Podcast interview with Pierre Robin Sequence parent

Osmosis.org is a health and medical education company that reaches nearly 500,000 health professionals, patients, and their family members. The company produces animated videos that have been viewed more than 25 million times in over 200 countries. Osmosis.org helps medical, nursing, dental, physician assistant, and other health professional students in the classroom, on board exams, and in the clinic. As part of the Osmosis.org Raise the Line Podcast series, Osmosis.org CEO Shiv Gaglani interviewed a Pierre Robin Sequence parent, Philippe Pakter.

“It’s a strange odyssey being a rare disease parent. It sort of forces you to question everything about life,” says Philippe Pakter, whose daughter Lysiane was born with Pierre Robin Sequence, a condition that impedes normal breathing and feeding. In this compelling interview with Shiv Gaglani, he shares the details of his family’s emotional, medical and legal journey. “It’s tough, but you just have to keep going, and from the hardship can potentially come very beautiful things.”





Shiv Gaglani: Hi, I’m Shiv Gaglani. As regular listeners know, Osmosis has a special commitment to educating clinicians, patients, and families about rare diseases. In partnership with the National Organization for Rare Disorders, we’ve worked with dozens of patient advocacy groups and subject matter experts to develop nearly fifty engaging videos on rare disorders that have been viewed millions of times.

Today on Raise the Line we’re going to broaden our scope and learn about how patients and family members in Europe work with clinicians and others to advocate for themselves and their loved ones. I’m delighted to welcome Philippe Pakter, an international lawyer based in Geneva Switzerland, whose daughter Lysiane was born with a serious form of Pierre Robin Sequence. Philippe is a great example of how well-informed rare disease family members are, and why clinicians should listen closely to what they have to say.

Before we get started I wanted to thank our CEO at Elsevier, Kumsal Bayazit, who first connected me to Philippe – because actually he published his patient experience about Lysiane with some very interesting conclusions that I think are broadly applicable beyond Robin Sequence, to the rare disease community; this was in one of the Elsevier journals, Seminars in Fetal & Neonatal Medicine.

So, Philippe, thanks so much for taking the time to be with us today.


Philippe Pakter: Thank you very much, and because you brought up Kumsal Bayazit, I wanted to take a quick moment to express again my sincere thanks to her, because she reached out to me personally – having read the article that I submitted to the journal as a rare disease parent – and she granted us Elsevier’s “Gold Open Access”. And that’s just such a beautiful, meaningful gesture. We wanted as many people to read the article as possible, and by giving us open access, for us it was monumental, and I thank her from the bottom of my heart. For the people in my family and in the rare disease patient group that I am with, giving us open access on that journal article meant a lot. It really did.


Shiv: Definitely. I will say, you know, now that we’re nine months into joining Elsevier… we knew about the values, we knew about the leadership team, but certainly, they live it. They walk the walk, they don’t just talk the talk. That was just one example. I told her about our rare disease focus, and she immediately said your name, sent me your article, and connected us. So truly, a wonderful leader. I’m privileged to work for her.

So let’s go into your story. I obviously know quite a bit about you and your background. We’ve spoken a couple of times before. But for our audience, many of whom are current and future clinicians, can you just give us a breakdown of your family story about Lysiane, and your journey dealing with Pierre Robin Sequence?


Philippe: Sure. Well first of all, Pierre Robin Sequence was first studied by a French stomatologist, which is like an orthodontist, over 100 years ago, and it has three diagnostic criteria. A baby is diagnosed with Pierre Robin Sequence if the baby is showing an anatomical defect – micrognathia – which is a very small undersized lower jaw. The mandible is very small, undersized.

The second criterion is glossoptosis, which is another anatomical defect. The tongue, instead of being in a flat, horizontal position in the mouth, is in a raised vertical position, in the back of the throat. And as you can imagine, if you visualize that, that raised vertical tongue is blocking the airway, creating breathing difficulties and feeding difficulties. So that’s the second thing, glossoptosis.


The baby’s tongue, instead of sitting flat in the mouth, sits up, in the back of the throat, in an angled or vertical position; the medical term is “glossoptosis”.


And the third diagnostic criterion is upper airway obstruction, UAO, as determined by polysomnography, by a sleep study – the baby is suffering from an apnea-hypopnea index which is above normal for a child of that age.

Now what this comes down to is that the baby is born, and the baby is struggling to breathe.  It’s like you’re watching your baby suffocating, or drowning – but there’s no water anywhere around. The baby can’t breathe, because the tongue is blocking the throat. Now it’s not a strictly mechanical issue; for instance there are babies that have micrognathia which is not so severe, the lower jaw is not so small – and the tongue is not so vertical – but still, there are breathing difficulties. So it’s a complex condition, and it does have neurological components – but what it comes down to is that in the vast majority of cases, this seems to be an anatomical problem of the tongue in that raised position blocking the airway, and causing the upper airway obstruction.

Another thing is that most of the babies that are born with Pierre Robin Sequence also suffer from a cleft palate. Not a cleft lip, but a cleft palate. This is actually a consequence of the fact that during the prenatal period, the tongue, being in that raised, vertical position, prevents the roof of the mouth from fusing; fusing normally happens in the prenatal period.

The important thing to understand for medical students, and for clinicians without experience in this rare disease, is that a Pierre Robin Sequence baby is not a baby with a cleft who happens to have a small chin. A Pierre Robin Sequence baby is a baby with a complex rare disease, who happens to have a cleft – and who may not even have a cleft.

In other words, expertise in cleft care does not confer expertise in Pierre Robin Sequence. Pierre Robin Sequence is a highly complex rare disease which is still being studied, and which experts are still trying to better understand. One of the many things that separates Pierre Robin Sequence from a standard case of cleft is that the mortality rate is substantially higher. In one Dutch study, the mortality rate of Pierre Robin Sequence babies was eight times higher than the mortality rate of babies with a cleft who did not have Pierre Robin Sequence.

Another striking fact: among babies born and diagnosed with Pierre Robin Sequence, over half of these babies will also suffer from another complex associated condition; then you start talking about “syndromic” Robin Sequence, or Pierre Robin Syndrome. So you don’t just have the glossoptosis, micrognathia, and upper airway obstruction; you have all three of those, plus you have Stickler Syndrome, or Treacher Collins, or some other complex rare disease. This makes treatment that much more difficult and complex. So Pierre Robin Sequence is a heterogeneous rare disease, and it’s extremely difficult to generalize from case to case.

Unfortunately, in many situations what happens – to the detriment of the child – is that the Pierre Robin Sequence baby will fall under the care of a cleft team – which may be absolutely expert with cleft care, but which may not have a whole lot of experience with Pierre Robin Sequence. Cleft is common, but Pierre Robin Sequence is a rare disease, which only appears in approximately 1 out of 10,000 babies.

Anyway our daughter was born with Pierre Robin Sequence. Unfortunately in our case, it was not prenatally diagnosed – although it can be. By simply examining the prenatal ultrasound images, it should be possible to identify a radically undersized lower jaw. I remember that my wife, when we looked at the prenatal ultrasound images, she said to me, “Philippe, it’s kind of strange – the baby looks like Bart Simpson.” You know, Bart Simpson, from The Simpsons – he has this very small, recessed chin. And I said to her, “Look, we don’t know anything. The experts know what they’re doing, and they would tell us if something was wrong.”

But in fact the experts didn’t know. They overlooked the micrognathia, and they also overlooked another warning sign: polyhydramnios, which is a severe excess of amniotic fluid. So we’ve got two big red flags for Pierre Robin Sequence; we’ve got severe micrognathia, and we’ve got a severe excess of amniotic fluid – and no flags were raised. Nobody said, “Hey, it looks like we may be dealing with something here, maybe you should consider giving birth in a center of expertise for this rare disease, because we just don’t have a lot of experience with this.” No, it was all overlooked. This underscores the importance of a prenatal diagnosis of this rare disease, and I think the diagnosis of rare diseases in general.

Diagnosing rare diseases is not an easy thing. Many rare disease patients suffer for many years in what’s called the “diagnostic odyssey”, where you’re just waiting and waiting to find out what it is that you’re suffering from. I’ll give you an example. Lysiane was diagnosed with Pierre Robin Sequence – but she also has an another, associated condition. A genome board that was put together to study her genes, and they identified a microdeletion in one of her genes – but they’re not yet sure if this microdeletion explains her many other symptoms. Our daughter has a number of very serious developmental problems which cannot be attributed to Pierre Robin Sequence alone.

As I said earlier, in over half of the cases, Pierre Robin Sequence arises together with another associated condition. She has another condition, but they just don’t know what it is yet. So we’re in this sort of diagnostic odyssey, of waiting and hoping to find out what else she has, which is causing her other problems. I’m sorry to speak so quickly about so many different things…


Shiv: No, you’ve covered a lot. I was going to reference a couple of things you mentioned, like the importance of prenatal screening. You gave a great talk at the Third Annual Robin Sequence Consensus Meeting back in April. I’ve seen the ultrasounds of Lysiane, and you’re right, these things were missed.

One of the main points you made was that as new parents, you were kind of just trusting in the clinicians – who are doing their best – but they just may miss something, or they’re not familiar with these rare conditions. Because as we’ve shared, when you’re in med school, when I was in med school at Hopkins, the saying is, “When you hear hoofbeats, think horses, not zebras.”

The thing is, there are 7,000 zebras out there – 7,000 rare disorders that affect collectively over 300 million people. And so for those people, they don’t want the diagnostic odyssey to be four to nine years – which it is, on average – but rather as short as possible. As you said, it has real implications. If the condition is caught, you could go to a center of excellence, and get the best care.  You guys in particular have a great story of how quickly you got informed, and where you’ve taken that.


Philippe: Yeah, there are very different ways that people respond to the same types of situations, in all sorts of different aspects of life. When we learned of Lysiane’s rare disease, our way of reacting was, “we need to learn everything we can possibly learn. We need to just dive in. We’re not trained, we don’t have a medical background – but we need to do our absolute utmost for our child to understand what is going on, what possibilities exist, and what the next step should be.”

Then there are parents that are so overwhelmed, so absolutely devastated, that they can experience a kind of temporary or even long-term paralysis. They just don’t know how to handle it emotionally. The way they react is that they adopt a passive role, of trusting the physicians to do what they need to do. They do not question things or attempt to get a deeper understanding; it’s just too hard, it’s too difficult.

There’s no right or wrong in this, it’s just a question of your makeup, how you react to things. We really dove in. We read everything we could.  I’m American, I was born and raised in New York, so English is my first language. That was a huge advantage, because although our baby was born in France, I wasn’t doing research in French. I didn’t go to Google French.  I was doing research in English – and because I was doing research in English, I successfully located a whole bunch of medical studies – which are written always in English – since English is the language which is used in international scientific research.

If you’re trying to do research in French or in Spanish or in other languages, you’re not as likely to hit the bullseye. By doing research in English, we found a number of fantastic studies coming from a certain center of excellence in a place we had never heard of before – Tübingen Germany. In Germany, Tübingen is well-known, it’s considered one of the very top universities in Germany. We didn’t know about it, but the more studies we read from this Pierre Robin Sequence center of excellence in Tübingen, the more we were convinced that this special, non-surgical treatment they offered really stood apart. It promised to resolve upper airway obstruction, and facilitate feeding – and Lysiane suffered from both of those symptoms, upper airway obstruction, and feeding difficulties. In the French ICU she was attached to a mechanical breathing machine, and also a feeding pump, which would feed her milk through a nasogastric tube.

