Is It Bioethical? Testing Kids for Adult-Onset Conditions

Steve Kraske

Welcome to Up to Date. I'm Steve Kraske. Will my newborn son develop cancer? Will my baby daughter one day have Alzheimer's? What about diabetes? The day is coming when undergoing whole genome sequencing will be almost as common as getting your blood pressure checked. But of course, that raises questions. How much information is too much? And do you really want to know when your baby is just months old what might lie ahead when it comes to disease and medical misfortune? That's our subject today. With us is Kelly Orman. She's a professor and director of the Master's Program in Human Genetics and Genetic Counseling at Stanford University. Kelly, nice to have you.

Transition and diarization artifacts

Thanks so much. Welcome to Kansas City.

Steve Kraske

Yeah. Philosopher Rosamund Rhodes is director of bioethics education at the Icahn School of Medicine at Mount Sinai in New York City, and she's associate director of the Union Mount Sinai Bioethics Program. And, Rosamund, nice to have you here, too.

Rosamond Rhodes

It's a pleasure. Thank you.

Steve Kraske

Dr. John Lantos is Director of the Pediatric Bioethics at the University of Missouri, Kansas City School of Medicine. John, good morning to you. Good morning. Well, Kelly, let's begin with you. So one of your patients is the parent of a newborn, and they are especially curious about what might lie ahead for their baby. They want to find out if their baby has cancer in his future. What do you say to them? If they're interested in exploring all that.

Kelly Ormond

Well, you know, as a parent of a 10-month-old, I can certainly understand how much you want to know about your child and how curious you are and you want to protect your child. So, of course, this is a question that comes up. But traditionally, we've really limited this prospective information.

Steve Kraske

That's right.

Kelly Ormond

And mostly it's been because there's not usually something you can do about it medically. And the idea is that if... Parents have this information. First of all, we're taking away the right of a child to decide as a future adult whether or not they would want to know. But then also that there can be a lot of anxiety that might be created in one direction or another. And we spoke about this a little bit on our drive over here, that we're really conservative when it comes to traditional genetic conditions that run in families. And we do worry a bit about it. And those thoughts have evolved.

Steve Kraske

When you say we're conservative, that means that doctors sometimes don't reveal to their patients what they might know.

Kelly Ormond

No, not necessarily. It's more that we don't go looking for things specifically if there's something we can't do about it. So, for example, newborn screening has been around since the 60s, late 60s. And we look for things that we might not know are there immediately but are going to have a medical impact and that we can do something about. So I think most doctors these days would really agree. There's no question that for most of the conditions included on traditional newborn screening, We can do something about it. It's what we call medically actionable. It's worth knowing about. But if it happens later on, either in childhood or adulthood, we go a lot slower and we're much more cautious. And 10 years ago, we would have said, no way, don't test. And I think now we're evolving more towards, well, let's think about it. And there may be some situations where it's appropriate.

Steve Kraske

Well, I was going to say, Rosamond, the world is changing here, right? Because it's easier to get these tests. Parents know about these tests. And some parents, at least, sort of want to know, everything that might lie ahead for their baby, right?

Rosamond Rhodes

Absolutely. And when we think about babies and families, we'll know, we were just hearing a lecture, that if you have three out of four of your grandparents had heart disease, you're more likely to get heart disease. And if two parents have heart conditions, this child is likely to have heart condition. And even if there's nothing to do about it now, we know that just by family history, and people live with it just fine. And if we can find out more of such information, usually we think having information is a good idea. It allows us to make plans that take that information into account.

Transition and diarization artifacts

Yeah.

Rosamond Rhodes

And even if there's nothing to do about it right now, you look down the road and you use your responsibility and your foresight to to make good decisions based on that information.

Steve Kraske

I guess my point is, even getting back to what Kelly was saying, this idea that we can test for all these different conditions, even those we can't do much about, today parents are finding out what might lie ahead for their baby because these tests have become so omnipresent and are becoming more common as the years pass.

Rosamond Rhodes

Absolutely, and they're becoming... more commercially available. So the parent who really wants to know can send off a cheek swab to one of these pay-for whole genome sequencing centers and get that information. But if you do it outside of the medical center, then you're doing it without the benefit and support of the genetics counselor and the pediatrician. And I think having the pediatrician and the genetics counseling on board can be valuable assets to parents. So seeing it commercially available, freely available to people outside of medicine but not inside of medicine strikes me as peculiar and conservative is the right word

Steve Kraske

and

Rosamond Rhodes

restrictive.

