Activity Transcript

Geneviève Baujat, MD, MSc: Hello, I'm Geneviève Baujat. I'm a pediatric geneticist working in the Centre of Reference for Skeletal Dysplasia in Paris, France. Welcome to this program called "Optimizing Care Pathways in Rare Bone Disorders." And joining me today, Nicky Muller, who is a mother of a child with FOP, and Christiaan Scott, professor of pediatric rheumatology at the University of Cape Town, South Africa.

In this program, we are going to discuss the consequences of ineffective care, best pathways in rare bone disorders, and the importance of multidisciplinary team required for optimizing the care of patients with rare bone disorders.

Rare bone disorders affect not only skeletal, but often other organs, which require complex management. Natural history of these patients are not often well known, especially by general practitioners. So, challenges exist regarding patient management.

The field of rare bone disorders is a very large field. We have the habit of dividing them into several categories, including chondrodysplasia, primary bone fragility, osteopetrosis, disorganization of skeletal components, and dysostosis. In our clinics, the three most frequent bone diseases are osteogenesis imperfecta, achondroplasia, and hypochondroplasia and multiple osteochondromas. But there are many, and the last international classification found more than 460 rare bone conditions and more than 90% of them are identified on a molecular basis.

So, what are the main characteristics of these bone disorders? First of all, these conditions make up about 5% of all nongenetic conditions. So, they are actually not so rare. The phenotypic variability is important, because a large proportion of these conditions are presenting with a wide spectrum of phenotypes and severity of symptoms. They can be very easily missed; for example, signs of early osteoarthritis or fractures in adulthood. But these patients usually have visible skeletal abnormalities associated with normal cognitive abilities.

The main skeletal symptoms associated with these conditions are, at first, stature disproportions, deformities, pain, fatigue, working difficulties, joint dislocations. So, all joint fusions and fractures, but other symptoms may arise, including pulmonary involvement, neurological compression, endocrine features, myopia, hearing loss, and others, such as renal or hepatic disorders.

In France, for more than 15 years now, we have an organization within a framework of a national plan for rare diseases called the Centre of Reference for Skeletal Dysplasia or Rare Bone Disorders. We have a real network of centres across the country with one coordinating centre, two constituent adjunct centres, and two pediatric ones. And we have 20 regional competence centres.

Our missions are to improve access, and to reduce time to diagnosis and treatment. And, at the national level, to try to optimize the care pathway including the care transition between pediatric and adult age. We have to improve knowledge on the natural history and also, of course, research -- translational research and therapeutic clinical research -- and also other types, such as epidemiology, and also social and human science. We belong to a global European network, BOND, and also to other societies, including the International Clinical Council on FOP. And we have regular meetings at a national level with exchange through a platform.

Our ideal pathway for patients with rare bone disorders is shown here. We first have the diagnosis period. This is for us not only one day, but a period of time, and for our skeletal dysplasia patients, some are diagnosed prenatally, others postnatally. Imaging is a very important tool and also now we have excellent molecular tools to try to decrease the diagnosis errors in this period of time. Usually, the first consultation within our network is about 2 months of life when the diagnosis was not performed before birth. We look for a clear explanation of the diagnosis history, the signs of possible complications, and we explain how we organize our assessment using a calendar of assessments depending on the disease.

Between the first consultation and the age of 3 years, we have more clinics, but we also organize reimbursement administrative duties and we try to include, as best as possible, the family and all the social elements in our practice. That is very important.

Then, between childhood and adolescence, we try to have a mandatory assessment at year 5, year 10, year 15, and year 18 before transition or more frequently if needed. After the age of 15, we prepare the transition between pediatric and adult care with several elements. First, we re-explain to the child what his disorder is, the genetic elements and genetic counseling and how to keep healthy, the importance of prevention measures, and how to prepare the adult follow-up.

Usually, around 18, we have a transition clinic, which is a type of multidisciplinary clinic with adult and pediatric teams all together to transfer information about history and other elements, and to discuss the next steps after 18.

After 18, in adulthood, we try to have at least one global assessment every 3 years, but of course, for some diseases and for some patients, we do that once a year.

It is true that we have some difficulties for the second part of the adult life for many skeletal dysplasias. So, the main approaches are prevention, therapeutic education, supports, professional inclusion, and, in the pediatric age, school inclusion, this transition and availability of a coordinating physician.