So Lysiane needed mechanical support for two of her primary life requirements, breathing and feeding – and this treatment in Tübingen offered the prospect of addressing both of these serious symptoms, without surgery. It is an orthodontic treatment. A lot of American kids get braces, and after the braces are removed, typically the child will get a retainer – this little thing that they place in their mouth, and it just sort of keeps the teeth in the position that they’re in, in the correct position.

The Tübingen Palatal Plate, developed at the Tübingen University Hospital, is similar to a retainer. It rests on the roof of the mouth – but it also has an extension, in the back. It’s an extension which descends almost vertically, and in the back of the throat – and what that extension does is that it pushes the tongue forward and down, instantly liberating the airway.


The Tübingen Palatal Plate.


An illustration of how the Tubingen Palatal Plate works. The large pink/red object is the baby’s tongue. In the cross-section image on the left, the Pierre Robin Sequence patient has no TPP device; the abnormal rear position of the tongue blocks the upper airway, creating potentially life-threatening breathing and eating difficulties. In the illustration on the right, the TPP device is in place; it is represented by a dark blue line. The dark blue line begins at the upper alveolar ridges (where the upper front teeth will eventually grow), continues along the upper palate, covers the cleft in the palate, and then extends down. In the image on the right, toward the right side, we can see this downward dipping dark blue line extension pushing the base of the tongue left, toward the front of the mouth. By shifting the tongue forward, the TPP device instantly liberates the throat – without any invasive surgery.


So it’s like this elegant mechanical engineering solution for an anatomical defect, and it instantly liberates the airway. It may seem like, “wow, that’s pretty straightforward” – but in fact it requires enormous precision to determine the correct length and angle of that vertical extension. In the Tübingen University Hospital, that’s done with fiber optic endoscopy. A camera is sent into the airway to determine whether or not this custom made prototype of the Tübingen Palatal Plate, successfully displaces the tongue forward, and opens up the airway, for this particular baby. And it’s a question of millimeters; if the angle is off by 2 degrees, it’s no good… it’s got to be perfect, and so it requires a great deal of expertise, and a multidisciplinary team, and substantial patient volume.

So it’s essentially an orthodontic treatment, but it’s quite radical, because the Tübingen Palatal Plate promises to resolve upper airway obstruction, and facilitate feeding, without surgery. And it successfully does so, as demonstrated in 15 years’ worth of peer-reviewed medical studies.

Now when you consider the other alternatives – because there are various treatments for Pierre Robin Sequence – the one that has become quite standard today, particularly in America, is MDO, Mandibular Distraction Osteogenesis. This is quite an aggressive procedure. It basically involves fracturing the mandible, the lower jaw, and inserting titanium rods. The rods have screws on them that the parents, over the course of several weeks, will turn each day, or every couple of days. This enlarges the gap between the pieces of the mandible; bone then develops to fill in the gap. So you’re actually enlarging the mandible by creating space between these two points where you’ve created the surgical breaks.


Mandibular Distraction Osteogenesis. The surgeon installs a device called a distractor, which uses special screws called “pins.”


Following the initial surgery, the screws on the distractor are turned, approximately 1 to 2 millimeters per day. This creates tension, and moves the bones of the baby’s lower jaw (“mandible”) apart.


New bone then grows (“osteogenesis”) and fills in the gaps created by the distractor. While the new bone is growing, the baby continues wearing the distractor device at all times.


Mandibular Distraction Osteogenesis involves hardware, and it involves at least two rounds of serious surgery. It is supported by evidence; it generally resolves upper airway obstruction, and in the best centers, they say that it’s over 90% effective. However, the thing is that the Tübingen Palatal Plate achieves the same goals, and it doesn’t involve surgery and anesthesia.

[Editor’s note: internationally peer-reviewed medical studies relying on objective criteria demonstrate that in the vast majority of cases, the Tübingen Palatal Plate successfully resolves upper airway obstruction, without surgery; e.g. 2020, 2019, 2019, 2017, 2017, 2016, 2014, 2011, 2009, 2007, etc.]

The Tübingen Palatal Plate is a remarkable, minimally-invasive alternative to surgery. And this is a fascinating thing, because I think that while physicians may not agree on the best treatment for any complex condition – there’s always room for disagreement – I think that there are certain principles that we can all readily agree on. One of those principles that we can all readily agree on is that surgery on a newborn baby should only be performed when it’s reasonably necessary. Surgery on a newborn baby is a big deal, and not just for the baby, but for the parents as well. It’s a type of trauma to send your newborn baby into aggressive surgery.

So: surgery on a newborn baby should only be performed when it’s reasonably necessary – and in the vast majority of cases, the Tübingen Palatal Plate successfully resolves upper airway obstruction in PRS babies, without surgery. The third step in this logical progression is that surgeons that are carrying out MDO on Pierre Robin Sequence patients are, in the vast majority of cases, carrying out unnecessary surgery on a newborn baby. And that’s a heavy thing. That’s really, I think, a provocative issue that demands exploration.

One of the things that I do, along with my colleagues in our rare disease patient group for Pierre Robin Sequence, is we interview leaders in this field. It’s a small world; that’s true of all of these rare diseases. You’ve got this small group of clinicians that are really fascinated by this condition, and they develop deep expertise in it. They generally know one another, and they read one another’s studies, pre-publication, and provide comments to one another. It’s this closely knit community, international, from all over the world.

I know a good number of the physicians in the clinician community for Robin Sequence. We interviewed a brilliant physician at Stanford named Dr. HyeRan Choo. She adopted this same orthodontic approach to treating babies with Pierre Robin Sequence, and we’re doing a really wonderful interview with her that is going to be published within a week.

[Editor’s note: the interview with Dr. HyeRan Choo at Stanford University was published, and can be read here.]


An illustration showing how the Orthodontic Airway Plate, which is administered by Dr. HyeRan Choo and her multidisciplinary team at Stanford, pushes the base of the tongue forward, toward the front of the mouth. By shifting the tongue forward, the Orthodontic Airway Plate instantly liberates the throat, without surgery.


I would love to provide a link if possible that you could include in your notes for this podcast, because the treatment has now crossed the ocean and has been adopted by Stanford in America. Also, it’s in the process of being adopted at Harvard, by another fantastic Pierre Robin Sequence expert named Dr. Cory Resnick.

Our organization did an interview with Dr. Cory Resnick last year on the prenatal diagnosis of Pierre Robin Sequence. Cory and his team have done fascinating research on how to use not only MRI, but also ultrasound, to correctly identify, with a very small margin of error, Pierre Robin Sequence – during the prenatal period.  This prenatal diagnosis comes with many advantages, as we talked about before. I mean a prenatal diagnosis allows us, the parents, to mentally prepare, emotionally prepare, for the rough road ahead – but it also allows us to plan. “Let’s give birth in this hospital, or in that hospital – but definitely not at home,” you know? It allows for actual planning. It allows you to begin thinking about which team you want to choose, for the treatment of your child, who has these special needs, and so on. So that was another interview that we really enjoyed doing, on the prenatal diagnosis of Pierre Robin Sequence.

We love when physicians push the envelope, when clinicians challenge established thinking, and say, “Why not? Why not try this? This looks promising. Let’s pursue it. Let’s do some studies, let’s really explore this.”  Because there is an unfortunate lack of sufficient research in rare diseases, across the board, for many complicated reasons. There are thousands of rare diseases, and they’re generally quite complex, and there is a lot of variation from patient to patient – and there are other challenges. For example, it’s tough for a pharma company to dedicate enormous investments into developing a treatment which really, at the end of the day, may have quite a small market size. You can’t argue with financial reality. I mean, it would be great if more resources were devoted to research into rare diseases. But these sorts of economic limitations result in the fact that the vast majority of rare diseases have no approved treatment or cure.

That’s one of the devastating realities which all of us rare disease patients and parents have to live with every day: 90% to 95% of rare diseases have no effective treatment or cure. So we are living day to day, week to week, month to month, in the hope that there might be some light at the end of a long tunnel. But it’s really a tough situation to be in. It’s really tough.

That’s why it’s so beautiful when we see support from the private sector, like the beautiful gesture of support from your CEO at Elsevier, when she provided us with open access for our article. We think that the article we wrote will help open the minds of clinicians that are involved in Pierre Robin Sequence, as well as students and clinicians that are still in a training period. We raised a lot of interesting questions in the article; the article is not some emotional tearjerker – “here’s what happened to us, here’s our painful patient journey.” It’s much more than that.  We talk about various treatments for Pierre Robin Sequence, from the perspective of the patient. And that’s important, because you’ve got data, but you also have people, and both are key in the mix. So please read the article, whether or not you know much about Pierre Robin Sequence. I think that it will help you to see things from a slightly different angle, and that’s always helpful in life, to see things from a slightly different angle.

[Editor’s note: the article is available here.]


Shiv: Absolutely, and I’m glad you touched upon that. There’s so many threads we can pull on based on what you were just saying. I did read the article and one of the things I love about meeting people like you in the rare disease community, in general, is just how clearly passionate you are about it, because it’s your daughter. It’s your family.  And this theme of partnering with patients and clinicians and researchers, all partnering – think about what would happen if patients or family members with the more common diseases, like diabetes and hypertension, took 0.01% of the motivation and passion that’s evident in so many of the rare disease community groups. We would be able to prevent so much needless suffering, and pain, and healthcare costs.

One thing I want to touch upon which you made clear in your talk, is that because it’s 1 in 10,000, or 1 in 100,000 for other rare disorders, there isn’t going to be a rare disease center of excellence for every rare disease, in every country. You make this point in your article. It’s important for governments and others to make it possible… not to hinder, but to help rare disease patients, to go to these centers of excellence, for the best care. So for instance, they’re not going to go to a cleft specialist, but they’re going to a Tübingen Palatal Plate specialist, whether that’s at Stanford, or in Tübingen.

Can you talk a bit about some of the challenges you faced? Lysiane was born in France, the treatment is in Germany. I think that with your legal background, you’re involved in getting France to pay for the healthcare costs that you and your family faced in Germany.


Philippe: I do have quite a bit of experience in this question of cross-border healthcare in Europe, which is a funny thing, because I’m an American. I learned a lot about cross-border care in Europe, particularly in the context of rare disease patients, because of this situation we faced with our daughter Lysiane.

She was born in France in a hospital which was not a center of excellence for her rare disease – and she really did need to be in a center of expertise for her rare disease. She has a syndromic form of Pierre Robin Sequence; she had and she continues to have very serious problems. France should have permitted us to transfer Lysiane to a center of expertise, and we had identified a Pierre Robin Sequence center of expertise, the Tübingen University Hospital, in Tübingen Germany. You might think, “well you’re in France, and now you’re talking about going to Germany” – but Germany is just across the border. It’s not a very long drive in an ambulance.

So we learned about the laws. I’m a lawyer, so I was able to do this legal research – and the most important law in question is called Regulation 883. This says that a patient in the European Union who has a rare disease has the right to access a rare disease treatment in another European Union country, if that treatment is not available where they live.

