Interview With Dr. Nazli McDonnell, Part 1

This is an unedited, complete transcript of ABC's interview with Dr. Nazli McDonnell.

OFF CAMERA COMMENTS]

INTERVIEWER

All right, so, [CLEARS THROAT] the first one is the obvious one, I mean if you can give us just a very…simplified, concise definition of what this mysterious EDS is.

DR. NAZLI McDONNELL

EDS, Ehlors-Danlos syndrome, is a disorder of the connective tissue, which includes the joints, the skin, and sometimes the blood vessels.

INTERVIEWER

But why is it so mysterious?

DR. NAZLI McDONNELL

It's mysterious because it's often missed. That's because the patients who have EDS look just like any other normal person, average person, when you look at them. But the defect is in their skin…because if they injure their skin it can take a long time to heal.If they scar it can become a very abnormal, big scar. Their joints look normal to look at, but they can dislocate, and they have a huge amount of pain associated with the joints. And the blood vessels, they…they're in the right places, but they can be more fragile than normal persons' blood vessels.

INTERVIEWER

Well…one of the things that…uh, one of the symptoms that is, is most obvious, is the stretchy skin, the, um…Tell me about that, that is so mysterious, that is such a…an enigma.

DR. NAZLI McDONNELL

The reason, uh, that the patients with EDS have stretchy skin is that the collagen found in their skin is abnormal. Therefore when you stretch it, it can -- it can stretch out, way past a normal person's skin. And for that reason in the old days, patients with EDS were often in circuses, showing off their stretchy skin.

[OFF CAMERA COMMENTS]

DR. NAZLI McDONNELL

It is mysterious to the doctors because, um…it is the same reason that it's mysterious to everybody else, the people who have EDS look just like a normal person. And often they present to the doctor, complaining of joint pain or that they have scars that are big and ugly…Maybe we should redo that one [LAUGHS]. I don't wanna say ugly. Uh, the, uh, the reason, um… EDS is mysterious to the doctors is for a number of, um…causes, and, uh, one of them is that, people with EDS look like just any other person to look at. And second of all, it's rare. Therefore the doctors may have heard about it in medical school but they have never encountered a person with it so it goes to the back of their mind and they don't recall it. Um…the patients with EDS often go to the doctor complaining of joint pain. And joint pain has many causes and it's not on the top of the doctor's list that the patient may have EDS. Therefore it gets often missed.

INTERVIEWER

Uh, why do so few people know about it? About EDS.

DR. NAZLI McDONNELL

Because it's a rare disorder. Um, it affects about, um, maybe one in 5000 to one in 10,000 persons. But we estimate that only about 10 percent of those who are effected have been diagnosed.

INTERVIEWER

That's amazing to me. All right, how can it be that only 10 percent of those who have it are diagnosed?

DR. NAZLI McDONNELL

There are several reasons for that also.

INTERVIEWER

Uh, could you repeat the question, there's several reasons for what, you know --

DR. NAZLI McDONNELL

There are several reasons for the low, uh, rate of diagnosis, for affected individuals. Um, one of them is that the disease is itself quite variable. [12:07:30:18] So there might be more than one person affected in a family with the same genetic disorder, but, one of them has severe manifestations, severe symptoms, and the next person who might have the same gene, is not affected so much. The symptoms are better controlled. T 27 [12:07:49:01] Uh, so the range is from mild to severe, and the patients who are more severe tend to be diagnosed. The ones who are milder tend to be missed. Um, the second reason why the rate of diagnosis is so low is that, um, many physicians are not aware of the disorder, they had only heard about it in medical school and had never diagnosed someone themselves. [12:08:16:01] Um, in addition, the disorder presents itself often in teenage or adulthood. It's not often noticed in childhood. And typically pediatric doctors, the children's doctors are more tuned in to genetic disorders. And adult doctors are not tuned in to diagnosing genetic disorders.

INTERVIEWER

[12:08:39:01] But, it may be rare but it's not new, I mean, uh, it's been described all the way back to Hi -- uh, Hippocrates I believe described…

DR. NAZLI McDONNELL

T 27 [12:08:48:22] There are, uh, reports of diag -- diagnosis of an EDS-like disorder dating back to the Greeks. But the formal, um, description of the disorder happened around 1899 -- 1899.

[OFF CAMERA COMMENTS]

DR. NAZLI McDONNELL

[12:09:13:12] Um…EDS has been described as, uh, far back as the Greek, but the formal diagnosis, um, and description happened around 1899 by a Danish dermatologist.

INTERVIEWER

But 1899 is a very long time ago.

DR. NAZLI McDONNELL

[12:09:30:13] Yes.

INTERVIEWER

I mean, it -- that makes it an old disease in my mind.

DR. NAZLI McDONNELL

Yes, it is an old disease, and human genetic diseases are all old. That means they're built into our genes and there has been examples of that…uh, since the origin of humanity. [12:09:47:20] But, the description and understanding of these disorders has come much later. Uh, what has happened about EDS in the last 15 or 20 years is the, um, identification of the genes that cause it. And that has raised awareness as well as improved the diagnosis.

