LP Doc Talk
Dr. William Wilcox, M.D., Ph.D./ Professor of Pediatrics, UCLA Schoolof Medicine
Topic: Supporting Dwarfism
October 30, 2012
Audio recording:
Moderator: Hello and welcome to the first episode of Growing Stronger’s LPDoc Talk. My name is Amer Haider and I am a parent of a little person and the parent cofounder of Growing Stronger. In this episode we have the pleasure of speaking with Dr. William Wilcox from Cedars-Sinai in Los Angeles who will answer 24 questions that were submitted online by the LP community. We hope you find this information useful and relevant. If you’d like to submit your own questions, you can do so by going online to and click on LP Doc Talk. Again, thank you so much for listening and we hope you support andjoin Growing Stronger. Thank you.
Dr. Wilcox: Any update [on the new BioMarin drug]? How long does a new drug (for rare conditions) typically take to go to market?On the treatment for achondroplasia, which I think some other people are asking about too, here is the update. I heard the presentation from BioMarin this morning on their Phase 1 results. They had releaseda press release, but didn’t have a lot of details. And this was a trial, this drugC-Natriuretic Peptide analog in adults, normal adults to see what its side effects were.It was pretty well tolerated and the only side effect that seem to be increased over aplacebo, or they just get a shot with nothing in it, is drop in blood pressure which is expected.And that will be the limiting thing that will inhibit how high a dose you can use in humans but it seems you can tolerate a fairly decent dose, the dose that’s even more than what’s necessary to make the monkeys grow. So the plan is for them to take their data to the FDA and have them sign off on thePhase 2 design. And hope to do that in the near future so that we can start administering the drugto patients probably mid-2013. Before anybody gets the drug, they will have to be in a growth study for at least 6 months where they get monitored to establish their baseline rate of growth. And the last time I saw the age range, it was 5 to 9 or so, for maybe 11, as high as 11 for patients that could be enrolled in a drug trial. So we have to wait and see for the final protocol to come out.As faras the growth study goes, we’re allowed to enroll 1 out of our 8 patients before the end of the year and then sometime early next year they will allow us to enroll the other ones. They just don’t like it to start too much ahead of time before the drug trial starts.
How long does it take?Well the Phase 2 trial is going to go on for a couple of years. They’ll probably start the Phase 3 trial, which will likely be doubled by placebo control before that 2 years is up. And it’ll probably take about 3 years to get approval. So I think 3 years is the soonest; so you’re talking 2016.
Moderator: And if I was to ask a question, what is the estimate on when it is approved in 4 years and 2 years?‘Till what age of childrenwill it benefit or is there no limit then?
Dr. Wilcox:Itwon’t benefit anyone who has finished growing,so boys stop growing at 18 and girls somewhere 15 to 17.
Moderator: So before that time, and then as much time as you get,will be beneficial, sounds like?
Dr. Wilcox: Right. So the longer you’re on it the more growth you’re going to have.
Moderator: Okay very good, very excited.
Dr. Wilcox:Okay the next question is someone having issueswith his knees and hips.“I am having issues with my knees and my hips.I have a meniscus tear in my right knee and had it repaired surgically. I have severe arthritis in my right knee. I am really interested in finding out about knee replacement for LPS. Is it recommended?What is the success rate?” I don’t know what kind of dwarfism he has but some of them have a lot of arthritis problems. We do hip and knee replacements. Knees are a lot tougher and have a lot longer recuperation period, but they’redone and hips are certainly done and the success rate is pretty high. Soit almost doesn’t matter what type it is.One recommendation that I make is make sure that the person isn’t too overweight. It makes it too hard to do the operation and a longer recovery period. So while you’re in the queue waiting for surgery and all the approvals and stuff to try and get the weight down to a decent amount because obesity is a big problem in a lot of little people.
“I am having issues with my hips. I have extremepain at times when I walk or stand for long periods. Any suggestions on how to relieve my pain?” Analgesics, it'sIbuprofen and, you know, that’s about it. Once you getanything else or have trouble walking, it's time to replace the joint.
So under thenext question,which is hypochondroplasia,it says, “Dr. Wilcox,our third daughter,Hannah, is 16 months old and has the common mutation of hypochondroplasia. What are your thoughts about the potential of treatment of hypochondroplasia with BioMarin's drug in trial?” Andyeah, theCNP should work fine on that. BioMarin just isn’t studying it first because there are less of them and they’re going to need less growth promotion than an achondroplast will so they probably won’t need a lesser dose. I don’tthink they’ll be doing a trial of the drug in hypochondroplasia for the near future that may not beuntil it’s approved even. So I wouldn’t hold your breath for the next 3 years waiting for it –because it may take that long until it’s available for hypochondroplasia. So that’s that one.
