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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 (χ 2 (5) = 38.46, R 2  = 0.571), aggression (χ 2 (4) = 25.12, R 2  = 0.414), property destruction (χ 2 (4) = 23.70, R 2  = 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., (© 2023. The Author(s).)

Background: There is a critical need for the development of dependable and valid anxiety assessment tools suitable for people with moderate to severe intellectual disabilities, particularly those who speak few or no words. Distinguishing anxiety from distress caused by physical discomfort (pain) or characteristics associated with autism, prevalent in this population, necessitates specialised assessment tools. This study (a) developed a parent-report anxiety questionnaire tailored for individuals with severe to moderate intellectual disabilities, potentially with a co-diagnosis of autism, and (b) evaluated the psychometric attributes of this novel measure., Methods: A comprehensive approach involving literature reviews, inspection of existing tools, and interviews with clinicians and parents guided the creation of the Clinical Anxiety Scale for People with Intellectual Disabilities. The tool was completed by parents or caregivers (N = 311) reporting on individuals aged 4 or older with intellectual disabilities., Results: Exploratory factor analysis indicated a four-factor structure encompassing anxiety, pain, low energy/withdrawal, and consolability. The anxiety factor explained the most variance in scores (26.3%). The anxiety, pain, low energy/withdrawal subscales demonstrated robust internal consistency (α = 0.81-0.92), and convergent, divergent, and discriminant validity. Robustness of these subscales was further evidenced by test-retest reliability (ICC = 0.79-0.88) and inter-rater reliability (ICC = 0.64-0.71). Subgroup analyses consistently demonstrated strong psychometric properties among individuals diagnosed with non-syndromic autism (N = 98), children (N = 135), adults (N = 175), and across diverse communication abilities within the sample. Moreover, individuals diagnosed with both autism and anxiety exhibited significantly higher scores on the anxiety subscale compared to those without an anxiety diagnosis, while showing no difference in autism characteristic scores., Conclusions: The findings indicate that the Clinical Anxiety Scale for People with Intellectual Disabilities is a promising measure for use across diverse diagnostic groups, varying communication abilities, and with people with moderate to severe intellectual disabilities., (© 2024. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

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; M age = 20.11 years; range 6.32 - 47.04 years) and Cornelia de Lange syndromes (CdLS; n = 27; M age = 18.42 years; range 4.28 - 41.08 years), two neurogenetic groups at high risk for anxiety, compared to neurotypical children (NT; n = 21; M age = 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., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

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 TPR 20,10 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., (© 2023. Crown.)

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., (©AAIDD.)

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022. The Author(s).)

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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2021 Wiley Periodicals LLC.)

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., (© 2022. The Author(s).)

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., (© 2021 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

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., (© 2021. The Author(s).)

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., (Crown Copyright © 2021. Published by Elsevier Masson SAS. All rights reserved.)

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., (© 2021 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)

Purpose of Review: While previous reviews have extended descriptions of the behavioural phenotype of Cornelia de Lange syndrome (CdLS) significantly, potential changes with age across the lifespan have been neglected. Age-related difference in the behavioural phenotype constitutes preliminary evidence of change with age. Documenting and understanding the developmental trajectories of behaviours is informative as it enables identification of risk periods for behavioural challenges and compromised mental health., Recent Findings: Recent cross sectional, longitudinal and mixed design studies report differing presentations of the behavioural phenotype across the lifespan. Of particular interest are autistic characteristics and behaviours consistent with compromised mental health, particularly anxiety and negative affect, which are reported to be more common and severe in older individuals. Preliminary evidence for identified causal pathways with consideration of biological, cognitive and environmental factors are discussed., Summary: Older individuals with CdLS appear to be at greater risk of poorer psychological wellbeing than younger peers with significant implications for risk informed preventive and early interventions. Further work is required to document the behavioural phenotype across the lifespan with consideration of multiple factors that may influence the trajectory and extent of negative outcomes., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Methods employed in genome-wide association studies are not feasible ways to explore genotype-phenotype associations in rare disorders due to limited statistical power. An alternative approach is to examine relationships among specific single nucleotide polymorphisms (SNPs), selected a priori, and behavioural characteristics. Here, we adopt this strategy to examine relationships between three SNPs (5-HTTLPR, MAOA, COMT) and specific clinically-relevant behaviours that are phenotypic of fragile X syndrome (FXS) but vary in severity and frequency across individuals. Sixty-four males with FXS participated in the current study. Data from standardised informant measures of challenging behaviour (defined as physical aggression, property destruction, stereotyped behaviour, and self-injury), autism symptomatology, attention-deficit-hyperactivity-disorder characteristics, repetitive behaviour and mood/interest and pleasure were compared between each SNP genotype. No association was observed between behavioural characteristics and either 5-HTTLPR (serotonin) or MAOA (monoamine oxidase) genotypes. However, compared to the COMT (dopamine) AG and GG genotypes, the AA genotype was associated with greater interest and pleasure in the environment, and with reduced risk for property destruction, stereotyped behaviour and compulsive behaviour. The results suggest that common genetic variation in the COMT genotype affecting dopamine levels in the brain may contribute to the variability of challenging and repetitive behaviours and interest and pleasure in this population. This study identifies a role for additional genetic risk in understanding the neural and genetic mechanisms contributing to phenotypic variability in neurodevelopmental disorders, and highlights the merit of investigating SNPs that are selected a priori on a theoretical basis in rare populations.

