Monday, October 22, 2012

Misunderstood: Genetic tests and the people who don't understand them


On Friday, I was made aware of a story about a boy in my town (Palo Alto, California) who was being transferred from his school to another school against his and his parents wishes. He didn’t do anything wrong and he didn’t want to leave. Instead, the administrators at his school made this decision based on genetic information they were given by the parents. Genetic information that they apparently did not understand fully.

The Story


The original story made a bit of a splash, with articles on major news sources. Here are a few links explaining the fiasco:
The original article that exposed what happened.
An official response from the superintendent of the school district.
An SFGate article that exposes important facts about this case.
The article I first heard about the story in.

The basic story goes like this:

A boy named Colman Chadam is being forced to transfer out of his current school in the middle of the school year because he carries mutations that cause cystic fibrosis (CF). CF is a relatively common yet fairly severe genetic condition.  Kids with CF should not be in close proximity to one another because they can easily infect each other with respiratory infections. In other words, a school would not want two kids with CF in the same class, and would probably be justified in keeping them separated for their own health (though it’s unclear if forcing them to go to separate schools is even necessary).

CF can be predicted genetically—we are aware of major CF mutations (in the CFTR gene) in the population and a standard genetic tests can identify them. But CF is typically diagnosed through a non-genetic test called a sweat test, and is otherwise a rather self-evident disorder because it is a serious condition. It affects one in twenty-five Caucasians. Moreover, the genetic tests are necessarily conclusive—one could carry mutations for the disease yet not have it.

The thing is, Colman was apparently never diagnosed with CF. He has never displayed any symptoms of the disorder. Instead, according to the SFGate article, Colman was found to have mutations in CFTR that could potentially cause CF. But they haven’t for him.

For whatever reason Colman had a genetic test including CFTR eleven years ago. It’s unclear in the articles I’ve found, but I’ve been told he’s likely to have tested positive for a sign of CF at birth and then had the genetic testing to confirm, but the disease never manifested later. So despite not having cystic fibrosis, his parents are aware that he carries mutations in the CFTR gene.

And, probably without thinking that there could be serious ramifications for Colman, his parents told the school that he carries mutations for CFTR when they were asked to report any pertinent genetic information.

The SFGate article discusses the progression from an innocuous bit of irrelevant “medical” information to Colman being transferred out of his school:

“A few weeks into the school year at Jordan Middle School, school officials took note of Colman's medical history, information that eventually was shared with another Jordan parent whose two children have classic cystic fibrosis and are predisposed to chronic lung infections.”

Can anyone else see some major problems with this little statement? First off, school officials were looking into this child’s medical history why, exactly? He does not have cystic fibrosis, so why was it being followed up so heavily by the administration? Second, his information should never have been shared with the other parent who has two kids with CF.

Moreover, with one in twenty-five Caucasians carrying mutations for CF, there’s likely to be numerous children at the same school carrying CF mutations who are not being transferred because they never had any symptoms and they never had a genetic test. That’s one of the things that makes this action by the school so unreasonable.

So I tried to think about how this could have happened.

I think what probably occurred was that Colman’s parents reported his CFTR mutations just in the interest of being fully compliant with school rules that say, “Tell us everything (or else),” which most parents are probably familiar with.

Then a nurse or administrator or someone (who hopefully had permission to see Colman’s records) who was familiar with cystic fibrosis (at least at the level of understanding that two kids with CF shouldn’t be in the same class) noted that Colman had CF mutations and misunderstood that to mean he has cystic fibrosis.

I’m not sure whether the other parents were really informed or not (at least one article suggests they were—if they were, they shouldn’t have been). But what I can imagine is that in the interest of avoiding any potential problems (imagined or otherwise), they decided to transfer Colman out without really understanding that he does not have cystic fibrosis.