So we asked the French government for authorization for our daughter to receive the Tübingen Palatal Plate treatment, just across the border in Germany. We prepared a really beautiful application; it included four internationally peer-reviewed medical studies. I mean, for the Tübingen Palatal Plate, there is a controlled study dating back to 2007, and a series of medical studies after that which have looked at this treatment from every angle – and always using evidence-based medicine. For Pierre Robin Sequence, that means pre-intervention and post-intervention PSG – polysomnography exams – and weight gain data. So this is not just a bunch of clinicians saying, “We think this treatment might be effective.” This is objective criteria, really high-quality studies, put out by the center of expertise for Pierre Robin Sequence at the Tübingen University Hospital.

Well, the application was rejected by the French government. So then, what we faced was an indefinite period in the ICU. Our daughter had already spent five full weeks in the French ICU, connected to a mechanical breathing machine, and a feeding machine. Anywhere in the world, five weeks in the ICU is going to cost a fortune. So in fact we were actually saying to the French government was: “Let us save you money. Let us get Lysiane into a treatment which promises to liberate her from the breathing machine, and get her out of the ICU, in two to three weeks.” That’s it, you know? And they said no. So this wasn’t a situation where the rejection was based on exorbitant cost, for instance gene therapy – or a treatment whose efficacy or safety was in question – it wasn’t that at all. Let’s just put it this way: the rejection was not based on medical reasons.

So we were now looking at keeping Lysiane in the French ICU for another five weeks, another ten weeks, we had no idea how long it might be – because there was no scheduled date of release. The ICU had already become our second home. I mean we would go there, we would put our stuff in the lockers, we would wash our hands and arms, wear the blue gowns, and spend the whole day and evening in the ICU. Then at night we’d have to leave, we’d go home. And then we’d come back again the very next day; the daily cycle. It was very painful.

We decided, “hey, we’re going to get a bank loan.” My father actually borrowed money against his home, and he transferred the money to the German hospital – and we transferred Lysiane to Germany. We decided that the top priority was getting her into the treatment, even if we have to pay for it ourselves, because the treatment is time-sensitive. The earlier the treatment begins, the better, and the more favorably the babies respond. We thought that the legal and administrative disputes should be secondary in importance.

Well, she got the treatment in Germany. As promised, she was liberated from the breathing machine. We were out of the German hospital in, I believe, 19 days – and it changed our lives. Remember Lysiane had never left the hospital; she was born in the hospital, and she never left – five straight weeks in the French ICU, with no hope of getting out in another five weeks. We didn’t have any idea when she would get out. And so we were very pleased with the results. And then, once we were back in France, we took up the administrative appeal. And this is kind of an incredible thing, because the appeal continues to this day.

We decided to sue France in 2019 for violating EU law. We knew that Lysiane had the right to access the treatment in Germany. The European Commission specifically looked into the case, and they concluded that France was in violation. Well, we’re in August 2022, which means we have waited three years and six months – and we still haven’t had a single case hearing. So France has already violated EU cross-border healthcare law… and now France has also violated human rights law, because it is a basic human right that every person has the right to a fair trial within a reasonable time. In America we call this “due process”. But the point is that you can’t make somebody wait three and a half years without giving them a single day in court – and yet that’s what France has done. But we’re not going to give up. We don’t care if we have to fight for five years, ten years, fifteen years – we are going to get vindicated.

What all of this points to is that when a rare disease treatment is available – in the relatively unlikely scenario that there is a safe and effective rare disease treatment available – patients should be facilitated in accessing that treatment. People, administrators, and healthcare systems, should be bending over backwards to do whatever they can do to get that treatment to the rare disease patient as quickly as possible. Help the patient, by all means – why put up obstacles?

At the same time, there’s a bright side to this. The hardship we face as we seek justice for Lysiane helps to shed light on a problem that many rare disease patients face – and that problem is access to care. For rare disease patients, access should be facilitated; in practice, access is often hindered.

I would like to make a request, a sincere and heartfelt request, to the students and young clinicians that are listening to this podcast. If you face a patient with a complex rare disease, then please remember – you are probably not the best-qualified clinician to treat that particular patient. Your job is not to “fake it till you make it.” It’s not to say, “I’ve got this.” Put your confidence to the side, and just accept the fact that there is probably a clinician somewhere out there who has spent years and years studying this particular rare disease, who knows it better than anyone else – or perhaps there’s a small network of highly specialized experts on this rare disease.

Your job as a young clinician or student is to be a resource locator. You go and read the studies on that rare disease. Look at the authors whose names are popping up again and again in the literature. Reach out to those people and say, “Look, you appear to be a real expert on this condition, and I’m dealing with a patient who I believe is suffering from this condition. I’d greatly appreciate your involvement, your ideas, your suggestions, as to a care pathway. What do you say?” They’ll write back to you, because those clinicians have a passion for that rare disease, and for the patients affected by that rare disease.

So please, young clinicians, find those experts that are out there; make the connection; and help to serve as the bridge between the rare disease patient who is in front of you, and that expert who is an email away. They might be in a different state. They might even be in a different country. But it’s very likely that based on their passion, and their fascination with this rare disease, they will do more than you can imagine to help you and to help your patient. Please think of that. I beg you to think of that.


Shiv: That’s incredible advice. You put me in touch with Durhane Wong-Rieger at the Canadian Organization for Rare Disorders, and we had a chat yesterday. She’ll be on the podcast in a couple of weeks. She mentioned similar things, and suggested we make a course that basically helps our audience and early-stage healthcare professionals to not only identify these rare disorders better, but also, to do a double take on it. Hopefully, with better AI, reading these ultrasounds – and things like that – it won’t be up to them to know every rare disorder.

Being that bridge and resource is not really taught. There are rare disease communities that are lucky to have advocates like you who are intelligent, and motivated. If anyone listening to this podcast missed the intro about who you are, and what your background is, at different points they would think, “Oh, this is a physician,” based on how easily you talk about all these different conditions.” Or, “this is a parent,” when you talk about your personal journey; “this is a lawyer,” when you talk about cross-border healthcare law; “this is an advocate, leading an organization, and doing rare disease work.”

That’s an important point too. You find the right combination – of a highly motivated individual, or group of individuals – and you build the care team together. The people who are listening to this most likely are never going to see certain conditions. But the fact is that if they listen to this, of if they watched an Osmosis video on this topic – then somewhere in the back of their head, they know that there are some things that they don’t understand – and they have that humility that they don’t understand it.  And they will think about being that bridge, and advocating for their patient – or having the nurse team do it, or having a social worker get trained up on how to do this. It’s really critical. I’m glad you mentioned that.

I did want to go into two other questions, and leave it open-ended. You’ve already given a lot of advice to our audience, but zooming out, what other advice would you want anybody listening to this to know about, especially when it comes to rare disease?


Philippe: I would like to encourage listeners to seriously consider exploring a rare disease, and diving in, and immersing yourself in it. These are really complex conditions. As students and young clinicians, you are all people with way above-average IQs – so it might be a really beautiful match. You’re really smart. You’re really ambitious. You’ve got this medical background – and here’s this profound mystery of a rare disease. You could become one of those global experts on that rare condition. You might find that the deeper you go, and the more you learn, the more you are loving this exploratory mission.

It can be really fascinating – and it can be discouraging – because so many of these conditions don’t yet have an effective treatment. You will see some patients come, and unfortunately, you will see them go. The mortality rate of these rare diseases is just unspeakably high, and it’s concentrated among very young patients. But that makes it more meaningful – because this is where the battle is being fought. I mean, one of the most overlooked areas of healthcare is rare diseases.

Like you said Shiv, there are thousands of rare diseases. Most of them have no effective treatment or cure. But based on what we’re learning about genetics, things could be changing. We could be turning the corner now, with gene therapy, and so you could be the one that makes a huge difference. Maybe not for the whole world, you know? Not like Jonas Salk – but for a small population of patients that desperately need help. They would be absolutely devoted to you for your efforts – for the very fact that you’re spending your time and your energy, trying to make a difference for them.

You cannot imagine the deep loyalty and devotion that we rare disease patients have for those hardcore clinicians who are at the conferences for our rare disease, and who are publishing the papers about our rare disease. We look at them as the shining hope for our children. So I would really encourage you to consider the rare disease space. It’s just an idea. The world is open for you. You can go in so many different directions – but think about this one – think about the rare disease path. It’s a worthy, worthy path.


Shiv: I think that’s beautifully articulated. It’s a story that keeps coming up… whether it’s “Chasing My Cure” [Dr. David Fajgenbaum], or John Crowley with Pompe Disease – one or more clinicians who dedicate their life to a rare disease. Whether because it’s intellectually challenging – or they have personal stories related to this condition – or they are just kind of curious about it, or want to throw a life raft out for this community that needs a lot of help.

I will say too though, as far as the Salk comparison goes, that there are examples where clinicians or researchers spend time uncovering why a rare disease happens – and there are far reaching consequences. For instance, familial hypercholesterolemia; the research behind that rare condition led to the development of statins, which are now used by over 200 million people around the world. So it’s very possible that with some of these very daunting and challenging conditions – underneath all those layers, there could be some foundational physiology or pathophysiology that could be used for many other conditions.

So I would make that clear to our audience; hopefully we can get some of them motivated to pursue this path. Two other questions. How is Lysiane doing now? She’s five years old, I think?


Philippe: Yeah, she’s five years old. She’s a handicapped child. And that’s a strange thing, because there’s this overlap between the rare disease community, and the handicapped community. She’s both.  She’s got a rare disease – one that’s been diagnosed, and a second one that they are still trying to identify – and she’s handicapped. It’s quite challenging. It’s very, very challenging.

We do our best, every day. You learn a whole lot about yourself as a person, and as a parent. You are pushed in ways… you’re being forced beyond what you thought were your limits. And it doesn’t really get easier. Honestly, it doesn’t really get easier. Things change, but – it’s a strange odyssey being a rare disease parent, for us, and I think for many rare disease parents. It just sort of forces you to question everything, and ask big questions about life.

You cannot keep asking “why us?” You’ve got to shift gears and ask, “what’s next?” you know, “what’s the next step?” You don’t have the luxury of indulging in self-pity. You’ve got to meet the challenges of each day. When you’re a rare disease parent, you do everything you can for your child, to the very best of your abilities.

One of the things that we worry about – and I know that a lot of people in our situation will understand exactly what I mean – you worry about what will happen when you’re not around. How will your child be cared for, and in what way, when you’re gone? That’s one of those weird things that the typical parent doesn’t really face.  You’re hoping your kid gets into an Ivy League college and gets the job that he or she wants, has a happy marriage. We actually worry about what’s going to happen when we’re dead. That seems really morbid, but it’s an example of the intense gravity of the rare disease experience – particularly when the rare disease has a neurological component – not just physical handicap, but intellectual handicap.

I mean it’s tough, it’s tough. But you just have to keep going. And I think that from the hardship can potentially come very beautiful things. In America, NORD, the National Organization for Rare Disorders – which has just been such an incredible game changer for rare disease patients in America – it was started by a woman, Abbey Meyers.  She described herself – and this is a quote – she said that she’s “a simple housewife from Connecticut with children who have a rare genetic disorder.” Well, that “simple housewife” created NORD, which is responsible for the passage of the Orphan Drug Act of 1983. No policy in the world – not anywhere in America or in Europe – comes close to the benefits that have been produced by the Orphan Drug Act of 1983.