Steve Kraske

Well, John Lantos with UMKC, this really is the dawning of a new era, and I'm wondering to what extent medical science is prepared for it, and for that matter, to what extent are consumers prepared for what's coming down the pike here? It is a new era,

Dr. John Lantos

and I don't think doctors or consumers have a clue what it's going to bring. We're talking here about information, whole genome sequencing, that was done for the first time about 10 years ago, and the first... Whole genome sequencing costs $3 billion, with a B. Over the last 10 years, we've gotten to the point where you can probably do a whole genome for $1,000 or $2,000, and most people think the price is going to come down. Right now, most of the information that we get from whole genome sequencing, nobody has any idea how to interpret. So part of the problem when we talk about this is it's one thing to say, can I test my child to know whether they're going to get cancer? That's not the situation in the real world. In the real world, the question is, can I find out 30,000 genes, each of which has hundreds of variations, none of which we know the meaning of? And is that information going to be useful or helpful as I raise my child?

Steve Kraske

But isn't that changing, though, John? Isn't five years down the road, 15 years down the road, some of these vagaries that you're talking about, they're eventually and gradually going to be removed, right?

Dr. John Lantos

So it is changing. And the reason Kelly and Rosamund are here this week is because Children's Mercy is putting on a conference this week about pharmacogenomics and personalized medicine, where some of the leading scientists in the world who are working on this and trying to figure it out are in town. presenting their results and trying to answer both the scientific questions and the ethical questions. But it's painstakingly slow. And each gene, each disease, whether it's heart disease or cancer or Alzheimer's, requires international collaborations among hundreds of researchers. And the more research they do, the more complicated it gets.

Steve Kraske

So how long will it be then, John, before we might be able to do this test for $1,000? and, in fact, find out if my son or daughter, what they are predisposed to in the decades ahead for them.

Dr. John Lantos

So as a general population screening test, I think it's going to be decades. Decades.

Steve Kraske

Years, 50 years.

Dr. John Lantos

What we're doing now at Children's Mercy and what a lot of places are doing, and Kelly and Rosamond can talk about their places, is targeted testing of children with AIDS. symptoms that suggest that they might have a rare genetic condition, but we don't know which one. So if a child has developmental problems or seizures and we do the three or four typical tests to make the diagnosis and they're negative, now we will look at the 50 genes that are known to be associated with that syndrome and see whether we can find some rare, maybe even previously undescribed mutation that may be associated with that. So it's being deployed on a case-by-case basis in a very targeted way for select subpopulations, and that's how we'll learn.

Steve Kraske

You know, Kelly Orman with the master's program in human genetics out at Stanford, what about this targeted testing that John was just talking about? What are you doing? Where is that headed?

Kelly Ormond

Yeah, so I would say that As John has alluded to, testing has really focused in the past on people who have a specific medical condition, either themselves or in their family, and we're looking for that cause. you know what you're looking for because of the clinical features or because of a previous diagnosis in the family. And that's going to be really different than sort of this Gattuck image. If you remember the first scene of that movie where the baby's born and they sort of put it in the computer and they get this long printout that says you have this risk for colon cancer and this risk for lung cancer and all of these other things that we don't have a clinical indication for. Although,

Steve Kraske

again, just to be clear, that too is in our future.

Kelly Ormond

I don't know, about 50 years, but I agree with John, decades. I think that we need to have a lot more prospective data in order to be able to interpret the genome information, and we're certainly not there yet.

Steve Kraske

It's too new. It

Kelly Ormond

is too

Steve Kraske

new. Ten years isn't long enough. And

Kelly Ormond

I

Steve Kraske

think

Kelly Ormond

it's kind of this question of, is it data or is it information? Can I use it? Does it actually mean anything to me? And then you get into the whole question that Rosamund raised of, well, I can get the information through a company database. Maybe I have the right to it. And even if I don't know what it means, I should still be able to get it, which is a whole different debate that we can get into if we have time. But, you know, even with adults, I mean, we've had some experiences at Stanford where we've taken relatively healthy adults. We've tried to look at their genome and interpret it. And I can tell you, we spend, you know, you get out thousands of variations from what we consider to be kind of the quote unquote normal human genome. And you have to look at every single one and try to decide, is this something that matters or not? And there's usually no data, so you're making your best guess. And then, you know, you look at it. At one point, there was a publication that came out from our institution, and then you look at it six months later, and maybe you're going to have a different interpretation. So I have to ask you as a parent, would you want me to give you that on your child? Do you want me to tell you something that's probably going to change ten times before they're even five, or do you want me to wait until I know something a little more certainly?