It is important to mention what a multidisciplinary team is. In France, we start with a core team. In pediatrics, this is usually a pediatric medical geneticist with a pediatric orthopedic specialist and, in adult age, it will be a rheumatologist or a rehabilitation specialist. So, it is important to know who is the coordinating physician and how to contact him. The rest of the multidisciplinary team involves several specialists that will be needed depending on the needs, and of course linked with the peri-medical team, such as physiotherapists, psychologists, occupational therapists, and others, and all these healthcare providers are, of course, linked together.

So, this is of course an ideal pathway, but many patients are not so lucky. And to illustrate this, we will have the pleasure now to have Nicky's video to illustrate her and her daughter's journey.

Nicky Muller: Hello, my name is Nicky Muller. I live in the UK. My daughter, Isla, has fibrodysplasia ossificans progressive, FOP for short. Isla was my first child, an 8-pound, healthy baby. However, I noticed that she had bent big toes. And it was noted at birth that she had congenital bunions.

I was let out of hospital the next day and started my journey as a first-time mother. I soon decided to have a look on the internet about what kind of treatment would be needed for her big toes that were bent. And I couldn't find anything. So, I kept looking, and I kept looking. And eventually, I saw some toes that were just like hers, and this child had a condition called FOP.

After seeing about FOP, I was incredibly scared. And I made an appointment with my GP. The GP told me I had postnatal depression. She'd never heard of such a disease and sent me on my way. My husband then contacted FOP Friends, the UK patient organization, who were very helpful and gave us the contact for the FOP expert in the UK.

On returning to the GP, I asked for a private referral to this person. We visited a few weeks later, and he said that it probably wasn't FOP, and he would take a blood test. But he didn't know how to take blood tests. Isla was only a little tiny baby at this point. So, he sent us to our local hospital, where we had the blood test. And we had to wait what felt like an entire period. It just went on and on.

And clearly, I was obviously a very anxious mother at this point. Isla started to develop soft tissue swelling, which is another very clear sign of FOP. So, it was on the back of her head. And we returned to the local hospital. They said, "Oh, no, it's nothing to do with FOP, that it's probably some kind of birthmark." Made the scans. They had lots of people involved. And again, we were sent on our way.

And then a few weeks later -- Isla was 3 months old --I was at home with my tiny baby. And I received a phone call from the FOP expert to say that the blood tests had come back, and she had FOP. My world fell apart, and I had nowhere to go. I felt incredibly alone, exhausted, and confused. I felt to blame.

I had so many questions of which I didn't have answers. So, we started the journey. We met back with the FOP expert at the orthopedic hospital. I kept thinking, "He's not a pediatric expert. He doesn't even know how to take blood of a child. You tried to dismiss [the signs, you tried to say] that she didn't have FOP." So, I lost trust in that expert.

However, I didn't know where else to go. And the GP, at that point, has not been involved and not really, to be honest, been involved since. As Isla has grown up at 5 months old, we did get to go to an FOP conference, which was massive. So, I think at this point, the FOP Friends were the biggest support for us. Actually, coming from other families and also to meet some of the experts from around the world was invaluable. So, we were very fortunate and very few people get that opportunity. So, that was fantastic.

Unfortunately for Isla, the progression of the disease has been quite bad. By 3 years old, she'd lost a lot of upper body mobility. And, that continued to kind of get worse. And she now has scoliosis, which is the biggest threat to her life. So, the thing that I think has been the hardest has been the transitions through the healthcare. So obviously, she was a baby. I then wanted to get her into nursery and go back to work part-time.

So, making that transition and then, obviously, into school, and making sure that she had the benefits that she needed and the right level of care. I remember very early being told, "You need to become the medical co-expert." And that was the scariest thing anyone could have said to me because I'm not an expert. I was a new mum. And I was trying to do the best for my child, but I didn't know what the best was.

With such a rare condition, it's very hard to know who to turn to. There was no one to turn to really. And I had to fight. And thankfully, I am that kind person, and I knocked on doors and made sure that she got the appointments she needed. Through the years, we went from, as I say, having the GP involved and the orthopedic hospital when she was a tiny baby and having a local hospital, pediatric department. I fought for that because I felt that my daughter needed a pediatric expert as part of her care.

All of this is managed by myself. There's no one that does the management or care plans. It's totally up to me to do this. Letters are shared, but very often not read. I, especially at the start, found it incredibly hard going to these appointments. No one's heard of FOP. No one can really tell me anything. I'm telling them. And I have to repeat my story hundreds of times. I mean I can't even tell you how many times I had to explain our story. And they worry because I've got so much on my plate. Am I missing things? Have I said the right thing? Have I explained? Is there something that I should have done differently? So, there's a lot of pressure on myself to manage that.

