Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement.

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.

The developmental trajectory of sleep in children with Smith-Magenis syndrome compared to typically developing peers: a 3-year follow-up study.

Study Objectives: To determine the trajectory of: (i) objective sleep parameters and (ii) caregiver-reported sleep questionnaire scores over 3 years in children with Smith-Magenis syndrome (SMS) compared to age-matched typically developing (TD) controls. We also aimed to (iii) describe individual profiles of change in sleep parameters over time. Methods: Week-long, overnight actigraphy and questionnaire data from 13 children with SMS and 13 age-matched TD children were collected at Time 1 and Time 2 (3 years later). Independent samples t-tests, paired samples t-tests, and Bayesian analyses were used to compare sleep parameters and sleep questionnaire scores between groups at each time point and compare data within groups to assess change over time. Results: Sleep parameters were consistently more disrupted in the SMS group than the TD group, with significantly reduced sleep efficiency, increased wake after sleep onset and earlier get up times at both time points. This was mirrored in the questionnaire data, with children with SMS evidencing higher scores for overall sleep disturbance, night waking, and daytime sleepiness. While TD sleep parameters demonstrated expected developmental changes over 3 years, in the SMS group sleep parameters and variability between and within children remained largely stable. However, some children with SMS showed substantial variation in sleep parameters over time. Questionnaire scores remained stable over 3 years in both groups. Conclusions: Overall, sleep disturbance appears to be a stable feature of SMS, indicative of a divergent sleep trajectory compared to TD peers. Proactive intervention approaches should be considered for poor sleep in SMS.

Behaviours that Challenge in SATB2-associated Syndrome: Correlates of Self-injury, Aggression and Property Destruction.

SATB2-associated syndrome (SAS) is a genetic syndrome characterised by intellectual disability, severe speech delay, and palatal and dental problems. Behaviours that challenge (BtC) are reported frequently; however, there is limited research on specific forms of BtC and the correlates of these behaviours. The current study explores correlates of well-defined BtC, self-injury, aggression, and property destruction, in SAS. Eighty-one parents/caregivers of individuals with SAS (53.1% male, Mage 10.12 years) completed questionnaire measures of health, behavioural, emotional, and autism characteristics. Individuals with SAS were grouped based on caregiver responses to the presence or absence of self-injury, aggression, and property destruction on the Challenging Behaviour Questionnaire. Rates of self-injury, aggression and property destruction were 42%, 77% and 49%, respectively. Between-group comparisons were conducted to compare characteristics between behaviour groups. Significantly differing characteristics were entered into separate hierarchical logistic regressions for each form of BtC. Behavioural comparisons indicated variation in the characteristics associated with each behaviour. All hierarchical logistic regression models were significant (p < .001): self-injury (χ2(5) = 38.46, R2 = 0.571), aggression (χ2(4) = 25.12, R2 = 0.414), property destruction (χ2(4) = 23.70, R2 = 0.346), explaining between 34.6% and 57.1% of the variance in behaviour presence. This is the first study to identify correlates of self-injury, aggression, and property destruction in SAS. Variability in the characteristics associated with each behaviour highlights the importance of specificity when examining BtC. Understanding correlates of specific forms of BtC has important implications for informing SAS-associated pathways to behavioural outcomes and the implementation of tailored behavioural interventions.

Behavioural and physiological indicators of anxiety reflect shared and distinct profiles across individuals with neurogenetic syndromes.

Anxiety is heightened in individuals with intellectual disability, particularly in those with specific neurogenetic syndromes. Assessment of anxiety for these individuals is hampered by a lack of appropriate measures that cater for communication impairment, differences in presentation, and overlapping features with co-occurring conditions. Here, we adopt a multi-method approach to identify fine-grained behavioural and physiological (via salivary cortisol) responses to anxiety presses in people with fragile X (FXS; n = 27; Mage = 20.11 years; range 6.32 - 47.04 years) and Cornelia de Lange syndromes (CdLS; n = 27; Mage = 18.42 years; range 4.28 - 41.08 years), two neurogenetic groups at high risk for anxiety, compared to neurotypical children (NT; n = 21; Mage = 5.97 years; range 4.34 - 7.30 years). Results indicate that physical avoidance of feared stimuli and proximity seeking to a familiar adult are prominent behavioural indicators of anxiety/stress in FXS and CdLS. Heightened pervasive physiological arousal was identified in these groups via salivary cortisol. An association between autistic characteristics and anxiety was evident in the FXS group but not in the CdLS group pointing to syndrome-specific nuances in the association between anxiety and autism. This study furthers understanding of the behavioural and physiological presentation of anxiety in individuals with intellectual disability and progresses theoretical developments regarding the development and maintenance of anxiety at the intersection of autism.