Steve Kraske

Well, how often are parents saying to you, yeah, tell me?

Kelly Ormond

Not that often for this level of information. They're saying it when there's an indication in the family. So maybe the parent has colon cancer and they're really worried about it. Or maybe the parent has an inherited mutation for breast cancer and they're so anxious about their child because they just had a baby girl and they're worried they're going to get breast cancer.

Steve Kraske

Yeah, and that might be a time when they do it.

Kelly Ormond

And that's going to be really different because those are things where you might have a 50-50 chance of inheriting the mutation and the family knows what life with that illness is like. They have a different drive versus if we're doing this on a healthy child where you're just looking for all the information you can get.

Steve Kraske

Rosamund Rhodes, how often are those tests being done now when you're looking more specifically for a certain condition? That's, I gather, much more common.

Rosamond Rhodes

Well, the looking... John and Kelly both said, when you have a child who's ill and you're trying to figure out what's going on, you do that. But virtually every newborn in the country goes through something that's called newborn screening, where they're looking for specific conditions. Some of them are bona fide diseases. Some are not. Some of them are treatable, and that's how it all got started, these conditions where it really mattered whether you start treating practically at day one or not. But some of them There is no treatment.

Steve Kraske

Are you saying babies now, almost all babies automatically as a routine part of newborn care are being screened that way?

Rosamond Rhodes

Yes. And in most places, it's without parents even knowing.

Steve Kraske

I was going to say, do parents know?

Rosamond Rhodes

Most cases, parents don't know. They take a little pinprick of blood from the child's heel and they put it on a cord and send it off to the state. And every state has their own panel of tests that they screen for. And these tests... the standards for reporting are set to be extremely sensitive. So some parents get a phone call saying something showed up on this newborn screening that you probably didn't know your child had, and we need you to come in and get retested. And this creates a period of great anxiety for the parents, and most of the people who are called back for this preliminary notification turns out their child is fine. But these are cases where we currently... are testing virtually every baby in the country born in a hospital for these conditions, some of which are very serious, life-threatening. Some of those are treatable, but some are not.

Steve Kraske

And these are genome testing of one? Genetic tests. Genetic tests of one kind or the other? Of looking for

Rosamond Rhodes

particular, particular diseases. John probably knows more than I do.

Steve Kraske

Well, just real quick, why aren't the parents notified, Rosamond, that these tests are going on? Why is this – why should this be a surprise to them?

Rosamond Rhodes

Well, I think it shouldn't be. So I think people should be told this is being done. If your child is affected, this could – help your child, and I think 99% of parents would say, please go ahead. But the people who set up the procedures are worried about what if that 1% says no and we perhaps miss a child who could be benefited. I think it undermines trust in the system. It creates extra problems by doing it without this kind of informed consent. It's also a burden to have to explain it to parents.

Steve Kraske

John Landis, I cut you off there. I'm sorry.

Dr. John Lantos

Just to be clear, the technology for doing this kind of testing existed before the current techniques for whole genome sequencing. So these are not genetic tests, although there are tests for some of the conditions are inherited.

Steve Kraske

Yeah.

Dr. John Lantos

So it's a subtle difference. But newborn screening has been going on for 40 years, long before the genome was… Of one variation or another. Exactly. Second thing is parents are notified, but they aren't asked to give consent. So before the test is done, parents are given a pamphlet explaining newborn screening. And if they say they don't want it, most hospitals will respect that, although in most states consent is not required and the screening is, in that sense, mandated.

Steve Kraske

We're talking this morning about whole genome sequencing and what might lie ahead for all of us in the years ahead as medical science can figure out more precisely what might lie ahead in your medical future. If you want to join our conversation this morning, 816-235-2888 is our phone number. Our email address is uptodate at kcur.org, or you can tweet us at kcur, uptodate. John, this might be a good time to talk about whole genome sequencing. and give us the 101 version of what on earth that is. What is it and how is it done? Everybody has about

Dr. John Lantos

30,000 genes. Give or take. Give or take on their chromosomes. Whole genome sequencing looks at every amino acid base pair, about 3 billion of them along that whole genome. So it's an enormously complicated process. technique for testing that gives whole computers full of information about each individual.