So the point is that parents without medical training, who have skin in the game – they have children with a rare disease, or they themselves are suffering from a rare disease – they can do good things. They can be meaningful parts of the movement. In the end it’s all about the clinicians, but those who are not clinicians can also contribute in a very meaningful way, and open doors for the clinicians. They can help to get research funding, they can help to push through legislation that creates incentives for pharma to invest in R&D, and so on.

And just like you said, R&D in rare disease orphan drug development often has unintended beneficial effects for the general population. When you study extreme conditions, you often learn about the more common conditions. So don’t look at it as like it’s just charity, for tiny sub-patient groups. No, it’s science – and through this research you can learn, and you can make a difference, for many many people, not just for rare disease patients.


Shiv: Absolutely. That’s such a beautifully stated example of this famous quote, “Don’t doubt that a small group of highly motivated people can change the world. Indeed, it’s the only thing that has.”


Philippe: Margaret Mead, right?


Shiv: Margaret Mead. Yeah, exactly. I paraphrased it, took a lot of liberties in that. But yeah it’s one of these quotes that’s very motivating. Whatever we can do to help raise awareness and education is something I know we’re committed to at Osmosis and Elsevier.

Philippe, is there anything else? We’ve covered a lot of ground. I’m deeply appreciative of your time. Anything else you’d like to leave our audience with today before we let you go?


Philippe: I’d like to say that sometimes physicians can feel like they’re on the hot seat. But you clinicians have one of the toughest damn jobs out there, okay? The stakes could not be higher, and there is so much that we don’t know. We know a lot, but there’s so much that we don’t know. And so I want to thank you for doing one of the hardest damn jobs that anybody can do. We appreciate you, and we need you. So keep working, and keep your faith, and please accept my thanks and admiration for your hard studies and your hard work and the stress that you face every single day, in your career as clinicians. Thank you very much. I appreciate it, and my whole family appreciates it. We do need you, and we thank you.


Shiv: Philippe, thank you so much for taking the time to share your story, and so many insights. It’s going to be very hard for us to choose the quote that goes with this podcast. And I’ll say that we’ve done over 300 podcasts; I’ve probably done about 70% of them, as the host. This is definitely one of my favorites, if not top favorite, just because I hear the passion. It has a lot of great takeaways – and I really want all of our listeners to engage in the ways you said. Whether it’s being that bridge, when they see something they don’t understand – or going all the way, and becoming a real advocate, or a leader – or attending the symposia for a specific condition – and maybe having an incredible impact from a policy perspective, or a research perspective, or a clinical perspective. Whatever they can do.

 I truly, truly appreciate your time. I’m so glad Kumsal connected us.


Philippe: Thank you. Thank you, Shiv. Thank you, Osmosis and Elsevier. I really appreciate you taking an interest. I really appreciate it. Thanks a lot for this opportunity.


Shiv: Well, our listeners can expect multiple more episodes featuring rare diseases. It’s a space we’re very passionate about for the reasons we just spent the last hour discussing. With that, let me say thanks for checking out today’s show, and remember to do your part to raise the line, and flatten the curve.


The 3rd International Pierre Robin Sequence Consensus Meeting

The 3rd International Pierre Robin Sequence Consensus Meeting was an international medical conference which brought together Pierre Robin Sequence experts from all over the world. The conference was held at the Tübingen University Hospital in Germany.

Over the past 20 years, experts at this hospital have developed and scientifically tested the “Tübingen Palatal Plate”. The Tübingen Palatal Plate is a breakthrough non-surgical treatment for babies suffering from Pierre Robin Sequence; Stanford University in California offers the same breakthrough treatment, and other major American university hospitals are currently in the process of adopting it.

The Tübingen Palatal Plate treatment has been medically proven to resolve breathing difficulties, and improve feeding (e.g. 2020, 2019, 2019, 2017, 2017, 2016, 2014, 2011, 2009, 2007, etc.). It allows PRS babies to avoid aggressive surgery, including MDO (mandibular distraction osteogenesis). And it eliminates the need for prone sleeping (sleeping on the stomach). Today prone sleeping has become highly controversial, because it significantly increases the risk of SIDS (Sudden Infant Death Syndrome).

The organizers of the conference invited Pierre Robin Europe to deliver a presentation on Pierre Robin Sequence from the patient’s perspective. Since the audience was composed of Pierre Robin Sequence experts, primarily surgeons and doctors, we did not provide an introduction to Pierre Robin Sequence. Instead of going over the basics, we decided to use our limited time to raise challenging questions which the clinicians could think about after the conference was over. Our presentation discusses evidence-based medicine; access to care; medical ethics; and quality of life. We also briefly mention the first lawsuit ever filed by a PRS family in the European Court of Human Rights. The lawsuit, which was officially supported by EURORDIS, the European Organization for Rare Diseases, was filed on Rare Disease Day, February 28, 2023.

About us without us

About us without us.

Letter to AMEQUIS, the Evaluation Body appointed to evaluate the EU’s ERN system

From: Philippe Pakter
Date: 22 March 2023
Subject: ERN-Cranio – feedback

Dear AMEQUIS Evaluation Body,

Last Friday 17 March you and your colleagues from AMEQUIS, the Evaluation Body appointed by the European Commission, were kind enough to gather feedback from the patient representatives of ERN-Cranio.

During the meeting you asked about patient involvement in the development of Clinical Practice Guidelines.

ERN-Cranio recently produced EU Clinical Practice Guidelines for the rare disease, Pierre Robin Sequence. Concerning this EU-funded ERN-Cranio project:

  1. ERN-Cranio’s working group to create EU Guidelines for Pierre Robin Sequence included zero Pierre Robin Sequence patients.
  2. ERN-Cranio’s consensus vote on these EU Guidelines for Pierre Robin Sequence included zero Pierre Robin Sequence patients.

Zero Pierre Robin Sequence patients in the working group and zero Pierre Robin Sequence patients in the consensus vote for ERN-Cranio’s EU-funded Clinical Practice Guidelines for the rare disease, Pierre Robin Sequence.

This EU-funded document which ERN-Cranio produced fails to meet the minimum standards of the EU’s ERN system, which legally requires that such EU-funded materials be “patient-centered”. Zero and zero does not equal patient-centered.

I am writing on behalf of Pierre Robin Europe, as the organization’s chairman. We represent patients with the rare disease, Pierre Robin Sequence. In ERN-Cranio, we are the only patient representatives who represent patients with Pierre Robin Sequence. We, Pierre Robin Europe, have been a member of ERN-Cranio since 2018; thus we were officially admitted to ERN-Cranio several years before this Pierre Robin Sequence Guideline development project began. ERN-Cranio’s Coordinator, Dr. Irene Mathijssen, intentionally excluded us from this EU-funded Guideline Development Project. This raises several questions, including the following:

  • why did ERN-Cranio Coordinator Dr. Irene Mathijssen exclude us from this guideline development project when we are the only patient representatives in ERN-Cranio who represent Pierre Robin Sequence patients?
  • why did the highly respected Coordinator of another ERN who won the EURORDIS “Black Pearl” award for his outstanding contributions to the rare disease movement send an official letter of complaint to the German Health Minister concerning this particular ERN-Cranio Pierre Robin Sequence guideline development project?
  • how can the European Commission, which provided ERN-Cranio with 50,000 euros of direct funding for this Pierre Robin Sequence guideline development project, claim that it is “patient-centered”, when the working group had zero Pierre Robin Sequence patients, and the consensus vote had zero Pierre Robin Sequence patients?
  • what mechanism is in place in the EU’s ERN system to ensure accountability when an EU-funded project demonstrates this level of dysfunction?


We look forward to speaking with you. Thank you.

Kind regards,

Philippe Pakter
Chairman, Pierre Robin Europe: ERN-Cranio’s official patient organization for Pierre Robin Sequence
Member, EURORDIS, The European Organisation for Rare Diseases
Member, VSOP, Vereniging Samenwerkende Ouder-en Patiëntenorganisaties
PhD candidate, law: “Access to healthcare in Europe: the effectiveness of EU legislation in the context of rare disease patients”


A letter to France’s President Macron about a French baby with a rare disease who was denied access to a safe and effective PRS treatment in Germany.

Dr. HyeRan Choo and the non-surgical Orthodontic Airway Plate treatment at Stanford

Dr. HyeRan Choo, Clinical Assistant Professor of Plastic and Reconstructive Surgery at Stanford University School of Medicine, speaks with us about the breakthrough non-surgical treatment she and her team offer to Pierre Robin Sequence babies at Lucile Packard Children’s Hospital Stanford in Palo Alto, California. Dr. HyeRan Choo is Director of Neonatal and Pediatric Craniofacial Airway Orthodontics and Dental Sleep Medicine in the Department of Surgery, Director of Neonatal and Pediatric Craniofacial Airway Orthodontic Fellowship, and a Faculty Fellow of the Stanford Byers Center for Biodesign at Stanford University. Read more

ERN-Cranio’s EU Clinical Practice Guidelines for Pierre Robin Sequence

When EU Guidelines for a rare disease are officially rejected by the EU’s top two experts on that rare disease, then the EU Guidelines are nonviable.


Wednesday 30 March 2022

From: Philippe Pakter
Date: Wednesday 30 March 2022
Subject: Request for final approval of the European Guideline on Robin Sequence
To: Dr. Irene Mathijssen
CC: All members of the ERN-Cranio Guideline Development Group for Pierre Robin Sequence

Dear Dr. Irene Mathijssen, Coordinator, ERN-Cranio,

Yesterday I asked an ERN-Cranio physician to share with me the final version of ERN-Cranio’s EU Clinical Practice Guidelines for Pierre Robin Sequence, because neither you nor your colleagues gave me access to these files. I went straight to the chapter on first line treatments. I read the following.

“Clinicians and many families will be aware of the general recommendation for infants is to be nursed in the supine position to reduce the risk of sudden death infant syndrome (SIDS), however, prone positioning is widely accepted and effective in up to approximately three-quarter of the RS patients. Close monitoring of O2 saturation should prevent SIDS… Positioning treatment is easily taught and there are few harms associated with this intervention although escalation of care must occur in non-responders.”

Our understanding of evidence-based medicine is that it involves a careful review of the medical literature in order to evaluate the benefits and harms of various interventions, according to objective criteria. Objective criteria in the context of Pierre Robin Sequence is polysomnography, the gold standard for objectively measuring the severity of upper airway obstruction among Pierre Robin Sequence babies.

Concerning benefits: these ERN-Cranio EU Guidelines recommend prone positioning as a first line treatment, based on the claim that prone positioning is “effective in up to approximately three-quarter of the RS patients”. However, a 2021 systematic review study published by the international Pierre Robin Sequence consensus movement – international Pierre Robin Sequence experts from all over the world – stated the following: “Three studies used PSG to estimate the effect of prone positioning and demonstrated that it did not completely resolve OSA in the majority of infants.” Thus, the number of evidence-based studies which actually relied on PSG to objectively gauge the benefits of prone positioning is extremely low – and in these studies, prone positioning failed to resolve OSA in the majority of cases.