We directly assessed the broader aspects of sociability (social enjoyment, social motivation, social interaction skills and social discomfort) in individuals with Cornelia de Lange (CdLS), fragile X (FXS) and Rubinstein-Taybi syndromes (RTS), and their association with autism characteristics and chronological age in these groups. Individuals with FXS (p < 0.01) and RTS (p < 0.01) showed poorer quality of eye contact compared to individuals with CdLS. Individuals with FXS showed less person and more object attention than individuals with CdLS (p < 0.01). Associations between sociability and autism characteristics and chronological age differed between groups, which may indicate divergence in the development and aetiology of different components of sociability across these groups. Findings indicate that individuals with CdLS, FXS and RTS show unique profiles of sociability.

We delineate the sequence that typically developing infants pass tasks that assess different early social cognitive skills considered precursors to theory-of-mind abilities. We compared this normative sequence to performance on these tasks in a group of autistic (AUT) children. 86 infants were administered seven tasks assessing intention reading and shared intentionality (Study 1). Infants responses followed a consistent developmental sequence, forming a four-stage scale. These tasks were administered to 21 AUT children (Study 2), who passed tasks in the same sequence. However, performance on tasks that required following others' eye gaze and cooperating with others was delayed. Findings indicate that earlier-developing skills provide a foundation for later-developing skills, and difficulties in acquiring some early social cognitive skills in AUT children.

Self-harm is purportedly common in autistic individuals, but under-researched, particularly in younger samples and those without intellectual disability. This study aimed to describe prevalence, profile and correlates of self-harm in autistic individuals without impairments in adaptive functioning. Parents of autistic participants (n = 83) completed questionnaires regarding the presence/topography of self-harm, demographic characteristics, autism severity, age of diagnosis, affect, activity levels and repetitive behaviour. 24.10% of participants engaged in self-harm. Self-harm was associated with significantly higher levels of impulsivity, over-activity, negative affect, compulsive behaviour and insistence on sameness. Low mood and overactivity/impulsivity predicted the presence of self-harm, with the model correctly classifying 82.9% of cases. Findings highlight a role for impaired behavioural inhibition and low mood in the aetiological mechanisms underpinning self-harm in autism.

