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In this lecture, I'm going to discuss Willams Syndrome.
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So Williams Syndrome is a microdeletion on chromosome 7q11.23
which contains the Williams-Beuren syndrome critical region or the WBSCR.
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The Williams-Beuren Syndrome Critical Region contains 25 to 28 genes
including: the gene ELN which codes for elastin.
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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.
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Losses of the genes CLIP2.
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and the other three in this row may contribute to characteristic
behavioral abnormalities, cognitive difficulties,
and learning disabilities, particularly visuospatial abilities.
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The loss of the NCF1 gene is actually protective in decreasing
the risk of hypertension.
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This is an autosomal dominant disease
that's mostly de novo mutations.
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and it happens in roughly 1 in 10,000 live births.
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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.
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They have a transient neonatal hypercalcemia.
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The cause of which is not at all understood
but it can be quite severe.
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So we worry about Williams Syndrome in patients who in the newborn period,
present with a hypercalcemia that will gradually resolve over several months.
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They can also have a congenital heart disease,
most commonly supravalvular aortic stenosis like you can see in this patient.
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These patients will have mild to moderate learning difficulties,
not severe but mild to moderate.
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They may have failure to thrive as well, difficulty growing early on.
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One of the classic features of these genetic syndrome
is a cocktail type of personality.
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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.
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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.
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They often have connective tissue abnormalities,
elastin defects that allow them to be maybe more hypermobile.
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So the cocktail party personality is interesting.
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They have a lower IQ but actually have a higher verbal IQ.
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Additionally, they have a lack of social inhibition which is truly remarkable.
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In many ways, children with Williams Syndrome
exemplify of what we should all be.
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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.
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These children engaged very well socially.
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So if we suspect Williams Syndrome, how do we test?
The diagnosis is based on a microarray genetic study.
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If we test someone and they are positive,
we should screen them for underlying abnormalities.
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They require an echo to check for cardiac anomalies
like the supravalvular aortic stenosis.
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They require a renal ultrasound.
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We need to do an eye exam on them to make sure that's normal.
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They require also an auditory exam.
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At birth, these infants need a calcium check
and we need to watch that very closely during the first few months.
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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.
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So we'll do all this as a screening approach if they test positive.
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So that's my brief review of Williams Syndrome in kids.
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Thanks for your time.