Concerning harms: these ERN-Cranio EU Guidelines recommend prone positioning based on the claim that “there are few harms associated with this intervention”. However, according to a landmark paper on SIDS published in the Lancet (“Sudden unexplained infant death in 20 regions in Europe: case control study”), prone sleeping increases a baby’s risk of SIDS by over 13 times. Once again, ERN-Cranio’s EU Guidelines: “there are few harms associated with this intervention”; and the Lancet: a 13 times increase in the risk of SIDS.

ERN-Cranio’s EU Guidelines state that “Close monitoring of O2 saturation should prevent SIDS”. No evidence at all is provided in support of this statement – and it gets worse. This close monitoring of O2 saturation which “should” prevent SIDS is entirely optional: “Consider positioning therapy (either prone or lateral positioning with or without a saturation monitor) as first-line to relieve mandibular-related OSA or UAO”.

The benefits of the intervention are exaggerated; the risks are minimized; contradictory studies are omitted outright – and, for good measure, these Guidelines engage in sheer speculation (monitoring “should” prevent SIDS). Dr. Irene Mathijssen, as Coordinator of ERN-Cranio, you accepted EU funds on the basis that you would produce evidence-based Guidelines of care for the EU. We and others – including some of the most internationally renowned Pierre Robin Sequence experts in the world – believe that this is not evidence-based medicine. What other critical evidence is distorted or omitted, how many other unsupported statements and recommendations might be found, scattered throughout this document?

In a June 2021 letter we warned Dr. Andrzej Rys, Director, European Commission DG SANTE, and Prof. Till Voigtländer, Co-chair of the ERN Board of Member States, that this is exactly what would happen, and this would be the inevitable result, of an allegedly “EU” Guideline development project for a rare disease which intentionally excluded the EU’s top two experts in that rare disease. When an allegedly “patient-centered” Guideline working group included not a single Pierre Robin Sequence patient or parent – not one single Pierre Robin Sequence patient or parent – a shocking situation which continues to this day. “It is expected that all stakeholders should strive to adhere to the recommendations set out in this Chapter”. We who represent the ultimate stakeholders, babies suffering from this life-threatening rare disease, reject this document.

It has been brought to our attention that your hospital, Erasmus Rotterdam Medical Center, and the Great Ormond Street Hospital in London, may be bound together in a relationship with a certain American body, ICHOM, involving common financial and funding interests. This pre-existing relationship between Erasmus Rotterdam MC, and the Great Ormond Street Hospital in London, potentially creates the impression of a perceived conflict of interest. Erasmus Rotterdam MC, which is in charge of ERN-Cranio, favored the Great Ormond Street Hospital, and included the Great Ormond Street Hospital in this EU project – in spite of the fact that the Great Ormond Street Hospital is not a member of ERN-Cranio. At the very same time, Erasmus Rotterdam MC excluded the EU’s top two experts on this rare disease, on the exact same basis – that they were not members of ERN-Cranio. We will ask the research oversight boards to investigate this matter, because if the EU’s top two experts on this rare disease had not been arbitrarily excluded from this EU project by Erasmus Rotterdam MC, then the “final version” of this “EU” Guideline we are discussing today would be a higher quality document.

As ERN-Cranio’s official ePAG patient organization representing Pierre Robin Sequence patients, we request an invitation and link to participate in the upcoming discussion scheduled for 31 March 2022 concerning this EU document which was produced about us, without us.

Best regards,

Philippe Pakter
Chairman, Pierre Robin Europe: ERN-Cranio’s official patient organization for Pierre Robin Sequence
Member, EURORDIS, The European Organisation for Rare Diseases
Member, VSOP, Vereniging Samenwerkende Ouder-en Patiëntenorganisaties
PhD candidate, law: “Access to healthcare in Europe: the effectiveness of EU legislation in the context of rare disease patients”

Friday 18 March 2022

From: Philippe Pakter
Date: Friday 18 March 2022
Subject: Request for final approval of the European Guideline on Robin Sequence
To: Dr. Irene Mathijssen
CC: All members of the ERN-Cranio Guideline Development Group for Pierre Robin Sequence

Dear Dr. Irene Mathijssen, Coordinator, ERN-Cranio,

You have released the final version of the EU Clinical Practice Guidelines for Pierre Robin Sequence.

The EU’s top two experts on Pierre Robin Sequence, Prof. Dr. Christian Poets at the Tübingen University Hospital, and Prof. Dr. Corstiaan Breugem at Amsterdam University Medical Center, have both formally rejected them.

When EU Guidelines for a rare disease are officially rejected by the EU’s top two experts on that rare disease, then the EU Guidelines are nonviable.

As ERN-Cranio’s Coordinator you may now be considering the option of moving forward anyway and rushing to publication, over the serious critiques of your internationally respected colleagues – Prof. Dr. Corstiaan Breugem, Prof. Dr. Siegmar Reinert, Prof. Dr. Christian Poets, Prof. Dr. Bernd Koos, and others. The ERN Coordinator is responsible for the way this project has been managed; in the same way you will be held responsible for what comes next. My colleagues and I are in touch with various Dutch and international bodies, including formal research oversight boards. They will receive a copy of this email and they will consider a number of issues, including the following.

  • In developing these PRS Guidelines, Erasmus MC intentionally excluded the EU’s top two experts on this rare disease: Prof. Dr. Corstiaan Breugem, and Prof. Dr. Christian Poets. Prof. Dr. Corstiaan Breugem organized the world’s first international PRS consensus meeting, thereby launching the international PRS consensus movement; he has also published more research on PRS than any physician we know of in the world today.
  • Erasmus MC also excluded Prof. Dr. Christian Poets, of the Tübingen University Hospital, who manages the multidisciplinary team of highly specialized experts which administers a breakthrough PRS treatment, the Tübingen Palatal Plate. The Tübingen Palatal Plate has been adopted by Stanford University, and by Harvard University – with training and support from Prof. Dr. Christian Poets and his team.
  • Although Erasmus MC excluded these two world-class PRS experts from this EU-funded PRS Guideline development project, Erasmus MC is not itself an Orphanet Center of Expertise for PRS, which makes the exclusion of the EU’s top two PRS experts even more troubling.
  • ERN-Cranio, in order to justify the exclusion of these two world-class PRS experts from this PRS Guidelines project, stated in writing that “we are not allowed to involve centers outside the ERN CRANIO network”. There is no such rule. Furthermore Erasmus MC’s Dr. Eppo Wolvius, who made this statement, knew when writing it that the Great Ormond Street Hospital, which is “outside the ERN CRANIO network”, was involved in this project – because he and others at Erasmus MC were working on the Guidelines alongside the Great Ormond Street Hospital physicians. Openness and transparency are absolutely vital for high quality research; arbitrary decision making based on relationships and politics make it impossible to achieve top quality research results.
  • In September we received a letter from the Dutch Ministry of Health indicating that ERN-Cranio had informed the Dutch Ministry that these top two PRS experts were now a part of this PRS Guideline development project. Nevertheless in November 2021, when ERN-Cranio organized a meeting in Rotterdam to discuss these PRS Guidelines, Prof. Dr. Corstiaan Breugem and Prof. Dr. Christian Poets were both excluded. Prof. Dr. Corstiaan Breugem, whose PRS research volume exceeds that of any living PRS expert, is based in Amsterdam. Thus ERN-Cranio excluded from this important PRS Guideline development meeting a PRS expert with incomparable PRS research experience, who was located only 80 kilometers away.
  • Under additional pressure from the Dutch Ministry of Health, ERN-Cranio finally permitted these two experts to provide written feedback on the draft document which ERN-Cranio had produced without them. In our 13 December 2021 letter to the German Health Minister Dr. Karl Lauterbach, we described some of the serious serious flaws, medical inaccuracies, misinterpreted research, unsupported conclusions, overlooked medical studies, and multiple forms of bias, which the Tübingen University Hospital identified in ERN-Cranio’s late 2021 draft.
  • From the perspective of research quality, the key question is this: what did ERN-Cranio do with this feedback? ERN-Cranio largely ignored it. After reviewing the most recent draft of these PRS Guidelines, the final version, the Tübingen University Hospital indicated the following. “Most of our comments submitted on Nov 4 were not included in the set of documents the Rotterdam team created… They were apparently largely treated as if non-existing.” Once again this is PRS knowledge and expertise submitted by a world-class PRS Center of Expertise, the Tübingen University Hospital, which has achieved a medical breakthrough in PRS care, a breakthrough which has been adopted by Stanford and Harvard. Top quality evidence-based research requires at a bare minimum that all scientific evidence is considered – particularly if the evidence is presented by an internationally recognized expert.
  • The Dutch Ministry of Health asked Erasmus MC if they were including PRS patients in the Guideline Development Group. The response from ERN-Cranio was to bring in Mr. Gareth Davies. Mr. Gareth Davies is a very dear man, but he represents patients with cleft lip/cleft palate. The goal of this project however was to develop Guidelines of care for PRS. There is a stark difference between cleft lip/cleft palate, and PRS – a complex heterogeneous rare disease characterized by high morbidity, high mortality, and a high level of associated conditions.
  • ERN-Cranio has an official patient group representing PRS patients; it is called Pierre Robin Europe. Starting in April 2021 Pierre Robin Europe raised valid, serious questions about the way this research project was being managed. Our most serious concern was the exclusion from the PRS Guideline development group of the EU’s top two PRS experts. Pierre Robin Europe also protested the fact that there were zero patients in the Guideline Development Group. ERN-Cranio responded to the valid concerns we had raised by excluding us completely, and in our place using a substitute who does not represent patients suffering from this complex life-threatening rare disease. ERN-Cranio excluded Pierre Robin Europe from every single meeting which has ever been held in relation to these PRS Guidelines. We at Pierre Robin Europe have not had the opportunity to interact with a single healthcare provider in the Guideline Development Group. Many, perhaps most of the healthcare providers in the Guideline Development Group do not know that we exist. We, ERN-Cranio’s official patient organization representing the PRS rare disease community, were not involved in the discussion of the scope of these PRS Guidelines. We were not involved in the discussion of the clinical questions which the Guidelines would address. We were not permitted to share our perspective on the relative importance of the clinical questions. We were not given the chance to rate the importance of outcomes. A local Dutch company called Qualicura was hired to provide training for the members of the Guideline Development Group, training which was paid for by the EU; we were not told that such training was taking place. We were not invited to the November 2021 meeting in Rotterdam to discuss these Guidelines. We were not even sent a copy of the final version of these EU Guidelines. We are not on the Guideline Development Group’s email recipient list. We are ERN-Cranio’s one and only PRS patient organisation, and ERN-Cranio excluded us altogether. Quality research is absolutely impossible when those who raise valid questions, or who present dissenting views, are marginalized or excluded.
  • The highly respected Coordinator of another ERN, after learning how this project in ERN-Cranio was being managed, signed an official letter of complaint to Prof. Dr. Karl Lauterbach, the German Health Minister, a fact which can be confirmed through the Minister’s office.

