Lecture 3 - Fragile X Syndrome And Williams Syndrome

Question 1

What is the prevalence of Fragile X Syndrome?

Answer 1

1 in 4000 males and 1 in 6000 females - symptoms are less severe in females.

Question 2

What is the cause of FXS?

Answer 2

An expansion of the CGG repeat at the beginning of the FMR1 gene on the X chromosome.
Can have full mutation (200-2000 repeats), permutation (50-200 repeats) or normal (5-50 repeats) allele based on the size of the CGG expanded region.

Question 3

How and when is fragile X identified?/diagnosed?

Answer 3

Typically diagnosed at 3-4 years when features start to become more obvious although it can be identified at birth.
It can be identified via a DNA blood test.

Question 4

What did Hoeft et al. (2010) find?

Answer 4

Looked at brains in boys age 1-3 in FXS and matched controls in a 2-year period.
They found enlarged grey matter volume in a number of brain regions - the caudate, thalamus and fusiform gyri.
Found reduced grey matter volume in the cerebellar vermis.
Found greater white matter volume in striatal-prefrontal regions.
These brain differences suggest early genetically mediated alterations in neurodevelopment and disrupted synaptic pruning.

Question 5

What are the physical features of FXS?

Answer 5

Long narrow face, prominent jaw, prominent ears, flat feet.
Physiological hyperarousal and stress is well documented e.g. elevated heart rate, elevated cortisol (Crawford et al., 2020).

Question 6

What are the common cognitive/behavioural features of FXS?

Answer 6

Intellectual difficulties, short attention span, distractibility, impulsiveness, restlessness, overactivity, sensory problems, social difficulties, emotional difficulties, communication difficulties.
Many of these are autism or ADHD features.
Also show specific problems with maths, reading and Visuospatial tasks (Crawford et al., 2020).

Question 7

What other conditions does FXS co-occur with?

Answer 7

Dual-diagnosis of autism is common (Bailey et al., 1998) - 50-90% have autistic features and 25-80% have ASD diagnosis.
Also co-occurs with ADHD (Sullivan et al., 2006) - prevalence of ADHD symptom is between 54% and 59%.

Question 8

What are the common strengths in FXS?

Answer 8

Imitation, visual learning and they are personable (sensitive, sense of humour etc.).

Question 9

What is the cognitive and behavioural profile for FXS like?

Answer 9

There are differences in how males and females present:
Males - really low IQ (mean=40), communication impairments (language deficits and social impairments), hyperactivity, impulsivity, inattention, hyperarousal (Baumgarder et al., 1995).
Females - higher IQ but still low (around 70), social difficulties such as being emotional and suffering with anxiety and depression (Freund & Reiss, 1991).

Question 10

What are the first signs of FXS?

Answer 10

Sensory-motor atypicalities at 9-12 months such as decreased object play, increased leg sterotypies, atypical posturing and prolonged visual attention to objects.

Question 11

What is the Vineland Adaptive Behaviour Scales?

Answer 11

It is a scale used to assess ‘real life skills’ and ‘independence’ - also used to see if individuals are developing on a typical trajectory or atypical trajectory,
It is a semi-structured interview/questionnaire that a parent completes independently or alongside a clinician.
Looks at communication, daily living, socialisation and motor skills.

Question 12

What does Adaptive Behaviour tell us about children with FXS?

Answer 12

A variable trajectory was found with children with FXS.
Found that positive environmental influences may act as protective factors (Glaser et al., 2003) such as parental expectations, parenting skill, organisation of the home.
IQ (in early years) was found to be the strongest predictor of outcomes.

Question 13

What is Williams Syndrome?

Answer 13

A neurodevelopmental disorder that impacts upon a person’s physical, cognitive and behavioural functioning.
It was first identified by Williams et al. (1961).
Features consist of aortic stenosis, learning difficulties and distinct facial features.

Question 14

What is the prevalence of Williams Syndrome?

Answer 14

Between 1 in 7500 (Stromme et al., 2002) and 1 in 20000 (Morris et al., 1998).

Question 15

How is WS diagnosed?

Answer 15

Can be diagnosed by a genetic test (FISH).
Prior to early 1900s the diagnosis was based only on its clinical phenotype and/or the presence of abnormal calcium metabolism (Martens et al., 2008).

Question 16

What is the cause of Williams Syndrome?

Answer 16

A hemizygous deletion of approx. 26-28 genes on chromosome 7q11.23.
Hemizygous = the problem is on one chromosome pair rather than both.

Question 17

What are the facial features of WS?

Answer 17

Broad brow, flat nasal bridge, short upturned nose, wide mouth, full lips, irregular dentition, ‘elfin-like’ (Morris et al., 1999).

Question 18

What did Reiss et al. (2004) find?

