Interview With Dr. Nazli McDonnell, Part 2
— -- This is an unedited, complete trascript of ABC's interview with Dr. Nazli McDonnell.
[STARTS MID-SENTENCE]
INTERVIEWER
-- born with EDS?
DR. NAZLI McDONNELL
[14:00:12:03] As far as all, all -- As far as we know, all races and ethnic groups can be affected with EDS.
INTERVIEWER
I … 'Cause I re -- I've done some reading and back in, um … 400 B.C., Hippocrates wrote that nor -- "nomads and Scythians were lax of joint and had multiple scars."
DR. NAZLI McDONNELL
[14:00:34:23] And it may have been true in Homer's time but the way we have all gotten mixed up I don't think it's the case. There is also erroneous statement in Wikipedia that EDS is more common than, uh, in redheads and it's not. [LAUGHS]
INTERVIEWER
That -- that's very important.
DR. NAZLI McDONNELL
[14:00:51:18] Okay, I was gonna go in and edit that but I didn't. [LAUGHS]
INTERVIEWER
Would you tell me that again?
DR. NAZLI McDONNELL
[14:00:56:20] [LAUGHS] There is an erroneous statement in Wikipedia that a form of EDS is more common on redheads, and that is not a finding in our study. [OFF CAMERA COMMENTS]
DR. NAZLI McDONNELL
[14:01:11:11] EDS is generally more symptomatic in women than in men.
INTERVIEWER
Why is that?
DR. NAZLI McDONNELL
[14:01:20:03] We are trying to understand that in our study. Uh, for about every seven women with EDS we see, we see only about one man. And when we examine, um, patients from the same family, although they may carry the same gene, uh, we see fewer findings on the men than in the women. So that is a mystery and we suspect that, uh, there are some hormonal influences on the expression of the disease in a person. [14:01:55:17] Also we have found that, many men with EDS have low levels of the main hormone testosterone. And we don't know whether that's the chicken or an egg situation, whether they have more manifestations of the disorder because they have low testosterone or it's a … it's a result of the disease.
INTERVIEWER
[14:02:13:17] The young man that we talked to last week, uh … said that he was living a normal life running around being an athlete, and he came home from, uh, school one day with a mi -- he developed a migraine one day, that lasted for eight days.
DR. NAZLI McDONNELL
Mm-hmm.
INTERVIEWER
[14:02:32:21] And, uh, or some period of time that was really a long period of time, and, the doctors gave him some steroids, and that kick … kick-started the EDS and he's never returned to school since. Can you, uh, tell me a little bit about something like that?
DR. NAZLI McDONNELL
[14:02:49:25] Actually my personal impression on that is that, the steroids did not have anything to do with it. However we do see that, um, there are some triggering events, that, um, often, uh, start the more severe symptoms. [14:03:05:20] And this could be a period of intense physical activity. I have seen that history in a number of patients. So, uh, they have undertaken a heavy exercise program either in competitive sports or in their personal life they have undergone heavy, um, weight training or a, uh … a rigorous running program. [14:03:26:26] And then subsequent to that, the joint pain is, um, amplified, and they're much more symptomatic. And I suspect that the wear and tear on the joints, uh, related to this, um, high level of physical activity, can, uh, lead to the onset of the pain, in these patients.
INTERVIEWER
[14:03:49:02] Um, because, another thing I read is that, uh, doctors, pediatric doctors when they see little kids will say, oh, you -- just clumsiness in kids or you're just having growing pains.
DR. NAZLI McDONNELL
Mm-hmm.
INTERVIEWER
What can you tell me about that?
DR. NAZLI McDONNELL
[14:04:02:29] Actually, it's an invariable history with EDS that in childhood, these patients had, quote-unquote, growing pains, to the point that they would wake them up from sleep. And I think that in this case, this was an early manifestation of EDS, rather than just being growing pains.
INTERVIEWER
[14:04:24:15] Are there such a thing as growing pains?
DR. NAZLI McDONNELL
That I do not know. I think there are people, there are children who experience pain when they're growing. But I think that if the growing pains are so severe that it's waking up the child from sleep, an examination of their joints might be in order.
INTERVIEWER
[14:04:43:20] But now parents sitting at home, who, like, me as a parent, uh, at -- Almost all parents at some point their kids say oh, you know, I have growing pains or somebody says, oh, that's just growing pains. Should these parents be running their kids to specialists?