The EU’s European Reference Networks are legally mandated to produce evidence-based patient-centered rare disease Guidelines of care, drawing upon the top rare disease experts in the EU. ERN-Cranio had all the resources it needed to produce outstanding PRS Guidelines. In support of this work, the European Commission spent approximately 4,000,000 Euros of EU taxpayer money (Tender N° SANTE/2018/B3/030) to create an official EU Methodology for the ERNs to use when developing Clinical Practice Guidelines for the EU’s rare disease community. The European Commission spent 100,000 Euros of EU taxpayer money (Tender N° SANTE/2017/B3/083) to hire a contractor to develop templates and documents for the ERNs. The European Commission DG SANTE informed us, Pierre Robin Europe, in a letter dated 1 October 2021 (Ref. Ares(2021)5983971), that the European Commission spent an additional 50,000 Euros of EU taxpayer money to provide ERN-Cranio with direct financial support, for this PRS Guideline development project. The financial resources were available. The necessary infrastructure and tools were available. Most importantly, the EU’s top two PRS experts were available – and they were ready, willing, able, and eager to contribute. So too was Pierre Robin Europe, ERN-Cranio’s official PRS patient organisation. In spite of the promising opportunity and abundant resources, this project has failed. The failure is managerial in nature, and the responsibility falls upon the Coordinator of ERN-Cranio. A formal, fully open and transparent investigation will follow.

Kind regards,

Philippe Pakter
Chairman, Pierre Robin Europe: ERN-Cranio’s official patient organization for Pierre Robin Sequence
Member, EURORDIS, The European Organisation for Rare Diseases
Member, VSOP, Vereniging Samenwerkende Ouder-en Patiëntenorganisaties
PhD candidate, law: “Access to healthcare in Europe: the effectiveness of EU legislation in the context of rare disease patients”

From: Dr. Corstiaan Breugem
Date: Saturday 12 March 2022
Subject: Request for final approval of the European Guideline on Robin Sequence
To: Dr. Eppo Wolvius; Mr. Gareth Davies
CC: Dr. Irene Mathijssen; All members of the ERN-Cranio Guideline Development Group for Pierre Robin Sequence

Dear Eppo,

I would like to congratulate you and your team for doing a lot of work.

When I support a Guideline, I make sure I support something that we can always comply to. It should not be the “ideal” world, but it should be practical and achievable, based on the current literature or include experts in the field. If I do not follow the guideline, there should be a good reason, and this should not happen regularly. Last year I gave you reasons why I think this current guideline is not a practical guideline. It does also not include some relevant literature.

We were given the opportunity to give suggestions in October 2021. I see that many have not been included. My pediatricians for instance say that it is not practical to say that everybody should have a “PSG” before and after palatoplasties and pharyngoplasties. We work in a National reference centre for Robin sequence and see many patients. This is just not practical. Also simply saying a “PSG” is not enough. What criteria do we agree upon are safe to do surgery. Do we really need a PSG in every patient before and after surgery. Maybe in an ideal world. What other ways eg questionnaires, lab test are more practical and should performed, before we suggest doing a PSG in everybody. We feel that suggestions are made in this guideline that are not in reality with what can be achieved in practical care.

I also have a problem with the name “European Guideline”. The European Reference Network includes specialized centers in Europe and is not representative of the whole of Europe. I think at the most, you can call this a ERN Guideline. I am unsure if the ERN has the authority to call this a European Guideline because no National Cleft Association has been involved in the development of this guideline.

Although I see that you and your team have incorporated a lot of effort in this guideline, I am sorry to say, but we cannot support this in its current form.

Best wishes


Kind regards

Prof. dr. Corstiaan Breugem (MD PhD)
Professor in Plastic and Reconstructive Surgery
Head Pediatric Plastic Surgery
President Dutch Cleft Palate Craniofacial Association
Vice-president European Cleft Palate Craniofacial Association

Department of Plastic Reconstructive and Hand Surgery
Amsterdam UMC, Emma Children’s Hospital
Location AMC, University of Amsterdam|
Room J1A. 210 | Meibergdreef 9, 1105 AZ Amsterdam
The Netherlands




From: Prof. Dr. Christian Poets
Date: Wednesday 2 March 2022
Subject: Rejection of request for final approval of the ERN Guideline on Robin-Sequence
To: Dr. Eppo Wolvius
CC: All members of the ERN-Cranio Guideline Development Group for Pierre Robin Sequence

Dear Eppo,

Thank you for sending the latest version of this guideline. After careful consideration, the Tuebingen team came to the conclusion that we have to reject this guideline in its present form. Please find our reasons for this decision outlined in the enclosed letter and in our annotations to chapters 1&2 (also enclosed).

We look forward to hearing from you.

Kind regards,

Prof. Christian F. Poets, M.D.
Medical Director
Dept. of Neonatology | Children’s Hospital
Calwerstraße 7 | 72076 Tübingen

A parent’s view on the care of their baby with Pierre Robin Sequence

A patient’s perspective on rare disease care. From “Seminars in Fetal & Neonatal Medicine”.


“Thanks, Philippe – this is tremendous and it emphasises the need or should I say absolute imperative that we obtain and heed the patient / parent perspective in the approach to rare diseases. This certainly provides aspects that we do not read about in the textbooks.”

– Prof. Dr. Peter A. Mossey
Professor and Personal Chair of Craniofacial Development & Dentofacial Orthopaeds, the University of Dundee; Associate Dean for Research; Director of WHO Collaborating Centre for Craniofacial Anomalies and Technology Transfer

A parent’s view on the care of their baby with Robin sequence


A Robin sequence parent presents the view that Robin sequence healthcare providers are engaging in practices which may be outdated, excessively invasive, and unnecessarily detrimental to quality of life, and proposes possible areas of research to improve patient outcomes.



AHI – Apnoea Hypopnoea Index

CPAP – Continuous Positive Airway Pressure

ICU – Intensive Care Unit

MDO – Mandibular Distraction Osteogenesis

OA – Obstructive Apnoea

RS – Robin sequence

SIDS – Sudden Infant Death Syndrome

TLA – Tongue Lip Adhesion

TPP – Tübingen Palatal Plate

UAO – Upper Airway Obstruction

US – Ultrasound


1. Introduction

I am the parent of a child named Lysiane who was born in France in 2017 and diagnosed with Robin sequence (RS). I am the chairman of Pierre Robin Europe, an RS patient advocacy organization based in the Netherlands. I am currently earning a PhD in cross-border healthcare law at the University of Geneva.

In this article I will present thoughts and suggestions concerning RS care, based upon my own experience as an RS parent. I will then conclude with five general recommendations, which may be applied more broadly to all rare disease care.

RS is a rare disease affecting approximately 1 in 10 000 babies. It is characterized by micrognathia, glossoptosis, and Upper Airway Obstruction (UAO). RS presents two main symptoms, of varying severity: UAO, and feeding difficulties. Treatment options include both non-surgical and surgical techniques.


1.1. Prenatal diagnosis and counseling

A prenatal diagnosis of RS can reduce trauma, improve care, and save lives; however the prenatal warning signs of RS are sometimes missed. Prenatal ultrasound (US) images showed that my daughter had severe micrognathia; this went unnoticed by the US team. The US team did however make note of polyhydramnios, over multiple screening sessions. Micrognathia and polyhydramnios are known potential warning signs of RS – but no RS flags were raised. This was at a tertiary care hospital in a major European city. Based on my ongoing contact with hundreds of other RS parents across Europe and America, this situation is not uncommon, and suggests that we need better criteria on how RS can be identified during prenatal US.

As a parent I am greatly encouraged by the promising research which is being carried out to improve the prenatal diagnosis of RS [1]. An early diagnosis of any disease benefits healthcare providers, patients and families in multiple ways. Also, many RS babies suffer from one or more associated conditions; a red flag for RS would alert clinicians of the need to vigilantly search for these associated conditions. Finally, the mandible is “a common site for defects associated with genetic conditions, a good number of which can be recognized prenatally” [2]. Additional time invested in studying the mandible, for instance by measuring the inferior facial angle, would not only yield potential warning signs of RS, and by extension various conditions commonly associated with RS; it would also help raise red flags about numerous other potential problems wholly unrelated to RS.

Anatomy does not correlate very well with severity when it comes to RS symptoms; a baby with moderate micrognathia can suffer from severe UAO, and vice-versa. However in carrying out prenatal screening for RS, the goal is not to predict severity; the goal is simply to identify a high risk that the baby will be born with RS. In such cases clinicians can advise the mother to give birth in an RS Center of Expertise, at a hospital offering tertiary level or comprehensive care, rather than at home.

Improving our ability to prenatally diagnose RS is one challenge, but what happens next? What type of counseling should be provided, who should provide it, and what form should it take? In a retrospective analysis of 1530 Dutch babies born with a cleft, the infant mortality rate of RS babies was found to be eight times higher than the infant mortality rate of the general Dutch population [3]. Stark figures like these are likely to horrify the average parent or parent-to-be, but making things even more complicated is RS’s dramatic heterogeneity. RS babies with certain associated conditions will face even higher infant mortality rates, while RS babies with isolated RS will face lower infant mortality rates. What kind of RS counseling is appropriate in the face of such great uncertainty? Further research to develop RS counseling practices, in partnership with the RS patient community, could help to improve patient outcomes.


1.2. Postnatal treatment: conventional cleft care versus RS care

Several years ago an international consensus was reached concerning the diagnostic criteria for RS – micrognathia, glossoptosis, and UAO; while most RS babies are born with a cleft palate, a cleft is not required for an RS diagnosis [4]. From my perspective as an RS parent, it seems logical to omit the cleft as a diagnostic criterion; below I will explain why.

In the Intensive Care Unit (ICU) our daughter was desaturating on a regular basis. The flashing red light, the urgent beeping sound, the doctors and nurses rushing over to silence the terrifying electronic alarms, our knowledge that repeated instances of oxygen desaturation cause brain damage – this was our day to day experience when we visited Lysiane in the ICU. In addition to her breathing difficulties, Lysiane was unable to drink sufficient quantities of milk; in the ICU she never once drank even 20 ml of milk in a single feeding, in spite of the fact that a specialist was doing her best to help her along. Lysiane required machines to meet two of her most basic needs, respiration and nutrition. Her cleft palate, which we knew had to be closed at or around the end of her first year of life, was low on our list of concerns.

While the RS baby’s cleft may be a part of the sequence, a possible result of the RS baby’s tongue position during the prenatal period, the cleft’s importance in the context of actual RS care seems limited. The functional difficulties these babies face, the breathing difficulties and the feeding difficulties, are not primarily a result of the cleft palate; the functional difficulties are more closely associated with glossoptosis and in some cases neurological problems. These are not issues which physicians typically have to address in the context of conventional cleft care, and indeed the breathing and feeding difficulties which we associate with RS can exist even if the baby has no cleft at all. Another characteristic of RS treatment which sets it apart from conventional cleft care is that among RS babies there is a pronounced risk of associated conditions, which can greatly exacerbate the RS baby’s immediate health problems and long term prospects. Taking all of this into account, it seems to make sense that a cleft palate is no longer required as an RS diagnostic criterion.


2. RS care

2.1. The RS baby’s need for multidisciplinary care

An RS baby is not a baby with a cleft who happens to have a small chin; an RS baby is a baby with a complex rare disease who happens to have a cleft. Some RS parents do not understand this, or have a hard time accepting it. It is important however that healthcare providers get this message across. Not only is RS rare, and complex, but the dizzying number of conditions which commonly arise in association with RS make it even more complicated and challenging [5]. Through a basic understanding of the complexity of this rare disease, parents may better appreciate the importance of the full multidisciplinary team of experts which RS care requires. Healthcare providers may consider actively engaging RS parents by explaining the role which each expert will play in their baby’s ongoing care.

