Okay. Welcome back. In this module, we're going to talk about Williams Syndrome. And if you've watched the video, you'll see that I think you'll see that it's really a fascinating,, and interesting behavioral syndrome. But if you haven't watched it, please do. Again, here are the links. Go to the webpage. Is about a five minute video, and I think it's a, I think you'll find it very interesting to watch it. So, please, look at that before you come back to this lecture. So, what is Williams Syndrome First of all, it's a syndrome and the syndrome then is, is made up of, of multiple symptoms not everybody with the syndrome would necessarily have, each of the syndrome, each of the symptoms, but in the case of William Syndrome individuals with William Syndrome have something called the aortic stenosis, it's a, a constriction of their, aorta which could lead to hypertension, high blood pressure so that needs to be. treated. inter, they have distinct, very distinctive faces. Hopefully you've watched the video by now. and, you probably picked up on it. the, the, the reporter mentions it. In the, in the video, by, noting that, i, individuals with Williams Syndrome have elfin like, faces. That's especially true, when they're younger. They have delicate chins. They have, large mouths. And the, the size of the mouth is often accentuated by, the fact that they're often smiling. They have small upturned nose, and a little puffiness around their eyes. That make, that give them kind of an elfin feature, appearance. There's growth retardation in terms of the medical presentation of Williams syndrome. And you probably picked up in this as, as well, when you watched the video. People with Williams syndrome are, are. Their height is within the normal limits, but it's on the low-ended normal for height. So a male might be, 5'5" or less and a female less than five feet. So, along about the five or tenth percentile of in the height, height distribution. And. Many individuals with Williams Syndrome have an intellectual disability, I'm going to come back to that, in a little bit. Williams Syndrome, occurs in about, one of out of 7500 births, and that's true from across the whole world in all ethnic groups, and we now know what its genetics is due to. Williams Syndrome is a, an example of what we talked about last time. A structural, variant. People with Williams Syndrome are deleted, approximately one and a half, to 1.8 million, or mega-bases of DNA, on their, long arm of chromosome 7. So let's look at chromosome 7. Here's chromosome seven. And there are approximately, about 2 million bases of DNA and this is the precise location, it's right about here, that, there just missing. Their parents are missing that region of, of DNA, usually, so it's what is called a de novo. It's a, a new mutation that occurred. And when the parents, DNA was duplicated, during meiosis, during the production of the gamete, one of the parents, the material, got deleted out. There was an error in the duplication process, so that, region of seven got deleted out in people who developed Williams syndrome. It turns out that there are, 25 to 28 genes in this gene in this region, approximately 2 million bases of DNA, on chromosome 7. Here's a list of the genes here. For example, the, this gene here, ELN, which is called the, Elastin Gene. That, th, people with Williams syndrome only have one copy of this gene, is thought to be the basis for them, having this constricted aorta. Because elastin is important, in in the construction of, of aortas. Presumably the behavioral phenotype, and I'll come back to this, a little bit later in this module. The behavioral phenotype. Of Williams Syndrome, is due to the fact, that people with Williams Syndrome are missing, these genes. They're, they're not totally missing them. Their other seven, has these genes, but they only have one copy, not two copies. So, presumably the unique behavioral profile, of Williams Syndrome, is due to the fact that they only have one copy of all these genes. What is that unique behavioral profile? First of all, Williams syndrome has a very distinct cognitive profile. I indicated before, that many people with William Syndrome, suffer from an intellectual disability. We'll talk about IQ's later in the course, but on average their IQ's, are typically in the, in the 50 to 60 range. Would, would be associated with a mild to moderate level of intellectual disability. But the overall IQ, in this range is a little bit misleading, because people with Williams Syndrome, have a very uneven cognitive profile. They have relatively intact, intact verbal and linguistic abilities. And I think that really comes out, in the video. Because when the reporter's talking, to the various children with Williams syndrome, you can see, that they're verbally, very articulate, much more articulate than you would expect, with a person with an IQ in this range. Where they are deficient, is in their visual-spatial abilities, and they're, really markedly deficient in this regard. Relatively intact verbal, skills but deficient, visual-spatial, skills. [SOUND] Let me illustrate that, with a couple slides here. In this case, what's being compared, the, what, what the individual is asked to do, is to just basically reproduce a model. And there are three different models