DR. NAZLI McDONNELL
[14:05:02:08] I think if the growing pains are persistent over a period of time, and if they're severe, if it's -- the child is waking up crying in the middle of the night, complaining of their legs or joints hurting, it warrants an investigation. [14:05:18:00] And I think the first step is a pediatrician, and the, um, family can ask if the joints on this child are hyperextensible. Um, if they are, um, then perhaps an evaluation by a geneticist would be recommended. Um, mind you, all children are hyperextensible to some extent, and I personally do not like making a diagnosis in a prepubertal child. [14:05:46:02] Because, um, it's a challenging diagnosis. I do make the diagnosis if there is a strong family history, for instance if we know that the mother is affected, and we see a child with significant joint hypermobility then, I can say, well, this child likely has EDS and should refrain from such things as contact sports or heavy physical activity as this can trigger, uh, the pain syndrome. [14:06:10:14] Uh, but on the average child who just comes in with some minor joint hypermobility, I hesitate to make a diagnosis until that person is through puberty and the joints are matured.
INTERVIEWER
[14:06:23:11] So you're saying that there is -- that someone can be born with EDS -- are, are people born with EDS or do they develop it?
DR. NAZLI McDONNELL
People are born with EDS. So if you have the defective gene, you have the propensity to develop the pain syndrome that can go with the EDS.
INTERVIEWER
[14:06:42:22] But … they could be born with it, and not know it, and then there's some kind of triggering event like you said, like turning a light switch, and …
DR. NAZLI McDONNELL
[14:06:53:29] Yes, um, so, let's put it this way. If a person is with -- born with EDS there is nothing they can do about that, they have EDS. What can differ is the extent of the manifestations of the disorder. So, um, in terms of a joint pain syndrome, um, the thing to do if it is already established that the child has EDS is to avoid the contact sports and the injurious physical activity. [14:07:20:23] This is not to say that they should not be active. Is it recommended that they sh -- they would be active, but the, um, the level of activity is what's, uh, important. You don't want the child, uh, being in a situation where they would actually pop their joints out of place frequently. [14:07:37:23] You don't want them exercising to the point of damaging joi -- their joints, and, uh, you don't want them exercising to the point that they're wearing and tearing their joints, so that they would develop the early arthritis.
INTERVIEWER
What about ballet and dance?
DR. NAZLI McDONNELL
[14:07:52:25] I think ballet and dance are all okay, as long as they're pursued in non-competitive fashion.
INTERVIEWER
Um … so, knowing everything you know about EDS --
DR. NAZLI McDONNELL
Mm-hmm --
INTERVIEWER
[14:08:06:26] -- and all the pain and all the suffering and everything, we still keep coming back to the, you know, sort of freak-show approach to it that some people take. And, does that offend you?
DR. NAZLI McDONNELL
[14:08:22:03] I think, um … if a person has EDS and they choose to, to pursue it in, in a lifestyle that they, uh, make a living out of it, it's of course okay by me as long as they're not suffering. So that means they may have found an adaptation that works for them. [14:08:45:08] But also please understand that not every person is going to find themselves a place in a freak show, or a circus show, and take advantage of their disorder in that fashion, many of them are not going to find an adaptation. And, they face the social isolation, they face a poor quality of life, and they face all the psychological problems that come with it.
INTERVIEWER
[14:09:11:29] So if we … I mean, this show is about medical mysteries, and --
DR. NAZLI McDONNELL
Mm-hmm.
INTERVIEWER
-- you know more about -- It's a myst -- this disease is a mystery, to pretty much everybody except you. [LAUGHS] Um --
DR. NAZLI McDONNELL
[14:09:25:16] I wouldn't say it's just me, there are quite a number of people in the United States who know about EDS, there are quite a number of doctors who know about it. Uh, most geneticists are extremely familiar with what it is. Um --
INTERVIEWER
[14:09:40:19] But why to the general public is it such a mystery then. Is it the freak show aspect of it?
DR. NAZLI McDONNELL
T29 [14:09:46:07] I think what's, what's a mystery about it is that, what you see is a normal-looking person. It's not that you're seeing a short-statured person that you identify as a dwarf, or it's not that, you know, this person has a … big abnormal finding on their skin that you visualize immediately. [14:10:06:02] The person looks normal. And, what's different about them is the glue that holds their body together, it's weak. And therefore they have all the complications associated with that. And, uh, I think what people don't understand is what lies under this normal appearance.
INTERVIEWER
[14:10:24:21] And they also don't understand the trick, you know, like the pretzel man and the --
DR. NAZLI McDONNELL
Mm-hmm.
INTERVIEWER
-- and the stretchy-skin man, they -- people don't understand that.