Steve Kraske

And again, the cost of that right now is about, what, $7,500 I read? Yeah.

Dr. John Lantos

It's hard to know exactly, but yeah, under $10,000 for sure.

Steve Kraske

Yeah. And you can envision a day, Kelly, when it might be how expensive?

Kelly Ormond

Well, you know, people talk about the $1,000 genome, and I think getting your sequence We're going to be able to do it for less than $1,000 probably fairly soon. I think the actual out-of-pocket or charge for most of the clinical companies is between $5,000 and $10,000 now. But I think that does not at all capture the interpretation of it. So we can get the data, but the hours of time that people have to spend sort of manually looking at every single one of those changes, we can't really capture how much that costs right now.

Steve Kraske

So are consumers being duped when they buy into these different companies that offer screening for one thing or another, or are those screens so narrowly focused that maybe it makes it a little more practical?

Kelly Ormond

Well, the screens that are being offered to consumers... you know, on the Internet now, what we call the direct-to-consumer genetic testing is completely different than the whole genome or whole exome sequencing. It's what we think of as genotyping. So within all of those base pairs that Dr. Lentos was talking about, there are variations that are associated at much lower predictive levels. for things like cancer or heart disease or diabetes. And so instead of my saying you've got 100% chance of getting this or you've got a 90% chance of getting this, having one of those changes might increase your chance by a couple percent. So instead of being the population chance of getting colon cancer of, I don't know, 8% or something like that, maybe you go up to 9%. So do you care about that difference? That's what those direct-to-consumer tests are looking at now is much smaller, less predictive sorts of changes.

Steve Kraske

Let's get our listeners involved here, moms and dads out there. Are you interested in performing whole genome sequencing tests on your kids? And what would you do if you found out that a potentially lethal disease could lurk in their future? Give us a call, 816-235-2888, and our email address, uptodate at kcur.org. Ginger on Facebook writes this, I would want to know, but as a parent, it is up to my discretion as to who would see the results after that. No, I don't want anyone else to know. Too many labels, too many stereotypes. My child should not be exposed to predetermined ideas about who they are now, much less about who they might be sometime down the road. And you're nodding your head there, Rose. Yeah.

Kelly Ormond

Yeah, so I completely agree that people worry a lot about discrimination, and they worry about it in terms of it getting into the medical system and their insurance risks, which Hopefully, some of the federal and state laws we have around genetic privacy are going to protect around this. But I think also she's hit on an interesting idea, which is that people treat kids differently when they suspect that they have a risk for specific diseases. And even parents could treat their children differently.

Steve Kraske

Well, some of the ethical questions here are just enormous. And again, this might be a little premature, but certainly medical science is beginning to deal with some of these questions. Here's one. Should doctors have to tell parents and patients... everything they learn, even about the risk of diseases for which there are no known cures. Rosamund, what about that? Where's the thinking there?

Rosamond Rhodes

Well, the thinking is across the spectrum. There are people who think absolutely not. You shouldn't be testing for it. You shouldn't be talking about it. And then there are a few of us who think that testing should be done and people should be talking about it. So we usually think that honesty is the best policy. And we usually think that people should know what's wrong with them and what's going to happen to them. And in medical ethics, we talk about the importance of truth-telling. And truth-telling is an important consideration in taking care of the patient who asks a lot of questions and wants to know, how much time do I have? But it's also important for the patient who doesn't ask. And I think doctors need to be guided by their usual consideration of of what's good for my patient. Now here, the patient is the child. And if there's something that's going to be affecting their lives, I think it's important to figure out what's best for them.

Steve Kraske

Even in the case when there's no known cure?

Rosamond Rhodes

Yes, even in the case when there's no known cure. There are children with different cancers and other terrible diseases. And pediatricians have recommended for those children, forget about the genetics for a moment, just in taking care of them, how should you treat them? You should tell them what's going on, what's likely to happen to them, and be open and forthright. Because most of us aren't trained to be great actors. And a child can tell when you're keeping something from them, deceiving them. And they get angry and they feel they're not entitled to ask questions. And that's why pediatricians generally recommend for known health problems that you communicate honestly and communicate even with very young children. Of course, what you say and how you say it has to be age appropriate. But the withholding is usually not a good idea. And when somebody finds out that you've been withholding information, they get angry. very angry, they feel they've been jerked around, they've been deceived, they can't trust you. So these are ordinary things that we all know about information and communication. And then when it comes to genetics, people take on an attitude that we call genetics exceptionalism, that this is different. And I don't see any reason for presuming that it's different. I think growing up knowing something... that in our family there are a lot of people who have cancer or heart disease or epilepsy or diabetes. People accommodate that information. They accept it. It becomes part of them. In that family, people wear glasses. In our family, we get diabetes.