INTERVIEWER

[12:10:08:13] Um…we -- you mentioned that, uh&30133ome families that carry the genes have different manifestations, some mild and some very severe. We talked last week with a mother and a son who both have been diagnosed with the disease. [12:10:24:25] The son is only 19 years old, and he's confined to a wheelchair. The mother has a…very mild case, wears braces on her arms. Talk to me about how…rare -- I mean, how…how often does it happen that it can hit a 19-year-old so hard? [PAUSE] Is this a common ex -- is this is a common…

DR. NAZLI McDONNELL

[12:10:55:01] [PAUSE] It is rather uncommon for a young person to be severely affected with EDS. Uh, but it has happened. And we have seen examples, uh, where, uh, a parent also carries, uh, the disorder but has mild manifestations. However, um, there is a, uh, younger person, a son or a daughter, who has severe manifestations, and it's -- Although rarely it has happened that, um, it's so severe, that the person is wheelchair-bound at a fairly young age.

INTERVIEWER

[12:11:31:21] Well I mean that's what I really wanna get at because the young man that we talked with, um, is in severe pain, um, and heavy pain medication, and, uh, is wheelchair… dependent, if not wheelchair-bound, uh…How rare a case is that?

DR. NAZLI McDONNELL

[12:11:51:09] It's fairly rare that a person is wheelchair-po -- bound or requiring, um, narcotic pain medications in teenage years or young adulthood, but it has happened. Um…part of the focus of this study here at the National Institutes of Health is that we are trying to understand the different manifestations in different members of the same family. [12:12:16:12] We think that there are some genes that modify the expression of the disease. And if we can identify those perhaps we can have an insight into how to treat the complications of the disease.

INTERVIEWER

How far along are you?

DR. NAZLI McDONNELL

[12:12:30:21] We have made some progress.

INTERVIEWER

Uh, how far into your study are you?

DR. NAZLI McDONNELL

Uh, we've been recording participants, uh, for the last three years. There was a prior study at the, um…um, at NHGRI.

[OFF CAMERA COMMENTS]

DR. NAZLI McDONNELL

[12:13:00:29] Um, there was a prior study at the National Human Genome Research Institute, uh, where several, uh, patients were seen as well, with this disorder. And, um, we've been continuing on that work. Um, we have enrolled about, um, 200 patients with various forms of EDS.

INTERVIEWER

[12:13:21:29] What does happen to the genes?

DR. NAZLI McDONNELL

[12:13:25:23] The patients with, um, EDS have a mutation, in one of the collagen genes. Meaning that there's a spelling error…in the gene that codes for the collagen. Therefore the collagen that's produced by the fibroblasts, and the, um…cells in that person, make the abnormal form of collagen, instead of the normal form of collagen. And the confers weakness to the, uh, skin and the joints and the blood vessels.

INTERVIEWER

[12:14:01:11] All right, you're gonna show us -- what are you gonna show us on the microscope in a little while?

DR. NAZLI McDONNELL

I'm going to show you the fibroblasts, meaning the skin cells that we have grown in a, uh, dish, from a patient with EDS.

INTERVIEWER

Okay.

DR. NAZLI McDONNELL

[12:14:17:11] And from the fibroblasts we can extract the collagens and study them, trying to understand what's happening with that patient.

INTERVIEWER

If you get a cure, are you anywhere near a cure or a treatment for this?

DR. NAZLI McDONNELL

[12:14:32:03] We're not near a cure or a treatment per se. But we're -- we've made headway into understanding all the complications of the disorder, so that we can address the symptoms. We're also looking at some new strategies into how to treat the disease. But those are in the early stages yet.

INTERVIEWER

T 27[12:14:52:27] What, what kind of new strategies?

DR. NAZLI McDONNELL

The new strategi -- strategies include, uh, trial with medications that can increase collagen production. It can also include some genetic strategies to shut down the abnormal copy of the gene. But that's, is going to be in the years to come.

INTERVIEWER

[12:15:16:05] Years, not…are you -- when you say years are you talking decades or…how many years. I mean --

DR. NAZLI McDONNELL

I think --

INTERVIEWER

-- I know you can't give a, an exact --

DR. NAZLI McDONNELL

[12:15:23:27] No, I -- I think in the next decade, we'll have, um, some approaches that are going to be successful.

INTERVIEWER

[12:15:32:15] If you get a…a cure, or some kind of treatment for EDS, how -- I mean EDS is very rare, so it will affect just a few peo -- some -- you know, the people who have it, but, how would that be applicable to the rest of us, say for like arthritis or other disorders, is there, is there a way that the research that you're doing on EDS can be applied to the larger population?

DR. NAZLI McDONNELL

[12:16:04:08] Yes. The, um, patients with EDS, can be seen as…persons who age prematurely in terms of their skin and joints. We see an incidence of arthritis at a much earlier age than the general population. The typical EDS'er develops arthritis in their thirties and forties as opposed to their fifties and sixties in the general population. [12:16:32:19] So we are hoping that the treatment approaches we develop for EDS will be applicable for the treatment of, joint and skin complications in the general population.

[OFF CAMERA COMMENTS]

INTERVIEWER

[12:17:03:20] I am trying to get at -- and I thought this was a very good answer, um, that, um, uh, the, um…you know…if the research you're doing for this rare disorder --

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

-- can have --

DR. NAZLI McDONNELL

[12:17:16:00] Generalized applications.