ACPSEM position paper: dosimetry for magnetic resonance imaging linear accelerators.

Consistency and clear guidelines on dosimetry are essential for accurate and precise dosimetry, to ensure the best patient outcomes and to allow direct dose comparison across different centres. Magnetic Resonance Imaging Linac (MRI-linac) systems have recently been introduced to Australasian clinics. This report provides recommendations on reference dosimetry measurements for MRI-linacs on behalf of the Australiasian College of Physical Scientists and Engineers in Medicine (ACPSEM) MRI-linac working group. There are two configurations considered for MRI-linacs, perpendicular and parallel, referring to the relative direction of the magnetic field and radiation beam, with different impacts on dose deposition in a medium. These recommendations focus on ion chambers which are most commonly used in the clinic for reference dosimetry. Water phantoms must be MR safe or conditional and practical limitations on phantom set-up must be considered. Solid phantoms are not advised for reference dosimetry. For reference dosimetry, IAEA TRS-398 recommendations cannot be followed completely due to physical differences between conventional linac and MRI-linac systems. Manufacturers' advice on reference conditions should be followed. Beam quality specification of TPR20,10 is recommended. The configuration of the central axis of the ion chamber relative to the magnetic field and radiation beam impacts the chamber response and must be considered carefully. Recommended corrections to delivered dose are [Formula: see text], a correction for beam quality and [Formula: see text], for the impact of the magnetic field on dosimeter response in the magnetic field. Literature based values for [Formula: see text] are given. It is important to note that this is a developing field and these recommendations should be used together with a review of current literature.

The Executive Function Account of Repetitive Behavior: Evidence From Rubinstein-Taybi Syndrome.

In this study, we focus on Rubinstein-Taybi syndrome (RTS) to explore the associations between executive function deficits and repetitive behaviors. Thirty individuals with RTS completed direct assessments of inhibition, working memory and set-shifting. Informants completed repetitive behavior and executive function questionnaires. Repetitive questions were associated with poorer inhibition and working memory. Stereotypy was associated with poorer inhibition. Adherence to routines was associated with poorer set-shifting, but only on the parental report measure. No other associations were evident. There is evidence of an association between specific repetitive behaviors and executive functioning in RTS, suggesting executive dysfunction may underpin behavioral difference in RTS. The findings point towards specific associations that are of interest for further research across populations in which repetitive behaviors are present.

Direct assessment of overnight parent-child proximity in children with behavioral insomnia: Extending models of operant and classical conditioning.

INTRODUCTION: Explanatory models of behavioral insomnia typically draw on operant learning theory with behavioral techniques focused on altering parent-child interactions to improve sleep. However, there are no data describing parent-child interactions overnight beyond parent report. In this study we used radio frequency identification technology to quantify parent-child proximity overnight in two groups at elevated risk of behavioral insomnia, Angelman syndrome (AS) and Smith-Magenis syndrome (SMS). MATERIALS AND METHODS: Nineteen children aged 4-15 years (8 with AS, 11 with SMS) participated in a week-long at-home assessment of sleep and overnight parent-child proximity. Sleep parameters were recorded using the Philips Actiwatch 2 and proximity data were recorded using custom-built radio frequency identification watches. RESULTS: Three patterns of proximity data between parent-child dyads overnight were evident: "checking" (six with AS, five with SMS), "co-sleeping" (four with SMS) and those who had "no proximity" overnight (two with AS, two with SMS). In the AS group, 25.45% of actigraphy-defined wakes resulted in a parent-child interaction. In the SMS group, 39.34% of wakes resulted in a parent-child interaction. Children who interacted with their parents when settling to sleep were not significantly more likely to interact at waking. DISCUSSION: The novel application of radio frequency identification technology is a feasible method for studying overnight parent-child proximity. Profiles of proximity between participants that are not closely aligned with operant models of behavioral insomnia were evident. These results have significant implications for the etiology of poor sleep and the application of behavioral sleep interventions.

Divergent presentation of anxiety in high-risk groups within the intellectual disability population.

