TRANSCRIPT:
Michael Kruer (00:00): There are different ways that misspellings in genes can actually come about. Most cases of CP are what we call sporadic, meaning that they occur seemingly out of the blue in families that don't otherwise have a history of.
Jason Benetti (00:19): Welcome to Let's Talk CP, the new podcast series about all things cerebral palsy presented by the Cerebral Palsy Foundation. Each episode features different clinicians, parents, people with CP and other experts talking about ways to help you better navigate your journey with CP. I'm Jason Benetti play-by-play announcer of the Chicago White Sox and ESPN. And I have CP.
Cynthia Frisina (00:47): And I'm Cynthia Frisina, the Vice President of The Cerebral Palsy Foundation, mom to a daughter with CP and an advocacy for Cerebral Palsy Research. Today's episode, we have an incredible guest one that we have been looking forward to having on for quite a while Dr. Michael Kruer, neurologist for Phoenix Children's Hospital is with us today. Welcome Dr. Kruer.
Michael Kruer (01:13): Good morning, Cynthia. So glad to be here.
Cynthia Frisina (01:15): So glad to have you here. One of the reasons that we are so excited to have you is you really have cracked the code on a topic that has plagued families of children with CP for quite a while. And that is the question of genetics and whether some types of CP is caused through something genetic or just this whole, like not knowing what causes a child CP has really been a challenge. So we're excited to talk to you about this topic today. Before we really get started, would love to hear a little bit more about you, your background and what all you do. We know that you're a neurologist at Phoenix Children's Hospital, but you do so much more than that with all of your research and would love to hear from you about that.
Michael Kruer (02:06): Yeah, thank you. As you mentioned, I'm a neurologist and developmental pediatrician focused at Phoenix Children's Hospital. I also run a research laboratory really focused on the causes of cerebral palsy and related disorders. And a big focus of our research lately has been the genetic basis of CP which is like you mentioned starting to lead us to an exciting direction.
Cynthia Frisina (02:33): What made you get interested in that topic? That's not common as we know. There's not many of you out there. I think our audience would love to hear what made you decide to sort of go in that path of researcher even think that there might be a possible genetic cause for CP.
Michael Kruer (02:55): Yeah, it's funny. Sometimes life leads us in unexpected directions, but you're absolutely right. I had been taught during my training as most of us are that CP is not a genetic disorder. And I think that, although we know quite a bit about many of the things that cause CP things like infections, things like prematurity, things like lack of oxygen to the developing brain. I became interested during my training in the possibility that the CP in some cases could be caused by misspellings in the genetic code. And it really was with a single family that I was caring for that led me in that direction. And what happened was I was just doing a clinic in developmental pediatrics like I often was at that point in time. And I was taking a routine history seeing a little girl with CP for the first time.
Michael Kruer (03:52): And I was talking to her dad and he was telling me just about her birth history and her symptoms and so forth. And I was trying to sort out how that could help. And then we covered family history. We kind of glossed over that and went on to other things. And then he stopped me and he said, "Well, when we talked about a family history, I didn't mention my other three kids with CP." And I kind of stopped and I looked at him and he said, Do you think that that could be relevant?" And I said, "Well, let's dig into that a little bit and figure that out." And it turns out that that particular family has five children and four of them had CP. And the little girl that I was seeing had a milder case than her other siblings, but none of the kids in the family had been born premature. None of the pregnancies had any complications. And so that really peaked my curiosity as to why that might be.
Michael Kruer (04:45): Long story short, we ended up enrolling that family in a genetic study that we were conducting and finding out that there was a misspelling in just one gene out of the 20,000 in the human genome that seemed to lead to their symptoms. And at that point I was hooked.
Cynthia Frisina (05:02): Oh my Gosh, that's an amazing story. It is amazing. I've heard that from other clinicians that one family could really change a perspective of a clinician. But you were one of the first, I think in the United States to really look at this issue and I think one of the questions that families sometimes are wondering about right now is, what is the difference between genetic or something that could be genetic and something that is hereditary? Are they the same? Is that a different thing? Can you talk a little bit about that?
Michael Kruer (05:39): Yeah, that's a great question and one that comes up often. Many families, especially parents will tell me, "Well, my child's CP couldn't possibly be genetic because no one else in the family has CP." And I think we were talking about genetic contributions. It's important to remember that there are different ways that misspellings and genes can actually come about. And in some cases they can be inherited through the family. It can run through different generations. For example, in other cases, it might be the case that both mom and dad are carriers for a particular condition. What's interesting though, is that most cases of CP are what we call sporadic, meaning that they occur seemingly out of the blue in families that don't otherwise have a history of CP.
Michael Kruer (06:32): And it turns out based on our research and data from colleagues that the most common reason for that is because mutations in CP often due to what are called Denovo changes, meaning out of the blue. And in this case, the mother doesn't have the genetic mutation, father doesn't have the genetic mutation, but somewhere during the course of child development, that child will actually pick up the genetic change. And we now know that roughly between 50 to 100 genetic changes will be picked up from one generation to the next. Many of those don't make a difference, but some of them if they happen to be in key parts of important genes can actually lead to CP.
Cynthia Frisina (07:20): Wow. I mean, that is not something that was even discussed in terms of CP just even a few years ago. Based on your research, what percent do you think of CP diagnoses actually may have a genetic component to them? I know you've just recently done some research and published some of that, which we shared on CPresource.org. But could you talk a little bit about what you think in terms of the percent of cases?