INTERVIEWER

Yes.

DR. NAZLI McDONNELL

[12:17:18:15] Yes, and that is why ge -- the National Institute on Aging has invested in this study, so that we can understand more, using the rare disorders as a focus of investigation, but having applications to the treatment of disorders that affect the… population that is aging in general.

[OFF CAMERA COMMENTS] DR. NAZLI McDONNELL

[12:18:10:28] The reason National Institute on Aging has invested in this study is that we are using EDS and other rare connective-tissue disorders as a tool to understand the disorders that affect the general aging population, such as arthritis, poor wound healing, and fragility of the blood vessels.

INTERVIEWER

[12:18:33:09] Because no one thinks of arthritis as an especially exotic disease, I mean it affects so many people but, um, this EDS, uh, is considered…well, I mean to us, I mean we're including it in our series on medical mysteries, it's --

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

[12:18:49:06] It seems so mysterious partly because of the symptoms, this, sort of stretchy skin, you know, talk to me about that, is a -- I mean you say people are, don't look any different but yet they can do these --

DR. NAZLI McDONNELL

Yes.

INTERVIEWER

-- um…you know, amazing things.

DR. NAZLI McDONNELL

[12:19:08:11] Yes, persons with EDS look normal, but when you look at them closely you can see the signs and symptoms. Uh, one of the important signs is that -- the stretchiness of the skin. So much that in the old days it was common for patients with EDS to be included in circuses because they could stretch their skin, especially on their neck or elbows or their face, much more so than a normal person, and they were considered curiosities. [12:19:35:03] In the same vein, uh, the, uh, patients with EDS have very hyperextensible joints.

INTERVIEWER

Say it again, in the same vein --

DR. NAZLI McDONNELL

[12:19:44:10] In the same vein the patients have EDS have quite hyperextensible joints and often can do things that were called, quote-unquote, circus tricks. So they were often found as contortionists, in circuses. And there were whole families with EDS who had a history of being contortionists in circuses.

INTERVIEWER

[12:20:05:00] Can you give me some examples of them?

DR. NAZLI McDONNELL

For instance it's not uncommon for a person with, with EDS to be able to lift their foot and be able to place it behind their head and take both of their feet and place it behind their head and make themselves into a ball, way into their forties and fifties. [12:20:23:23] It might be that some children are able to do that at a very young age but most of us as we go into their teens and -- twenties we are no longer very flexible. People with EDS remain flexible. Although they do eventually get stiff also, but they are always more flexible than their age-mates.

INTERVIEWER

[12:20:42:17] I used to be able to do that with my legs. Roll in a ball. I'd roll and roll and roll. [LAUGHTER] Um, anyway, uh -- we actually --spoke, we interviewed a man named -- uh, not me myself, I haven't met him but, um, we interviewed a man named Gary "Stretch" Turner in England, who says he has the stretchiest skin in the world. Um, do you -- have you ever heard of him?

DR. NAZLI McDONNELL

No, I have not heard of him.

INTERVIEWER

[12:21:09:06] Uh, uh… He performs, in a…carnival show.

DR. NAZLI McDONNELL

Yes.

INTERVIEWER

And, he…he -- he maintains, that, uh, he's taken his, um, affliction and turned it into a way of making a living. What do you -- what do you think about that.

DR. NAZLI McDONNELL

[12:21:31:11] Well, uh, people with EDS have taken their affliction and turned it into a way of living, and, uh, as I mentioned there were, there were circus families who made a living that way. If you actually look amongst, uh, dancers, you would find a higher incidence of EDS amongst them than you would find in the regular population. [12:21:52:05] Since they are flexible from early on they are, um, attracted to, uh, using their skills in a way that they can excel. Unfortunately we also do see a higher incidence of premature arthritis, uh, in persons who have used their body in that fashion, because they're putting extra stress on those joints and, uh…it's not uncommon then then [sic] they would need a joint replacement and so forth at a fairly young age as a result.

INTERVIEWER

[12:22:22:09] All right, the young man that we talked to last week, the 19-year-old who is confined to a wheelchair --

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

[12:22:29:23] -- um, uh…he has taken a completely different approach to EDS from what Gary "Stretch" Turner has taken. He basically lives in his bedroom, his bedroom is his world. How, how rare is that that, um, someone is so -- their lives are just so confined by EDS?

DR. NAZLI McDONNELL

[12:22:54:05] As unfortunate as it is, I have seen many cases where the individual was so disabled that they have confined themselves to their bedroom. And it can happen to young persons and it can happen to older persons who, um, are just so burdened with arthritis and pain that they are unable to continue a normal working life. Um, and they are, um… con -- they -- their life is very limited as a result.

INTERVIEWER

[12:23:20:27] But, for a 19-year-old, is that…isn't that highly unusual?Primetime_NazliMcDonnell_InterviewTranscript2 DR. NAZLI McDONNELL

It is unusual for a 19-year-old to find themselves in that predicament, but it has happened on more than one occasion.

INTERVIEWER

[12:23:35:22] Mmm. Do you think your perspective is a little different because you see so many EDS patients?

DR. NAZLI McDONNELL

[PAUSE] Perspective different from what --

INTERVIEWER

[12:23:44:13] You -- well, I mean, most doctors can't even diagnose it.