There’s some pretty strong evidence of this in a letter from the superintendant that was posted on PaloAltoPatch. I’m pasting it below for posterity:

“The Palo Alto Unified School District strives to meet the needs of all students and to ensure that a safe and welcoming learning environment is provided for all our students and staff. To be clear, this commitment includes caring for our students with medical needs.
“At this time, our District serves students who are diagnosed with Cystic Fibrosis (CF), a serious medical condition that creates a need for our staff to observe strict protocols on cleanliness in order to help protect these students' fragile condition. I am proud that our staff energetically and compassionately works to observe the necessary protocols for these students. Further, I am proud that our staff thoughtfully embraces these, and all, students.
"A recent story that appeared in the San Francisco Chronicle addresses the distance -- the literal physical distance -- that must be constantly maintained between children with CF in order to avoid bacterial cross contamination. I want to stress that medical authorities clarify that CF is not a health threat to the general public (a theme that was touched on in the story), but it is a topic of concern for non-sibling children with CF.
“As background, at the beginning of this school year, we became aware that students (not related) with CF were on the same middle school campus. Based on the advice of medical experts, who stress the need for non-sibling CF patients to constantly maintain a specific distance from each other, we thought it best to place the students at different campuses. Again, based on the advice of medical experts, this is the zero risk option, and most certainly helps our District deliver on its commitment to provide safe learning environments.
“We asked the family of the student who is new to our District if they would consider moving their child to Terman Middle School. We asked because Board policy gives priority site choice to students who are established at a site, and the other students have been with our District for years. Sadly, it was this request that caused the controversy, and the media coverage.
“I want to stress a few critical points.
“First, at both of these schools the dedicated staff are stepping up and working to provide these students with excellent learning environments. We are grateful for their professionalism and compassion.
“Second, we are education professionals, not medical experts. I assure you that we will take action based on recommendations from medical authorities. Expert advice will be balanced by the PAUSD Board policy that strictly instructs our District to ensure we provide a safe learning environment for all students. To be clear, our Board of Education places the highest priority on student safety, in all situations and in protecting the privacy interests of all students.
"Finally, we must be honest about the fact that we are talking about public schools, not medical facilities. We will strive to implement all health and safety protocols to help protect the health of these children; however, the harsh reality of a busy middle school campus, where students ranging in ages from 12 to 15 share a cafeteria, restrooms, the gym and locker room, a library and other settings, is that it might be virtually impossible to maintain a specified separation and sanitation protocols at all times. This reality is what made us gravitate to the separate campus option. CF is a life-threatening condition, and in this context, based on the information provided to us at the time by all parties, we believed that zero risk was the best course of action. We hoped that these families would agree.
“This topic is understandably emotional for the families involved, and we will work with them to meet the needs of their children. However, I must again stress that we will follow the advice of medical experts, who we trust will help us understand the option that eliminates, if possible, all risks.”
Sincerely,
Charles F. Young, Ed.D.
Associate Superintendent Education Services
Palo Alto Unified School District

I feel that this letter clearly shows that at the very least, Dr. Young here was under the impression that Colman has cystic fibrosis. But he apparently does not. He carries mutations in CFTR, but he doesn’t have CF. Here’s another piece of evidence that Dr. Young and the other administrators are misinformed, thinking that carrying CFTR mutations is equivalent to having CF:

“The administrators sought medical advice, Silverman said Thursday, which resulted in a recommendation from Dr. Carlos Milla, of Lucile Packard Children's Hospital, saying that, ideally, children with cystic fibrosis would attend separate schools.
The recommendation was not based on knowledge of Colman's specific medical history, his parents and their attorney said prior to Friday's court appearance.”

Why else would they seek medical advice about whether children with cystic fibrosis should attend the same school unless they thought that Colman actually has cystic fibrosis? Rather than speaking with a medical doctor, they should have consulted with a board certified genetic counselor (which Stanford, where they received consult on this issue, has a number of). At the very least they should have spoken with a medical geneticist or even just a geneticist like yours truly. They didn’t even know that, though, because they collectively did not even realize genetics makes a huge difference here.

The Lesson

I honestly do think this is all a big misunderstanding. I hope that the administration is willing to admit a mistake was made and rescind their decision to transfer this kid over a misunderstanding about how cystic fibrosis works.

