Genetics: Pectus Innovations

Let's say thank you and Now for something completely different, we're going to talk about genetic evaluation for pectus excavatum, and there are a couple of different reasons we do this, um, and we can actually look for a lot of different syndromes, but it really boils down to just a few that we are looking out for primarily. The first one would be Marfan syndrome. And what we do in our clinic is really the skeletal evaluation, which is an examination of the um various physical findings that we might see, such as the wrist sign where the thumb and the pinky finger overlap, um, if you wrap them around the wrist. We look for the ah protrusion of the thumb past the ulnar border, and what we're doing is we're trying to evaluate for overgrowth of the long bones in relationship to the trunk. This is one of the main skeletal findings that we see, so this is what contributes to our patients being tall and having longer legs and arms in relationship to their bodies. So we'll also evaluate for um. Arm span to height ratios and upper to lower segment ratios. There are a number of other findings that we look for as well, so pectus excavatum and carinatum being some of those scoliosis, hind foot deformities, and things like that. The reason that we are looking for these is really related to the cardiac risk associated with Marfan syndrome and the other complications which can include retinal detachments. The cardiac risk. Would be aortic dissection, uh, but we also know that there can be other complications including mitral valve prolapse. The diagnosis of this condition rests on the findings that are largely centered now on the cardiac findings, so an echocardiogram or the MRI are the main tools that we often employ to evaluate whether there's dilated aortic root. We will also evaluate for the uh lens dislocations, and in cases where we have suggestive findings, we can do testing of the fiberlin gene. There are some patients that have some Marfan-like characteristics where we may actually extend that evaluation to other genetic syndromes that have to do with TGF beta signaling because that is one of the pathways that seems to be employed in some of the cardiac or the aortic remodeling and may contribute to some of the long bone overgrowth. The other condition that we evaluate for and is by far the more common condition is Ehlers-Danlos syndrome. For many of us, Ehlers-Danlos syndrome is a condition that we heard about once, maybe in medical school, and I can actually remember the exact slide that I saw, and it was one slide. And what we know about Ehlers-Danlos is that it is not one condition, or I should say that Ehlers-Danlos actually represents a grouping of related conditions that have to do with connective tissue. The classic type is due to defects in collagen 5 and is characterized by joint hypermobility as well as abnormal skin. That skin is very fragile and thin and has very weak and papery thin scars. That is not the most common thing that we see. Another type of Ehlers-Danlos that is commonly considered is the vascular type, and that is caused by mutations in collagen 3. This is the one that freaks most surgeons out because when they hear about Ehlers-Danlos syndrome, they think, oh, I shouldn't do anything at all because if we cut into you, you will fall apart. All of your tissues will degrade. In fact, that is actually one of the least common conditions that we see in our clinic, and it is uh. Not necessarily a condition of hypermobile joints, but really of internal organ fragility. So with that condition, what we're looking for is a family history or personal history of ruptures, bowel rupture, aortic rupture, or uterus rupture. If the patient doesn't have that and the family history is negative for that, then that's not really what we are considering. Um, every so often that, uh, um, condition comes up as a consideration, and what's very nice about that is that it has genetic testing which is 99% sensitive, so the testing is very good for that, and rarely do I actually find that in our clinic. What we are typically evaluating is for the hypermobile type of veer stamos, and this is a patient who is very flexible, and we can put the slides up now. Uh, and so here's a little girl who can do activities with, uh, seem to test the limits of flexibility. And we test this more formally using the Biton score. The Biton score is a test of 9 different joints, and it's scored, um, 1 for each side except for the hips. Whoops, let me go back here. What we see here is hyperextension of the arms, and they are hyperextended past 10 degrees. We are looking for a hyperextension of the pinky past 90 degrees, apposition of the thumb to the forearm. And hyperextension of the knee past that 10 degree line, uh, 10 degrees past straight. Uh, this, all of these are scored bilaterally, so if you have these findings on each side, this would encompass 8 points in total. And the other is placing the hands flat on the floor without bending the knees, and this is assessing for hypermobility of the hips. It's considered that if a person has 5 or more joints that are hypermobile, they meet the criteria for generalized hypermobility. Then what we will look for is other findings with that family, which are of that patient or family. So we're looking for mild skin changes. It might be mild. hyperextensible, have easy bruising. There may be some scarring abnormalities, and stria, but usually on the fairly mild side. We also look for the family history of hypermobility, and then we look for the presence of problems, and I think those were all my slides here. So the idea with this condition. I often get the question is what's the difference between being flexible and having Ehlers-Danlos, and that is a really excellent question because at a certain point, the dividing line between these may be very fuzzy. What we look for is really the presence of similar findings in other family members, and we look for the presence of problems. The problems may be that the joints are loose and dislocate, and that is one of the more common findings. But what we also have noticed is that our patients exhibit a constellation of findings that include chronic pain. Associated with the joint hypermobility, we also see chronic headaches and migraines, jaw problems like temporomandibular joint dysfunction, easy bruising and bleeding. We see orthostatic hypotension or dizziness or blacking out with standing with episodes of racing heartbeat, chronic constipation with irritable bowel syndrome. Panic and anxiety disorders and sleeping problems. So basically if you take everything that doctors don't like to treat very well because they don't respond and throw them all into one condition, these are the kinds of problems that our patients have. Most of our patients when they come in and see me as an adult, have almost all of those problems. In the children, what we often see is that they have very mild problems where they may not even be evident, but they may actually begin to come out during the time of puberty, and that for some of the patients may be the time in which they begin to actually consider having this pectus surgery. And that becomes problematic because that chronic pain aspect can play into whether they are at risk for more pain from that surgery. One of the things that we have found from the patients who are hypermobile is that it is a risk factor for fibromyalgia, and fibro teenagers who have been diagnosed with fibromyalgia, 50% of them have hypermobility. One of the ideas behind fibromyalgia is that there is a central sensitivity to pain, meaning that these patients are unable to filter out unwanted pain signals in the same way as other persons. So if we track it back to a patient who's hypermobile, this would be a person who may be at risk to having more problems with chronic pain. We will be addressing that aspect a little bit further down the line, so I won't go uh further into that aspect, but these are the reasons that we are looking for these connective tissue, uh, conditions in our patients. Um, and this is one of the reasons why, uh, Derek and his team are a central component in our evaluation of, of our practice patients. Uh, thank you very much, Derek. So when do you, do you send every, who do you send? So, um, Becca, do you wanna Well, basically, I, I, when I, uh, see a patient in evaluation, I, uh, I, I check them for a lot of those things. Are they double jointed or do they have that appearance of someone that has more fan's disease, you know? Do you have arachnodactyly? Do they have stria? And if they have some of those findings, like I had one little girl, she put her leg above her head and stuff. I mean, I'm pretty clear that she shouldn't be able to do that, and that's probably abnormal. And so those are, you know, things that I look for. And then if, if I find some of those findings, then I'll send them to genetics to be evaluated. I'm gonna make a plea which may already be done, but I, I can tell you that I don't do nearly a thorough thorough enough evaluation for my Pus patients because as I'm listening to this holistic approach, I don't think enough about all these things. I would love to have a paper that, that just said this is the workup of the appropriate workup of a Pus patient. Uh, I, I would love to know who I should be sending to genetics as someone who doesn't see it that often. You see them so much because you guys do these, but for someone who sees them seldom like me, I, I, I would love to have a resource. So I'll have that, is that a plea.