BACKGROUND: Anxiety symptomatology is common in individuals with intellectual disability (ID). Symptomatology includes both traditional Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) anxiety disorders and autism spectrum disorder (ASD)-related anxiety traits. Some genetic disorders such as Cornelia de Lange (CdLS) and fragile X syndromes (FXS) are at very high risk of anxiety and afford the opportunity to examine prevalence, profiles and associated person characteristics. However, prevalence and associated characteristics of anxiety in these high-risk groups remain poorly described and understood. The aim of the current study was to examine the prevalence and profile of DSM-5 and ASD-related anxiety symptomatology in individuals with CdLS and FXS and associated behavioural and cognitive characteristics. METHODS: Questionnaires and interviews assessing DSM-5 and ASD-related anxiety were conducted with caregivers of individuals with CdLS (n = 49) and FXS (n = 36). RESULTS: DSM-5 anxiety symptomatology was present in both groups with high co-morbidity across anxiety diagnoses. ASD-related anxiety was also prevalent with specific difficulties related to intolerance of uncertainty identified in both groups. Symptomatology was persistent over the lifespan for both groups. Anxiety type was partially associated with repetitive behaviour but not measures of overall ASD phenomenology in CdLS. CONCLUSIONS: DSM-5 and ASD-related anxiety are common in these high-risk syndromes associated with ID. Prospective syndrome specific presentations and associations, which may implicate specific underlying mechanisms, are discussed. Clinicians should be aware of the risk and difficulties involved in assessment of anxiety in individuals with ID, including atypical types, to ensure these individuals do not "miss" diagnoses and support in general clinical practice.

Phenotypic characteristics and variability in CHARGE syndrome: a PRISMA compliant systematic review and meta-analysis.

BACKGROUND: CHARGE syndrome (OMIM #214800) is a phenotypically complex genetic condition characterised by multi-system, multi-sensory impairments. Behavioural, psychological, cognitive and sleep difficulties are not well delineated and are likely associated with biopsychosocial factors. METHODS: This meta-analysis investigated the prevalence of clinical features, physical characteristics and conditions, behavioural, psychological, cognitive and sleep characteristics in CHARGE syndrome, and statistically evaluated directional associations between these characteristics. Pooled prevalence estimates were calculated using reliable, prespecified quality weighting criteria, and meta-regression was conducted to identify associations between characteristics. RESULTS: Of the 42 eligible studies, data could be extracted for 1675 participants. Prevalence estimates were highest for developmental delay (84%), intellectual disability (64%), aggressive behaviour (48%), self-injurious behaviour (44%) and sleep difficulties (45%). Meta-regression indicated significant associations between intellectual disability and choanal atresia, intellectual disability and inner ear anomalies, sleep difficulties and growth deficiency, and sleep difficulties and gross motor difficulties. CONCLUSIONS: Our comprehensive review of clinical features, behavioural, psychological, cognitive and physical characteristics, conditions and comorbidities in CHARGE syndrome provides an empirically based foundation to further research and practice.

Prevalence of anxiety symptomatology and diagnosis in syndromic intellectual disability: A systematic review and meta-analysis.

Individuals with syndromic intellectual disability are at increased risk of experiencing anxiety. Comparing prevalence estimates of anxiety will allow the identification of at-risk groups and inform causal pathways of anxiety. No known study has explored estimates of anxiety symptomatology and diagnosis, including specific anxiety profiles, across groups whilst accounting for methodological quality of studies. This systematic review and meta-analysis aimed to fill this gap. Prior to review completion, methodology and analysis plans were registered and documented in a protocol (CRD42019123561). Data from 83 papers, involving a pooled sample of 13,708 across eight syndromes were synthesised using a random effects model. Anxiety prevalence ranged from 9 % (95 % CI: 4-14) in Down syndrome to 73% in Rett syndrome (95 % CI: 70-77). Anxiety prevalence across syndromic intellectual disability was higher than for intellectual disability of mixed aetiology and general population estimates. Substantial variability between syndromes identified groups at higher risk than others. The identification of high-risk groups is crucial for early intervention, allowing us to refine models of risk and identify divergent profiles.

The behavioural phenotype of SATB2-associated syndrome: a within-group and cross-syndrome analysis.

