Chapters Transcript Marfan Syndrome and other Aortopathies Dr. LaRossa speaks on aortopathy syndromes, what they are, why they matter, and when to refer. All right, good evening, everybody. Um, thanks for joining this evening. Uh, as you know, I'm gonna be talking about aoropathies today. Uh, just for a little background for myself, I am, uh, as my husband said, a pediatric cardiologist over at Saint Louis Children's Hospital. I do general cardiology, I do fetal cardiology, and I am the co-director of our erytopathy clinic with one of our geneticists. I have no disclosures. So, for tonight, Europathies can be kind of a dense in the weeds topic, and my goal tonight is, we may get into the weeds a little bit, but is to talk about them in in a way that I hope will matter to uh the folks listening. Um, so, sort of practical ways to think about them and how we deal with them during childhood. Uh, so we'll be talking about, first of all, what they are, why they matter. We'll to go through some erotopathy syndromes, uh, including Marfan syndrome. Uh, Louis-D syndrome, um, vascular lois, Turner syndrome, and, uh, vicuspi aortic valve. We'll talk very briefly about congenital heart disease with aorytopathy, um, because that is something that does come up occasionally. We'll spend some time on activity and aortopathy, which I think is actually a really important topic that I spend a lot of my own time, but I'm talking to patients, uh, about, um, erytopathy syndromes and Uh, uh, and how we should be managing them, and then talk a little bit about when and where to refer. Should also say that uh there should be time at the end for questions. Um, this will probably take us about 45 minutes. Um, but if you do have questions in the middle, I do encourage you to just sort of shout out, and we don't have to let things sit, uh, till the end either. So first of all, uh, what are aoropathies, um, so neuropathy is really just a group of disorders, which is characterized by aneurysms or dilation of the aorta. And the reason that we, you know, think about these is that they can ultimately lead to a catastrophic rupture or dissection of a blood vessel. There's a number of different types of aerotopathies. Uh, we're gonna spend most of our time on the syndromic, uh, ones, a little bit of time on non-syndromic ones. We're not gonna get too much into the familial and sporadic, uh, varieties, and then, like I said, we'll talk briefly about the ones that are associated with congenital heart disease. So, why does this matter? Going back to, for most of us probably high school physics, um, this all comes down to uh a little calculation for wall stress. Uh wall stress, which is essentially the force that the blood vessel is feeling, uh, is proportional, directly proportional to, um, the blood pressures, the pressure inside the vessel, the radius of the vessel, and inversely proportional to the thickness of the wall. So, if you think about a blood vessel as something that is stretching and getting bigger and bigger, As that radius increases, as our blood pressure increases, and as we stretch, as the wall thickness decreases, the wall stress goes up. And when the wall stress becomes greater than the wall strength, We can end up with a dissection. Um, so, dissections, as I'm sure you know, are a tear in the blood vessel, which creates a false lumen. Not all uric dissections are catastrophic, although they certainly can be, and untreated, they eventually will be. So why does this matter uh going on? So dissection in childhood is really, really rare. Um, it happens, but it is exceedingly rare, but progression of aortic dilation in our aeropathies during childhood is, is quite common, um, and more common or less common. Depending on the type of aoropathy that we're dealing with, but it certainly happens frequently. And so, because of this, we take a three-pronged approach to care for patients with aoropathies. First is surveillance, so monitoring the growth of the blood vessel in a way that lets us know if things are changing in a way that we don't like before it becomes clinically significant, so we can intervene or um monitor more closely or treat. Which, of course, is the second prong to the approach which is treatment. So the mainstays to treatment are medical therapies, and those are beta blockers and antiotensin receptor blockers. Um, all of the data for treatment comes from adults. The numbers that we have in kids just aren't big enough to create, um, statistically significant data, um, but there are certainly trends toward, uh, what works in adults to also working with kids. And then the last prong is really prevention, and this relates primarily to Things like physical activity, um, contact sports, heavy weight lifting, things like that, and we'll talk a lot about that at the end of the talk this evening. So, the syndromes that we'll cover today are Marvin syndrome, which is far and away, uh, the most common syndromic uh erratopathy uh syndrome. We'll talk a bit about Lowey's DIET syndrome, which shares a lot of characteristics with Marfan syndrome, um, but is less common. We'll talk about vascular alias down those, not because it is common, it's actually very rare, um, but because of how different it is from other aopathy syndromes and uh how serious it can be. Uh, I'll talk about Turner syndrome, cause that is quite common, and I actually think that is something that oftentimes, uh, sort of gets forgotten about or swept under the rug with Turner syndrome is that there it is associated with erytopathy. And then by custo aortic