Steve Kraske

Yeah, but it's one thing, John Lanto, is to know that cancer is a possibility. It's a different thing if, in fact, if I'm hearing you right this morning, some years down the road, that patients will, newborns or... Folks my age will know with some certainty that by the time you turn 60 or 62 or 35, you're going to have colon cancer of one kind or another. That's a whole different idea, isn't it?

Dr. John Lantos

Right. So the general trend over the last 30, 40 years, at least in the United States, has been towards more and more disclosure, more and more truth

Steve Kraske

telling, and the

Dr. John Lantos

idea that the paternalistic doctor who knows best and decides what you need to know or not know is a thing of the past. You have the right to your own health information. You can get access to your medical record. You can look at the information yourself. And the juggernaut, the trend in that direction, is getting stronger and stronger. So I think soon patients will be able to see their whole genome results online at the same time that the doctor does. The problem is in interpretation. So as a doctor, I know more about how to interpret that than you do, presumably. So when you come to me and say, Doc, what do I need to know from this mass of information that I can't interpret? I have to make lots of judgment calls along the lines of Rosamond's careful qualifications. If it affects your health, in my judgment, I should tell you about it. If in my judgment it doesn't affect your health, I have no obligation to tell you about it. So what if I know that instead of the 8% chance of colon cancer Your genes predict that you have a 9% chance. Does that really affect your health? Maybe. Maybe not. What if I think the test has a 50% false positive rate, so you only have a 50% chance of having 9% risk rather than 8%? And I can play the numbers game so that I can convince myself that really... There's nothing important there that I need to disclose.

Steve Kraske

But again, if I hear you correctly, what you're suggesting is that years down the road, it might be a few decades or who knows, given the pace of things, it'll be more definitive than that, that you will know with some certainty that the baby who just came into your world is in fact predisposed to cancer at 75%. risk factor when that baby turns, becomes 25 years old or

Dr. John Lantos

45 years old, right? Am I hearing that right? That's correct. And the more definitive it becomes, the harder it will be to withhold information. And there are examples of things that have followed this trajectory that most people have experienced in our lifetimes. I mean, look at fetal ultrasounds. It used to be we knew nothing about the fetus. Couldn't get an x-ray. Couldn't get an ultrasound. Baby was born. You didn't know if it was a boy or a girl or had any problems.

Steve Kraske

And just a few decades later, we know all kinds of

Dr. John Lantos

stuff. We know all kinds of stuff. And some of the stuff we know is definitive. And when we get that information, we disclose to a pregnant woman and her parents and talk about what the options are. Sometimes the information that we get is impossible to interpret. There's a little something that showed up on the echocardiogram that we've never seen before and we have no idea what it means or whether it's going to be important. Do we tell people? If we do, we increase anxiety with no compensatory benefit. And so the more meaningless it is in our judgment, the less likely I think we are to disclose, feeling that disclosure both takes time and has no benefit.

Steve Kraske

You know, Kelly, again, recognizing that we're years away from this, I'm trying to wrap my arms around the idea of going through life knowing that when I hit 30 or 40, I've got this incredible roadblock ahead of me that what a burden to put on people that... will be at much greater numbers of people dealing with that than we're seeing today.

Kelly Ormond

Yeah, you know, it's interesting because I feel like before we can even get to thinking about testing kids, you have to look at how adults feel about getting this information. So competent adults who have this in their family history can often choose to undergo a genetic test. And if we think about some of the inherited colon cancers and breast cancers, only about half of the people who are adults who are at 50% risk of these diseases

Kelly Ormond

high likelihoods of cancer, decide that they want to know one way or the other. For cancer, where you can undergo early screening, and they probably are undergoing early screening anyway. But then you look at something like Huntington's disease, which is a very rare neurologic condition where there's no treatment. And about 10% or 20% of people who are at risk for that decide that they want to undergo a test and know, am I going to get this or not? So then when you try to extrapolate to kids... It becomes a lot harder, and that's one of the reasons why people who work in clinical genetics feel like we should be cautious, that we should allow these individuals to at least reach adolescence where they've got some developing sense of what they want to know or not.

