Neuropsychiatric aspects of Williams Syndrome

2009. 7. 3Department of Psychiatry

(Division of child and Adolescent Psychiatry) Children's Hospital, Seoul National University Hospital

Williams Syndrome

Rare neurodevelopmental disorder Prevalence of 1 in 7,500 to 1 in 20,000 Deletion of about 28 genes on chromosome

7q11.23

“Elfin" facial appearance

First identified in 1961 by Dr. J.C.P Williams of New Zealand

Symptoms

Highly verbal and sociable but lack of common sense

Developmental delay and low intelligence, particular difficulty with visuospatial skills

Hyperacusis

Love of music, and perfect pitch

General intelligence

Mean IQ of individuals with WS between 50 and 60, with a range of 40–100

A relative verbal strength

in comparison to significant visuospatialweaknesses

Language skills

언어 능력은 상대적인 강점

언어 능력이 “intact” 하다는 의미는 아님

어휘력에 비해 의사소통능력은 더 취약

언어 치료의 도움이 필요

Language skillsNarrative

Outperform than normal controls of similar mental age

Used significantly more affective enhancers such as ‘Oh my, oh my!’ and ‘Suddenly’

In contrast, the typical children used more cognitive inferences ‘the boy thinks’, ‘because the boy was…’

Intentionally keep the listener engaged

Language skillsReceptive vocabulary versus general intelligence

윌리엄스 증후군 아동의 수용언어가 정상 아동에 비해서 뒤쳐지지 않는다는 기존 연구

최근 들어서는 이에 대해 상반되는 연구결과들이 보고되고 있음

Receptive vocabulary의 문제

Visuospatial and face processing skills

Visuospatial function의 문제

원인은 불명확

Weak dorsal visual stream (process information about the position of objects)

Motor planning deficit

Visuospatial function deficit

Drawing of a bicycle by a 9 year old withWS showing pronounced problems with visuospatial construction.

Visuospatial and face processing skills

Facial processing skill은 상대적으로 보존되어 있음

Equivalent to mental age-matched controls

Significantly below chronological age-matched controls

Behavior patterns and hypersociability

‘Unusually sociable, friendly, and empathic’

Hypersociability phenotype 은 일반적인 친근함과는 다르다.

Sociability의 neural substrate에 대한연구들이 진행되고 있음

Toddler with WS shows atypically focused attention to the experimenter’s face

Parental characterizations of sociability contrasting WS,DS,Autism,and typical controls(TD) (SISQ)

Musical skills

Having affinities with music and preserved musical skills

It has been suggested that individuals with WS possess absolute pitch

Hyperacusis

약 95%의 WS에서 hyperacusis 보고됨

Distortion in the neural coding of the auditory input abnormal growth in loudness

반응을 습관화하는 중추신경계 능력의 결함

WS에서 흔히 보이는 fear, anxiety와 연관될수도 있음

Brain structure and function

Cerebral volume 유의미한 감소

Cerebellar volume, temporal-limbic volume은 보존

Cerebral white matter volume 유의미한 감소

Cerebral gray matter volume 은 상대적으로보존

Parietal / occipital lobe volume 에 비해frontal lobe volume의 비율이 높음

Brain structure and function

Apparent sparing of limbic structures

in contrast to significant volume reductions in parietal and occipital cortex

-> Exaggerated hypersociability and deficient visuospatial skills

Brain structure and function

Perisylvian / inferior temporal region의enhanced cortical thickness 가 관찰 상대적으로 보존되어 있는 언어 능력, 음악 능력과

연관되어 있는 것으로 추정.

Functional study Striatum, dorsolateral prefrontal cortex, dorsal

anterior cingulate cortex에서 activity 감소

행동 억제의 문제와 연관

Prevalence of psychopathology in children with WS (N=119)

Am J Med Genet B Neuropsychiatric Genet.2006

Type of specific phobias

Am J Med Genet B Neuropsychiatric Genet.2006

WS에서 흔한 정신과 질환

ADHD 유병률 64.7%

약 2/3는 inattentive type (68.8%)

약 1/3은 combined type (27.3%)

특정 공포증 53.8%

큰 소음 27.7%

천둥 6.3%

소리에 대한 민감성

WS에서 흔한 정신과 질환

GAD 약 12%

Anticipatory worry

다양한 사건들에 대한 예기불안

막상 사건이 일어나면 불안은 사라짐

강박(obsessiveness)과 염려(worry)의 경계선상에 있는 듯한 증상들

시간 소모, 환아들을 힘들게 함

Treatment

No curative therapy

Supportive care

Developmental and psychoeducational assessment

Many other examination, laboratory, and anticipatory guidance recommendations

Reference Research Review: Williams syndrome:a critical review of the cognitive,

behavioral,and neuroanatomical phenotype

<Journal of Child Psychology and Psychiatry 49:6 (2008), pp 576–608>

Insights into brain development from neurogenetic syndromes: Evidence from fragile X syndrome, Williams syndrome, Turner syndrome and velocardiofacial syndrome

<Neuroscience (2009), doi: 10.1016/j.neuroscience.>

Williams Syndrome:15 Years of Psychological Research

<Developmental neuropsychology, 23, 1-12 >

Language and communicative development in williams syndrome

< Mental retardation and developmental disabilities 13:3-15(2007)>

Brain abnormalities in Williams syndrome: A review of structural and functional magnetic resonance imaging findings

< European journal of paediatric neurology 13(2009)305 – 316>

Defining the social phenotype in Williams syndrome: A model for linking gene, the brain,and behavior

<Development and Psychopathology 20 (2008), 1–35>