valve, uh, which is very common and very commonly, uh, deals with dilated aorta as well. So starting with Marfan syndrome, um, as you likely know, it is related to a mutation in the FBN1, uh, gene. It is autosomal dominant and, you know, half to slightly greater than half of all, um, our diagnoses are, um, inherited. There is some correlation between genotype and phenotype, so, you know, a parent's phenotype can help guide us as far as what we might expect for a child. However, it's not always the case in either direction, um, you know, somebody with a mild phenotype can have a, uh, child with severe phenotype and vice versa. Um, and, uh, it's, there's also gene negative, um, Marfan syndrome, which is a little bit of a tricky entity, and we'll talk a little bit about that as well, um, so meeting clinical criteria, but actually having negative testing for mutations of the FBN1 gene. I think it's important to talk about the diagnostic criteria for Marfin syndrome, uh, because this is something that you can have pretty high clinical suspicion for. You'll notice in what is listed here, each one of these does have either genetic testing or an echocardiogram to sort of cinch the diagnosis. Um, however, I think having high clinical suspicion is important as far as uh referring for the appropriate testing. So, The four main ways of diagnosing Martin syndrome are a dilated aortic root, uh, with uh ectopia uh lentus, so uh lens dislocation, but eric root as well as a causal uh FBM1 mutation. You'll notice that just the FBM1 mutation by itself is not enough to make that diagnosis. Um, a dilator root as well as a systemic score, which really those are physical exam plus, um, findings which we'll review shortly, and then lens dislocation as well as a causal FPM one mutation. So, you know, the two sort of hallmark findings are dilator group and lens mutation, and then uh genetic testing or other exam findings to disin it. So, systemic score, um, so the systemic score cutoff that is used in the diagnostic criteria is 7, and this list can be found all over the place, uh, Morphan.org, um, is a really nice advocacy site for kids with Marfan syndrome or adults for that matter with Marfan syndrome, and they list that on there as well. Um, but, uh, you'll see things listed here, there's a number of things which you can't do in the office, like, Uh, spine MRI to diagnose dural ectasia. Um, uh, but I think the main things to focus on are, you know, the characteristic physical findings of the hand. Uh, you'll see the picture on the left of the wrist and thumb sign, um, pectus deformities, hind foot deformities in the lower right hand corner, you'll see a picture in there, spontaneous pneumothorax, um. Uh, the, uh, acetabulum deformity can't be diagnosed without an X-ray, but, uh, that, um, can be seen as well. The arm height discrepancy, so the arm span greater than the height, uh, with a ratio of greater than 1.05, uh, scoliosis, reduced elbow flexion, there are a number of facial features, they tend to have sort of long narrow faces, dolichocephaly, uh, and ophthalmus skin skin stria is a finding in morphine syndrome without, you know, significant weight loss or things like that. Uh, significant myopia and mittropo prolapse, which again, not gonna diagnose in the office. So if you look at this, you know, having the wrist and thumb sign, the pectus carinatum, and hindfoot deformity gets 7 points right there. Um, so depending on what you see in a patient, you can, you can get a pretty high systemic score pretty quickly. I think it's also worth pointing out that systemic scores are primarily studied on um Caucasian people, and I don't think it's well understood how well they apply to other races and ethnicities. Um, so I know, for example, the geneticist that I work with closely, she tends to uh have a lower threshold um for non-white race when it comes to the systemic score just because she doesn't know that it fully applies to patients with that. As far as monitoring is concerned, um, most kids with Marfan, uh, syndrome get yearly monitoring. Um, they get an echo at the time of diagnosis to look at the aortic root, 6 months later, to assess for sort of a rate of growth, just to get two data points, and after that, with stable root measurements, um, they tend to get an annual imaging. Cross sectional imaging like CT scans or MRIs, um, is not really indicated in Marfan syndrome because most of the findings are dedicated to the um proximal thoracic aorta, which is usually able to be well imaged on echo, although if echo images are suboptimal, or if you're seeing things like rapid growth and you just want a slightly more precise measurement, uh, cross sectional imaging, uh, can be obtained for those, for those reasons. Uh, I put a lot of thought in cross sectional imaging as well, just because, uh, kids and adults with erratopathy syndromes tend to get a lot of it across the course of their life, and so once a child is able to sit still for an MRI or an MRA I should say, um, I prefer that just to reduce, uh, lifetime radiation dose, and Um, we're able to do MRAs now without ganolenium as well, uh, since there are concerns about brain deposition and stuff like that for ganolenium. So that's my preferred for older kids, but younger kids, obviously they're not gonna sit still for a 45 minute test in a small tube, so I do use CT scans for them if I need to. And then as far as uh management of morphine syndrome, we talked about the, the mainstays. So, when there is an existing aortic aneurysm or dilation of the aortic root, uh, treatment is