BACKGROUND: SATB2-associated syndrome (SAS) is a multisystem neurodevelopmental disorder characterised by intellectual disability, speech delay, and craniofacial anomalies. Although the clinical presentation of SAS is well-delineated, behaviours associated with SAS are less well-defined. Given the varied social profile reported in SAS of a 'jovial' predisposition and autistic behaviours, there may be phenotypic overlap with both Angelman syndrome (AS) and non-syndromal autism. This study aimed to describe behaviours in SAS in relation to chronological age and level of ability and contrast aspects of the behavioural phenotype with AS and non-syndromal autism. METHODS: Informant report questionnaire measures of behaviour, emotion, and autism characteristics were completed for 81 individuals with SAS (aged 1-36 years; 43 male). Within-group associations were analysed, and categorical data were compared between pre-school (1-5 years), school-age (6-15 years), and adolescent and adult SAS sub-groups (16 years and over). Cross-syndrome subscale and item-level analyses were conducted for 63 individuals with SAS (aged 1-27 years; 31 male), who were matched according to age and level of ability to 63 individuals with AS (aged 2-25 years; 32 male) and 63 individuals with non-syndromal autism (aged 3-26 years; 53 male). RESULTS: In SAS, higher rates of overactivity were moderately associated with lower self-help ability, and higher general anxiety scores were reported for males compared with females. Cross-syndrome subscale analyses uncovered several significant differences (p < .01), with comparatively low rates of stereotyped behaviour, overactivity, insistence on sameness and positive affect, and comparatively greater interest and pleasure and compulsive behaviour in individuals with SAS. Item-level analyses revealed a distinct profile of repetitive and autistic behaviours. LIMITATIONS: Developmental analysis was based on a cross-sectional rather than a longitudinal research design, the contribution of pain and sleep to behaviour was not explored, and molecular genetic testing to determine genotype-phenotype behavioural relationships was not possible. CONCLUSIONS: This study highlights the importance of behavioural comparisons to well-delineated groups and the utility of fine-grained item-level analyses to elucidate aspects of behaviour that might be syndrome related or shared across neurodevelopmental disorders. Future research is needed to further describe the distinctive repetitive and autistic behavioural phenotype in SAS.

Caregivers' experience of sleep management in Smith-Magenis syndrome: a mixed-methods study.

BACKGROUND: Smith-Magenis syndrome (SMS) is a rare genetic syndrome associated with a unique profile of early morning waking and daytime sleepiness. Children with SMS evidence high rates of self-injury and aggression and have a preference for adult over peer attention, with strong motivation to interact with a particular caregiver. In addition, people with SMS have lower adaptive functioning skills relative to cognitive abilities and demonstrate high levels of impulsivity. Taken together, these factors may result in individuals being awake overnight requiring vigilant caregiver supervision. Despite these complexities, no study has described the strategies caregivers take to keep their children with SMS safe overnight or considered the impact of these experiences on caregivers or the wider family. METHODS: The current study used a mixed-methods approach to consider sleep management strategies and challenges for caregivers of people with SMS at different ages. Caregivers completed an international online survey about sleep management and related difficulties, use of interventions and access to services and support. Semi-structured interviews were conducted with 14 caregivers in the UK to increase understanding of caregiver experiences and priorities for change in the UK context. Interviews were transcribed verbatim and coded using thematic analysis. RESULTS: Evidence from the online survey (n = 40) revealed wide-ranging impacts of poor sleep on the person with SMS and the wider family. Only 5% of caregivers reported that the sleep problems had no impact on their child, and 76% reported a moderately or extremely significant impact on themselves. For some individual caregivers, sleep management difficulties improved over time whereas for others no change was reported. Weekly respite emerged as the ideal provision for 49% of caregivers, although only 14% had access to this. The majority of caregivers (54%) received no respite. Thematic analysis of qualitative interviews revealed interactions between aspects of the behavioural phenotype of SMS which may contribute to complex and unusual presentations in relation to sleep management and safety. CONCLUSIONS: Caregivers' priorities for sleep management and support were delineated, with key implications for services in terms of the use of SMS-sensitive strategies and respite provision.

Executive function, repetitive behaviour and restricted interests in neurodevelopmental disorders.