And the next one, “Will removing tonsils and adenoids improve obstructive sleep apnea?” Usuallyin many types of dwarfism particularly achondroplasia,there’snot much of a mid-phase so there’s not a lot of room for error to pass;when you fall asleep it’s even worse. So removing tonsils and adenoids is routinely done inpatients who have obstructive apnea. If there’s another problem, tonsilsand adenoids are not enlarged and not blocking the space, then it won’t work, so it all depends in a particular situation. So that answers that question.
Moderator: The next one is from Uganda.
Dr.Wilcox:What causes bones not to grow after a fracture? I guess it means not healing.It depends what the problem was and how thatfracture was but sometimes if it’s a compound fracture rather than a simple one, you could have some dead bone in there that just is blocking the healing process. So what’s done here, I can’t say how it’s done in Uganda, is you take a bone graft from somewhere else in the body and put it into the gap between the two ends of the bone and you can even add some growth factors to promote the fracture healing. So if it’s not been healing this many years there’s no way except surgical and a graft that’ll help it out.
“I need more information on acromesomelic dysplasia. I cannot find up to date information on the internet. My daughter is 7 1/2 years old 39 inches 45lbs.” Acromesomelic dysplasia, that’s the one dwarfism that will never respond to C-Natriuretic Peptide. I don’t know whether theachondroplasia ones will and hypochondroplasia, but probably many of the dwarfisms will respond but this one won’t because its problem is in the receptor for C-Natriuretic peptide,they don’t have any functionalreceptors so they can’t respond. There isn’t a lot of new information and discovering what the gene was a few years ago. Nobody has published much on it in sometime, and it’s pretty rare so there really isn’t a ton of information to kick in to anybody. I looked it up and there don’t seem to be any major complications to be on the look out for. It has a short forearm and short hands but also has some of the facial features that are like achondroplasia which kind of makes sense. So it may have some of the same problems with obstructive sleep apnea and ear infections that achondroplasts have. So, sorry I can’tprovide any more than that.The French group might, they may have some more patients. That’s whereit’soriginally describedby Professor Maroteaux in Paris.
Okay.“I have been reading about a new drug which makes bones grow for people with achondroplasia. Is this true? My four year old daughter has the condition. Will this drug help her or does it have to be used on babies. We are going to take the limb lengthening route, so the thought of her not to have to go through all the ops sounds too good to be true!” A new drug that makes bones grow.That’s the BioMarin and no, you don’t have to do it on babies but the sooner you get them on it the better once it’s available. Limb lengthening won’t be until she’s a teenager and pretty well done growing.
“I am an LP with 3M syndrome which is still being genetically confirmed. I am looking to find a family doctor who is familiar with dwarfism as all my present and past family doctors have not dealt with dwarfism other than myself and 3M is rare.”For 3M syndrome, there are no family doctors that arefamiliar with dwarfism and not a chance.You really have to see geneticists and not all of them are familiar with dwarfism either.It’s just a fact of life.There are people in Montreal and Toronto and Vancouver that you could see as well asSaskatchewan. I don’t know about Ontario. So really, all that you can do is to go to a geneticist and have them look up the 3M. If it gets confirmed, which is possible these days and make recommendations, usually the 3Ms do pretty well. They’re just very short from birth on. I had a family of 3 boys and 3Mso that’s all about all I can suggest there.
“I live in British Columbia,Canada and I am looking for a doctor and an orthopedic surgeon in BC that specializes in dwarfism and all?”Someone in British Columbia, I suggest it’s in Perfecta, where the best place to go is the clinic at the British Columbia Children’s Hospital in Vancouver. And that’s whereI’d suggest and go to the children’s hospital and ask for the skeletal dysplasia clinic and they should be able to get in there. If they want anyone of the world’s experts, I suggest it’s inPerfecta, whohappens to be also in Canada. He’s in Montreal at the Shriners Hospital there, his name is Francis Glorio and he could provide them the most up to date information that’s possible, not that there’s anything that’s wonderful and newthat’sout there. So hopefully people in Vancouver could help them.
Dr. Wilcox: Okay the next one is 2 year old with achondroplasia who is crying at night.
Moderator: From Dubai.