DR. NAZLI McDONNELL

Yes. INTERVIEWER

You've seen [LAUGHS] many --

DR. NAZLI McDONNELL

T27[12:23:50:29] Yes. Yes, um, I have a different perspective on things because I see a lot of patients with EDS. Whereas the average physician -- might see one in their career and might not even seen one. Um, as a result, I understand about the pain and disability caused by EDS. Unfortunately when many of these patients present to outside physicians the disorder is not recognized. And the physician suspects that the, um, pain is not real. And the symptoms that the patient is describing are not real.

INTERVIEWER

[12:24:30:27] Wait, can you say that for me again because I'm not understanding exactly what you're saying. The doctors are…are not believing the patients?

DR. NAZLI McDONNELL

[12:24:39:10] Yes, unfortunately, there are many cases where the physician would not understand about EDS and will not believe that the patient's pain was real. And this doesn't just apply to the patient's pain. [12:24:52:15] There are a number of other symptoms of EDS. Um, such as disregulation of heartbeat. Can be very disturbing to the patient involved. Uh, disturbance of sleep, chronic sleep disturbance is very common. [12:25:07:19] Uh, patients often have gastrointestinal problems with irritable bowel syndrome, uh, chronic constipation or diarrhea. Uh, bloating in the stomach which is a result of tho -- those tissues being lax. And, when the patients keep going to their doctor with all these complaints, [12:25:28:01] the physician tends to not believe them, and…perhaps even think that the patient is making these up or they have an outside gain they're pursuing. They could be drug-seekers, they could be hypochondriacs. They could be, uh, I have heard patients called, um, histrionic. Um…unfortunately these, as -- this is not uncommon.

INTERVIEWER

T 27 [12:25:53:03] Um, I've -- I've read that it's been said, um -- [AUDIO DROP-OUT] -- EDS person has a horror story. What kinda suffering do you see in the people that you see?

DR. NAZLI McDONNELL

T27 [12:26:06:29] I see a big burden of pain and poor quality of life in the patients with EDS. We're actually collecting data on that, we're trying to quantify the burden of pain and impaired quality of life on the EDS patients. Um…to give you an example, for, for -- amongst the patients who have come to my study in the over-45 age group, I have only one person who is working full-time. [12:26:34:18] All the other persons have been on disability, because they have not been able to continue a working life, as a result of orthopedic complications, pain, cardiac complications, and so forth.

INTERVIEWER

[12:26:47:27] Well let's just go over that again, because the door slammed right in the middle of your --

DR. NAZLI McDONNELL

Okay -- [LAUGHS]

INTERVIEWER

-- sentence but, um, uh --

DR. NAZLI McDONNELL

Okay, what did I say? [LAUGHS]

INTERVIEWER

[12:26:55:12] You were talking about the suffering that you see --

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

-- and, and, I'm not asking you to use names, but give me some examples of, uh, the kinds of human suffering that you have seen in EDS patients. Things that people would not expect.

DR. NAZLI McDONNELL

T27 [12:27:13:05] Um, an example of, um, an exceptional burden of disease would be the amount of dislocations a person can experience in daily life. Um, I actually have some patients from lifting a comforter on their bed have torn a tendon, dislocated their shoulder. They're not able to go up the steps on two feet, they have to go up on all fours, because their EDSers cannot support them. [12:27:37:22] Uh, we see advanced spine disease in a fairly young group of patients with EDS, I have some EDS'ers who are only 18 years old and their spine looks like someone who should be 80 years old. And they have the pain and suffering associated with that, uh, as well as the impaired qualify of life from the daily pain and impairment of their movement.

INTERVIEWER

[12:28:02:29] You said something to me about, um, how many times a day, you have some -- one patient what -- who dislocates --

DR. NAZLI McDONNELL

Mm-hmm --

INTERVIEWER

Can you tell me that again?

DR. NAZLI McDONNELL

[12:28:11:08] In the most extreme cases a person can experience dislocations or subluxations…

INTERVIEWER

What --

DR. NAZLI McDONNELL

-- 20 times a day.

INTERVIEWER

[12:28:19:00] I don't understand dislocations or sublu…

DR. NAZLI McDONNELL

Okay --

INTERVIEWER

Uh, remember, you're talking to my mother.

DR. NAZLI McDONNELL

Okay.

[OFF CAMERA COMMENTS]

END TP 27

TP 28

[OFF CAMERA COMMENTS]

INTERVIEWER

[13:00:18:08] Okay, so…we'll get back to what we were talking about -- DR. NAZLI McDONNELL

Okay. [LAUGHS]

INTERVIEWER

[13:00:23:01] Um, uh… You -- we were still probing the suffering that people go through --

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

And, um, I would like you to give me some examples of what you have seen, um, in terms of, uh, the -- the real agony that people experience.

DR. NAZLI McDONNELL

T28 [13:00:44:04] Yes, it's very common to have an excessive burden of pain and, uh, problems with EDS. An example would be, um, one of my patients, uh, was lifting a comforter from a bed and she ended up tearing her -- a tendon in her shoulder. Um, I have other patients who, uh, are so severely affected that their joints pop out of place, 20 or 30 times a day. [13:01:10:23] These could be large joints like shoulder, or it could be small joints in their fingers, it could be their wrist. It could be a frank dislocation meaning that the joint actually came out of place and had to be put back into place. [13:01:26:20] It could be a subluxation meaning that it just slipped, causing pain. Um, and often, these patients have to learn how to put their joints back into place. So if a shoulder comes out, they know how to pop it back. On occasion, they have to go to the hospital to have it popped back in.