Purpose: Specialized treatment machines such as the CyberKnife, TomoTherapy, or the GammaKnife, utilize flattening filter free (FFF) photon beams and may not be able to generate a 10 cm x 10 cm reference field. A new Code of Practice has recently been published (IAEA TRS483) to give recommendations for these machines. Additionally, some standard laboratories provide measured beam quality correction factors for the user's reference chamber, which can be used instead of the published tabulated beam quality correction factors. The purpose of this study was first to assess how different recommendations, as outlined below, affect the reference dosimetry at the CyberKnife, and second, to assess the impact of using measured rather than tabulated beam quality correction factors on measured dose., Methods: Following recommendations in TRS398, three field chambers (IBA CC04, Exradin A19, and Exradin A12S) were cross-calibrated with a user's reference chamber (IBA FC65-G), which was calibrated in a Cobalt-60 (Co-60) beam by a primary standards laboratory. The chamber response was corrected for influence quantities such as temperature, pressure, ion recombination, polarity, and beam quality. Additionally, correction factors for volume averaging and differences due the FFF beam spectrum were determined for the CyberKnife beam. Three different methods were utilized - TRS398; Intermediate (i.e. TRS398 with additional published recommendations); and TRS483. The measurements were undertaken in a 10 cm × 10 cm field defined by jaws for a uniform flattened (WFF) 6 MV photon beam of a Varian TrueBeam linear accelerator (linac) with a source to detector distance (SDD) of 100 cm, and in a 60 mm diameter circular field for a 6 MV flattening filter free (FFF) Accuray CyberKnife beam with SDD of 80 cm. All measurement was performed at 10 cm deep in a full scatter phantom as defined in TRS398., Results: Differences between the three methods in volume averaging correction factors ranged from 0.01% to 0.45% depending on the chamber assessed. As expected, an increased chamber length leads to a larger correction factor. The differences in beam spectrum correction factors range from 0.09% to 0.3%. Negligible differences in beam quality correction factors were observed; however, differences up to 1% were found between measured and tabulated values. Differences in cross-calibrated chamber calibration coefficients range from 0.05% to 0.51% depending on the chamber assessed. Differences in measured dose are up to 0.87% between Method TRS398 and Intermediate, again chamber dependent, and 0.28% between Method Intermediate and TRS483., Conclusion: Using chambers cross-calibrated in the linac beam can lead to differences in measured dose per Monitor Unit (MU) in the CyberKnife beam of approximately 0.5% between chambers. Using Method Intermediate vs using recommendations given in TRS483 led to a difference of 0.28% in measured dose per MU, which is due to differences in volume averaging and beam spectrum correction factors. Using TRS483 is recommended as the cross-calibration is done in the CyberKnife beam and accounts for its specific reference conditions. It will also ensure consistency between different centers. The measured beam quality correction factors agree within the uncertainties with the tabulated values., (© 2020 American Association of Physicists in Medicine.)

Study Objectives: The objectives of the study were (1) to compare both actigraphy and questionnaire-assessed sleep quality and timing in children with Smith-Magenis syndrome (SMS) to a chronologically age-matched typically developing (TD) group and (2) to explore associations between age, nocturnal and diurnal sleep quality, and daytime behavior., Methods: Seven nights of actigraphy data were collected from 20 children with SMS (mean age 8.70; SD 2.70) and 20 TD children. Daily parent/teacher ratings of behavior and sleepiness were obtained. Mixed linear modeling was used to explore associations between total sleep time and daytime naps and behavior., Results: Sleep in children with SMS was characterized by shorter total sleep time (TST), extended night waking, shorter sleep onset, more daytime naps, and earlier morning waking compared to the TD group. Considerable inter-daily and inter-individual variability in sleep quality was found in the SMS group, so caution in generalizing results is required. An expected inverse association between age and TST was found in the TD group, but no significant association was found for the SMS group. No between-group differences in sleep hygiene practices were identified. A bidirectional negative association between TST and nap duration was found for the SMS group. In the SMS group, increased afternoon sleepiness was associated with increased irritability (p = .007) and overactivity (p = .005)., Conclusion: These findings evidence poor sleep quality in SMS and the need to implement evidence-based interventions in this population., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Sleep problems are common in Smith-Magenis (SMS) and Angelman syndromes (AS). Effectiveness of interventions depends on appropriate assessment, complicated by compromised self-report and health and behaviour difficulties. Studying settling and waking in these syndromes could inform assessment., Aims: To describe settling and waking behaviours in children at high-risk of sleep and health problems, using direct observation., Methods and Procedures: Video and actigraphy data were collected for 12 participants with AS (Mean age = 8.02, SD = 2.81) and 11 with SMS (Mean age = 8.80, SD = 2.18). Settling (30 min prior to sleep onset) and night waking were coded for nineteen behaviours relating to pain, challenging behaviour and caregiver interaction. Lag sequential analyses were conducted for pain-related behaviours., Outcomes and Results: Percentage of time spent in behaviours was calculated. Parent-child interactions (0.00-9.93 %) and challenging behaviours (0 %) were rare at settling and waking in both groups. In the AS group, pain-related behaviours were more likely to occur before waking than by chance (p < 0.001)., Conclusions and Implications: Findings highlight the importance of considering pain as a cause of sleep problems in AS. The principle and methodology could be extended to individuals with ID experiencing sleep problems., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Self-injurious behaviours, such as head banging, hair pulling, skin picking and scratching, are common in individuals with autism. Despite high prevalence rates, there is a paucity of longitudinal research to refine models of risk and mechanism and inform service planning. In this longitudinal study, we investigated self-injury in a cohort of individuals with autism over 10 years to identify behavioural and demographic characteristics associated with persistent self-injury., Methods: Carers of 67 individuals with autism completed questionnaires relating to the presence of self-injury and relevant risk markers at T 1 (mean [SD] age in years 13.4 [7.7]) and T 3 (mean [SD] age in years 23.9 [7.7]) 10 years later. Forty-six of these also took part at T 2 (3 years after initial participation). Analysis assessed demographic and behavioural risk markers for self-injury, as well as the predictive value of items assessed at T 1 and T 2., Results: Self-injury was persistent in 44% of individuals over the 10-year period, with behavioural characteristics of impulsivity ( p < .001) and overactivity ( p = .002), identified as risk markers for persistence. A predictive model of self-injury was derived from LASSO analysis, with baseline impulsivity, interest and pleasure, stereotyped behaviour, social communication and adaptive functioning predicting self-injury over 10 years., Conclusions: In this unique longitudinal investigation into the persistence of self-injury in a non-clinical sample of individuals with autism over a 10 year period, we have identified a novel, robust and stable profile of behavioural characteristics associated with persistent self-injury. Findings support an early intervention strategy targeted towards individuals identified to be at a higher risk of developing self-injurious behaviour., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Unique socio-behavioural phenotypes are reported for individuals with different neurodevelopmental disorders. Here, the effects of adult familiarity and nature of interaction on social anxiety and social motivation were investigated in individuals with fragile X (FXS; n = 20), Cornelia de Lange (CdLS; n = 20) and Rubinstein-Taybi (RTS; n = 20) syndromes, compared to individuals with Down syndrome (DS; n = 20). The Social Anxiety and Motivation Rating Scale was employed whilst participants completed four social tasks, each administered separately by a familiar adult, and also by an unfamiliar adult. Compared to participants with DS, those with FXS and RTS exhibited high levels of social anxiety but similar levels of social motivation. Participants with CdLS showed heightened social anxiety and reduced social motivation only during interactions with an unfamiliar adult when active participation was voluntary.

