Genetic conditions Flashcards
1
Q
fragile x syndrome
brief intro
A
- known etiology
- cause of neuro dev diffs - brain and physiological diffs
- single gene abnormality: study of link between specific genetic etiology, cog and beh outcomes
- studied from early childhood & factors interplay
- 1/4000 males & 1/5000-1/800 females
- distinctive physical, intellectual, beh & emotional features
2
Q
physical profile of FXS
A
- physical signs may or may not be present
- more common in males than females
- cornish et al. (2004): elongated face, large prominent ears & forehead, hallucal crease, highly arched palate, hyperextensible metacarpophalangeal joints
3
Q
behavioural profile of FXS
A
- social avoidance & anxiety
- hyperarousal to sensory stim
- distractibility
- irritability
- high activity level
- repetitive motor behs
- difficulty coping with change or unpredictable events
- lang problems
- strengths in: imitation, visual learning, sensitive to others emotions, good sense of humour
4
Q
causes of FXS
A
- narrowing at end of some of X chromosomes
- FMR-1 gene located at fragile site - produces FMRP protein (brain dev & function)
- triplet in FMR-1 is CGG, repeated
- if num of repeats is too large, gene becomes faulty
- short sequence –> repeat 6-50 times, seen most ppl
- medium sequence –> 50-200 times = premutation
- long sequence –> >200 times = full mutation (faulty gene no longer producing FMRP protein)
cornish et al. (2004) - increased grey matter & thalamic volumes
5
Q
sex differences in FXS
A
- all men who have full mutation will have FXS
- women with full mutation will be carriers
- in women only 1 copy of X chromosome is “switched on” in each cell
- so about half cells will have faulty gene switched on
- produce less protein but at least some will be produced
6
Q
inheritance of FXS
A
- tends to be passed on by mother carriers
- their daughters will also be carriers
- sons may have full FXS
7
Q
down syndrome prevalence
A
1/750-1000 live births (Morris et al., 2012)
8
Q
physical profile of DS
A
- facial - round face, flat facial profile, small chin, almond shaped eyes, flat nasal bridge, protruding tongue due to small oral cavity and enlarged tongue
- short neck, broad head, shorter arms and legs, single palm crease
- congential heart defect (up to 50%)
- gastroesophageal reflux
- sleep apnoea
- thyroid dysfunctions (Gibson, 1978)
- leukaemia more common, tumours less common (Hasle et al., 2000)
- average life expectancy 58.6yrs (Glasson et al., 2002)
9
Q
behavioural profile of DS
A
- collacott et al. (1998): adults with DS compared to adults with other learning disabilities
- DS lower for aggression, antisocial beh, property destruction, disturbing others at night, scattering objects, attention seeking, self-injury, untruthfulness, excessive activity, absconding & excessive noise (less antisocial beh)
- collacott et al. (1992): DS have predisposition to depression
- fidler (2006) - poor persistence & stubborn personality
10
Q
what did purser (2014) say in regards to beh profile of DS?
A
issues with intrinsic motivation which may impair task performance
11
Q
neurological profile of DS
A
- reduced size of brainstem & cerebellum
- global diffs e.g. delayed myelination & reduction in num of cortical granular neurons (Nadel, 1999)
- hippocampal vols have been found to be smaller than for typically dev inds (Pinter et al., 2001)
- increase in num of Alzheimer-like plaques seen in ppl with DS after the age of 35yrs (Arai et al., 1997)
12
Q
why are FXS & DS wellsuited for comparison?
A
similarity in IQ level (40-60)
13
Q
mervis & robinson (1999) and cross-syndrome comparisons
A
- group matching designs based on assumptions that are difficult to meet
- suggests specific deficits to be defined as abilities that are below the level expected given an ind’s other skill levels, regardless of syndrome group to which they belong
14
Q
key features of FXS & DS
A
- intellectual disability is implicated in many genetic conditions including both FXS & DS - but are there syndrome-specific profiles?