INTERVIEWER

[13:01:45:04] We actually last week when we were interviewing this young man, um…he showed -- he told us first of all that, his, his shoulder would pop out -- his shoulder once popped out when he lifted a gallon of milk.

DR. NAZLI McDONNELL

Yes.

INTERVIEWER

[13:02:00:17] And, um, and then he showed us his shoulder sort of dislocating and, and he put it back in, um, can you talk a little bit about, I mean is that…is that extreme, is that rare, is that…

DR. NAZLI McDONNELL

[13:02:14:17] Actually the joint dislocations and subluxations are the hallmark of the hypermobile form of EDS, where it is the main symptom.

INTERVIEWER

What do you mean hypermobile.

DR. NAZLI McDONNELL

[13:02:25:11] EDS has different forms. One of the more common forms is the hypermobile form where the main symptom is joint dislocations. The skin symptoms are not as much, it's a little bit stretchy, but not as stretchy as the classical form. [13:02:41:26] The patients with this classical form have very stretchy skin, and they're also the ones who develop the more disfiguring scars. The vascular form which is not as common as the hypermobile and classical form have complications with their blood vessels. [13:02:58:01] That mean that their aorta can rupture which is the main vessel that comes out of their heart and supplies the blood to the rest of their body. So that's usually -- usually a fatal complication.

INTERVIEWER

[13:03:11:02] But I mean…what do you say to a 19-year-old whose shoulder pops out when he lifts a gallon of milk?

DR. NAZLI McDONNELL

[13:03:22:27] [PAUSE] Unfortunately for a patient whose shoulder pops out when they lift a gallon of milk, there is very little we can do, except to recommend strengthening of the muscles around that joint. And, that's not so easy because these patients have, some of them at least, have difficulty building muscle. [13:03:42:13] So with the same amount of exercise that a quote-unquote normal person can build muscle they're not able to build their muscles at the same rate. And the exercises you do to build the muscles sometimes can pose a risk to your joint as well, so, uh, you have to approach it very carefully. [13:04:02:05] Uh, if they're working with a physical therapist to strengthen that joint, the therapist needs to be really aware of the limitations of what they can do with this person.

INTERVIEWER

[13:04:13:10] What about, um -- the same young man -- complained a lot about…his -- the main pain he had is in his knee.

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

[13:04:25:21] And we asked him, why don't you get a knee replacement. And so now I'm asking you. Uh, would, why…would…would a knee replacement help someone like this young man that we talked to last week.

DR. NAZLI McDONNELL

[13:04:42:19] My experience with this group of patients is that, uh, replacing the joints is not the solution. Um, first of all, they often do not heal well from orthopedic-type surgeries, and they tend to go back in with complications. [13:04:59:25] Um, if any of their own tissue is used in reconstruction, um, it weakens the tissue, the, um…original tissue where the, uh, replacement tissue was taken from, and it increases the complication risk if the replacement knee often is not stable either because the, um, surrounding tissue is not stable.

INTERVIEWER

[13:05:25:28] All right… Well, we, we know that pain is a huge problem with EDS. Um, uh, and they, and, and you've already said that the doctors, um…that patients complain that the doctors don't believe them because it doesn't show up on X-rays.

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

[13:05:42:08] Can you talk to me a little bit more about how, uh, EDS does not, you know, even though they have this, uh, terrible joint pain, that one of the reasons it remains a mystery with doctors is that they do all the tests and the tests come out normal?

DR. NAZLI McDONNELL

[13:06:02:14] When you take an X-ray of a joint in a person with EDS, it looks normal. Because the issue is not in the joint space. It's the ligaments that hold that joint together, the tissue around it, is what's weak. And you cannot pick that up in a static X-ray. So when the doctor looks at that X-ray they say oh, this is a normal knee, there is nothing wrong with it. [13:06:28:13] And until that joint sustains damage, even an MRI may not show anything different. However, over a period of time, with the joint laxity, the, um, joint will sustain damage and it'll be then visible in an MRI.

INTERVIEWER

[13:06:46:24] Um, how old are patients usually when they're diagnosed, finally?

DR. NAZLI McDONNELL

I think the average age -- age of diagnosis is in patients, late teens or early adulthood.

INTERVIEWER

[13:06:57:09] Mmm. Because we thought it was rare that the young man that we saw last week got it so young.

DR. NAZLI McDONNELL

[13:07:05:19] Um, just to give you an idea, about a third of the patients who have enrolled in the connective-tissue study at the National Institutes of Health are under the age of 25. Um, another third is between the ages of 25 and 45, and then, um, the remaining of them are over 45.

INTERVIEWER

Is that because you chose them that way or…

DR. NAZLI McDONNELL

[13:07:28:18] No, I think that just represents the, um -- mixture of ages that are diagnosed, and often I get, um, a call from a patient who was recently diagnosed, so, there have been patients who have been diagnosed in their fifties, and a good few of them are diagnosed in their teens.