BACKGROUND: Individuals with genetic syndromes show unique profiles of repetitive behaviours and restricted interests (RRBs). The executive dysfunction account of RRBs suggests that in autistic (AUT) individuals executive function impairments underpin RRBs, but not communication and social interaction autistic characteristics. AIMS: To 1) describe profiles of behavioural manifestations of executive function (EF behaviours) and 2) explore the relationship between EF behaviours and autistic traits across individuals with Cornelia de Lange (CdLS), fragile X (FXS) and Rubinstein-Taybi syndromes (RTS), and AUT individuals. METHOD: Carers completed the Behavior Rating Inventory of Executive Function - Preschool Version and the Social Communication Questionnaire. Data reporting on 25 individuals with CdLS (Mage = 18.60, SD = 8.94), 25 with FXS (Mage = 18.48, SD = 8.80), 25 with RTS (Mage = 18.60, SD = 8.65) and 25 AUT individuals (Mage = 18.52, SD = 8.65) matched on chronological age and adaptive ability were included in analyses. RESULTS: All groups showed impairments across EF behaviours compared to two-to-three-year-old typically developing normative samples with no differences between groups. Different EF behaviours predicted RRBs in the syndrome groups with no associations found in the AUT group. CONCLUSIONS: Syndrome related differences should be considered when developing targeted interventions that focus on EF behaviours and/or RRBs in these groups.

Cornelia de Lange syndrome and the Cohesin complex: Abstracts from the 9th Biennial Scientific and Educational Virtual Symposium 2020.

Cornelia de Lange syndrome (CdLS) is a spectrum disorder due to variants in genes of the cohesin protein complex. The following abstracts are from the Cornelia de Lange Syndrome Scientific and Educational Symposium held virtually in October 2020. Aspects of behavior, including autistic features, impulsivity, adaptive skills, executive function, and anxiety are described. Applied behavioral analysis is a promising approach for autism, and an N-acetylcysteine trial is proposed. Children below 6 years with CdLS have an increased number of and further travel to medical providers, with insurance type comprising a significant barrier. Speech, language, and feeding abilities fall significantly below expectations for age in CdLS. Augmentative alternative communication can yield potential barriers as well as interesting benefits. Developmentally, studies in animal models further elucidate the mechanisms and roles of cohesin: link with mediator transcriptional complex; facilitation of enhancer-promoter communication; regulation of gene expression; allocation of cells to germ layers; and repair of spontaneous DNA damage in placental cells. Genome and RNA sequencing can help identify the molecular cause in the 20% of individuals with suspected CdLS and negative testing. The phenotypes in individuals with variants in the SMC1A gene are distinct, and that with intractable seizures has been further evaluated. AMA CME credits provided by GBMC, Baltimore, MD. All studies approved by an ethics committee.

The development of early social cognitive skills in neurogenetic syndromes associated with autism: Cornelia de Lange, fragile X and Rubinstein-Taybi syndromes.

BACKGROUND: Cornelia de Lange (CdLS), Fragile X (FXS) and Rubinstein-Taybi syndromes (RTS) evidence unique profiles of autistic characteristics. To delineate these profiles further, the development of early social cognitive abilities in children with CdLS, FXS and RTS was compared to that observed in typically developing (TD) and autistic (AUT) children. METHODS: Children with CdLS (N = 22), FXS (N = 19) and RTS (N = 18), completed the Early Social Cognition Scale (ESCogS). Extant data from AUT (N = 19) and TD (N = 86) children were used for comparison. RESULTS: Similar to AUT children, children with CdLS, FXS and RTS showed an overall delay in passing ESCogS tasks. Children with CdLS showed a similar degree of delay to AUT children and greater delay than children with FXS and RTS. The CdLS, FXS and RTS groups did not pass tasks in the same sequence observed in TD and AUT children. Children with CdLS (p = 0.04), FXS (p = 0.02) and RTS (p = 0.04) performed better on tasks requiring understanding simple intentions in others significantly more than tasks requiring joint attention skills. CONCLUSIONS: An underlying mechanism other than general cognitive delay may be disrupting early social cognitive development in children with CdLS, FXS and RTS. Factors that may disrupt early social cognitive development within these syndromes are discussed.

The adaptive functioning profile of Pitt-Hopkins syndrome.

BACKGROUND: There are few cohort studies describing the adaptive functioning profile for Pitt-Hopkins syndrome (PTHS). In this study we examine the adaptive functioning profile for PTHS and compare it to Angelman syndrome (AS). METHOD: Caregivers of 14 individuals with PTHS, 33 with deletion AS and 23 with non-deletion AS, completed the Vineland Adaptive Behavior Scales-II. RESULTS: The profile of adaptive functioning in PTHS was characterised by strengths in socialisation, followed by motor skills, communication then daily living skills. The PTHS group scored significantly lower than the non-deletion AS group on all domains except socialisation and significantly lower than the deletion AS group, for motor skills only. CONCLUSIONS: An uneven adaptive behavior profile for individuals with PTHS mirrors that of AS, with implications for assessment and intervention.

Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile.

