knowledge help them
or help their family members?
Even if it's not helping them directly,
how would it help their family members?
And weighing the costs and benefits,
the risks and benefits
along each of these metrics
in both short term and long term.
All right, so with that, summary.
Through all stages of life,
genetic testing requires careful consideration
of all possible implications of results
for the patient and family.
Decisions and actions that may be informed
or influenced by genetic test results
differ depending on the life stage.
Advances in genetic testing technologies
and interpretation of results
must be approached with great care,
with ethical, social, and legal implications
these results can have
on the patient as a whole person.
All right, well, with that,
we are going to transition into the next module
in the following week where we're going to just kind of take
like a potpourri approach,
and we're gonna do a little bit
of a couple of different things.
We're going to talk about genomics and wellness
and some different interesting topics there
that may be useful to you
for you to share with your patients.
And then we're going to just take kind of a step back
and review the nursing competencies
in genetics and genomics
we looked at in the very first week
and see where we are with those
and kind of assess and take it from there.
All right, well, thanks very much for your attention,
and I look forward to talking with you all
on the discussion board.
Take care.