indicated, when it's moderate or severe, it's oftentimes recommended to use two agents uh for these patients. And the goal of this is to reduce the rate of growth, not necessarily to, uh, we're not gonna make the air root smaller, but it's to reduce the rate of growth. Um, in the setting the normal aorta, the indication is actually less clear. Um, the official recommendations say you could consider a medication, and we oftentimes take into account family history, uh, if there is a, uh, familial Marfan syndrome, so somebody who has had an aneurysm or a dissection, um, and assuming that the risk with the same gene is similar, uh, we may put those kids on medication as well. Evidence for medication in children is lacking. Like I said, this is primarily based off of adult studies, but thankfully, actually just this past August, the HA put out a scientific statement, which is really expert consensus, so not perfect, but it's the first time, uh, actual guidelines for treatment and management of children with the airopathies was was put out. As far as intervention is concerned, pretty rare. And, um, in kids with the exception of early onset, which was previously uh known as neonatal Marfan syndrome. Um, it can happen, and I have, I take care of some patients for whom it has happened, but, uh, it is pretty rare. Um, the, the cutoff for most people with morphine syndrome is 5 centimeters, 50 millimeters with higher risk factors that sort of bumps down to 4.5 centimeters, uh, so a family history of dissection, um. dilation of more than just one segment of the ureter, so the aortic root and the ascending a ureter, or if there's some tortuosity, which does. Indicate potentially higher risk. Other indications, which are really specific to kids and not to adults, are growth of more than 1 centimeter per year, and then taking the aortic area divided by the height, and having that be greater than 10. And then the aortic root, which is commonly what dilates in Marfan syndrome, is is a big support structure for the aortic valve, and so sometimes we can see that the aortic valve will start to leak uh when the aortic root dilates, and if that becomes progressive and significant, that would be an indication to, to do surgery for these kids as well. As I said, dissection is extremely rare under 12 years and is rare even past that, um, irrespective of the degree of your dilation. So, you know, very high Z scores don't necessarily mean that a child is going to dissect. Um, but early onset, Marfan syndrome is a bit of a different beast and does have more aggressive criteria, which I don't think we need to get into right now. Lois'-D syndrome, um, more recently described than Marfan syndrome, um, and generally has a more severe phenotype than Marfan syndrome. Um, that phenotype does vary significantly by the genotype, and there are a number of genes that are associated with Lois'D syndrome, um, and we'll talk a little bit about that as well, but generally speaking, more aggressive than Marfan syndrome. The, uh, these mutations are, uh, causing the TGF uh beta pathway, uh, so TGF beta and, uh, uh, TGF as well. Lens dislocation, although there's a lot of exam findings that are similar to Marfan syndrome, lens dislocation is unique to Marfan syndrome. It is not seen in Louis syndrome. Uh, and conversely, cerebral and neck vascular tortuosity, as well as thoracic and abdominal tortuosity, is associated with Loisste syndrome, where it is not associated with Marfan syndrome. Even though the phenotype here is more severe, uh, dissection is still very rare in childhood, more common in lowest deeds than Marfans, but still, uh, rare, and then, again, depending on the genotype that can uh influence that risk as well. And dissection, uh, is known in LoD syndrome to happen at smaller dimensions than Marfan syndrome, so the criteria which we'll talk about is a little bit more aggressive. Includ some pictures here just to sort of know what we're looking at. I don't know if you, hopefully you can see my mouse cursor on the screen here. Um. You'll see that in these pictures, the, even the abdominal aorta takes a lot of twists and turns and bends, and it's sort of ball disappearing, the head and neck vessels are ball disappearing, uh, and don't have that nice sort of thin look that we oftentimes see. This is somebody who had a dissection involving really the entirety of their descending aorta, so all the way from the proximal transverse arch and down through into the abdominal aorta, um, and you'll see that tortuosity there as well, as well as really significant dilation up here. And then this is a 3D reconstruction of an MRA of uh the head and neck vessels of a patient with Loisste syndrome, showing that really significant tortuosity that we see, um, in not all patients, but some patients with lowest syndrome. The TGFBR 1 and 2 genes are the ones that tend to confer the higher risk, whereas TGF uh beta 2 and 3 as well as SMAD 3 are considered to be lower risk. Um, uh, genes, and these two tend to be more associated with higher tortuosity of the blood vessels as well. And then findings for LoisD syndrome, which I think are important, uh, if we're gonna, you know, pick these kids up before something bad happens, is, um, uh, easy bruising. There's skin translucency is pretty common, easily visible with easily visible veins, dystrophic scar formation. I have a picture up here of persistent facial mia into later childhood and even adulthood, uh, which is pretty unique to Loy D's syndrome. Um, and then skeletal features are pretty similar with Marfan