Dr. Wilcox:“My son is 2 years and 2 months old with achondroplasia. We visit the doctor every 6 months. All of his test reports are normal including his head scan from the past two months. He gets up during the night 6-7 times and cry. I make him sleep again by putting him on my lap. I don't know the reason but he cries a lot at night. He started to walk at the age of 2 and can say just a few words but he is very sharp and active, he eats homemade food. I stopped giving him breastmilk when he reached 2 years old. I want to know why he is so uncomfortable and sleepless during the night.Well,I don’t know if he’s having night terrors,which kids at this age can have, they can wake up screaming but I would be concerned that he doesn’t havesome sort of obstruction. There are kids that can have foramen magnum stenosis that presents later and becomes more obvious when they’re sleeping especially if they flex their head so they’re putting their chin on their chest when they’re sleeping. If he tends to sleepwith his head extended backwards that’s a sign that he maybehe compressing his spinal cord,if he’s complaining of headaches although that’s kind oftough ina 2 year old,they may not be able to say it. Another possibility is he could have obstructive sleep apnea, which would be really common. He’s just choking and unable to sleep,so he’s snoring, that’s a pretty good indicatorthat he might have obstructive sleep apnea and the way to find that out is with a sleep study. I think they should be able to do it in Dubai, otherwise,you might have to go to Saudi or something.
Okay. “I have achondroplasia and so does my daughter who is 2 years old, how often do you think she should have sleep study test done? She had one at 6 months old and everything was fine.We moved and went to another sleep study doctor and he would like to have one done on her now to keep for his records but didn't see she had any sleep apnea problems but wanted to make sure. I am just nervous with her being 2 years old, how will she handle this and if you think she should have a sleep test done?”If she’s not got any problems with sleeping, she isn’t snoring, she isn’tmouth breathing all the time because of the tiny little nose, she may not need one. If she’s snoring, if she’s sleeping during the daytime when she shouldn’t be, she’shaving headaches in the morning, those are all indications that she’s obstructing and needs a sleep study so it’s a judgment call. Some people do it much more routinely, I tend to just ask the questions and be concerned if there’s a need for it then.Okay.
Moderator: Next one is Marky from Australia.
Dr. Wilcox: “Please help me. I am looking to find more information on SMD Kozlowski and wondering how can I find other people with this condition?”SMD Kozlowski, there’s not a lot.Howyou can find other people?I don’t know if Australia has equivalent of little people. England does but I don’t know about Australia.In Sydney, they probably should see Dr.Silinsand he may be able to help with them and contact with somebody, because I believe he is in Sydney. Otherwise in Melbourne is Robby Salbert Ryan, he knows some people with SMD Kozlowski in Australia. Okay.
Moderator: From Ukraine. Nadine from Ukraine.
Dr. Wilcox: “My question is about my friend family's case. They have a 4-year old son with double genetic pathology -achondroplasia with mitochondrial myopathy. Have you ever encountered such cases in your medical experience?What would you advise to his family on supervision such a baby? Could you recommend specialists to address to in Europe? The family lives in Odessa,Ukraine.”4 year old son with achondroplasia and a mitochondrial myopathy?” No. The mitochondrial myopathy is far more serious than anything that achondroplasia’s going to do to you if the diagnosis is correct. I don’t know how it was established,it’s often done poorly even in the United States and overcalled. Achondroplasia has poor muscle tone particularly when they’re young and could get labeled as mitochondrial even though they don’t have it.
Specialists in Europe? Nothingin Ukraine that I know of or not much for Soviet Union either. Really you’d have to go to Western Europe to get anything on the combination of this two that I find it hard to believe they’ve got that, it’s just bizarre. But the mitochondrial stuff is by far the more serious and they need a metabolic person to take care of that.I don’t know if that helps any.
Moderator: No, Thank you so much. They can always follow-up. The next one question is from Ventura,California.
Dr. Wilcox: “My daughter is five years old with Achodroplasiaand a history of central and obstructive sleep apnea. She is due for another sleep study. It is important to have the sleep study done at a children's hospital or can any sleep lab perform an accurate sleep study?” Well they should go to see me. They’re not that far. The sleep lab has to deal with kids. That’s the major limiting factor,so it doesn’t have to be at Children’s Hospital but there arenot very many placesto do sleep studies withkids.So –they may be able to do itat College Hospital, it’s just in Santa Barbara that’s closer to them than LA is. So if they can’t get it donein Ventura, which I suspect they can’t, they might want to try College Hospital in Santa Barbara.
Moderator:And the last one is again from Ukraine, it looks like I think there are a couple of people who had some other questions through this one person sending email.
Dr. Wilcox: Okay. “How do you assess growth hormone deficiency in achondroplasia and hypochondroplasia, respectively? And do you have/know examples of increasing height in achon- and hypo- due to GH?”Growth hormone deficiency achondrolasia and hypochondroplasia? Well, if they’re not growing according to the curve for achondroplasia or hypochondroplasia ,–so not growing as expected, then they get worked up for hormone problems including growthhormone deficiency, but the combination of both of those is very rare to be both growth hormone deficient and have achondroplasia or hypochondroplasia so it’s usually not a problem. Growth hormone does not increase height in achondroplasia and hypochondroplasia.In a regular patient who is not growth hormone deficient,it’s not going to do anything, it’s not worth using so don’t waste time and money.