Chad Perlyn, M.D., a pediatric plastic surgeon at Nicklaus Children’s Hospital in Miami, Florida, talks about a rare genetic syndrome that causes children to be larger than normal.
Interview conducted by Ivanhoe Broadcast News in June 2016.
Dr. Perlyn: When Katie was born, 15 years ago or so, there really were no Centers of Excellence here in south Florida. As you heard from her story she bounced around a lot from a local hospital here in Miami to Philadelphia to St. Louis, but one of the thing that we recognized over the last decade and a half or so, is the importance of real Centers of Excellence. That’s something I worked hard to build here at Nicklaus Children’s Hospital, is a program that really understands this very rare disease and how to treat the kids who have it.
Okay, you mentioned that it’s rare, how many children are diagnosed with it each year?
Dr. Perlyn: We don’t exactly know, because in some cases even physicians don’t make the diagnosis properly. But, we estimate around 300 children a year are born in the U.S.
Okay, and let me make sure I’m pronouncing this correctly, is it Beckwith–Wiedemann syndrome?
Dr. Perlyn: Wiedemann.
Wiedemann. What is your interest in it? It’s a rare syndrome why are you interested in this?
Dr. Perlyn: Well, I trained in St. Louis, where you heard Katie went many years ago and I studied under a physician, named Jeff Marsh, he’s now retired. Dr. Marsh really was the world expert in making large tongues smaller. I remember when I was his trainee, the first time I did this operation with him I could see how it so changed these children’s lives in just a short period of time. In an hour you can change these children’s lives by reducing the size of the tongue. I was just so fascinated by not only the disease process but how we can so effectively treat it, and the Beckwith-Wiedemann community it was very welcoming to me and I have just so enjoyed taking care of these kids as part of my career.
Well, tell me about that, I mean you know at first glance it doesn’t seem like that big of a deal, okay you make somebody’s tongue smaller, but it is a big deal?
Dr. Perlyn: No, that’s a great question, having a big tongue is a real problem for these children. First, when they are born, airway issues can be a major even potential life threatening concern. If you have a large tongue that’s blocking your airway you can’t breathe. Some of these babies need oxygen and even a small subset of them need intubation, a breathing tube and so forth. That’s an early term issue of having a large tongue. As the kids get older, feeding can become a major issue, drooling, of course psychosocial concerns. The kids are teased and so forth but really the most important thing is the relationship of the tongue to the teeth and the jaws. The large tongue acts like a piston, 24 hours a day, 7 days a week pushing on that lower jaw. But if left untreated those bottom teeth push forward and the jaw elongates, really causes very significant deformities to the teeth and the jaws.
Wow. Typically how much bigger is the tongue in this Beckwith–Wiedemann syndrome than in kids who have a normal sized tongue?
Dr. Perlyn: Well, Beckwith–Wiedemann Syndrome or BWS is what we call it. It has a full spectrum. We can see children who have essentially a normal size tongue or we can see a new born baby who has the tongue of a 300 pound man. It’s really quite variable. The majority of the children have a large tongue which is protruding from the mouth outside of the lips and wide, and some of those as I mentioned can be quite sizeable and really cause very significant issues and others can be on the mild. The key for us as surgeons involved in the care of these kids is really to individualize each child care and see who needs what.
Okay, so now let’s back up again. And exactly what is this syndrome?
Dr. Perlyn: BWS is a syndrome, it’s an over growth syndrome. It’s related to an issue on chromosome 11 and it causes several things to occur. The children can be born with abdominal wall defects. They can be born with large tongues as we mentioned, issues with their ears, issues with low blood sugar, issues with over growth of one side of their body which we called hemi-hypertrophy or hemi some of the kids call it, and also perhaps most significantly there is an increase risk in some of the children of having abdominal malignancies.
Why the abdominal malignancies?
Dr. Perlyn: Well, the relationship of the abdominal malignancies is likely due to the over growth, to the drive of cells or the proliferation of cells to grow and that’s what we suspect is the relationship. The good thing is we can adequately screen the children; so when a diagnosis is made and this is why it so important that we make an early diagnosis by doing blood test and ultra sounds we can screen children. If there was something to develop we can pick it up very early and that’s key in managing these kids properly.
What causes BWS?
Dr. Perlyn: BWS is caused by a mutation in chromosome 11 and because of the change in that chromosome we see over growth in the developing fetus. That over growth can really lead to a significant number of issues related not only to the limbs, but to the tongue the abdominal wall and so forth.
Can it be, can it be diagnosed in utero?
Dr. Perlyn: Yes, BWS can be diagnosed in utero; in fact we see that in many of our patients. A lot of times we’ll see a large tongue and many times the patients, the first ultrasound, the second ultrasound look at it and neither they or the signographer doing the ultrasound, oh look, the babies tongue is out of the mouth; how cute. But then they look closer we may see other defects, things in the abdominal wall, may one leg is bigger than the other and that clues us in the potential diagnosis of BWS and from there testing can be done in utero to confirm the diagnosis.
Is it genetic?
Dr. Perlyn: Yes, it is genetic and there are some types that can be passed on and there are some not.
Currently, what is the treatment for it?
Dr. Perlyn: The treatment for Beckwith–Wiedemann is managing the symptoms. In terms of the macroglossia (the large tongue), surgery is the best treatment for that and we can vary significantly improve the quality of the child’s life and either prevent or even reverse the jaw deformities that can occur. For abdominal wall defects, if a baby is born with their intestines outside of their body, of the course the treatment is for surgery as well. For the malignancies the key is screening. Screening, screening, screening, the earlier we can catch these things the better the survival rate, which often times in the ninetieth or even in the ninety-fifth percentile survival rate. That’s great news, so really that is what we focus on.