Rosamond Rhodes

Rosamund? I hear the same data, and I draw very different conclusions. So from this data that 10 to 20 people at risk for Huntington's want to get the test, I draw the conclusion that something funny is going on psychologically. So from numerous psychological studies, we know that people dealing with uncertainty are worse off than people who have answers. So if I'm worried about the colon cancer, and I will be worried about it every day forever, forever. But if I find out, look, I'm not one of those people who's going to get colon cancer. I'm relieved. And even if I find out the bad news that I am, at least the anxiety is gone. So from the point of view of a disease like Huntington's, 50% of the people who will be tested will get the good news. So they will get a significant benefit from the results. And 50% will get the bad news, and at least they'll get the anxiety relieved. Then there's another bit from normal human psychology. It goes under the title of affective forecasting. So we used to think we were rational beings. Now we know that a lot of our thinking is affected by biases. And a large component of these biases goes under this name of affective forecasting, that when we're asked to predict our future pleasure or displeasure, happiness or unhappiness, we are notoriously bad. And involved in this testing for something like Huntington's, you ask people, how will you feel if you get this bad result? And what happens is they overestimate the degree at which they will be unhappy, and they overestimate how long they will feel unhappy. So this is called focalism, that you focus on one thing, and durability bias. So if I ask you, Kansas City Royals, if they don't make it to the World Series, How miserable will you be? We've been

Steve Kraske

miserable here a long time, Rosamond.

Rosamond Rhodes

So

Steve Kraske

people say really, really miserable. That's a bad example to pick out here.

Rosamond Rhodes

But I think it's dear to your heart. So if they lose the next game, how miserable will you be? You ask a real fan, my brother-in-law, and he'll tell you on a scale of 1 to 10, I'll be 11 miserable. And how long will you be miserable? The whole day. And if you go and test him after... the Royals lose. How miserable will he be on a scale of one to ten? Three. And how long will he be miserable? Three and a half minutes. Because he's a real fan.

Steve Kraske

And your point with talking about all this is what exactly?

Rosamond Rhodes

What's going

Steve Kraske

on here? People adapt.

Rosamond Rhodes

One, people adapt and people make a mistake in not getting tested that the mistake is driven by bias, not by rational judgment. And if you go to your doctor, who is presumably more aware of these biases and can make judgments without being influenced by the bias, they can say, look, 50% of the people get good news. That's a clear benefit. Everybody will find out an answer to something they've been anxious about, so everybody will be benefited. So for adults, it's a good thing to get tested, but then you see people, only 10% to 20% get the test, which tells me that they're under the influence of these psychological, normal human biases.

Steve Kraske

Let's take a break on that point. When we come back, we'll continue our good conversation here about genetic testing and what might lie ahead in all of our futures in terms of how much we know about the diseases we might contract when we get older. We'll get phone calls from Kim and Heather. Don't go anywhere. I'm Steve Kraske of the Kansas City Star, and you're listening to Up to Date on KCUR.

Steve Kraske

back. I'm Steve Kraske. If you missed yesterday's conversation with author Anne Lamott or our talk about First Lady Abigail Adams with her many times great-grandson, you can find those in all of our previous broadcasts at kcur.org. He didn't look anything like John Adams, by the way. Just be close, but not anywhere close. On tomorrow's program, experience the Vietnam War with a group of aboriginal singers and hold hands with a pair of London girls who find their world changed by the Cuban Missile Crisis. Our indie, foreign, and Documentary film critics will be back to share their favorite showing on area screens. This hour, we're talking about genetic testing, what might lie ahead in our futures as we learn more and more about the diseases we might contract as we get older. We're visiting with Kelly Ormond. She's with Stanford University. Philosopher Rosemond Rhodes, she's Director of Bioethics Education at... Mount Sinai School of Medicine, and also Dr. John Lantos. He's director of pediatric bioethics at Children's Mercy Hospital. Our phone number here, 816-235-2888, and our email address, uptodate at kcur.org. Heather from Overland Park, good morning.

Heather Kirkwood

Hi, good morning.

Steve Kraske

Hi, go

Heather Kirkwood

ahead. Yeah, my name is Heather, and I am a patient with Hermansky-Pudluck syndrome. but I'm also the vice president of the Hermansky-Podluck Syndrome Network. And HPS is a very rare genetic disorder, but many more of our parents are finding out that their kids have HPS at younger ages as awareness of the syndrome improves. The initial test is a blood test, but after the blood test, parents have to decide if they want to know the gene type, the type of HPS that their kid has. Some types of HPS are very mild and result in normal lifespan, but some types are more severe, and the kids will develop fatal pulmonary fibrosis, usually in their 30s to 40s. So it's a really big decision, as you might imagine.