Temper outbursts are a severe problem for people with Prader-Willi Syndrome (PWS). Previous reports indicate that vagus nerve stimulation (VNS) may reduce maladaptive behaviour in neurodevelopmental disorders, including PWS. We systematically investigated the effectiveness of transcutaneous VNS (t-VNS) in PWS. Using a non-blind single case repeat measures modified ABA design, with participants as their own controls, t-VNS was evaluated in five individuals with PWS [three males; age 22-41 (M = 26.8)]. After a baseline phase, participants received four-hours of t-VNS daily for 12 months, followed by one month of daily t-VNS for two-hours. The primary outcome measure was the mean number of behavioural outbursts per day. Secondary outcomes included findings from behavioural questionnaires and both qualitative and goal attainment interviews. Four of the five participants who completed the study exhibited a statistically significant reduction in number and severity of temper outbursts after approximately nine months of daily four-hour t-VNS. Subsequent two-hour daily t-VNS was associated with increased outbursts for all participants, two reaching significance. Questionnaire and interview data supported these findings, the latter indicating potential mechanisms of action. No serious safety issues were reported. t-VNS is an effective, novel and safe intervention for chronic temper outbursts in PWS. We propose these changes are mediated through vagal projections and their effects both centrally and on the functioning of the parasympathetic nervous system. These findings challenge our present biopsychosocial understanding of such behaviours suggesting that there is a single major mechanism that is modifiable using t-VNS. This intervention is potentially generalizable across other clinical groups. Future research should address the lack of a sham condition in this study along with the prevalence of high drop out rates, and the potential effects of different stimulation intensities, frequencies and pulse widths., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: HAR reports grants from National Institute for Health Research (UK), outside the submitted work.

Objectives: To assess sleep quality and timing in children with Angelman syndrome (AS) with sleep problems using questionnaires and actigraphy and contrast sleep parameters to those of typically developing (TD) children matched for age and sex. Methods: Week-long actigraphy assessments were undertaken with children with AS (n = 20) with parent-reported sleep difficulties and compared with age and sex matched TD controls. The presence of severe sleep problems was assessed using the modified Simonds and Parraga sleep questionnaire. Sleep hygiene was measured using the Family Inventory of Sleep Habits. Results: Actigraphy and parent-completed sleep diary data indicated that children with AS had significantly earlier bedtimes (p = .003, Cohen d = .47) and poorer sleep efficiency (78%, p = .04, d = .33) than TD children (84%). No significant differences in total sleep time, sleep onset latency or wake after sleep onset were found between the two groups. The expected relationship between later bedtimes and increasing age found for the TD group (p < .001, β.78) was not evidenced for the AS group (p = .09, β.39). Considerable inter-individual and night to night variation in actigraphy assessed total sleep time and wake after sleep onset was found for children with AS compared to TD children. Parent report indicated that a greater proportion of children with AS had severe night waking problems compared to TD children (81 versus 5%). No significant differences in sleep hygiene and excessive daytime sleepiness were found between the two groups (p > .05). Conclusions: This study reports the largest objective dataset of sleep quality parameters in children with AS. Sleep quality in this group was characterised by poor efficiency and significant intra- and inter-individual variability that warrants further investigation. This variability should inform assessment and intervention for sleep in children with AS, as averages of total sleep, even across a 7 day period may not capture the difficulties with night waking highlighted by parental questionnaire report., (Copyright © 2019 Trickett, Oliver, Heald, Denyer, Surtees, Clarkson, Gringras and Richards.)

