Download WILLIAMS SYNDROME

WILLIAMS SYNDROME
http://wiki.ggc.usg.edu/wiki/Williams_Syndrome
MODULARITY
•  Williams Syndrome (WS):
–  (more or less) general cognitive retardation except in language
–  Results from a gene deletion in chromosome 7.
•  Specific Language Impairment (SLI):
–  Language problems without any obvious cause.
–  fifty to seventy percent of children with SLI have at least one other
family member with the disorder
!  If the brain is a general purpose problem solver, one’s
general intelligence should be predictive of abilities such as
language.
!  For people affected by WS or SLI that’s simply not true.
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Utube clips:
https://www.youtube.com/watch?v=gF4DiqEdN3w
https://www.youtube.com/watch?v=AHT4-dB4MiI
Williams Syndrome
•  Caused by a sporadic deletion of one copy
of 20 or so genes.
•  Affects about 1/20000 births, boys and
girls equally.
•  IQ about 50 (range 40-90) but cognitive
profile very uneven.
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•  WS caused by the deletion
of one copy of a small set
of genes on chromosome
7, band 7qll23.
•  Approximately 26-28 genes
deleted. Little variability in
the breakpoints.
•  For most of these genes,
their role in the Williams
phenotype is unknown.
•  ELN: the gene for elastin, a
protein that provides
elasticity to organs and
tissues.
•  LIM-kinase 1: has been
argued to be responsible for
aspects of visuo-spatial
cognition.
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•  Interesting: The first case of duplication of the WS
region was reported in Somerville et al. (2005).
•  The phenotype included severe speech and
expressive language delay in the context of
visuospatial construction skills that were at the
level of other family members, thus contrasting
strongly with the WS phenotype.
Somerville, M. J. et al. Severe expressive-language delay related to
duplication of the Williams–Beuren locus. N. Engl. J. Med. 353, 1694–1701
(2005).
Williams Syndrome physical appearance
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Williams Syndrome medical features
•  Cardiovascular problems
•  Developmental delay (infants height & weight <
5th percentile)
•  Infantile hypercalcemia (elevated calcium level in
blood)
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Persons with WS are bad at:
•  Spatial cognition tasks
•  Coordination
•  Piagetian conservation tasks
–  Ability to recognize that number, mass or volume
does not alter when physical appearance alters.
–  E.g.
=
•  Math and number
•  Folkbiology (Johnson & Carey, 1998)
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Model:
Williams
Age 11;1
Williams
Age 9;1
Control
Age 6;1
From: http://www.ling.udel.edu/colin/courses/ling101_f98/lecture1.html
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http://www.udel.edu/PR/UDaily/2004/WSDrawingslg.jpg
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Persons with WS are bad at:
•  Spatial cognition tasks
–  But they know that their models are not correct.
•  Contrast between visuo-spatial and language abilities:
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Persons with WS are bad at:
•  Spatial cognition tasks
•  Distinct modes of failure in WS and Down:
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Persons with WS are good at:
•  Language
•  Auditory short term memory.
–  Recall: This is precisely what’s impaired in dyslexia
and SLI
•  Social cognition
–  overly friendly, uninhibited, personality
–  Emotional, and sensitive to emotions of others
–  Theory-of-mind
•  Face processing
•  Music
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Persons with WS are good at:
•  Music.
–  Individuals with WS generally have a higher rate of
musicality.
–  WS persons tend to have an “affinity” for music -this, however, does not necessarily entail musical
talent.
–  The percentage of individuals with Williams
syndrome who have perfect pitch is higher than the
percentage among individuals in the general
population.
•  Music is often considered the most closely
related cognitive ability to language.
–  E.g., ERP responses to ill-formedness in music and
language similar in many cases.
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Persons with WS are good at:
•  Face processing.
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Persons with WS are good at:
•  Language
–  Often compared to Down Syndrome as overall IQ is
similar.
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Individuals with Down’s and Williams Syndromes
have similar IQs
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WS Language
•  However, whether language is really spared has been
heavily debated.
•  For example, it’s been reported that WS kids perform
badly on embedded relative clauses. (Karmiloff-Smith et al, 1997;
Volterra et al.,1996; Mervis et al., 1999)
–  but who doesn’t?
•  [The juice [that the child spilled _ ]] stained the rug.
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What does the test look like?
“The circle the star is in is red”
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•  Hardly surprising if a person with general
mental retardation does not do so well on this
task.