syndrome, but also include clubfoot, which is not associated with Marfan syndrome, as well as Atlanta axial instability, uh, which can, you know, undiagnosed or untreated, can lead to a spinal cord injury. And then lastly but not least, um, these patients can have somewhat bluish lara similar to what you might see in osteogenesis imperfecta. As far as monitoring for Lois'D syndrome, it's not that dissimilar to Marfan syndrome with a few notable exceptions. Similarly to Marfan syndrome, we get an echo at the time of diagnosis and after 6 months to assess for growth. If that was all stable, we go go to yearly uh monitoring. With higher risk genotypes, so the TGFBR 1 and 2, the recommendation is to get a baseline head to pelvis, cross-sectional imaging, looking at all the branches for aneurysm, tortuosity, uh, dissection, and then depending on what the findings are there, that's suggested to be repeated anywhere from yearly to every 5 years. With lower risk genotypes, it's thought to be OK to wait until early teen years, uh, to get that cross-sectional imaging done, and so we can usually avoid doing that extra testing in those patients. And indications for intervention are more aggressive. So, for all comers, except for TGFB 3, those are done at 4.5 centimeters as opposed to 5 centimeters, which was the cutoff from Marfan syndrome. And with higher risk criteria, so things like rate of growth, and family history of early dissection, uh, that can even bump down as low as 4 centimeters, uh, for, uh, the criteria for intervention. And this is unique to Lois's deeds, but for these patients, they may need a referral to neurology or neurosurgery, depending on those cerebral blood vessel findings. It's pretty uncommon that a neurosurgeon is gonna want to do anything about them, but they will monitor them over time, looking for any issues that they uh may deem necessary for intervention. Bassor Ehlers understandless. This is a tough one, because we don't understand it as well as I would like, uh, and it It tends to do do bad things uh without a whole lot of warning. So, extremely rare, uh, 1 in 50,000 to 1 in 100,000, um, and it's uh involves the Cole 3A1 gene. Um. The severity does seem to be related to the gene itself, so if we know a gene has a severe phenotype, it tends to carry along with that gene, uh, although, again, nothing is set in stone. And this is associated with spontaneous aortic and arterial dissections and rupture, sometimes at young ages, and really irrespective of the size. So even if we're monitoring these vessels and they're not growing out of proportion to what we might expect, these patients are still at risk for Um, dissection. In fact, um, vascular stlois is the most leading cause in adults of, uh, spontaneous coronary artery infection. Um, so, a really, really kind of a nasty disease. Um, classic il demos is different, that is associated with uric root dilation, although almost never rupture dissection. In fact, if at the time of diagnosis, there is no root dilation, they're not. Um, they don't have to follow up with any additional imaging, and hypermobinos is even more different. That's not associated with anything cardiac. So, when we think about iliac downloads, vascular adlos when it comes to erotopathies, it's really where it's at. Challengingly, these children tend to have subtle or no dysmorphic features, and so physical diagnosis is challenging, and so that can lead to to the diagnosis being uh delayed or missed. Similar to Lily's DT syndrome, these kids can have more translucent skins with easily visible veins, you know, deep set eyes with dark circles, pretty non-specific, small narrow nose, and lips. Um, usually there's a history of easily, easy bruising or bleeding. Or needing stitches or staples for things that other kids might not need stitches or staples for. Uh, this one sounds weird, but it, I have seen multiple patients who, who have this characteristic, so affected children will often sleep with their eyes open. Um, of course, that is not specific to vascularil down those, but it's sort of an interesting observation. Um, and these patients can have flat feet or even club feet, um, and can have small joint hypermobility. Medications have been studied in vascular stalo and are not statistically significant, but have shown a trend toward improvement. So most people, uh, will treat these patients, um, just because it's hard to know what else to do. Um, there's a lack of guidelines surrounding, uh, surrounding surveillance and intervention because of a lack of data, and also because, again, depend, it it's not clear that Aggressive surveillance necessarily prevents uh a dissection from happening, given that it can happen at really any a dimensions. We do tend to survey them routinely, um, and then sometimes with cross-sectional imaging as well. This rarely applies to children, but I think it's really important to point out is that pregnancy in these folks is really high risk, so they're also at risk for uh hollow organ rupture. Either spontaneously or with little stress. And so, in pregnancy, uterine rupture is a real risk, and it is with a known diagnosis of vascular stlo, these women tend to undergo early C-section, you know, 34, 36 weeks to avoid labor and the risk of uterine rupture. And again, we'll talk about activity restrictions at the end, but I do treat activity restrictions with vascular iles down a little bit different than I do other aerotopathies, just because the risk seems to be higher. I think the last thing to really point out here is that surgery for vascular ailer