But to me, it’s also a troubling sign. I’ve sequenced my own exome. I know genetic facts about myself, and if Colman’s case is any indication, I would have no immediate recourse if that information were to be used against me in a legal way. What’s happening to Colman has yet to be ruled on, but regardless, his life is still being thrown to the wind while these decisions get made based on misunderstanding and ignorance about how genetics and disease work.

Moreover, what of my own future children? Or my current relatives? Information comes out about me and that information is shared by my relatives, at least in part. Could it be used against them by people in positions of power who don’t understand genetics?

These are major reasons I’ve yet to share my genetic information with others openly. I would absolutely love to make my data public, to reap the benefits of the community at large studying my genome. I had plans to do just that, but I have yet to enact them for these reasons. Because the current protections do not consider all possible problems—like this issue with Colman Chadam.

Solutions

Currently, I can’t stress with people enough that they have to protect themselves. I love the idea of living in a perfect world where we can share our genetic data and not be subject to prejudice (intentional or unintentional) as a result. But we honestly don’t live in that world yet, so those of us who have been sequenced should seriously consider whether sharing our data is in our best interest.

That includes not sharing genetic information with, for example, your kid’s school district. Of course we think it’s pertinent information they might need, but they do not need to know that your child carries CFTR mutations (only whether or not the child actually has CF).

As for Colman and his family, I think they need to push this. At the personal level, what’s happened to Colman is certainly unjust and possibly illegal. And for the PAUSD and its administrators, they need to learn a lesson here—that they need to fully comprehend what’s going on with students medically before making blunt-ended decisions about what to do with them. That if they are confronted with genetic information, they need to see a genetic specialist to interpret it correctly.

On a more general level, it needs to be recognized that genetic information cannot be used to discriminate against people even in the most innocent-seeming way, even when it feels like the right thing is being done. Until then, we who have genetic information about ourselves need to be careful with it and how we share it.

This issue is starting to spring up as genetic testing becomes more common. Imagine if a young person has genetic predisposition to asthma, but has yet to have an asthma attack. Do you stop that child from playing soccer or do you give her an inhaler just in case? The first one is, in my opinion, genetic discrimination. The second one is just common sense (or at least it should be).


7 comments:

  1. Your understanding of CF is not correct. 1 in 25 people carry the CF mutation, but it does not manifest as CF unless they carry two copies of the mutation. In other words, it's a recessive trait. This boy carries two copies of the mutation, and thus "has cystic fibrosis" from a genetic perspective. The fact that he has not yet manifested symptoms is irrelevant.

    Cystic fibrosis progresses differently in each individual. Many children with cystic fibrosis are relatively healthy and display no sign of lung or gastrointestinal symptoms of the disease. It's progressive, but it usually catches up to you eventually. It's true that there are mutations of the CF genes that cause fewer problems than others, but without knowing what he has, it's not unreasonable to assume that eventually his disease will catch up to him. Further, boys do better than girls due to horomonal effects on the chlorine channels.

    If I were that boy's parents, I would be hesitant to expose him to other children who do carry bacteria that are especially dangerous to CF patients. Just because he has no problems now does not guarantee him a healthy life. His parents are in denial if they think so. However, since the other children pose more of a danger to him than he does to them (if he has no bugs, and is healthy he poses no threat to anyone) it should be up to his family to decide what to do, and not the school district.

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    1. Thanks for your post.

      First of all, I'm pretty well versed on the genetics of CF given my field of expertise. I also spoke with a few genetic counselors about it to get an impression of the more intricate details of genetic testing of CFTR, though I did not share them in the post because I do not know what this boy's test results really were.

      This is important: Did you know that having two mutations in the CFTR gene detected by a genetic panel done eleven years ago does not mean the individual will have cystic fibrosis?

      I ask this because it demonstrates that even those close to the disease or with an intricate knowledge of it on a medical level may not understand the genetics.

      For example, if the two mutations are in a compound heterozygous state and in cis rather than trans, the person will have two different mutations in the same copy of CFTR and still have one functional copy of CFTR and not have cystic fibrosis. This can and does happen.

