Williams Syndrome

00:01 In this lecture, I'm going to discuss Willams Syndrome.

00:04 So Williams Syndrome is a microdeletion on chromosome 7q11.23 which contains the Williams-Beuren syndrome critical region or the WBSCR.

00:18 The Williams-Beuren Syndrome Critical Region contains 25 to 28 genes including: the gene ELN which codes for elastin.

00:26 The loss of this gene causes cardiovascular and connective tissue abnormalities. The loss of the gene GTF2IRD1 may contribute to the distinctive facial features of Williams syndrome.

00:37 Losses of the genes CLIP2.

00:40 and the other three in this row may contribute to characteristic behavioral abnormalities, cognitive difficulties, and learning disabilities, particularly visuospatial abilities.

00:50 The loss of the NCF1 gene is actually protective in decreasing the risk of hypertension.

00:57 This is an autosomal dominant disease that's mostly de novo mutations.

01:01 and it happens in roughly 1 in 10,000 live births.

01:04 How do these patients present? They often have short stature and they have characteristic, what we would say, 'elfin" facies. They look like little elves.

01:16 They have a transient neonatal hypercalcemia.

01:18 The cause of which is not at all understood but it can be quite severe.

01:22 So we worry about Williams Syndrome in patients who in the newborn period, present with a hypercalcemia that will gradually resolve over several months.

01:33 They can also have a congenital heart disease, most commonly supravalvular aortic stenosis like you can see in this patient.

01:42 These patients will have mild to moderate learning difficulties, not severe but mild to moderate.

01:51 They may have failure to thrive as well, difficulty growing early on.

01:55 One of the classic features of these genetic syndrome is a cocktail type of personality.

02:01 Let me explain what that means.

02:03 What that means is they're incredibly friendly, they're incredibly engaging and when you speak with them verbally, they seem very astute, but when you drill down into a subject, you discover they have not such a sophisticated understanding of any sort of depth of content of what they're speaking about.

02:22 In other words, they're like somebody you might encounter at a cocktail party, fun to get along with them, fun to meet them but maybe you don't get to know them so well.

02:31 They often have connective tissue abnormalities, elastin defects that allow them to be maybe more hypermobile.

02:40 So the cocktail party personality is interesting.

02:45 They have a lower IQ but actually have a higher verbal IQ.

02:50 Additionally, they have a lack of social inhibition which is truly remarkable.

02:56 In many ways, children with Williams Syndrome exemplify of what we should all be.

03:02 In one study of behavior of these children, researchers found that 100% of them had a kindred spirit approach, 90% sought the company of others, 87% empathized with others in pain, 84% were caring and 75% were happy when others did well.

03:23 These children engaged very well socially.

03:26 So if we suspect Williams Syndrome, how do we test? The diagnosis is based on a microarray genetic study.

03:35 If we test someone and they are positive, we should screen them for underlying abnormalities.

03:41 They require an echo to check for cardiac anomalies like the supravalvular aortic stenosis.

03:47 They require a renal ultrasound.

03:50 We need to do an eye exam on them to make sure that's normal.

03:54 They require also an auditory exam.

03:56 At birth, these infants need a calcium check and we need to watch that very closely during the first few months.

04:02 That hypercalcemia can be very challenging to manage and it's very reasonable to check them also to make sure that their thyroid hormones are normal.

04:11 So we'll do all this as a screening approach if they test positive.

04:16 So that's my brief review of Williams Syndrome in kids.

04:21 Thanks for your time.