stenosis thought is described as extremely technically challenging, and the reason for that is that the blood vessels tend to be very friable. And so doing surgery on the blood vessels themselves, getting sutures to hold, is very, as I understand it, very challenging, um, and so doing surgery is not a straightforward or easy process on these patients. Turner syndrome, um, which I'm, I'm sure most of us take care of some kids with Turner syndrome, uh, which is might as well be X. It's also important to point out that there's a lot of mosaicism with with Turner syndrome as well, which gives you a much less predictable phenotype. In fact, I saw uh somebody for a fetal echo recently, um, who was pregnant with the diagnosis of Turner syndrome, and it was just a mosaic Turner syndrome where most of her um her cells were unaffected. Uh, it is associated with a number of cardiac findings, including bichospiric valve, cartation. Partial anomalous pulmonary venous return, and then what we're talking about today is it is associated with dilation of the aorta. But you see in the picture here, very typical physical exam findings, short stature, uh, sort of broad web neck, uh, widely spaced nipples. For patients with Turner syndrome, um, the way that they are monitored actually changes at age 15, and this all has to do with the short stature, and so understanding the risk of absolute sizes relative to the size of the person changes a little bit. And so we use something called the aortic size index, which is just the diameter of the aorta divided by the BSA, um, and we use that number actually to, to make decisions about treatment and intervention. Um, and There are things that confer a greater risk to uh kids with Turner syndrome, um, so the history of carication, history of bicuspi eric valve, hypertension, those things all uh increase the risk of aortic dissection and can change the uh the, the threshold for treatment and intervention. Turing or monitoring is actually pretty lax. Um, there's an initial TTE and cross-sectional imaging done at the time of diagnosis, um, but without risk factors and without findings in childhood, we repeat things every 5 years, um, to see if there's any significant changes in, you know, in adults, it's every 10 years for or for somebody who becomes pregnant, uh, repeat it at the beginning of pregnancy or prior ideally prior to pregnancy, if the pregnancy is planned. Um, In patients with an irritide index of greater than 2.3 centimeters per meter squared, we surveil them a little bit more closely and then modify that based on the rate of growth as well. Then in patients greater than 15 years old, greater than, I think I say greater than 2.5, um, The recommendation is not strong, but you could start thinking about replacing the recruit or sending a or both, depending on what is dilated, um, and depending on whether or not there are any other risk factors involved. Like because the aortic valve is sort of a weird thing that straddles um erytopathy syndromes as well as uh congenital heart disease. So bicuspi the aortic valve is obviously something that you're born with. Uh, it's extremely common, so it affects somewhere between 1 and 2% of the total population, um, and is associated with the eric root and more commonly ascending aortic dilation, uh, depending on the data that you look at, somewhere between 1 and 4/5 of patients with percus with a valve will, will have that. My personal experience it's it's close to 50%. Um, Interestingly, bicuspi aortic valve is also associated with a number of a top of these syndromes, such as Lois des and then notch actitudes, some things we're not gonna talk about, uh, today, but, um, so the back aortic valve is not always uh working on its own, it could also be associated with uh the erottopathy syndrome. As far as the initial evaluation, uh, we do an initial echo for patients, uh, with the bicus of health, obviously, um, if there's inadequate imaging, uh, getting cross-sectional imaging to assess the asending aorta. Uh, genetic consultations, um, different people treat this different way. My typical approach is that if I feel like I have a bicuspi aortic valve is behaving out of bounds for what I expect from a bicospheric valve, so the aorta dilating more rapidly than I might expect, I'll oftentimes make a referral to genetics because there is that association with other aortopathy syndromes to get genetic testing done, looking for uh connective tissue disease. We also do routine screening of first degree relatives, so, uh, the heritability of biosid valve is quite high, um, and first degree relatives, it's about 10% heritability, so we do recommend screening of first degree relatives. And then routine surveillance really depends on the size and the rate of growth, as well as the function of the aortic valve, um, and You know, the recommendations here are very non-specific, but with a well functioning aortic valve and no, um, aortic dilation, you know, in older kids, we may see these kids every 2 or 3 years, and for somebody who has valve dysfunction or significant dilation of the a aorta, as frequently as every year or maybe even every 6 months. There are uh additional risk factors that are associated with bicuspiiaic valve, um, so if there's a family history of dissection, and interestingly, there was a push a few years ago to call bicuspiiaic valve bicuspiaric valve, aortopathy syndrome. Uh, and the reason for that is that, uh, even without a bicuspieric valve, in families, you can sometimes see uh aortic dilation, uh, in the absence of bypass a