BACKGROUND: Sleep disorders are common in people with intellectual disability (ID) and autism, with growing evidence of diverse sleep profiles across ID associated genetic syndromes. Documenting the prevalence and profile of specific sleep disorders in syndromes will quantify syndrome-driven 'risk', inform prognosis and enhance understanding of aetiology of sleep disorders. METHOD: Following PRISMA guidelines for meta-analysis, we searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, Web of Science and PubMed Central with use of syndrome-specific keywords and 60 sleep-related search terms. We screened and extracted papers that reported sleep disorder prevalence data for five or more individuals within a genetic syndrome, and applied quality criteria to produce a quality-effects prevalence model of six types of sleep disorder across nineteen syndromes. Relative risk estimates were calculated for the prevalence of each sleep disorder in each syndrome. RESULTS: Two hundred and seventy three papers were identified, generating 463 prevalence estimates for Angelman, CHARGE, Cornelia de Lange, Down, fragile X, Prader-Willi, Rett, Smith-Magenis and Williams syndromes, mucopolysaccharidoses (MPS disorders), neurofibromatosis and tuberous sclerosis complex. Prevalence estimates were higher in genetic syndromes than published equivalents for typically developing individuals, with few exceptions. Between-syndrome differences for some disorders were evident; sleep-disordered breathing was most prevalent in MPS disorders (72-77%), while excessive daytime sleepiness was highest in Smith-Magenis syndrome (60%). Conversely, insomnia, which was reported at a higher rate than TD estimates in all syndromes except fragile X, was not associated with specific genetic risk. This suggests insomnia could emerge because of the individual's environment or associated developmental delay, rather than any specific genetic syndromes. LIMITATIONS: Due to the broad scope of the meta-analysis, only syndromes previously identified as reporting preliminary sleep research were included. Other syndromes may also experience elevated prevalence rates of specific types of sleep disorder. Only English language papers were included. CONCLUSIONS: Differing prevalence rates between types of sleep disorder suggest differing causal mechanisms, such as cranio-facial morphology in Down and Prader-Willi syndromes and the build-up of mucopolysaccharides in MPS disorders. Priorities for clinical assessment and intervention for sleep disorders are discussed.

Anxiety characteristics in individuals with Williams syndrome.

BACKGROUND: Williams syndrome anxiety research predominantly focuses on disorder prevalence and symptomatology, categorised using standardised mental health classifications. However, the use of these assessments may not fully capture the phenotypic features of anxiety in Williams syndrome. In this study, we examined characteristics of anxiety using a formulation framework. METHOD: A semi-structured interview was conducted with thirteen parents of individuals with Williams syndrome (median age: 19, age range: 12-45, 8 females). RESULTS: Various anxiety triggers were reported, including anxiety triggered by phobias, uncertainty and negative emotions in others. The range of described behaviours was diverse with both avoidant and active coping strategies for anxiety management reported. CONCLUSIONS: Many of the characteristics described were consistent with findings in the intellectual disability and typically developing literature, although novel information was identified. The study demonstrates the utility of a formulation framework to explore anxiety characteristics in atypical populations and has outlined new avenues for research.

Acquired mild cognitive impairment in adults with Down syndrome: Age-related prevalence derived from single point assessment data normed by degree of intellectual disability.

BACKGROUND: Individuals with Down syndrome (DS) are at significant risk for early onset Alzheimer's disease (AD), likely due to the triplication of genes on chromosome 21 that facilitate AD neuropathology. To aid the effective early diagnosis of dementia in DS, we demonstrate the strategy of using single point assessment of cognitive performance with scoring normed for degree of intellectual disability to generate age related prevalence data for acquired mild cognitive impairment (AMCI). METHODS: Four hundred and twelve adults with DS were assessed using the Neuropsychological Assessment of dementia in adults with Intellectual Disability. Normative data, banded by degree of intellectual disability, allowed identification of AMCI by atypical deviation from expected performance. RESULTS: AMCI was evident in approximately 20% of adults with DS aged 40 and under, 40% aged 41-50 and 45% aged 51 and over. Relative risk increased significantly in those aged 46 and over. Analysis of prevalence by 5-year age bands revealed two peaks for higher prevalence of AMCI. CONCLUSIONS: Psychometric data indicate single point assessment of AMCI is possible for the majority of adults with DS. Two peaks for age-related prevalence of AMCI suggest the risk for onset of AD conferred by trisomy of chromosome 21 is moderated by another factor, possibly ApoE status.