      You state that the disease is progressive and that's absolutely true. In fact, because of his genetic testing results (which are eleven years old), his parents and doctors have kept close track of whether or not he is developing CF (this is described in the articles I linked to at the beginning of the post). So far, he has demonstrated no evidence of CF medically, and therefore he does not have CF. Might it develop at some point? Possibly. But he does not have it now and they are continuously monitoring him.

      If I were the boy's parents, I would try to have my doctor and insurance sponsor a more modern genetic test to determine if he actually has CFTR mutations that would be likely to cause him to have CF. I would see a genetic counselor about the results to get the correct answer.

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  2. I'm pretty well versed on CF, since I have it and know a lot of people with it. However, I admit I did not know that it is possible to have 2 versions of the CF gene and not get CF. That's really interesting! I think that your wording in the beginning of the article ("But CF is typically diagnosed through a non-genetic test called a sweat test, and is otherwise a rather self-evident disorder because it is a serious condition. It affects one in twenty-five Caucasians.") suggests that 1 in 25 Caucasians carry two copies of the CFTR mutation and are affected by CF. It's a lot closer to 1 in 10,000, though it's true that 1 in 25 carry one copy of the mutation. I think that's what you were saying, but I misunderstood your wording, causing me to flail mightily. :)

    I do think it's important to note that the sweat test is not a conclusive test. One of the symptoms of CF is increased saltiness of sweat. The sweat test just measures how salty sweat is. My cousin, who is now nearly 40, but who has cystic fibrosis, passed the sweat test on multiple occasions, while showing other (mostly gastrointestinal) symptoms of the disease. He did really well with his CF until he picked up pseudomonas aeruginosa, which is one of the classic "CF bugs" that I assume this kid's classmates have. Conversely, I did not display any symptoms of CF at all until I was almost 3 (usually CF is diagnosed at birth due to failure to thrive) when I started to get pneumonia a lot. A sweat test is what diagnosed me. Just because I didn't show symptoms until I was three doesn't mean that I didn't have CF the whole time and that I just developed it at 3 years. My point is that just because you do not display classic CF (failure to thrive, lung problems, failing a sweat test, etc.) does not mean that you don't have CF. Every mutation can have different effects while still being CF.

    I guess my bottom line is that just because you pass the sweat test and are generally healthy does not mean you do not have cystic fibrosis. Your argument is that just because your genes say you have cystic fibrosis does not mean you do. It does sound like he needs a bit more genetic testing to determine whether he actually does have it, and I agree with you that I don't think that he should be forced to switch schools. However, until his parents know one way or the other whether he does or does not have CF, I'd still be hesitant to place him in close proximity to children who might carry CF bugs b/c once you get them (assuming you have CF) they never go away and the countdown to lung transplant starts ticking.

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    1. Thanks so much for contributing! That last point you make is immensely important.

      I should not have made it seem like the sweat test is the be-all and end-all of diagnosis, so please excuse me and thanks for sharing your experience. Also, I think I should not have said it is "rather self-evident" because like you pointed out, it can progress, and I'm sure that can be a risky time.

      Also yes, to be clear I meant that 1 in 25 Caucasians carries a CFTR mutation, not that 1 in 25 has CF or anything like that.

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  3. Yay, this was fun, and I'm glad to see that we agree in the end. :)

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  4. When I wrote about this ( http://biojournalism.com/2012/10/lack-of-understanding-leads-to-genetic-discrimination/ ), I took it as evidence that there needs to be a better scientific knowledge base in the general population

    The administrators, even if they didn't fully understand the implication of the genetic test indicating CF, should at least know enough to get the information they need.
    Or if someone pointed out the difference between having CF and having a genetic test that indicates CF, realizing that this was likely a misunderstanding.

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    1. I think there's no doubt that the general public is woefully under-informed about modern science. The people making these decisions may not have even learned basic 1980s genetics information, let alone understanding the intricacies of the CFTR genetic test.

      While solving that is a much bigger issue, at the very least the administration (and general public) should know to go to the correct type of professional to help them make an informed decision. Going to a medical doctor and asking about CF is not the same as going to a board-certified genetic counselor and asking about CF genetic tests. That's where they really flubbed up, I think.

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