We're now at a point where we have, I think, 5 different hospitals involved in Isla's care. So, I manage all of those and the kind of appointments. And we average probably 1 appointment every 2 weeks. And they could be all sorts. So that's not just appointments in hospitals with doctors. But it's also things like physiotherapy, occupational therapy, social services, educational healthcare plans to make sure she gets the support she needs in schools, et cetera, et cetera. So, I'm having to juggle all of that whilst also having another child, a job, and being a mom.

So, it has been really challenging. And I think the other thing is because FOP is a progressive condition and, as I say, her progression has been rapid, the grief and the heartache and the emotional side of that is very hard to bear. And trying to make the right choices is tricky.

All that said, I feel incredibly fortunate and thankful that Isla was diagnosed so young, one of the youngest probably in the world. And we do have an incredible FOP community. We live in the UK where we get healthcare for free. And I get a lot of support from other families with the condition. And for those in less fortunate circumstances, it must be incredibly difficult.

Dr Baujat: Thank you, Nicky, for sharing your experience. And maybe Chris, do you want to comment first?

Christiaan Scott, MBChB, FCPaed (SA), Grad Cert Paed Rheum (UWA): Yes. Thanks very much, Nicky, again, for sharing such a powerful story. I mean, it really tells the story of how you had to navigate the medical system and the challenges that you faced. We always think in FOP that half the battle is won once we've made the diagnosis. But you've shown us very clearly that, in your case, making the diagnosis only works if you have a care team that's willing to accept the diagnosis, and willing to go an extra mile and learn about a disease that they've never heard of.

And I think this is something that we hear a lot from patients is how they struggle to engage with the medical system, and how powerless patients feel and how voiceless they feel when it comes to making the diagnosis, because our medical systems are generally not geared to looking after patients who come with their own diagnosis or patients who come with rare diseases that we're not trained to look after.

So, I guess apart from commending your courage, is just to ask you how do you think the system could have been better done? It's not a particularity in the UK, I'm sure, but I wonder if you see some kind of way that the system could work better. And is it perhaps as simple as training doctors to listen to patients rather than always having their own opinions first?

Ms Muller: Yes. Thanks, Chris. For me, the hardest part, I think -- yes, obviously, discovering FOP -- but also was the way that we were told. I believe that in the UK, they do try to give a diagnosis face-to-face and with the right experts around. That wasn't our experience.

I think if we'd had the right people, even if it wasn't necessarily FOP experts, but people that knew how to work, and how to advise, and how to support a family, that have just been given such a diagnosis, would've been very helpful and really just made that start of the journey so much easier.

And I think, then, the second part is the holistic piece. So, a condition like FOP which, yes, comes under rheumatology, you end up in an orthopedic-style hospital. However, there are a lot of other elements that need to be looked at. So, I'd love to be able to see that in the future.

Dr Scott: And I think Geneviève's example of how things have been working in Paris offers that sort of possibility that you can have a team of people who are not necessarily disease specific, but at least regionally specific in terms of disease and who can adapt their workings, which are very similar across many rare conditions to have a certain way of dealing with this problem rather than each disease needing its own multidisciplinary hyper-clued up setup where you've got a trained psychologist who only works with FOP. Of course, that kind of thing's never going to be possible any area in the world.

I think in our setting in South Africa and in Africa, we don't have those multidisciplinary setups necessarily at all. And you alluded to that in some of your talk. But it gives us something to work with in terms of developing these things going forward, so that each FOP patient doesn't have to redesign a healthcare system around themselves or any rare bone disease patient doesn't have to, as you've had to do -- create a healthcare system, in a way, to look after your child, who deserves every right to expect the best possible care.

Ms Muller: I think the piece that really interested me with the French system as well is the time points of which the Centre of Reference gets involved, because those points of going to school, for example, they're massive. And they're very hard to navigate as a parent trying to tell the education system or whoever needs to know that if it's the county or whoever that's providing funding for maybe a one-on-one or something like that.

As a parent, it was very hard to show the importance of those kind of resources because actually, at the time, for example, my daughter could walk very well. But the risk to her was from having a fall. And to try and explain the importance of that, and the fact she couldn't move her neck and those kinds of things, was really hard. So, I think to have a medical expert involved in being able to support those applications would've been really great.