Answer 18

Looks at MRI data from 43 individual with WS and 40 neurotypical individuals.
They found the total brain and occipital grey matter volumes are significantly reduced in WS (area to do with visuo-spatial) - this is what they have reduced visual-spatial processing.
Amygdala and ventral prefrontal grey matter volumes are significantly increased compared to controls - this is why their processing of risk/fear/inhibition of emotions differ.

Question 19

What is the cognitive profile of WS?

Answer 19

Riby and Porter (2010):
Mild-moderate learning disability.
Mean FSIQ 50-60 (Martens et al., 2008).
Relative strength in language (VIQ = 63).
Relative strength in face processing.
Poor visuospatial processing (PIQ =55).
Strength in musical ability e.g. Martens et al. (2008) BUT Don et al. (1999) found 15% were either indifferent or displayed a dislike to music.
Martens et al. (2008):
Development of spontaneous skills in young children similar to neurotypical children.
Use fewer gesturing skills.
Display level typical to controls on tasks of verbal comprehension and phase repetition.
Specific aspects of grammar follow a typical (but delayed) developmental course.
Use more lexical expression and vocal prosody than mental age-matched adolescents with DS.
Outperformed neurotypical group with narrative skills and lexical expression with exception of the use of emphatics.

Question 20

What did Brock (2007) find?

Answer 20

People with WS have relative strengths in:
- Speech production.
- Phonological short-term memory.
- Receptive vocabulary.
- Grammatical abilities such as syntax.
They have relative difficulties in:
- Pragmatics - the ability to work out intended meaning.
- Reciprocal conversation.

Question 21

What are the Visuospatial abilities like in WS?

Answer 21

Showed poorer performance on pattern construction and block design tasks compared to other tasks that measure cognitive abilities.
Phase related to motor planning deficit which is a relative weakness for individuals with WS.
Martens et al. (2008):
Display a bias in their attention to local features and show deficit on global processing.
Show difficulties on visual search tasks.
Some findings suggest visuospatial deficits are impaired in the dorsal stream (processes info about position of objects) but not ventral stream (involved in face recognition).

Question 22

What did Cornish et al. (2007) find?

Answer 22

Looked at attention in infancy through the anti-saccade task and an orienting task.
Found individuals with WS have problems with attention disengagement - showed problems with disengaging where the cue appeared to look at the target (anti-saccade task).
Also found infants with WS displayed greater interference effects of invalid cues than those with FXS - suggests they have greater difficulties in disengaging from an attended location - therefore problems with visual orienting and attentional control.

Question 23

What is the anti-saccade task?

Answer 23

Participants are required to orient away from suddenly appearing peripheral flashes and direct eye movements to the contralateral location in space (opposite side of).
At the offset of the fixation stimulus a small black circle was presented to the right of left of fixation for 100ms and consistently predicted the appearance of an interesting animated target stimulus 700ms after cue onset at contralateral location in space.
Trials then divided into a first and second half to compare decreases in looks towards the cue stimulus and saccades anticipating the appearance of targets at the contralateral location in the absence of orienting towards the cue.

Question 24

What is the orienting task?

Answer 24

Looks at the automatic orienting of attention.
At short intervals between cues and targets, latencies to detect targets are typically faster to validly cued targets and slower to invalidly cued targets, even when cues do not predict the location of the target beyond chance.

Question 25

What are executive function abilities like in WS?

Answer 25

Have difficulties with planning, spatial working memory and inhibition (Rhodes et al., 2010).

Question 26

What other conditions co-occur with WS?

Answer 26

Leyfer et al. (2006):
It co-occurs with ADHD (65%) - have problems with hyperactivity.
Also co-occurs with specific phobia (54%) - such as being burned in a fire, getting lost, getting in a fight.
Show an increase in generalised anxiety disorder with age (GAD) - fears such as the unknown, spooky things and failure.

Question 27

What is the behavioural profile of WS?

Answer 27

Friendly, empathetic, social, affectionate, little restraint towards unfamiliar people, exuding happiness.
Experience auditory abnormalities e.g. fearfulness to specific sounds and lowered pain threshold for loud sounds.
Martens et al. (2008):
Female adults with WS are more argumentative and less cheerful than males.
Infants with WS gaze at mothers and strangers more than neurotypical infants.

Question 28

How does WS differ to autism and how are they similar?

Answer 28

Those with WS are hyper-sociable whereas ASD are withdrawn.
Those with WS are empathetic whereas ASD show social impairment.
Those with WS have a relative strength in language whereas ASD has communicative impairment.
Similarities = both distractibility, inflexible in routine, ritualistic, obsessive and show pragmatic deficits.

Question 29

What are some potential interventions for FXS?

Answer 29

Crawford et al. (2020):
Psychological evaluations and interventions e.g. relaxation training and desensitisation.
Speech and language therapy.
Occupational therapy.
Social and welfare input.
Special educational input.
Vocational guidance.
Use of medication e.g. SSRIs.