•  Challenge: to devise tasks that tap onto
language without being taxing for other cognitive
resources.
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Example
(from Andrea Zukowski’s work)
Method: Elicited production technique
(Hamburger and Crain, 1982)
Children are asked to tell a parent which of
two similar characters a change happened to.
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Which cow is Max looking at?
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(12-year-old Williams Syndrome male, IQ = 56)
“The cow who um the boy’s pointing to.”
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(12-year-old Williams Syndrome male, IQ = 56)
Object
Gap
Relative
“The cow who um the boy’s pointing to.”
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Which boy turned blue and which boy
turned purple?
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(16-year-old Williams Syndrome male, IQ = 40)
“The boy that’s pointing to his arm turned purple, and the boy that turned blue is pointing to his finger”
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(16-year-old Williams Syndrome male, IQ = 40)
Subject
Gap
Relatives
“The boy that’s pointing to his arm turned purple, and the boy that turned blue is pointing to his finger”
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(16-year-old Williams Syndrome male, IQ = 40)
Centerembedded
structures
“The boy that’s pointing to his arm turned purple, and the boy that turned blue is pointing to his finger”
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What was each WS individual capable of producing?
SG
OG
CE
RB
Child Relative Relative Relative Relative
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Control Children
SG
OG
CE
RB
Child Relative Relative Relative Relative
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Every WS child except one was capable of producing examples of
each of the components of embedded relative clauses
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WS and language
•  WS kids produce complex syntactic
structures as long as the task demands
are otherwise low.
•  At the lexical level, WS individuals tend to
show an absence of typical frequency
effetcs.
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WS brains
•  Total volume of the brain is reduced.
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WS brains
•  Somewhat conflicting results on regional preservance
and enlargement.
•  Some studies have reported preserved or even enlarged
frontal areas, neocerebellum, temporal limbic areas
and superior temporal areas but a large-scale 2005
study did not replicate most of these finding.
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Neocerebellum
–  Involved in movement.
–  Among the brain's newest parts, appearing in human ancestors about the
same time as the enlargement of the frontal cortex, which controls much
of rational thought and reasoning.
–  The neocerebellum is significantly smaller in people with autism, who are
generally antisocial and poor at language, the reverse of people with
Williams.
Limbic system
–  memory, emotions
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Robust finding: thicker RH cortex in WS
•  Classically right-lateral functions
that WSs are good at:
–  music
•  Classically right-lateral functions
that WSs are bad at:
–  Spatial cognition
•  Studies such as this one constitute important progress in solving the
mystery of WS but they do not point to any simple explanation to
understanding the complex behavioral profile of WS.
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•  No significant
thinning.
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Further structural abnormalities
•  Circumscribed symmetrical grey matter volume reductions in
three regions
–  the intraparietal sulcus
•  visuospatial construction deficit of WS?
–  around the third ventricle
–  the orbitofrontal cortex
•  OFC has been linked to hypersociability
Meyer-Lindenberg, A., Mervis, C. B., & Berman, K. F. (2006). Neural mechanisms in Williams syndrome: a unique
window to genetic influences on cognition and behaviour. Nature Reviews Neuroscience, 7(5), 380-393.
Further structural abnormalities
•  Overall curvature of the brain is reduced in WS
Schmitt, J. E., Eliez, S., Bellugi, U., & Reiss, A. L. (2001). Analysis of cerebral shape in Williams syndrome.
Archives of Neurology, 58(2), 283-287.
Abnormalities in WS cellular biology
•  In WS, layer V/VI cortical neurons characterized by longer
total dendrites, increased numbers of spines and synapses
and altered network connectivity.
•  “.. an increased number of synapses may result in the
altered network activity, which could contribute to the
characteristic behaviour of individuals with WS.”
Chailangkarn, T., Trujillo, C. A., Freitas, B. C., Hrvoj-Mihic, B., Herai, R. H., Diana, X. Y., ... & Stefanacci, L.
(2016). A human neurodevelopmental model for Williams syndrome. Nature, 536(7616), 338-343.
Williams Syndrome upshot
•  WS is complicated combination of cognitive peaks and
valleys, as well as many physical/medical abnormalities.
•  As neuroscience methods develop, the neuroscientific
description of abnormalities in WS keeps getting more and
more detailed.
•  The linkage between the genetic and neurophysiological
profiles still remains largely a mystery.
•  Understanding the detailed genetic mechanisms
underlying WS will likely require the combined study of
animal models, atypical participants and the examination of
variation in WS region genes in the general population.