Michael Kruer (07:56): Yeah, that's a great question. And one that... Let me just say upfront, I don't think we have a good answer to in part because there was this concept in the field that if CP is not genetic, then no proportion of CP cases can caused by genetic findings. I think that this really deserves a careful look and I think we're still waiting for some of those studies to be conducted. However, our best approximation at this point in time is somewhere between 20 and 30% cases may in fact be genetic which is a surprise to many.
Cynthia Frisina (08:37): Wow. That could be like hundreds of thousands possibly.
Michael Kruer (08:40): Absolutely.
Cynthia Frisina (08:43): Let me ask you then this question. If a family has either a young child or even an older one where the cause of their cerebral palsy diagnosis was never really understood, which is like most cases. I know with my daughter we never even knew what the cause of it was. But if you have a child where the cause is unknown, should all of those families go and try to find genetic testing or what is your advice for families when they have a diagnosis of CP but the cause is not clear.
Michael Kruer (09:22): Good question. It's a little bit tough because I think that these are rapidly changing times and that the recommendations that we currently have for the workup of a child with CP are probably getting to be out of date and need to be updated. But my thoughts would be this, for family if you don't feel like you know the cause of your child's CP or even if you have questions about it, it's at least worth a discussion with your child's doctor to see if a genetic etiology, if a genetic cause could be on the table.
Cynthia Frisina (09:59): Can any doctor do that or do families need to go to a certain kind of specialist for that?
Michael Kruer (10:06): Yeah. That also is rapidly changing. I would say that the types of doctors that are probably the most comfortable in general would be child neurologist and clinical geneticist, but that's something that's also shifting. And I know that many other practitioners be the developmental pediatrician, pediatric rehab doc and others are starting to become very interested in this space and so I think that just having the conversation with the person that you identified as your child's primary CP doctors is a great place to start and he or she can then either help you go to the next step or get you to someone who can.
Cynthia Frisina (10:49): If a child is sent for genetic testing or does do that, are there... Based on your research so far just what you're learning, are there three or four common genetic causes of CP or should a family think about it? Is there an untold number of different kinds of genetic mutations or just a few?
Michael Kruer (11:15): Yeah. I think that the findings we have so far suggested that like a lot of aspects of human biology, it's very complex that there's certainly hundreds of potential genetic causes of CP. And as I mentioned briefly earlier, we're still discovering additional causes. And so I think that this is something that is rapidly changing and is going to continue to evolve for the next few years. With that said, there are some genetic causes of CP that are being seen over and over but each of those probably amount for about 1% or less cases.
Cynthia Frisina (11:57): There is not something that is super common, but something common that is a genetic cause that families might need to know about?
Michael Kruer (12:07): Yeah. There's definitely not just one CP gene if you will. However, I think that we're taking heart in the fact that the CP genes that we are identifying, they're really pointing us toward early brain development. And the findings they're suggesting that for many individuals who have a genetic cause their CP, it may in fact be the case that their brain development turns left when it should turn right so to speak, meaning that there's something in that typo in the genetic code that actually causes very early brain development to go a bit off track. Now, for many kids an awful lot is still going right. But there's something that's different about brain development based on those genetic changes that it's actually leading to a change in the way that the brain is wired up. And we're hoping that based upon the research findings so far that we may be able to start targeting some of these things for treatment in a focused way in the near future.
Cynthia Frisina (13:13): Wow. This is really kind of breakthrough information I think in this field which is incredible. And we all thank you so much for your work. If a family wants to learn more, are there clinical trials happening right now that they should be looking at or research studies or how would a family sort of learn more about this area and what they might want to consider?
Michael Kruer (13:40): Yeah, so we have an active trial going on right now where we're sequencing a new wave of families to try to identify additional genetic causes of CP and also understand how the different pieces of the puzzle fit together. So that's the trial that's being conducted in partnership with the Cerebral Palsy Research Network. And for those of you who are interested in learning more about that, you can find more information at www.cprn.org or conversely you can always check out my laboratory website which is Kruerlab.org.
Cynthia Frisina (14:21): Now, can a family do that from anywhere in the country if they don't live in the Phoenix area?
Michael Kruer (14:27): That's a great question Cynthia. The model that we've developed it has been because there is such an interest in this. We've had to partner with key centers, key CP centers around the country. And so that's where the CP research network comes in. That's been a bit of an evolution of our prior focus, but essentially families can get involved by going to their local CPRN center and talking to their child's doctor about the study.
Cynthia Frisina (15:02): This is awesome. Thank you. Thank you, Dr. Kruer. This is great.
Michael Kruer (15:06): My pleasure.
Cynthia Frisina (15:07): Thank you again, Dr. Michael Kruer for joining us today on this episode of Let's Talk CP. You'll be able to find this episode on CPresource.org as well as your favorite podcast platforms. Thank you for listening to part one of our discussion with Dr. Michael Kruer. Stay tuned for part two coming soon.
Jason Benetti (15:27): Thanks for joining us for this episode of let's talk CP I'm Jason Benetti, CPF ambassador and sports television announcer. If you like our show and want to know more, please visit our new CP Resource page at cpresource.org where you can listen to all of our episodes and subscribe so you'll never miss a show. While you're at it, if you found value in Let's Talk CP, we'd appreciate a rating. And please tell a friend or another family member about the show to help others and increase cerebral palsy awareness and education. Be sure to tune in to Let's Talk CP for our next episode.
Speaker 1 (16:05): This podcast represents the opinions of our guests and the content should not be taken as medical advice. Each person and situation is unique. So please consult your healthcare professionals for any medical questions.