Steve Kraske

Right. Who wants to tackle that one? John? Specific

Dr. John Lantos

question, Heather?

Heather Kirkwood

No, no. I wanted to comment that most of our parents decide that they want to know the gene type, although, of course, we would respect any decision any parent would make. And part of it is what one of your parents was speaking to before. Once they know this, they're anxious about it and finding, you know, getting the good news. The opportunity of getting the good news is sometimes better than what you're already assuming might be the bad news.

Dr. John Lantos

So it's an interesting situation you describe with that disease where it's a two-stage testing process. Right. So people only get tested... That's not on the newborn screening panel as far as I know. No,

Heather Kirkwood

no.

Dr. John Lantos

So people only get tested if the disease has already been diagnosed in a family member. They get the preliminary test. So they've already decided they want to get information about this test. Usually they're

Heather Kirkwood

unaware they have a family member, but it involves albinism

Dr. John Lantos

and

Heather Kirkwood

a bleeding disorder. So when the kids are toddlers, they start bruising and things like that. So that's usually the impetus for the test.

Dr. John Lantos

Okay, that makes it even more interesting and complicated. If the kid already has some symptoms of something, then the test is more a diagnostic test than what I would consider a screening test.

Kelly Ormond

It almost sounds like you already have the clinical diagnosis, and this is using a genetic test to give you specific information about the prognosis.

Heather Kirkwood

Right.

Kelly Ormond

So it's a little different than doing a genetic test strictly for prediction.

Dr. John Lantos

But it's interesting that most parents do choose that and want to know that and find it useful.

Heather Kirkwood

I feel like our parents are maybe living this a little ahead of the curve of what would happen for the general society, you know what I'm saying? Yeah. Since they are doing that. A lot of them want the testing because knowing that your kid's at exceedingly high risk for lung disease, you want to do anything that you can to keep their lungs healthy. And part of it is empowerment, that once you have this information – You know, whatever is medically true today might not be medically true tomorrow, and those changes only happen with advocacy and involvement.

Steve Kraske

All right. Thank you, Heather. I appreciate it. Thank you.

Kelly Ormond

I want to make one more comment to Heather's point. And there's a lot of people who feel like if we do genetic tests for some of these adult onset conditions in childhood, we can alter behavior. We can convince that child who's at higher risk for lung disease that they don't start smoking as a teenager and that maybe they're going to avoid those smoky environments and things like that.

Steve Kraske

Or if you're predisposed to Alzheimer's, don't play football. Don't play soccer, for that matter, or ice hockey, because a head knock might... cause more problems. They'll do a lot of crossword puzzles though.

Kelly Ormond

Yeah, exactly. There's a lot of really interesting debates. And what I would argue for is some controlled research. And Heather, you're the president of a parent support group. Collect some data on what's going on here as people move forward. If they have this information, how are they doing with it? What are they trying to do with their kids to alter this? And then ultimately, how is that influencing what we call the natural history of the disease? Are they getting lung disease at a lower rate or not? Because I think that to the big question. And for those of us in clinical genetics, we want to know if it makes a difference because there are a lot of people I talk to and I say, oh, look, you have this risk. And they say, I'm going to go out. I'm going to do those crossword puzzles. This is my favorite argument with the Alzheimer's disease patients I counsel predictively. They say, if you tell me I have this risk, I'm going to do the crossword puzzles. And I sort of devil's advocate here. I say, well, what's keeping you from doing that now? And they kind of chuckle. I don't have time. How are you going to have more time later? So, you know, that That's the question. I want research on that.

Steve Kraske

You know, John, the other thing that strikes me about all this that argues in favor of telling patients sort of everything is the potential for massive cost savings in the medical system at large. I'm thinking of someone who finds out that she might be predisposed to breast cancer by the time they turn 45, something that's way too close and near and dear to my heart. But you find that out, and if you know that going in, your ability to sort of ward that off and deal with it at the time and save yourself so much trouble going forward is enormous.