- FXS (males) & DS often have similar IQ levels e.g. mental age, MA often falls behind CA
- but diffs in beh & psychopathologies
15
Q
receptive language
A
- comprehension of lang (receiver)
- includes listening/attending to message, understanding message
- can be tested using BPVS (British picture vocabulary scale)
16
Q
BPVS
A
- presenting children with series of single words verbally
- set of 4 pics
- which pic matches particular word
- only understanding which is important i.e. can point to picture
17
Q
expressive language
A
- ability to produce lang (sender)
- includes verbal & written lang
- tested using vocab subscale of WAIS/WASI
18
Q
WAIS/WASI
A
- intelligence scales
- series of words verbally
- try to generate definition of the word
- e.g. what is a bird
- utterances scored according to guidelines of tests
19
Q
abbeduto et al. (2003)
receptive language
A
- test for auditory comprehension of lang - revised (TACL)
- present with word pick one of three pics
- DS, FXS, typically developing (TD)
- matched on non-verbal MA
- FXS performed better than DS
- TD fell between FXS & DS but not sig diff from either of syndrome groups
- even though both have dev delay they don’t perform same
20
Q
Finestack & Abbeduto (2010)
expressive language
A
- OWLS
- DSS
- DS, FXS, TD matched for non-verbal ability
- didn’t matter which measure used - sig diffs in groups
- OWLS: FXS group better than 2 groups, no diff between DS & TD
- sentence point (DSS): FXS & TD same and a little bit superior to DS in scores
- DSS total score: TD outperformed the other 2 groups
- variability depending on which measure - general pattern is that DS performed worse
21
Q
OWLS
oral and written language scale
A
- test that requires child to produce diff types of utterances
- e.g. ask questions, finish sentence, produce whole sentence
- tested on range of things including word knowledge & syntax
22
Q
DSS
developmental sentence scoring
A
- applied to naturally produced lang samples
- sample of everyday use of lang & assess using scoring system
- produces sentence point score: proportion of sentence produced that are correct
23
Q
attentional profile
munir et al. (2000)
A
- compared boys with FXS, DS, 2 MA groups (good vs poor att)
- battery or attention & EF tasks: selective att, divided att, sustained att, EFs (walk task, same-opposite task)
- tasks that are similar in nature show diff responses
24
Q
selective attention task
munir et al. (2000)
A
- visual search task
- presented with array of objects
- chid had to find black eggs within array
- click on egg - monster popped out as reward
- FXS < DS < control group
25
Q
divided attention task
munir et al. (2000)
A
- dual search task
- presented with array of objects including black and pink eggs
- alternate between black & pink eggs
- FXS = DS < control
26
Q
sustained attention task
munir et al. (2000)
A
- rather than searching for targets just had to watch
- wait for event to happen then respond
- over a long period of time
- FXS = DS = poor attenders < good attenders
27
Q
walk task (EF)
munir et al. (2000)
A
- correct inhibitions
- FXS < DS = poor attenders < good attenders
- child presented with paper with columns on it
- dot in each column every time they had a beeping noise
- if hear screeching noise with beep = don’t put dot
- motor inhibition task
28
Q
same-opposite task (EF)
munir et al. (2000)
A
- time difference between same & opposites conditions
- DS < FXS < poor attenders < good attenders
- series of 1s and 2s
- say aloud the number
- then asked to swap: when see 1 say 2
- quick as possible
- cognitive inhibition
29
Q
what did cornish et al. (2004) say about attentional profile
A
- FXS: profound impairments in inhibitory control, fundamental neurocognitive deficits is in controlling the flow of input and output information sequences
- underlying dynamic deficits in inhibition and info processing
30
Q
what did purser (2014) say about attentional profile
A
DS: atypicalities found in a variety of attentional functions, particularly attentional shifting (constanzo et al., 2013)
31
Q
executive functions
wilding et al. (2002)
A
- further analysis on patterns of errors in visual search tasks in Munir et al. (2000)
- types of errors differed between control groups & syndrome groups
- FXS & DS pattern similar but FXS more impaired
- probable difficulties in inhibiting previously successful response
- identified 4 type of errors typically made: repetitions on targets, returns to targets, shape confusions, other false alarms
- FXS in particular (& DS to some degree): most errors on repetitions on targets, then some returns to targets
- TD - more likely to fall into shape confusions
- not so much about poor visual search, FXS & DS are having issues inhibiting previous correct responses (difficult to move on & not come back)
32
Q
working memory
munir et al. (2000)
A
- phonological loop: nonword repetition, forward digit span
- visuospatial sketchpad: spatial memory task
- central executive: backward digit span, story retelling task
- results: more items less correct, FXS generally did worse in all but story telling task
33
Q
adaptive behaviour
will et al. (2018)
A
- explored adaptive beh between 0 & 36 months