valve. So, a family history of uh a ortic dissection. The history, a personal history of cocation of the aorta, which is associated with bicus with a valve, um, or root dilation is actually thought to be higher risk than ascending aorta, uh, dilation, which is, again, root dilation is less common, but thought to be higher risk. Medication management is a sort of a uh an interesting beast with mycuspiric valve, um. It has been studied in adults pretty extensively without compelling evidence that it is helpful, um, compared to um not using any medication at all. The official recommendations that came out for kids do to recommend considering um medication at, you know, more moderate or severe dilation. Um, there are some people who just won't ever use them because there's not much data to support it, and there are other people who do use them. My own personal practice is if, again, I have a, a patient who's Aorta is dilating out of proportion to what I might expect, um, for, for their size, then I'll sometimes consider using medication, and they usually make it a shared decision with the family, given that there is not much compelling evidence, and medications are not without side effects either. In general, bicuspiic valve, uh, has a significantly lower risk of dissection than genetic erytopathy syndromes, so the connective tissue diseases that we've covered already. It and it's also really uncommon to need intervention in childhood. Uh, the cutoff for intervention is higher, 5.5 centimeters, that can be a little bit lower with higher risk features like we had mentioned before, cotation, the family history of dissection. Um, but it's pretty uncommon that this is something that needs to happen before, uh, a kid is, uh, into adulthood. You know heart disease, I do want to touch on this briefly. Uh, it's a really completely different beast than these other things that we're talking about. Um, there are certain types of congenital heart disease, specifically the conotrunkal abnormality, so things like tetralogophylo, truus arteriosis, transposition of the great vessels, um, that are extremely common to have aortic uh root dilation, and A lot of that has to do with the fact that those vessels are even at birth, quite large, because they are accommodating more blood flow than they typically do when you grow. Approximately 50% of adult patients meet criteria for aneurysm, and 14% meet criteria for severe aneurysm, so greater than 5 centimeters, which is oftentimes, you know, what we talk about for an indication for intervention. However, And and growth seemed to stop around age 40, and uh of You know, about 8000 patient years, there were zero dissections seen in these patients, so the risk of something bad happening to these patients is extremely low, and you know, typically not intervened upon unless we're doing surgery for something else. I also wanted to touch on this briefly because we see a lot of kids with this. So, Child gets a echocardiogram for some reason, maybe it's a murmur, maybe it's a family history of a participated aortic valve, something like that. And we end up seeing that the aortic root is mildly dilated. And, you know, the child has no syndromic appearance, there's no concerning family history. Uh, so what do we do with these kids? Um, we see this all the time, and there aren't great guidelines about what to do for this, but most of us will follow these kids clinically. I always tell families that this goes one of three ways, that either the child will grow into their aorta, so their, their somatic growth will outpace the growth of the aorta, and they will normalize over time. They'll grow in parallel, um, and in which case a mildly dilated aortic root remains mildly dilated, but doesn't increase to a size where where it causes problems, or rarely that the aortic uh root growth outpaces the growth of the child, in which case, um. We sometimes are dealing with significant aortic aneurysm. And kids who have an aortic root that remains dilated for several years, and so if I see this child as a 2 or 3 year old, and they're 5 and 6 now, and it's still dilated, I'll often make the referral to genetics because it does impact not only how we counsel these patients, but whether or not treatment might be helpful. Um, and it also impacts them for the rest of their life as far as, you know, decisions about having children and stuff like that. Um, And, you know, it's about a 1 in 5 hit rate as well, uh kids who have nothing else going on, but have is your group atation we, we do find things in these kids. That said, medications are really only indicated if some kind of a genetic aurytopathy is found. Now, I wanna spend some time on this. This is getting into activity, uh, and exercise, um, because Historically, um, the guidelines and recommendations for activity and exercise restriction were really, really draconian, um, really significant restriction, you know, even limiting things like light aerobic exercise and and stuff like that. Um, and this is a chart that was pulled directly from the new pediatric guidelines that I mentioned were were put out last August. And it breaks it down, I think, really appropriately into a number of different categories, talking about counseling, and we'll talk a bit about that as to talking about, uh, you know, prescription for exercise and activity, and, you know, the darker the blue here, the higher the risk activity, and even in the most high risk things, it says specifically, you know, maybe the competitive sports, for example, may be considered with a regular risk benefit