I have a question about the over growth of the tongue. What about speech impediments, does it affect the speech?
Dr. Perlyn: Interesting enough having a large tongue itself really doesn’t adversely affect speech. Unless the tongue is so huge that it becomes an issue and there are a few kids every year who are born like that. It’s really not a problem. Most of the kids, even with the large tongue, don’t really have a significantly issue with speech.
What are the newest breakthroughs in this development?
Dr. Perlyn: Well, the newest breakthrough in this syndrome is what we would call personalized or individualized medicine. There are many mutations that are related to BWS. Some of the children as we mentioned will go on the have intra-abdominal malignancies, cancer of the abdomen, that number is small. But, because of that right now, we are forced to screen every child who has the condition. Every child with a diagnosis of BWS based on our current practices should get a blood test every six weeks and then an abdominal ultrasound shortly thereafter. That’s a lot of testing for a young child and what we see and what’s coming in the future is personalized care based on a patient’s individual genetic mutation. We are beginning to understand and will shortly know the answer to the question. If you have this mutation, what is your exact risk of malignancy as compared to that mutation? That would really let us provide much more pin-pointed targeted care for the patients and that’s something we all are looking forward to.
If I understand you correctly, just because you have the same syndrome doesn’t mean you have the same risk for the various effect of it?
Dr. Perlyn: Absolutely, absolutely, absolutely. What we see is that the fetal type is the word we use for the different presentation of the syndrome is remarkably different based on the mutation. Some of the children may have hemi-hypertrophy, larger limbs, and a cancer risk which is x , while other children may have a very large tongue and a cancer risk of y. It does change significantly based on the mutation and that’s quite important for us to understand and learn more about.
Right, so one child might need to get tested every six weeks and another one may only need to get tested once a year?
Dr. Perlyn: Exactly, exactly, that’s exactly right.
How devastating is the condition for the kids who that have it?
Dr. Perlyn: Well, BWS again is a wide spectrum so there are some children’s who are quite mild, maybe they don’t have any tongue issues, maybe they have no abdominal issues, no cancer issues, but they have hemi-hypertrophy, one leg is bigger than the other one, they may wear a separate shoe, a lifting shoe, maybe they’ll have surgery to correct that. But at the opposite end of the spectrum some may struggle with blood sugar issues. Your blood sugar issues, who struggles to breathe at birth, goes home from the ICU, has a tough time feeding, a tough time breathing, maybe they have a large tongue, may need a tongue reduction, maybe they need abdominal surgery, maybe they are one of the kids that develops a mass who need surgery. It’s such a wide spectrum and that’s our job as physicians is really to understand what to look for, when to look for it and how to best manage these children.
Sometimes if it’s caused by a gene mutation, that’s heredity and sometimes it’s the mutation just happens; why is it? What causes the mutation in the gene like that? Why in the case of Katie after conception the gene was mutated?
Dr. Perlyn: I don’t know the exact answer to that despite the fact that I have a PHD in genetics. Such a complicated process of how those mutations occurs. I would defer to answering that because I don’t know the exact right answer. This is the subject of huge amounts of research right now, is trying to understand how these things happen. We do know that there are some babies who are born via IVF, fertilization that can have Beckwith. There’s some thought that different types of mutation or related to the IVF process, how the cells get processed and again even that right now being very actively studied.
What do you think has worked for these kids, the physical components or the psychological components?
Dr. Perlyn: Well, the question is what works for these kids, the physical components or the psychological components. The best answer that I can give as a surgeon is that I hope neither. Our goal at the center, like this, where we really understand these rare conditions like BWS, to take care of the children when they’re small so they grow up to live normal lives that are happy, productive, and there’s really no sequelae to the issues that they have as a child. If we do jaw surgery early the baby, they may have no recollection of surgery. Their jaw grows normal, they developed normally, they go through speech therapy and they speak normally and they have essentially a normal happy life. That’s our goal, that’s what we really want is that it’s neither the physical nor the physiological that affects the child. We really do try the good thing about this disease although it has so many things if we enter intervene early we can prevent so much. What happens when that jaw gets pushed forward it’s quite deforming. Even in young babies, this is how you can ask. Even in young babies that jaw gets so far forward the children developed a huge overbite and if left alone they develop a very course, very full heavy lower jaw with their teeth open, with a big space open between their teeth called an anterior open bite or cross bite. And by doing the tongue reduction surgery early and stopping that force of the tongue pushing forward we not only stop the defamation, in terms of the mechanical sense of the jaw but we’re able to allow the body self-correct itself and it’s amazing how it does in children.
I know you talked about the breakthrough being personalized care based on what we’re learning about genetics. Anything else on the horizon in terms of treatment, diagnosis, for instance?
Dr. Perlyn: That’s really the main issues in terms of screening. The same holds true not only with mutations for the cancers but we hope to be able to predict this well in the future based on mutations, what children will have jaw issues and so forth. Most of the research today is about that; understanding the relationship between the genetic mutation that the child has and the outcome as a result of that particular mutation.
When you talk to a parent who just learned that his or her child has BWS, what do you say to them? What is the most important thing you tell them?
Dr. Perlyn: Well, I’m very fortunate to be able to talk to many families from around the country, even around the world who have newborns with BWS. I’m always happy to talk to families and help them get through those tough, first few days and the thing that I tell them the most is that we can fix their child. That with proper monitoring and proper screening and watching the children not only for the abdominal malignancies but for teeth and jaw development we will be able to correct things and let them go on to live normal, happy, productive lives. As a parent who has a new born with an issue being able to hear that and to know that there are places that are out there that understands these rare conditions that are dedicated to them I think that gives them, the parents, so much hope and alleviate so much anxiety.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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