The RS baby’s feeding difficulties can result not only in a failure to thrive; the feeding difficulties can also be profoundly demoralizing for RS parents. Since the RS baby’s feeding problems are not the same as those of a baby with a conventional cleft, the RS baby’s multidisciplinary team should include highly specialized nurses and speech therapists who have worked specifically with RS babies.

For parents, the RS baby’s feeding difficulties can be demoralizing; the breathing difficulties, terrifying. To treat the RS baby’s UAO, options include both non-surgical and surgical techniques. I will discuss some of these treatments below, from the RS parents’ perspective.


2.2. Prone sleeping

Prone sleeping was proposed for RS babies in the early 1900s, half a century before the term Sudden Infant Death Syndrome (SIDS) was ever mentioned in the medical literature. Today prone sleeping is condemned by healthcare providers throughout the entire modern world. This sets the stage for an enduring tension in RS care.

Every time we visited our hospital’s maternity ward for prenatal care, we saw a large poster in the waiting room reminding us: “Couché sur le ventre, votre bébé court un risque mortel. Ne faites pas cette erreur. Couchez toujours votre bébé sur le dos” (in English: “A baby sleeping on her stomach runs a mortal risk. Do not make this mistake. Your baby should always sleep on her back”). After our daughter Lysiane was diagnosed with RS, however, our physicians told us that stomach sleeping was suitable. As parents we were torn. Prone sleeping increases a baby’s risk of SIDS by a factor of five, ten, and possibly more [6]. As RS parents we kept asking ourselves, “if Lysiane’s UAO poses an even greater threat than SIDS, un risque mortel, then shouldn’t her healthcare providers be providing her with some kind of a healthcare treatment?” It seemed to us that with prone sleeping, Lysiane’s physicians were asking us to swap one known danger for another – to resign ourselves and our newborn baby to the lesser of two evils.

In 2019 I attended an RS Symposium at the European Cleft Palate Craniofacial Association’s International Congress. During a period of open discussion between clinicians, one of the physicians insisted that if it were her own baby, she would not place the baby to sleep in the prone position; she therefore refused to recommend this practice to RS parents. I suddenly realized that as RS parents, our serious concerns about prone sleeping had not been unreasonable; the tension between this century old “prone sleeping for RS babies” protocol, and current medical knowledge, is very, very real.

Medical studies which looked at “side sleeping” (“lateral sleeping”) found that it too significantly increased the risk of SIDS [7]. Babies move when they sleep, and when placed on their sides, fall easily into the prone position; exhausted parents cannot stay up all night watching them. Given the notoriety of prone sleeping, the term “side sleeping” may serve to some extent as a polite euphemism for prone sleeping; in practice however this may be a distinction without a difference.

If there were a convincing body of RS medical research demonstrating, with polysomnography, that the clinical benefits of prone sleeping significantly outweighed the risks, then this entire analysis would be different. But the evidence-based research on prone sleeping for RS babies is scarce [8]. Based on its known risks, prone sleeping cannot properly be described as “conservative”; based on its questionable benefits, it may be ambitious to call it a “treatment”.

Years ago the American Academy of Pediatrics, which strongly advises parents to always place babies to sleep on their backs, warned Fisher-Price about the design of its “Rock ‘n Play Sleeper”. The reason: this sleeper was designed in such a way that made it easy for a baby to roll over onto her stomach and fall asleep, in the prone position. Fisher-Price sold the product anyway, all over America, and in Europe as well – and a number of babies did indeed die in these sleepers. Eventually Fisher-Price issued an international recall of over 4.7 million units, at tremendous cost [9]. Here however, in the context of RS care, healthcare providers are actually recommending prone sleeping – at home, without a pulse oximeter, and without any parental training in cardiopulmonary resuscitation. Can this century-old “prone sleeping for RS babies” protocol be reconciled with 21st century medical knowledge? This question seems to call for both evidence-based research, and careful reflection.


2.3. Mechanical ventilation assistance

In the COVID-19 era many non-healthcare practitioners have gained at least some passing familiarity with Continuous Positive Airway Pressure (CPAP) and other forms of mechanical ventilation assistance. In CPAP we see a desperate attempt to maintain life, in the absence of any readily available treatment or cure. No COVID-19 patient wants to be hooked up to a breathing machine, but the patient accepts the burden of care – the ongoing hospitalisation, the substantially reduced mobility, the considerable sacrifice in quality of life – because the patient, who wants to live, has no other choice. Most COVID-19 patients receiving CPAP ventilation assistance have indeed lived life to some extent, up to adulthood, and many into their senior years. For RS babies on the other hand life is just beginning; CPAP’s burden of care is particularly painful for the entire RS family.

In addition to its considerable burden of care and reduced quality of life, CPAP has also been shown to create a significant risk of causing facial deformities in children, due to the constant pressure which the CPAP mask exerts on the growing facial structures of the child’s face. “Global facial flattening was observed in 68% of the patients and concerned the forehead (43%), malar area (38%), and maxilla (28%). One or two anatomical regions were concerned in 37% and 18% of the patients, respectively. A concave face was observed in 12% of the patients … This observational study underlines the high prevalence of facial side effects of nasal mask use in children” [10].

The known risk of facial deformities is understated in certain studies proposing CPAP for RS babies. One such study suggests that the risks are minimal, and can be constrained, based upon the relatively short treatment duration required. The authors write, “This relatively short period restricts the potential side effects of long-term noninvasive continuous positive airway pressure such as facial flattening and maxillary retrusion” [11]. To support this conclusion, this CPAP study cites another CPAP study for support [12]. However the study which is cited indicates that the mean duration of treatment was not in fact short; the treatment periods for the observed patients were all at least seven months long, and the majority of patients received ventilation assistance well beyond the one year mark [12].

Furthermore the above-mentioned study on CPAP and facial deformities underscored the fact that maxillary retrusion (“maxillary retrusion was observed in 37% of the patients”) did not correlate with treatment duration at all; “In univariate and multivariate analyses only daily use (>10 h per day) was associated with maxillary retrusion” [10]. The substantial risk of maxillary retrusion was triggered not by months and months of use, but rather by daily use which exceeded 10 h per day. RS babies suffering from UAO require ventilation assistance when they sleep; babies sleep more than 10 h per day. Unless the baby is prevented from falling asleep, the risk of maxillary retrusion seems inescapable. At issue here are facial deformities, among babies who already suffer from facial deformities. “This relatively short period restricts the potential side effects of long-term noninvasive continuous positive airway pressure such as facial flattening and maxillary retrusion” [11]. Such a problematic statement should have raised serious questions during the process of peer review.

High flow nasal cannula exerts less pressure on the baby’s face, but like CPAP, high flow nasal cannula calls for substantial medical equipment, and often requires long term hospitalisation. In the event that the mechanical ventilation equipment is transported into the home, major challenges remain. Even when the baby is not sleeping, the ventilation equipment must be on stand-by, because babies tend to take unscheduled daytime naps; this makes it difficult for the mother to put her baby into a baby carriage and take a quick trip to the supermarket, or take the baby for a stroll in a nearby park.

Lysiane began her life receiving mechanical ventilation assistance, so my family and I know its arduous burdens first hand. Eventually we transferred Lysiane from the French ICU to Tübingen Germany to undergo the Tübingen Palatal Plate (TPP) treatment. The TPP ended Lysiane’s dependance on mechanical ventilation assistance, eliminated the need for prone sleeping, and allowed us to finally leave the hospital, and bring Lysiane home.


2.4. Surgery

The majority of RS babies are born with a cleft, so surgery for RS babies is in most cases a given. There seems however to be an increasingly strong push to subject these babies to additional surgeries, to resolve the baby’s UAO. These surgeries are generally performed in the first few months, or even the first few weeks of the baby’s life. How effective are these surgical procedures?

The effectiveness of Tongue Lip Adhesion (TLA) is particularly difficult to gauge. To begin with, TLA studies produce noticeably different results, depending upon which healthcare provider published the study. Furthermore studies published on TLA often present vague and subjective assessments, which can be difficult to understand. Virtually everyone agrees on the importance of practicing evidence-based medicine, using objective criteria. Virtually everyone agrees that polysomnography is the gold standard for measuring the severity of UAO. Nevertheless many TLA studies simply ignore polysomnography altogether.

Some of the more recent TLA studies do mention polysomnography, and emphasize its singular importance in the context of RS research and care. “Tongue-lip adhesion is a surgical technique proposed in the treatment of airway obstruction related to glossoptosis, but few published studies have been based on objective criteria. The purpose of this study was to evaluate the efficacy of tongue-lip adhesion, as determined by polysomnography, in children with Pierre Robin sequence … Preoperative assessment was based on nap polysomnography in the sleep laboratory when the child was stable … Follow-up polysomnography was performed an average of 1 month after tongue-lip adhesion” [13]. These explicit references to polysomnography are reassuring, and this study’s conclusions make TLA appear quite promising: “The postoperative clinical assessment revealed resolution of signs of respiratory distress in 30 cases (81%),” and in the group of 37 babies who underwent the procedure, TLA “resolved obstructive sleep apnoea in 29 patients” [13].

What data did the polysomnography yield? “The apnoea-hypopnoea index (AHI) decreased in all patients. The median postoperative AHI was 27 events per hour (range: 5–65) (P < 0.0001)” [13].

At issue here is a surgical procedure which is being proposed for newborn babies with a rare disease. How can a median postoperative AHI of 27 events per hour support a finding that TLA “revealed resolution of signs of respiratory distress in 30 cases (81%)” and “resolved obstructive sleep apnoea in 29 patients” out of this group of 37? [13] It cannot. Serious questions should have been raised during the process of peer review.

Another study, carried out by Harvard/Boston Children’s Hospital, which looked at both TLA and Mandibular Distraction Osteogenesis (MDO), and which focused on the exact same variable – pre- and postoperative AHI – indicated that TLA failed to do its job over half of the time: “Successful resolution of OA [Obstructive Apnoea] occurred in 9 patients (47%) in the TLA group and 22 patients (92%) in the MDO group” [14]. Given the inconsistent results across the various TLA studies, and the inconsistent ways in which the researchers arrived at their conclusions, it is not easy for an RS parent to have faith in this particular procedure. An RS mother does not want to send her newborn baby into two rounds of TLA surgery, three rounds or more in the event of dehiscence, if she knows that the odds of success are at about the same level as a coin toss.

The studies on MDO tend to show a greater reliance on polysomnography than the studies on TLA. Also, MDO’s success rate, based upon pre- and post-intervention AHI, appears to be higher, and also more consistent from one study to the next. However compared with TLA, MDO is a more aggressive surgical procedure; even the physicians who express enthusiasm for MDO readily admit that this invasive procedure is associated with various risks, and various unknowns, some of which are long-term.