discussion. Avoiding certain things, and those are the heavy contact sports. We'll talk about why, as well as things like heavy weightlifting. Um, things like amusement parks are not often. Thought about in these kids, but high intensity rise can sort of impact um the pressures on the blood vessels, and so that's something that we think about, but it's usually OK. And then down at the bottom here, they talk about some of the sort of special considerations or the extra cardiac considerations. So kids with Marfan syndrome who have joint issues and joint laxity, and may have difficulties with joint dislocations in certain sports, and same thing with LoisD syndrome. Vascular downloads, we talked about, you know, internal organ issues, um. That one's a bit of a tougher one, for me, and then, uh, back after the aortic valve, the function of the auric valve also has an impact on um activity restrictions. So as I mentioned up front, this is a really big part of what we do for patients, or at least what we talk about for patients who have uh dilated aorta. Um, and the reason for that is that There is no activity for a patient with ador that is zero risk, you know, if we take a sport like baseball, for example, that's probably a pretty good one. it's not a lot of intense exercise. Um, there's also the possibility of getting hit in the chest with the line drive, right? And so with the dur, we worry about. Uh, trauma to the chest, causing a traumatic injury to the aorta. Is that a high likelihood of happening? No, um, but it all really comes down to the value for the child of being active. Being in from a social standpoint, being involved in organized sports, from from a developmental standpoint, both physically and socially and emotionally, um, really sort of important to development. So, early on, when kids are When I first meet a family, even if a kid is less than a year old, I'll start talking about this stuff up front, uh, because I want them to have the opportunity to be thoughtful about helping to sort of organize and plan, um, what their kids may take on, uh, in the future. I always tell people it's much, much easier to not start something than it is to take something away. And so when we talk about things like football or wrestling or hockey, um, you know, I I strongly encourage people to not start those activities, knowing that there is a chance that down the road, that's gonna be, there's a few hard stops that I have and and those are those are them, um, at that. We may have to take that away, and that can be really hard for a kid who has fallen in love with a sport. But beyond those sort of few hard stops, I do think it's, it's really comes down to what the family and the child's values are, um, because, like I said, nothing here is without risk. So understanding that You know, doing more strenuous activity has the potential to increase the rate of dilation of an aorta. If that is a decision that the family is comfortable making, I may make some decisions as far as trying to monitor the child more closely to see if it actually is impacting things in any meaningful way, um, but I try to support that decision because I do feel like there is a lot of value to kids being active and being in sports. As far as when to refer, um, I do think that this is an important thing to talk about, and, you know, this could be the first and last bullet, but ultimately, it's when you have a concern, right? If you think there is a child, for whatever reason, who may have anortopathy syndrome, it's not ever wrong to send them our way and get them checked out. Um. That said, you know, how do you sort of pick those patients out? I think History and exam are like all things, sort of the most important things here. So from a history standpoint, a personal history, um, so this is really focused on extra cardiac things, right? Uh, aortic aneurysms tend to be silent, um, aortic dilation tends to be silent, and so understanding what other systems are involved and how can be really helpful on its dislocation, really severe, uh, nearsightedness at a young age. Joint issues, um, you know, the typical findings of my friends with always des like the long spiddly fingers, the arm length discrepancies, um, easy bruising, um, you know, skin, a good, you know, easy bleeding, things like that are really important for the personal part of the history. I think family history is even more important in in these uh families. Uh, since so many of these are are are are passed down, um, understanding whether there's any family history, and I go, I think it's important to go back a few generations because You know, we'll often see families who, you know, a number of people on one side of the family died suddenly, um, and their descendants never got checked out, and so we don't really know what their status is, um, but having a history where you have another number of people who had aortic dissections or aneurysms or, you know, sudden unexplained death, I think is really important. People throw around the term heart attack colloquially all the time, and I never really know what that means, and so I always like to clarify, do you know, Was this a coronary artery blockage? Was this something else? Was there an autopsy done? You know, understanding that family history, and when, when those things are really unknown, if there's something weird going on, I think that's all the more reason to, to refer. Exam, you know, the cardiac exam, as we talked about for these kids is, is pretty unremarkable, uh, right? Um, with the exception of back aortic valve, which, even