DR. NAZLI McDONNELL
[14:10:33:25] No they don't, and also people often don't understand their own disorder. If you go into a website like this YouTube or, you know, Daily Motion, these places, I often see, uh … people, uh, who have made videos of themselves doing these circus tricks, looping their arms around, putting their leg in their back and so forth. [14:10:57:29] And, um, they, um, you know, they think they're being funny but they actually are not being funny and by doing those things they're making more damage to their joints and they're probably gonna end up, uh, needing an operation on that joint, 10 years down the road.
INTERVIEWER
[14:11:12:27] Well that's interesting, we didn't really think about that, um …
DR. NAZLI McDONNELL
Go on YouTube. [LAUGHS]
INTERVIEWER
I will. Um --
DR. NAZLI McDONNELL
[14:11:21:05] There are probably about 500 videos posted of people doing the circus tricks.
INTERVIEWER
Really. DR. NAZLI McDONNELL[14:11:27:04] That they made these videos themselves and put them there, I often thought of going on there and e-mailing them saying, you know, you really have a genetic disorder and you shouldn't be doing those things [LAUGHS]. But I don't do that.
INTERVIEWER
Well, you just did it.
DR. NAZLI McDONNELL
[14:11:40:29] Well … I didn't send them personal e-mails. [LAUGHS]
INTERVIEWER
Interesting. So, how can a person have this disease, I mean, like you're saying that, this can be a mystery to their own -- This disease can be, like … a mystery to the person who even has it.
DR. NAZLI McDONNELL
T29 [14:12:01:17] Yes, it's often a mystery to the person who has it, and it's -- often a person comes here and I ask them to -- I ask to examine them and I'm looking at their hands and feet and knees and, you know, I measure how, um, hyperextensible their skin is and how, how their knees are and their elbows are and how their fingers are. [14:12:19:23] And then they look at me and they say, you mean you can't do that? You mean other people can't do that? What the pat -- what the person experiences themselves is the pain that's coming from the joint, they don't think of their own joints as abnormal, they don't think that they can do something that's unusual. To them that's how they always were. But they come seeking for treatment of pain.
INTERVIEWER
[14:12:47:12] [PAUSE] That's interesting. Um … so I do wanna ask one question about, like a formal question about the … you're doing the -- Is this correct. You are conducting the first-ever longitudinal study on EDS. And how many participants do you have and what are you hoping you'll learn, and why are you doing it.
DR. NAZLI McDONNELL
[14:13:10:28] Okay. Uh, we've been doing a longitudinal study of EDS patients at the National Institute on Aging for about the past three years. Formerly the study was located at the National Human Genome Research Institute. [14:13:24:28] As far as I know, this is the only longitudinal study where we're going to be following the patients for more than one visit, to look at what happens to them in the long run. So, uh, we wanna study what happens to their joints over a period of time, what happens to their spine, what happens to their blood vessels, what happens to their psychological well-being. [14:13:46:24] What happens to them in terms of the amount of pain they're experiencing over their lifetime, and what their life expectancy is and what their quality of life is. [OFF CAMERA COMMENTS]
INTERVIEWER
How, how much does this run in families?
DR. NAZLI McDONNELL
[14:14:52:11] So EDS is what we call a dominant disorder, meaning that, when -- you only need to have one affected parent to be able to inherit the disease. And for each affected person, they have a 50 percent chance of passing it on to their children. [14:15:10:20] Most forms of EDS are autosomal-dominant, meaning that this is how they're inherited, with 50 percent risk to each child, if one parent is affected.
INTERVIEWER
Does it run through the mother's side or the father's side more?
DR. NAZLI McDONNELL
[14:15:23:16] It runs both in mother's side and father -- father's side, so it's not, uh, it's not a sex-dependent disorder, in terms of it -- its inheritance.
INTERVIEWER
[14:15:33:11] The young man we talked to last week, uh, has … who is confined to the wheelchair, his mother has a slight case of it, he has four older brothers.
DR. NAZLI McDONNELL
Mm-hmm.
INTERVIEWER
None of who [sic] have been diagnosed.
DR. NAZLI McDONNELL
[14:15:48:24] Well, so if a mother -- affected mother has four children, the odds are that at least two of them are going to be affected with the disorder. But as I mentioned, there is a lot of intrafamilial variability, meaning that there could be different manifestations in each of those children. So it wouldn't be uncommon that one child could be severely affected and the other child who may be affected, is mildly affected.
INTERVIEWER
[14:16:15:26] Why hasn't this gotten more into the medical schools, uh, if it's, like … I see dates here of 1657, 1899, you know, Hippocrates, I mean, why is it … so ignored by, uh, the medical schools?