INTERVIEWER

[13:07:47:13] Um…but I just wanna go back again to that issue of how…common it is in society in general, and how often it's missed as a diagnosis. We talked about a little bit before --

DR. NAZLI McDONNELL

[13:08:04:15] Did we -- was that one of the things that got messed up?

INTERVIEWER

Um, well, I just think that it goes…it -- it -- it's important to relate it to this, um, you know.

[OFF CAMERA COMMENTS]

DR. NAZLI McDONNELL

[13:08:25:03] Often a young person, uh, will get diagnosed because of what we call postural orthostatic tachycardia. Meaning that when they stand up their heart beats very fast to the point that it bothers them and they feel ill. And the same syndrome is seen when they're sleeping at night when they could be sleeping in bed motionless and their heart is suddenly beating over 120 beats per minute. And this disturbs their sleep. So they present to the doctor complaining of this syndrome. This postural orthostatic tachycardia. [13:09:01:11] A good few of these youngsters actually have EDS. We are collecting data on this at, um, at the National Institutes of Health. So, um, unfortunately when the young person presents to the doctor with this complaint, most often nobody ever thinks of examining their joints. [13:09:24:28] So if the doctor is astute enough to examine the joints and notices joint hyperextensibility or skin stretchiness, they would put the whole picture together and understand that this patient actually has EDS and the, uh, fast heart rate is a part of the syndrome.

INTERVIEWER

[13:09:41:28] Well the young man that we interviewed last week, his mother said that, um, one of the reasons so many doctors miss the diagnosis is that it's a paragraph in medical school.

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

Can you talk a little bit about that --

DR. NAZLI McDONNELL

[13:09:54:00] Yes, and, uh, most doctors, we have learned about EDS in the medical textbook, and have never seen a case, during their training. Therefore it's very difficult for them to pick it up. The groups of doctors who might be more familiar with it, of course include geneticists who are trained to pick the disorder up, but also dermatologists, who are tuned in to it because of the skin symptoms. [13:10:19:17] Also some rheumatologists, who see a fair amount of EDS because the patients often complain of joint pain. Uh, and some orthopedic doctors who may treat them with, uh, because of frequent dislocations.

INTERVIEWER

[13:10:36:19] So then why is it, I mean…if there's so many people, so many specialties that could diagnose it why is it such a mystery to, or why is it so undiagnosed, um, so often?

DR. NAZLI McDONNELL

[13:10:54:25] The reason, um, it may be missed even when they, uh, the patient presents to one of the specialists is because, the doctor may not look at the whole person. So if the dermatologist is only focused on the skin, and doesn't examine the joints, they might not come to the conclusion that the person has EDS. [13:11:14:22] And similarly, if the orthopedic doctor focuses only on one joint, and doesn't examine the rest of the joints on that person, then the diagnosis will be missed as well.

INTERVIEWER

[13:11:23:29] So it sounds like it slips through the medical cracks.

DR. NAZLI McDONNELL

I think it does tend to slip through the medical cracks.

[OFF CAMERA COMMENTS]

INTERVIEWER

What -- Just plain and simple, what causes the skin to stretch and the joints to dislocate.

DR. NAZLI McDONNELL

[13:12:00:08] The patients with EDS with abnormal collagen in their skin and joints. Collagen is the building block of what we call connective tissue, the glue that holds ourselves together in our body. To give you an idea, if you extract all of the proteins from the sa -- from the human body, about 70 percent of it is collagen. [13:12:23:11] And the patients with EDS have abnormal collagen, throughout their skin and throughout their joints, which makes it more susceptible to damage.

INTERVIEWER

[13:12:33:02] So are you…this notion, I mean I -- I can, I think people can relate to the idea that collagen is the glue that holds us together. Are you saying that these people lack the glue?

DR. NAZLI McDONNELL

[13:12:46:19] People with EDS do not lack the glue. They just have a weak form of the glue or an abnormal form of the glue. So that the glue doesn't do its job right.

INTERVIEWER

[13:12:57:17] Wait, we have to the say the glue of what, though.

DR. NAZLI McDONNELL

Oh. [LAUGHTER] Okay.

INTERVIEWER

Uh, people who -- people -- All right, is what you're saying -- let me try this again, um, is what you're saying that people…don't have the right kind of glue to hold their joints together and their skin together --

DR. NAZLI McDONNELL

T28 [13:13:13:11] Yes, yes. So, uh, if we consider collagen to be the glue that holds, um, our, our cells of the body together, the patients with EDS have a weak form of the glue in their body that doesn't hold their skin or joints together in the right way. So they're more susceptible to damage to their joints and damage to their skin.

INTERVIEWER

What kind of lifespan can a patient who has diagnosed with EDS expect?

DR. NAZLI McDONNELL

[13:13:40:28] The lifespan with EDS is different for different forms of EDS. The hypermobile and classical forms of EDS, we expect them to live a normal lifespan, but a reduced qualify of life.

[OFF CAMERA COMMENTS]

DR. NAZLI McDONNELL

[13:14:09:09] Um…for the -- okay. For the most common forms of EDS, the lifespan is not affected. If the main symptoms of EDS in a person is skin and joint problems, we expect them to live a normal lifespan but we suspect that they will have a reduced quality of life. [13:14:30:17] For patients where the major problem is in the blood vessels, we do expect them to have a reduced lifespan.