As pointed out by the President of the International Confederation of Cleft Lip and Palate and Related Craniofacial Anomalies, Dr. Felicity Mehendale, “surgery is trauma; it is always good to remember that” (presentation at the 2019 European Cleft and Craniofacial Initiative for Equality in Care COST Action). When the surgery is performed on a newborn baby, then the surgery is not just traumatic for the patient, it is also traumatic for the parents as well. Surgery on newborn babies should only be performed when reasonably necessary. An emergency decision to carry out tracheostomy to save a baby’s life stands out as a relatively straightforward call, based upon the necessity and proportionality of the intervention. The rationale for MDO is less clear, because the TPP treatment offers, in most cases, a completely viable non-surgical alternative [15]. MDO is perhaps most questionable for RS babies in the European Union; in the EU, patients have a legal right to access cross-border healthcare in another EU Member State. The parents of an RS baby in France, wishing to avoid TLA and/or MDO, have a legal right, under EU cross-border healthcare law, to travel to Germany, and receive the non-surgical TPP treatment in Tübingen.


2.5. Access to rare disease care – Lysiane’s patient journey

Lysiane did not have the benefit of a prenatal diagnosis; as a result she was born in a hospital which was not an RS Center of Expertise. Every single day we would go to the ICU in order to spend time with her. When visiting hours were over we had to leave the ICU and go home without her, a difficult separation which we were forced to repeat every single evening. Lysiane remained in that French ICU for five straight weeks, receiving mechanical ventilation assistance; there was no release date in sight. The ICU became our second home. It would be difficult to adequately convey the boundless pain of that time period.

After five weeks in the ICU, we submitted an application to the French healthcare authorities requesting prior authorisation for Lysiane to receive the TPP treatment in Tübingen Germany. That is, we asked that Lysiane be transferred from her hospital in Lyon, which was not a Center of Expertise for RS, and which could offer her nothing more than to keep her in the ICU indefinitely, connected to a mechanical breathing machine – to a hospital in Tübingen, which was a Center of Expertise for RS, and which offered a highly specialized, medically proven, safe, non-surgical, cost-effective treatment for her rare disease. In our application we included a letter from the coordinator of the Tübingen RS Center of Expertise, translated to French, distinguishing the TPP from other RS treatments. We also included four internationally peer reviewed medical studies, all evidence-based (with pre- and post-intervention polysomnography data, and weight gain data), demonstrating the safety and efficacy of the TPP treatment [16,17,18,19].

France’s main RS Center of Expertise in Paris, which does not offer the TPP treatment, would not support the transfer to Tübingen. Instead of providing the medical referral letter we required as part of our application, they instead issued a statement suggesting that France’s treatment, CPAP, and Germany’s treatment, the TPP, are equally effective.

The French healthcare authorities subsequently refused our request for prior authorisation. The basis of the refusal was that France’s treatment is equally effective as Germany’s treatment, echoing France’s main RS Center of Expertise in Paris. My father took out a bank loan, using his home as security for the loan; we transferred Lysiane to Tübingen and paid for the TPP treatment ourselves, using the borrowed funds. The TPP did its job; it resolved Lysiane’s breathing difficulties, liberated Lysiane from the breathing machine, and permitted us to finally take Lysiane home, changing her life, and changing our lives too. We documented our rare disease patient journey in meticulous detail in an open letter to the President of the French Republic Emmanuel Macron [20].

The European Commission’s SOLVIT Network, after carefully analyzing Lysiane’s case, formally concluded that France, in refusing Lysiane’s application for the TPP treatment in Germany, violated EU cross-border healthcare law (SOLVIT Case Number 2569/17/DE). We, Lysiane’s parents, are now engaged in an appeal procedure to reverse France’s refusal. Our supporters and allies include Members of European Parliament from every major EU political party; the executive directors of the two largest patient organizations in Europe, the European Patients’ Forum and EURORDIS; professors of EU law, human rights law, health care policy, and medical ethics, from the Sorbonne, Sciences Po, Erasmus University, Oxford, New York University, and elsewhere; a major international law firm supporting our case on a pro-bono basis; as well as physicians, medical researchers, patient organizations and patient advocates, demonstrating a consensus that crosses all political, professional and national boundaries [21].


2.6. Tübingen Palatal Plate: international uptake of the TPP treatment

RS was named after a stomatologist, Dr. Pierre Robin, who studied the condition almost a century ago. It is perhaps fitting that RS care has now been transformed by an orthodontist, Dr. Margit Bacher, who invented a safe and effective way to save these babies from their breathing difficulties, and facilitate feeding, without machines or surgery. A prospective multicenter study as well as a retrospective study analyzing longitudinal data from 307 RS babies admitted to the Tübingen University Hospital both demonstrated that the TPP not only resolves UAO, but also improves weight gain in RS babies [16,22]. In addition to its safety and efficacy, the TPP comes with a relatively low burden of care, and improved quality of life: limited hospitalisation, unrestricted mobility, no cumbersome equipment, and no surgery. Babies from around Europe and Russia and even America have been transferred to Tübingen to benefit from the TPP treatment, which is now administered by multiple healthcare providers in Germany. Recent advances have rendered this already economical treatment even more economical to administer [23,24].

In most of Europe’s RS Centers of Expertise, however, the TPP remains unavailable. As an RS parent who has seen the remarkable effectiveness of the TPP treatment first hand, I sometimes wonder why this is the case. The European Union is supposed to function as a union. In medicine in particular, the European Reference Network system was established, and receives EU funding, precisely in order to promote collaboration and pooling of rare disease knowledge and expertise. In practice, the TPP treatment will likely have to travel from Tübingen, across the Atlantic ocean to America, and then back across the Atlantic ocean to Europe once again, before babies in major EU Member States outside of Germany can expect to benefit from the breakthrough TPP. What can explain this inertia?

The English author and philosopher Gilbert Keith Chesterton wrote: “It isn’t that they can’t see the solution. It is that they can’t see the problem” [25]. As an RS parent I believe this strange situation applies in the world of RS care. Every healthcare provider in the international community of RS experts knows about the efficacy, safety, and quality of life benefits which the TPP treatment provides. Even physicians lacking any familiarity with RS can readily learn about the TPP’s medically proven ability to resolve UAO and increase weight gain by accessing the numerous, peer-reviewed, evidence-based medical studies which have been published on this highly effective technique [15,16,17,18,19,22,23,24,26,27].

However, RS experts are familiar with the TPP, they do see it; but they do not see the problems inherent in their own RS treatments of choice. They do not see that parents are terrified about placing their baby to sleep in the notorious prone position. They do not see that parents do not want their baby to depend upon and remain attached to a mechanical breathing machine, turning the hospital into a second home, or the home into a second hospital. Parents do not want their baby to undergo Tongue Lip Adhesion, a hideous procedure first proposed a century ago, whose benefits remain in question. Parents do not want to send their newborn baby into even more aggressive surgery, such as MDO, unless there really are no other good options.


3. Conclusion

Using Lysiane’s experience as a case study, what useful lessons can be drawn? First, as noted in the beginning of this article, an improved RS prenatal screening protocol could reduce trauma, improve care, and save lives. At the same time, there seems to be a need for further research to determine what kind of pre- and postnatal RS counseling would be appropriate in the face of this complex and heterogenous rare disease [28].

Second: by actively involving rare disease patients and parents as engaged participants and stakeholders in a collaborative rare disease care team which includes researchers, clinicians, genetic counsellors, psychosocial counsellors, and other healthcare providers, we may gain greater visibility on patients’ needs and concerns, and produce better patient outcomes.

Third: the vast majority of rare diseases lack any approved treatment or cure. Lysiane’s case may serve as a useful reminder that when a safe, medically proven, economical rare disease treatment has been developed, healthcare providers should facilitate access to that treatment. Unless there is a strong justification for denying access to a particular treatment – danger, questionable efficacy, excessive cost – a family should not have to take out a personal bank loan as a condition for accessing safe and medically proven rare disease care [29].

Fourth: Lysiane’s experience demonstrates that in Europe there is a promising opportunity to facilitate access to cross-border healthcare for rare disease patients, through a properly designed program of education and training. In the EU, prior authorisation for cross-border healthcare is subject to strict legal scrutiny. EU law states that “individual decisions of refusal to grant prior authorisation shall be restricted to what is necessary and proportionate to the objective to be achieved, and may not constitute a means of arbitrary discrimination or an unjustified obstacle to the free movement of patients” (Directive 2011/24/EU on the application of patients’ rights in cross-border healthcare). The EU Court of Justice specifies that every refusal to grant prior authorisation must be justified by “an overriding reason in the public interest” (Case C-173/09 Georgi Ivanov Elchinov v Natsionalna zdravnoosiguritelna kasa [2010] ECR I-08889). These standards for refusal are high and very difficult to meet, because by EU design, refusals should be exceptional events. In order for rare disease patients to benefit from meaningful access to care, these rules must be respected – but in order for healthcare administrators to respect these rules, they must first understand them. How can the legal standards governing EU cross-border healthcare be clearly and effectively explained to Europe’s numerous and diverse healthcare funds and administrators? Who should provide the training? What form should it take? And how can this information be communicated to EU citizens, including those from socially and economically disadvantaged backgrounds, so that they too can benefit from European advances in rare disease care? These questions call for further research and action, preferably on an EU level.

Fifth: Lysiane’s case demonstrates the limits of digital healthcare, and the idea that “information and knowledge should travel, so the patient doesn’t have to.” Sometimes the patient does have to travel. The patient has to travel to receive treatment at a light ion hadron therapy facility; likewise, the patient has to travel to receive a highly specialized rare disease treatment such as the TPP. The TPP treatment requires a relatively large team of individuals and disciplines and concentrated expertise, including neonatologists trained in upper airway nasopharyngeal fiber optic endoscopy, pediatric sleep medicine, orthodontics, cranio-maxillofacial surgery, neonatal nursing, and speech therapy. A treatment like the TPP cannot be offered in every hospital, or even in every country, and it does not need to be. The important point though is that if the patient does have to travel to access one of these highly specialized treatments, then the patient, especially the rare disease patient, should be helped, not hindered.

I appreciate this opportunity to contribute the patients’ perspective, and I hope that it fosters useful dialogue. A healthcare provider’s work can be extremely difficult. The responsibility you have taken on is profound. I wish you strength and courage as you face the tremendous moral challenges which constitute such a routine part of your day-to-day job.



This work received no grant from any funding agencies in the public, commercial, or not-for-profit sectors.


Declaration of competing interest

The author has no conflict of interest to declare.



I sincerely thank Mr. Americanos, Dr. Barman, Dr. Breugem, Mr. Davies, Mr. deBronkart, Mr. Elffers, Dr. Graeβner, Ms. Harris, Mr. Houÿez, Dr. La Scala, Dr. Logjes, Dr. Mossey, Dr. Oosterwijk, Ms. and Mr. Pakter, Dr. Palmier, Dr. Persson, Dr. Railavo, Dr. Resnick, Dr. Römmler-Zehrer, Mr. Russell, Dr. Sireau, Mr. Tavin, Dr. Wong- Rieger, and my beloved Delphine. Ms. Kumsal Bayazit, CEO of Elsevier, my family, and our friends and colleagues in the rare disease patient community, will never forget your kindness and support. Thank you.



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Dr. Cory M. Resnick, Oral & Maxillofacial Surgeon at Boston Children’s Hospital and Assistant Professor at Harvard Medical School, describes the exciting progress he has made on the Prenatal Diagnosis of Pierre Robin Sequence.

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