- vineland adaptive beh scales administered to parents
- broke sample into 5-12m, 13-24m, 25-45m
- matched on CA which meant that MA of TD was always higher than syndrome groups
- TD group higher adaptive scores
- clear signs of lower levels of adaptive beh in syndrome groups
- doesn’t matter what age sampled, adaptive score similar - TD
- FXS: youngest age higher scores on adaptive scores than DS, as we go to higher age groups there is a decline in adaptive scores, difficulties shown
- DS do not show a clear decline, some fluctuation
34
Q
key cognitive features of FXS
cornish et al. (2004)
A
- propose FXS is characterised by a primary deficit in behavioural inhibition leading to
- difficulties attending to/processing of complex sequential info (tendency to repeat responses rather than switch)
- tangential & perseverative lang: don’t follow expected sequence in lang production
- pattern of difficulties isn’t consistent with the notion of impaired & intact modules
35
Q
key cognitive features of DS
A
- DS seems to involve particularly impaired processing of verbal/language information (compared with relative strength in visuospatial processing; Grieco et al., 2015)
- includes both aspects of lang & severely impaired verbal/auditory working memory
- verbal STM capacity may be just 1 item (Purser & Jarrold, 2010)
- DS is associated with increased risk of early onset Alzheimers Disease: by age ~60yrs, 75% of those with DS will have AD (Roizen & Patterson, 2003)
36
Q
linking genes, brain, and cognition in FXS
A
- involves changes to a single gene (FMR1)
- studies examining the correlation between measures of the FX gene mutation & cog/bio measures aim to understand the impact of the FMR1 gene expression
37
Q
linking genes & development in FXS
bailey et al. (2001)
A
- 53 boys with FXS (39 with full mutation)
- assessed with Battelle Developmental Inventory (cog/adaptive/lang/motor/personal-social)
- blood smears taken to measure FMRP (protein production controlled by FMR1 gene so acts as a proxy measure of the gene itself)
- for whole sample, FMRP sig predicted total BDI score, as well as score in each of the 5 subdomains
- but when run on just those with full mutation, analyses were non-sig
- relationship may have been due to some ppts having partial mutation
- or lack of relationship when some ppts removed was due to sample size being smaller meaning that it had less power
38
Q
linking genes and brain activity in FXS
menon et al. (2000)
A
- 10 females with FXS
- WM task: symbol presented every 2s at one of 9 locations, key press if current location identical to location 2 steps back, have to update mem on location
- blood test measuring FMRP
- fMRI during task
- looked at relationship between amount of FMRP & brain activity in regions
- areas implicated in WM task areas of frontal & parietal cortex
- FMRP corr with activation of brain regions = more activation and more FMRP
39
Q
linking genes and cognition in FXS
cornish et al. (2008)
A
- 40 premutation carriers of FXS & 60 comparison inds
- battery of cog tasks: inhibition, selective & sustained att, visual spatial function, visual mem function
- only inhibitory control was poorer in premutation group, & this interacted with age
- +ve corr between num of CGG repeats & strength of inhibitory control deficit
40
Q
linking genes, brain, and cognition in DS
A
- an entire chromosome is implicated - much harder to map between genes and brain/cog
- having an extra chromosome appears to involve greater expression levels for some of the genes but not all (Yahya-Graison et al., 2007)
- widespread ind diffs in intellectual ability & impact of ageing
41
Q
linking brain and cognition in DS
thomas et al. (2020)
A
- link between brain vols & cog dev in DS infants
- MRI scans for brain structure
- Mullen Scales of Early Learning (MSEL): gross motor, fine motor, visual reception, receptive lang, expressive lang
- report data from 5 infants compared with published group averages
- anatomical data: brain vols e.g. cerebellum vol, increase with age, tends to be slightly lower then TD, but still variability
- variability on MSEL: less steep increase than TD
- looking at ind cases there seems to be some sort of consistency between vol & abilities but this is not always the case
42
Q
abbeduto et al. (2001)
DS & FXS comparison
A
- focused on 3 dimensions of DS: (1) receptive language, (2) expressive language, (3) ToM
- DS impairments across all 3 dimensions, not shared by those with fragile x
- Q: which domains of functioning are especially impaired in individuals with DS: pedagogical perspective = answers allow us to design more effective education and therapy, theoretical perspective = answers provide insights into dependencies among domains (illuminating mechanisms of development)
- Q: which aspects of the linguistic and cognitive profile of DS are syndrome specific: pedagogical perspective = when know what is syndrome specific, help plan assessment or therapies, theoretical perspective = identification of behavioural phenotype is essential to understand role of genes
- FXS useful comparison as: similar IQ, differences in incidence of maladaptive behaviours & pathologies