DR. NAZLI McDONNELL
[14:16:35:01] Well, I don't think it's purposefully ignored by the medical schools, I just think that it's relatively rare. The, the medical students are unlikely to see an affected patient during their training. Uh, if the doctor is an adult doctor, an internal medicine doctor, it's unlikely that during their training they've been exposed to genetic disorders, and therefore, they often would miss a case of it if, um, the patient comes to them with complaints of ja -- joint pain.
INTERVIEWER
Okay --
DR. NAZLI McDONNELL
[14:17:06:28] They do the usual laboratory studies, looking for disorders, acquired connective-tissue -- tissue disorders like rheumatoid arthritis or systemic Lupus, and when they don't find evidence of these acquired disorders they tend to think that there is no identifiable cause to the patient's pain.
INTERVIEWER
[14:17:26:18] So, just the final question, just tick off for me really quickly, the, the basic symptoms of EDS. Uh, I -- I understand the tallness, hyper …
DR. NAZLI McDONNELL
T29 [14:17:38:17] Not all of them have to be tall, um … The patients with, with EDS can come in all sizes, some of them can be quite short and others can be quite tall. Um, the hallmarks are joint hyperextension, meaning that they can extend their joints further than the average person. [14:17:58:27] The second, um, finding is, abnormalities in the skin. These could be stretchy skin, or formation of abnormal scars. And the third manifestation would be in the blood vessels. And this would -- usually would not be picked up in adulthood. [14:18:16:24] But, um, an early manifestation of that could be very easy bruising. So if you have the three findings, joint hyperextensibility, stretchiness of the skin or excessive scarring of the skin, and severe bruising, you likely have a form of EDS, and you need to be evaluated.
INTERVIEWER
[14:18:39:27] Okay, well, I think that's, I think we covered just about everything. Um … [PAUSE] I guess the last thing is, um, before we, you know … The one thing my correspondent said to me when I came, you know, when I called him up and I said … what, what's on your mind, and he said, what is the medical mystery here.
DR. NAZLI McDONNELL
[14:19:11:28] Hmm. What is the medical mystery here? Well, to me, the mystery is -- and it still is a mystery to me, that, how this defect in the glue of the body, the collagen, leads to so many different findings in a person, that we don't necessarily connect with the connective tissue. [14:19:41:03] Meaning, how there are findings in every part of the body, that cause so much pain and reduction in quality of life, in these persons. The mystery to me is trying to understand that part.
INTERVIEWER
[14:19:55:17] Could you say that one more time a little more, um …
DR. NAZLI McDONNELL
Okay, yeah, let me think about it --
INTERVIEWER
The real mystery to you.
DR. NAZLI McDONNELL
[14:20:03:21] The real mystery to me about EDS is to understand how the defect in the genes that make collagen, uh, lead to so many different manifestations and different parts of the body, what those pathways are, and how we can fix them.
INTERVIEWER
So then, the mystery has to do with, what's wrong with the glue.
DR. NAZLI McDONNELL
[14:20:30:12] Yes.
INTERVIEWER
[PAUSE] Can you explain that?
DR. NAZLI McDONNELL
Okay. [LAUGHS]
INTERVIEWER
I'm trying to get it in a way that people will really be able to --
DR. NAZLI McDONNELL
Okay, let me think for a second --
INTERVIEWER
Yeah.
DR. NAZLI McDONNELL
[14:20:47:18] What we're trying to understand at the NIH study is how the problem with the glue that holds the body, leads to so many different findings. All the way from joints to skin to blood vessels. [OFF CAMERA COMMENTS]
INTERVIEWER
[14:21:32:18] Just, again, I mean … it's the simplest question, and it's the basic question of this … uh … show, or this, you know, what we're trying to get across is what is … the mystery, the medical mystery here.