Dr Scott: So if I may, one of the things I realized from your story was that there was a central breakdown in your story, was the fact that there was not a central medical personnel or medical individual who took control of the whole endeavor, who acted as the glue holding the multidisciplinary team to get a person that you could go to for specific referral letter, someone who could write as a counsel if you needed assistive support or housing support in terms of getting your pavements more wheelchair friendly. You need someone like that who's got a voice within that people can respond to in various levels of authority. And I think that that person, every team needs a champion to be able to rally the troops, to be able to launch this assault on the system that is required for a patient with FOP.

Dr Baujat: Chris, can you tell us -- how does it work in your country for diagnosis and then management of patients?

Dr Scott: Thanks for that question. So, I mean South Africa's 52 or 60 million people now. So, 60 million people, we should have about 60 FOP patients. We know about just under 20 FOP patients now. So, we've got a long way in just finding the patients as FOP and diagnosing them.

But having done that, I, as a pediatrician, have found it very difficult to develop a multidisciplinary team that is cohesive and keeps wanting to be involved with FOP. So, in a way, we're sort of recreating a little care package every time we diagnose a patient based on where they live in the country, et cetera. We don't have a very solid central referral system to be able to manage complex rate diseases in a uniform fashion for all comers with rare diseases.

So, it's really cobbling together a team based on every child's need. But it does leave me, as a pediatrician in charge of, or in support, rather, of a team that looks after 60-year-old patients with FOP, and 50- and 40-year-olds who start. Some in their twenties started with me as children. And it's very difficult to hand that baton over to someone. And that's one of the magic things about the FOP communities, that you see that someone needs to make that decision to hold that space. And it's difficult to give to someone else. You can't force it.

Dr Baujat: Yes. Most important is communication between physicians, between FOP experts, the medical coordinator, and all the specialists that will be required depending on the disease and the symptoms. Maybe we can summarize the most important of the messages for this discussion. For the diagnosis, that the aim is to decrease diagnosis errors with education, and the expert centres are very important once the diagnosis is suspected and confirmed, because this allows for regular touchpoint with relevant rare bone disease experts and avoiding unnecessary assessments, and ensures the right multidisciplinary team is involved.

And, for example, in FOP, the prevention measures -- including preventing muscle injuries at school or from vaccinations and so on -- are very important in order not to harm the patient. Today, conventional treatments are much better organized and we now have guidelines, recommendations, and consideration from the ICC group and also, of course, by IOFPA, which gather many associations from all the world with adaptation to the language, but also for countries.

Dr Scott: Thanks, Geneviève. Yes. I completely agree with you. And I think the point you make about education is really important, and the need not to do harm in FOP and to avoid us allowing patients or people living with FOP to be harmed by our colleagues who don't know any better. So, that's a key thing. And the root to that, for me, is I always muse about the fact that we know as medical professionals, as pediatricians, we do the reflex looking for retinoblastoma, which is rare.

We do look at the sclera to see if it's blue for osteogenesis imperfecta. But it means something to us. And we look for those things. I think in a diagnosis that is as simple and as straightforward as FOP -- and Nicky's story illustrates how simple the diagnosis actually is of FOP -- it doesn't take complicated diagnostics or clinical reasoning skills.

It's very simple pattern recognition. And if we can, just by advocacy and by intent, change medical training in a way that alerts people to the fact that this is a very easy thing to think of, very easy thing to diagnose, and you don't have to know anything other than that you shouldn't do a biopsy and the patient should be referred to someone who knows something about FOP, that cannot be so difficult. And I always wonder how something like some of the screenings that we do for Kayser-Fleischer rings has entered the medical teaching, for instance. And we all know about it, but it's by accident. So, we need to kind of reverse that accident and actually engineer an accident to happen in terms of FOP and other rare bone diseases, so that people have the bare tools to be able to know this is trouble. [The training] needs to go there.

Ms Muller: And I think, even when you have a diagnosis, something we've seen is, my daughter was rushed to hospital after a fall the other day. I wasn't there. And trying to explain FOP to the paramedics is really, really hard. And as much as you're saying, You can't do this, you can't do that," they're going to ignore you because they think they know better. And those kinds of situations can be very dangerous even if you have a diagnosis. So, being able to have the tools or the people in place to make those situations easier and prevent, yes, anything catastrophic happening, obviously, if it's saving lives, then measures have to be taken. It's a lot of pressure and I really hope that the changes can be made.

Dr Scott: Yes. If I may comment on that, I mean, I think you're absolutely right. And it's almost a change of culture within the medical community that needs to happen. Information is everywhere, and doctors who don't listen will come up short every time.

Dr Baujat: Thank you, Nicky, and thank you, Chris, for your participation in this presentation. Thank you to the audience. Please continue and complete the evaluation.

This transcript has not been copyedited.