if it's functioning well, can sometimes have a murmur and will oftentimes have a click, um, you know, the cardiac exam for a kid with Marfan syndrome is usually normal, same with, with everybody, uh, all the other syndromes that we're talking about. So knowing the criteria or findings for diagnosis can be, can be really helpful. Uh, and also, you know, if There's a parent in the room, uh, being able to compare them side by side to sort of understand are these heritable uh uh traits, or are they something that's really sort of unique to the child. As far as where to refer, this is actually not a super straightforward thing. I think ultimately referring to cardiology or genetics, either one is fine. Um, as a cardiologist, you know, if I have a suspicion, Even in the absence of an echo finding, or particularly in the presence of an echo finding, I will always refer them to genetics anyways because they're going to need genetic testing. Geneticists, on the other hand, can do the genetic testing, which I'm not allowed to do, but they'll always get an echo, if they have suspicion. So, either way you're sort of going in both directions, uh, I think. At least at Saint Louis Children's, I do think the waitlist for getting in to see cardiology is probably shorter than the waitlist for getting in to see genetics. Um, cascade testing is, uh, extremely useful in settings where there's a positive family history. You know, if there is a parent who has a diagnosis and has a gene, geneticists can do very specific targeted testing and sort of rule in or rule out that diagnosis very quickly. Similarly, if there is a history, Um, but not, there is no genetic testing that's been done, so, you know, a parent who had an aortic aneurysm or a grandparent who had an aortic aneurysm, our geneticists will see entire families and sort of find the person far this back and do their genetic testing first and then do cascade testing if they find something. Um, I did mention up front that I am one of the co-directors of the erytopathy clinic. This is relatively new. We started this last summer, um, and this is, there's two different flavors of the erytopathy clinic, the referral clinic, so one's for new patients who do not have a diagnosis, it's really just a joint clinic between me and Doctor Sarah Procno, who is one of our geneticists with a particular focus in aortopathies and and vascular abnormalities. Um. We also have a follow-up clinic for these kids where we get PMNR involved, uh, as well as uh ophthalmology to try and make it sort of a one stop home for these kids where they can get a lot of the care that they need, um, and, uh. Cause they come from from farther away, and so we can get everything all done at once. Um, so, if you have somebody who have really high suspicion for uropathy clinic, um, you can put in a referral that you'd like them to be seen by that clinic, and all those patients go into a queue, we evaluate them, sort of make a decision, should they be seen in the neuropathy clinic? Should they be seen by genetics, Should they be seen by cardiology, um, and so, you know, we have limited patient slots, so we don't see everybody who gets that referral, um, but it's hopefully a new resource, um, for people out in the community that Can help hopefully be helpful for our our patients and and getting them into care and getting a diagnosis more quickly. So ultimately, I, I'd like the takeaways from today to be uh aeropy has a variety of causes and it's really a heterogeneous. Type of disease. Genetic opathies do tend to be amenable to medication management. One thing I, I left out earlier is that um medications are not perfect. Um, I, I don't like using beta blockers in teenagers, for example. It's one of the only tools in our belt, so I do, but they're messy medications. They have issues on mood, they have issues on energy, um, and so for somebody who has, you know, depressive symptoms going into it, I really try to steer away if I can, um. And so knowing, you know, those things, as particularly the primary care doc, um, I think could be really helpful in understanding what's what's working, what's not working. Um. Jaguar have these do tend to be, you know, we tend to be more aggressive regarding intervention because there's, you know, abnormalities to the blood vessel wall, uh, that makes them more prone to dissection. Dissection or other catastrophic complication, tends to be very rare in childhood, um, but I think of this is that we're setting the table for the future here. We're getting healthy habits started that can be relatively safe. We're getting, you know, if medications are, are indicated, we're sort of making that part of the daily routine, um, and, you know, part of what we're doing is educating patients and families, so they understand what is going on with them, and they know what the risks are, what the risks are, and I don't know what is, what is safe for them. Um, and then I do think this is really truly one of the most important things, the physical activity and shared decision making, understanding that there are real risks to certain types of activity, uh, and that nothing is without risk, but it, it's also a real detriment to quality of life, to growth, to development, to take away as a sort of blanket thing, a lot of the um the things kids do to stay active. And so being really intentional and thoughtful about that. Um, and understanding sort of where our family is coming from, I think it's really important. Created by Presenters Peter LaRossa, MD Pediatric Cardiology, Cardiology View full profile