here. Four blocks arranged in a square. The letter D comprised of little y's and then this, geometric form here. And this is what, somebody with Williams Syndrome, did in trying to reproduce these and this is, somebody with Down Syndrome, here. And, the, the point here to, to highlight with someone with William Syndrome. Is, they reproduce the stimulus, but in kind of a, an inorganized way. What they have a very hard time to do, and maybe this is easiest to see with the D, is, they have a very difficult time of integrating the parts into the whole. And so, in trying to reproduce the D. What they end up doing is, having a lot of disjointed little Y's, and they don't get the overall distal here, whereas somebody with Down Syndrome has the overall, thing, they don't have the smaller parts. Here's another illustration of that. In this case, a young girl with Williams syndrome, was asked to draw a bike, bicycle. And you can see that here when she's about ten years old, here's her drawing of a bicycle. Now she sees a bicycle just like you and I see a bicycle, but when she tries to reproduce it, she can't integrate the various parts into the whole. She gets much better as she gets older, so here's, the same girl at age 12, three years later. You can see that she's beginning to integrate things. But, what you see in Williams' syndrome is this, deficiency in, in being able to, integrate parts into a whole, spatially. That's one very unique feature of this, particular syndrome. The other unique, behavioral feature, and this really came out in the, in the video, is that individuals with, William Syndrome are extremely friendly, and very happy individuals. They're hyper social. They're so social, to the point that it's actually. Parents of children of Williams syndrome, become concerned because they don't have, stranger anxiety. They'll approach, strangers and start talking to them. And I think, at the end of the video they had a girl, going up and asking about dogs and that. And, they have this very friendly, disposition that's associated with. This, this syndrome. They are at increased risk for some forms of, of, of behavioral problems, the tendency, or an increased risk for being hyperactive or inattentive. And actually suffer, although they don't suffer from stranger anxieties, they do have an excess risk from suffering from other anxiety disorders. A third, unique behavioral feature of Williams syndrome. And this did come out in in the video, is they have what's called hyperacusis, which is they have very sensitive hearing. [BLANK_AUDIO]. The unique be, behavioral and cognitive profile, of Williams syndrome. Must be due to having only one copy, of those 25 genes. You would think then, that we could then go down look at those 25 genes and figure out, well, which this is the gene that makes them, overly friendly because they only have one copy. And this is the gene that leads them to have very sensitive hearing. And this is the gene the produces, the deficiency in their spatial visualization, but despite many years of trying, we still don't really understand, how it is that having only one copy of this gene, leads to this very distinctive, behavioral and cognitive profile. It's very difficult, even when you know it has to be something going on. In this very specific region of the genum, it's still very difficult to go from, very complicated things like how friendly you are, how you integrate parts in a whole. To right to down to the gene level to figure out how that happens. The last thing I want to mention about William's Syndrome before moving on, relates to the appearance, as well as the behavioral features of William's Syndrome. The genetic disorders that we know about today, Huntington's disease, that will talk about later, William's Syndrome that will talk about now, of course, they've existed. Throughout human history. But it's only today that we really understand their origins. Our ancestors, though, would have seen these same, distinctive, phenotypes, and probably would have come up with different explanations, for what Williams Syndrome was. Most cultures. Have a notion of elves or weed people or leprechauns, and the representation, of weed people, leprechauns, or elves are pretty similar across, multiple cultures and some people have speculated, that actually individuals with William syndrome, might have been the model for leprechauns or weed people. Or else. Usually the representation of, in folklore of individuals, leprechauns, wee people, or elves. The distinctive face, like the face of somebody with with Williams syndrome. The very happy disposition. Often they're musical. That's another feature of, of Williams Syndrome, that comes out very nicely in the vid, video. People with Williams Syndrome are very interested in musical pursuits. And another thing in, in, in, is actually illustrated here with this cell, is that, often the depictions have, individuals with large ears. And, the thought is, that, of course, people with Williams Syndrome don't have large ears, but they have highly sensitive hearing. And maybe that was the way that our ancestors, in their folklore, represented that sensitive hearing. Next time, we'll move on, and we'll actually talk about just one chromosome in the human chromosome, the x chromosome. [SOUND]. [BLANK_AUDIO]