DR. NAZLI McDONNELL
T29[14:21:49:28] Okay, the medical mystery to me is, to understand how the problem with the glue that holds the cells together leads to so many symptoms in the affected persons. All the way from their joints to their skin to their blood vessels. And, of course the biggest challenge is how to fix all those symptoms, that result from the problem with the glue. [OFF CAMERA COMMENTS]
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[OFF CAMERA COMMENTS]
DR. NAZLI McDONNELL
[15:10:53:24] So what we're looking here is, um, skin cells, which are called fibroblasts that are, uh, growing on a dish, uh, from a patient with EDS. And, um, the fibroblasts secrete collagen as they grow. What we do is we analyze the collagen that is secreted from these fibroblasts, trying to identify what has gone wrong with this particular patient. [15:11:22:12] We can do that in more than one way. We can directly analyze the collagens, and see if they migrate normally on a gel. Or we can actually go directly to the gene, that we isolate from the patient's blood, and I'll show you an example here … Um … [15:11:46:19] And directly analyze the sequence of the gene, trying to identify if there is a spelling error in the collagen gene. [OFF CAMERA COMMENTS]
DR. NAZLI McDONNELL
[15:12:33:08] What you see with the letters that are, um, seen here are, these are the codes for DNA, that spell out what the gene should read. And if you find a code that's wrong, that means that there is a problem with the collagen gene for that patient. [OFF CAMERA COMMENTS]
INTERVIEWER
[15:13:19:07] And what are you looking for?
DR. NAZLI McDONNELL
So what you see here are, the --
INTERVIEWER
Don't stop scrolling, keep going.
DR. NAZLI McDONNELL
[15:13:25:13] -- the, um … letters that spell out the code for the collagen gene. And what we're looking for is a spelling mistake, in the collagen gene that we think might cause the, the disorder in this patient.
INTERVIEWER
Have you found one?
DR. NAZLI McDONNELL
Um, for this one we're looking for, not yet, but we're looking for it. [OFF CAMERA COMMENTS]
INTERVIEWER
And what is this, Doctor?
DR. NAZLI McDONNELL
[15:14:47:02] This is the sequence of a collagen gene, the letter code, in a patient with EDS. And what we're doing is looking for a spelling error …
INTERVIEWER
But what are the points in the, the … keep scrolling, keep moving. Keep the thing scrolling. Keep scrolling --
DR. NAZLI McDONNELL
[15:15:03:27] Each peak represents a letter in the genetic code. So, uh, we know what the correct sequence for a collagen gene should be, and what we do is we look for a spelling error in a collagen gene in a patient with EDS.
INTERVIEWER
[15:15:23:15] And have you found one?
DR. NAZLI McDONNELL
Not for this patient yet.
INTERVIEWER
Keep scrolling. [PAUSE] It's huge.
DR. NAZLI McDONNELL
Yes. Collagen genes are very large genes. [OFF CAMERA COMMENTS]
INTERVIEWER
And tell me again what this is, Doctor?
DR. NAZLI McDONNELL
[15:16:14:13] This is the letter code, the genetic code for a collagen gene, in a patient with EDS, and what we're doing is we're looking for a mistake, a spelling mistake, that may explain why this person has EDS.
INTERVIEWER
[15:16:31:16] And have you found it?
DR. NAZLI McDONNELL
We have not found it yet for this person. But we keep looking for it.
INTERVIEWER
How long will you look?
DR. NAZLI McDONNELL
[15:16:39:29] Uh, we will look until we have analyzed all the known collagen genes, there is actually more than 27 collagens in the body. Several of them are known to cause EDS if there is a spelling mistake. There may be others that also cause EDS and we're looking for those genes. [OFF CAMERA COMMENTS]
DR. NAZLI McDONNELL
[15:17:40:14] Okay, so, um … those round things you see on -- in this picture, this is an electron micrograph, a very high magnification of collagen from a normal person. Those, uh, round, uh …
INTERVIEWER
Point to them with the pointer --
DR. NAZLI McDONNELL
[15:17:57:12] Okay -- The -- these round forms are actually collagen fibrils, that are found in the skin. [OFF CAMERA COMMENTS]
DR. NAZLI McDONNELL
[15:19:08:12] So this is skin from a normal person who does not have EDS. And this is an electron microgra -- graph which magnifies the skin many, many, many times, so we can actually see the collagen fibrils. The collagen fibrils you see are round, and dense, as you see in this cut-off, there are not very many spaces between them. They're all about the same size, they're round and uniform. [OFF CAMERA COMMENTS]
DR. NAZLI McDONNELL
[15:20:00:09] This is skin from a person who has EDS. And this is also a comparable electron micrograph at the same magnification. What you notice here is that the collagen fibrils are abnormal. They have different sizes, they have a lot of spaces between them, they are not -- not nicely and densely packed, like the normal person. This causes the weakness in the skin of a person with EDS.
INTERVIEWER
[15:20:28:10] Would that person's skin be stretchy?
DR. NAZLI McDONNELL
Yes.
INTERVIEWER
Well, can you say that?
DR. NAZLI McDONNELL
[15:20:34:09] This person's skin is expected to be stretchy, it's also expected to heal with bad scars. [OFF CAMERA COMMENTS]
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