INTERVIEWER

Because the blood vessels fall apart?

DR. NAZLI McDONNELL

[13:14:41:20] Yes. They, uh, the patients who have problems with the blood vessels, experience dissection of the blood vessels meaning that the, uh, the layers of the blood vessels separated apart and the blood flow went in places it's not supposed to go to, or that the blood vessel ruptured or, uh, burst. And, um…as a complication of that they could lose their life.

INTERVIEWER

[13:15:09:08] Um…how do, um, I understand that, uh, young people with EDS are often not just good at dancing but also good at sports, um, can you --

DR. NAZLI McDONNELL

Yes --

INTERVIEWER

-- tell me a little bit about that?

DR. NAZLI McDONNELL

[13:15:22:25] Um, young people with EDS can be quite good in certain sports, that, um, takes advantage of their nimbleness. Therefor they're attracted to these sports. Some of them also can be quite tall and it -- are attracted to things like basketball. [13:15:38:00] Um, unfortunately the, uh, competitive sports tend to take a heavy toll on an EDS youngster's body. So that we see increased complications, increased need for joint replacements, increased disease in their spine, increased, um, incidence of dislocations where the joints pop out. Uh, they might even need surgical intervention for dislocations.

INTERVIEWER

[13:16:06:24] Um, the young man we interviewed last week is quite tall. Uh, he used to be taller than he is now, he was six-three and now he's six feet. Why is that?

DR. NAZLI McDONNELL

[13:16:17:09] One of the complications we see with EDS appears to be no bone density. As well as, um, increased inci -- incidence of scoliosis which is a curvature of the spine. So, um, a young person who might start up as six foot two, might be six foot one by the time they're 19 or 20. [13:16:38:23] And this may be because they lost some height because of loss of bone density, also it may be that they lost height because of curvature of the spine.

INTERVIEWER

[13:16:50:18] But still these people remain an enigma to the rest of us, I mean you see someone like Gary Stretch, you know --

DR. NAZLI McDONNELL

Mm-hmm --

INTERVIEWER

[13:16:58:23] -- or like the young man we in -- interviewed last week, and they seem -- why is it that they… The young man has no friends. You know, and, um…why is it that they are such an enigma to the rest of us?

DR. NAZLI McDONNELL

T28 [13:17:18:01] Some of the more severely affected patients with EDS, uh, tend to get very isolated. And they feel different to, um, all the other friends they meet. And, um, teenage and young adulthood is an, um, is a time when one is very conscious of their body and their self-image. [13:17:38:22] And, um, it's difficult for these youngsters to integrate to the mainstream of life, because they feel different to everybody else, they also often feel misunderstood. Nobody else understands their pain. Nobody under -- understands why they're different. [13:17:53:01] So they can end up with social isolation. The psychological aspects of EDS are not a minor part of the disorder, it's a major part.

[OFF CAMERA COMMENTS]

INTERVIEWER

Tell me -- or, you were saying the psychological aspects are very important.

DR. NAZLI McDONNELL

[13:18:30:21] Mm-hmm. One of the things we are trying to understand at the study here is the, um, psychological aspects of the E -- of EDS. Um, we are actually collecting, uh, a personality inventory on all patients who come to the study. And, uh, we're trying to quantify what's happening, what the impact of the disorder is.

INTERVIEWER

[13:18:55:04] What are you finding.

DR. NAZLI McDONNELL

I can't really reveal those yet. [LAUGHS]

INTERVIEWER

Oh. Do you have any early findings that you can talk about --

DR. NAZLI McDONNELL

[13:19:02:04] Yes, um --

INTERVIEWER

I mean and you can couch it in --

DR. NAZLI McDONNELL

Yes, I -- I can say --

INTERVIEWER

-- maybe's and possibly's and all that --

DR. NAZLI McDONNELL

[13:19:09:00] Yes, um…uh, we are generally observing increased levels of anxiety and social isolation, in patients with EDS, um, as a result of their disorder. As well as an increased incidence of depression.

INTERVIEWER

[13:19:27:02] We wondered whether the drugs that the young man we interviewed…has to take for the pain was affecting his, um, personal --

DR. NAZLI McDONNELL

Mm-hmm.

INTERVIEWER

-- his personality. Can you talk about that?

DR. NAZLI McDONNELL

T28 [13:19:40:13] One of the issues with, um, the treatment of pain in EDS is that, um, often you're prescribing narcotics which can, um, increase the burden of depression, increase the sense of soc -- social isolation, um, the physiological dependence on the narcotics, uh, that occurs over a period of time. [13:20:02:29] These are all serious issues with EDS. It's not uncommon that the patients are on more than one pain medication to control their pain, and they require them in increasing doses.

INTERVIEWER

What is the biggest complaint that patients themselves give you?

DR. NAZLI McDONNELL

[13:20:21:14] I think for -- the biggest complaint with EDS that patients subjectively have, is pain.

INTERVIEWER

[PAUSE] And what's the biggest problem they have?