Dr. John Lantos

With particular diseases, there may be massive cost saving. I mean, the newborn screening program, for example, if you diagnose hypothyroidism, congenital hypothyroidism in a newborn, you put them on a cheap thyroid replacement hormone, and they have no problems. If you didn't,

Steve Kraske

they'd have

Dr. John Lantos

lifelong cognitive delays. dependence on social welfare systems on the other hand there are diseases that you can diagnose that in the past before they were diagnosed the kids would just die and now they could get a bone marrow transplant or a very expensive enzyme replacement

Steve Kraske

therapy for life yeah

Dr. John Lantos

at

Steve Kraske

three hundred thousand dollars a year ouch kim from kansas city missouri kim thanks for holding on for us

Kim

Thank you for having me. As a mother of an adopted child, I wouldn't like to have the testing done because I know nothing of her family history of the parents or the grandparents.

Steve Kraske

Makes sense. Any thoughts, Rosamund?

Rosamond Rhodes

Well, I think it's a good idea to proceed with knowledge. And before, Kelly was suggesting some kind of studies she would like to see coming out of this disease, I would like to see a different kind of study. The people who are opposed to testing talk about there is no benefit and there are psychological harms. So I would also like to know for these families who get the testing about what their experience is, if they get the bad news, how long are they upset, how has it changed family dynamics, if it has or if it hasn't, because if... It turns out that the presumed harms just aren't there and the benefits are significant. It's a very different picture for making these decisions.

Dr. John Lantos

John, you'll be happy to know that we're doing just that at Children's Mercy. And I know Kelly's doing some studies at Stanford. The Bioethics Center is collaborating with the Genome Center so that for the parents whose kids are getting this innovative whole genome sequencing, we're trying to figure out what they understood going in. whether they're happy they got the test, and also from the doctors, whether they think the test... was valuable or changed therapy at all.

Steve Kraske

Yeah, Kelly Orman, you wanted to talk a little bit about genetics counseling, your own experience with genetics counseling when it comes to folks who might be predisposed to Huntington's disease, a very rare disease, right? That's correct. What have you been through with that?

Kelly Ormond

So I've been working with families who have Huntington's disease for almost 20 years. And what we often will see, you know, again, traditionally we're not offering this testing to people under age 18. We're waiting until they reach the age of majority so they can make a decision about about if they want to know or not, because this is a condition where it's actually what we call 100% penetrant. If you have the gene mutation, we know you're going to get this condition if you live long enough, and usually that's in your 40s and 50s, and there's no treatment for it. So it's quite different than doing breast cancer genetic testing or colon cancer genetic testing. What I often see is it's only that minority of people who kind of work up the guts to come in and even talk about getting the testing. So when we talked about 10 or 20 percent of people at risk get it, a larger percentage will come in and get the testing. And then what I would sometimes see, I'm guessing kind of in half the cases, is they come in, they talk about it, and we really have these rigorous conversations about how are you going to feel if you're positive? How are you going to feel if you're negative? What's your life plan? How is this going to impact your life? And then about half of them will sort of go away and not come back for some extended period of time while they continue to mull this over. Because this is pretty hardcore information to get about your life. And then many times they'll come back a year or two later and they'll say, I'm ready for it now. So some of it is life circumstance about being in a place. where you're sort of emotionally ready. And I think that the data that Rosamund is talking about, where we see that people, they have this spike in anxiety if they find out they have it. And then it goes back to their baseline usually within a year. And I think that's pretty consistent data we have for lots of diseases. They just need to be ready for it. The people who aren't ready, who aren't going to have that good response, don't show up for the testing usually.

Dr. John Lantos

Just one more quick response to Kim, was it, the caller? Yeah, Kim. With adopted children, it is a different situation, but it also reminds me that with your biologic children, you already know a lot about their genetics without getting genetic testing because you know what runs in the family.

Steve Kraske

I gather if you have a son or daughter who's interested in medicine but maybe doesn't want to be a doctor, that the whole field of bioethics research is just a hot field right now. Do I have that right? Put that

Dr. John Lantos

on your list. Absolutely. And we have a certificate training program for people who want to learn more, childrensmercy.org. In fact, you could go to childrensmercy.org. Kelly and Rosamond are going to do a debate about testing children for adult onset conditions tomorrow at noon. So if you want to hear these two brilliant bioethicists and scholars face off and really go at it. Tomorrow at noon, www.childrensmercy.org.

Steve Kraske

And more information about that on our website, kcur.org. I want to thank Kelly Ormond with Stanford University, Rosamund Rhodes with the Icahn School of Medicine at Mount Sinai, and Dr. John Lantos with Children's Mercy Hospital for a great conversation. Thank you all very much for coming in. So good to have you.