DR. NAZLI McDONNELL

T28 [13:20:36:24] I think, um, globally speaking, the biggest issue with EDS patients is the quality of life. And, whether they can have a positive experience of life while carrying this disease. Um, I once had a young man say to me, that in his twenties he suddenly understood that the pain he experienced on a daily basis was not normal, that other people did not have that. [13:21:03:13] He said to me, when he was seven years old he used to wake up and he said, he thought to himself…if this is what life is about, why does everybody wanna live. Why are we all here if this is what -- what life is about. That's what his experience was as a seven-year-old because of joint pain.

INTERVIEWER

[13:21:22:22] Oh. What does that do to you as a person to hear that out of so many patients?

DR. NAZLI McDONNELL

[13:21:34:03] I think, um, as I see more and more patients with complications of EDS, of all the different forms of EDS, including the, um, hypermobile form which affects the joints mostly, [13:21:48:06] The classical form our patients have disfiguring scars, and the vascular form our patients are facing a shortened life expectancy because of rupture of the blood vessels. I'm more and more motivated in our search for a treatment. [13:22:06:20] Um, I'm really hoping that in my lifetime I'll have something to offer to this group of patients, in terms of hope.

INTERVIEWER

[13:22:16:15] I hope you do too. Um…but the -- did you… Did you talk about all of the early findings that you're able to -- I mean is there anything you can hold out for hope now?

DR. NAZLI McDONNELL

[13:22:35:07] [PAUSE] Let me think about how to answer that. [LAUGHS]

INTERVIEWER

Mm-hmm.

DR. NAZLI McDONNELL

[13:22:38:17] Um… I think there is a point, where we're trying very hard to understand the natural history of the disorder, and discover all the manifestations of the disorder, so we can address all the symptoms. [13:22:54:12] Um, there are many ways of approaching a disease. And, of course the fundamental treatment for a genetic disorder is to shut down the genes that are causing the problem. While we hope that that is in the future somewhere, um, it is not without its own controversies. [13:23:13:27] Uh, so what we can hope right now is to understand the disorder enough that we can at least offer symptomatic treatment to various manifestations.

INTERVIEWER

[13:23:24:07] Well the young man we talked to last week who complained so much about pain he experienced and especially in his knee, uh, said that he was going to be trying very soon a, uh, a sort of nerve-deadening or a nerve blockage --

DR. NAZLI McDONNELL

Mm-hmm. Yes --

INTERVIEWER

What do you…what do you say about that?

DR. NAZLI McDONNELL

[13:23:41:08] Well, um, I think in extreme cases where the pain is located to one joint, um…the nerve-block approach can be taken. Um, local, um, anesthesia-type efforts can be undertaken to, um, treat the, um, focus of that pain. Um, unfortunately for many patients there is pain in more than one joint. And it's not possible to nerve-block their whole body.

INTERVIEWER

[13:24:16:11] One thing that's been -- that I've read, and that's been said to us that I find really hard to believe and I would really appreciate it if you could clear this up is that…uh, I've read that EDS is more common than, than leukemia. If it's more common than leukemia how can it remain such a mystery to the doctors?

DR. NAZLI McDONNELL

[13:24:39:14] Hmm. Now I don't really know the numbers, and I don't -- I can't say EDS is more common than leukemia, I think perhaps if you take into account all forms of leukemia, leukemia may be more common. [13:24:51:11] The reason EDS is not recognized as frequently as leukemia is number one, leukemia can be diagnosed with a simple blood test. And EDS cannot be diagnosed with a simple blood test. Therefore it can be missed. Secondly, leukemia often leads to death, if untreated in a short space of time. T 28 [13:25:10:24] EDS does not lead to death, it only leads to, leads to misery. So, uh…therefore it's rather easy for, um…doctors to think that these are nuisance patients who are knocking on their door with daily complaints of pain and not understand that this is a serious disorder.

INTERVIEWER

[13:25:31:02] That's a very good point. Uh, we interviewed Dr. Howard Byrd in Leeds, England, have -- are you familiar with him at all?

DR. NAZLI McDONNELL

Yes, actually I am. I don't know him personally but I -- I've read his work.

INTERVIEWER

[13:25:43:20] Can you, uh, tell me a little bit about his work?

DR. NAZLI McDONNELL

Well actually --

INTERVIEWER

Or how --

DR. NAZLI McDONNELL

[13:25:47:07] -- I couldn't tell you much about his work, I mean I read his work and I think they are making some very important contributions in England, in terms of understanding of the disease as well.

INTERVIEWER

Is -- how does his work differ from yours?

DR. NAZLI McDONNELL

[13:26:00:14] We're doing it in different countries. And I think, uh, Dr. Byrd's work is more clinical, and while I'm also doing the clinical work we're doing full clinical evaluations on all patients. Uh, the approach to treatment that I'm trying to develop is through laboratory investigations, so a lot more -- my work is in the laboratory.

INTERVIEWER

And so, what does he do instead?

DR. NAZLI McDONNELL

[13:26:24:05] I don't believe he has a laboratory program.

INTERVIEWER

I think he treats Gary Stretch.

DR. NAZLI McDONNELL

Yes, I think he…you know, he diagnoses and treats the patients symptomatically, but I don't think there's a laboratory program there actually looking for, um…you know, working with mouse models or, um…uh, genetic approaches, um, to, to treat the disease.

[OFF CAMERA COMMENTS]

END TP 28