Aim: A scoping review was conducted to examine and evaluate empirical data on the communication profile of Angelman syndrome beyond the described dissociation between receptive language and speech., Method: Three databases (PsycINFO, Embase, and Web of Science) were searched to retrieve articles investigating communication in Angelman syndrome. Seventeen articles investigating the broader communication profile were found; their methodology was evaluated against quality criteria., Results: Despite the absence of speech, individuals with Angelman syndrome have a wide repertoire of non-verbal communicative behaviours, mainly characterized by gestures, although advanced forms such as symbolic communication are used by some individuals. The use of communicative forms differs between the genetic aetiologies of Angelman syndrome; individuals with non-deletion aetiologies typically have greater communicative abilities., Interpretation: The broader communication profile of Angelman syndrome is characterized by diverse and multimodal abilities, including some use of symbolic forms of communication that appears atypical given the absence of speech. This is suggestive of a probable dissociation between speech and other expressive forms of communication, indicating an isolated speech production impairment. This highlights a need in this population for alternative communication and specific input from services tailored to support the nuances of the communication profile of Angelman syndrome., What This Paper Adds: Although absent speech is near universal, a diverse profile of other communicative abilities has been reported. Parental reporting has been predominantly used to assess the communication profile of Angelman syndrome. Literature that investigates the specificities and possible dissociations in such a communication profile is limited., (© 2019 Mac Keith Press.)

Background: Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS)., Methods: Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex., Results: Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS., Conclusions: Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research.

B vitamins are essential for optimal brain and body function, and are particularly important for cortical metabolic processes that have downstream effects on mitigating oxidative stress. Oxidative stress has been linked to poor psychological outcomes including psychological distress, which has wide-reaching implications for the community and the workplace. Given work-related stress has been associated with poor mental health outcomes, high-dose B vitamin supplementation may be effective in improving brain function and psychological outcomes via attenuation of oxidative stress. This randomized, double-blind, placebo-controlled study investigated psychological outcomes following 6-month supplementation of a high-B-vitamin multivitamin in a large sample of healthy adults ( n = 108, aged 30-70 years), as well as changes in default mode network functional connectivity in a subset of the original sample ( n = 28). Improvements in occupational stress, general health, perceived stress, depressive symptoms, and mood profiles were identified for both active and placebo groups over time ( p < 0.05 corrected ). Seed-based functional connectivity analysis centered on the posterior cingulate cortex (PCC) showed that connectivity between the PCC and the caudate increased for the active treatment group, but decreased for the placebo group ( p < 0.05 corrected ). These findings reveal a substantial intervention effect for both active and placebo treatments, which could in part be associated with a placebo effect in subjective measures. There was, however, a significant treatment effect in the objective measure of functional connectivity, suggesting that reduced psychological stress and high-B-vitamin multivitamin supplementation may lead to an increase in DMN and caudate functional connectivity, which might reflect a strengthening of neurocircuitry within areas associated with reward and emotion at rest. Future studies should consider a placebo run-in methodology to reduce the placebo effect on the subjective measures of stress., (Copyright © 2019 Downey, Simpson, Ford, McPhee, Suo, Myers, Oliver and Stough.)

Background: There is limited research into the nature and aetiology of temper outbursts in people with intellectual disabilities. In this study, we describe the phenomenology and environmental context of temper outbursts in Lowe syndrome, a rare genetic syndrome in which outbursts are purportedly frequent., Method: A temper outburst interview (TOI) was conducted with caregivers of seventeen individuals with Lowe syndrome to generate an account of the behavioural sequence, common antecedents and consequences of temper outbursts, and to enable comparisons with similar work on Prader-Willi syndrome., Results: Outbursts in Lowe syndrome were frequently triggered by thwarted goal-directed behaviour and were associated with high levels of physical aggression and property destruction., Conclusions: Form and sequence of outbursts showed similarities to Prader-Willi syndrome and to behaviours reported in literature on typically developing children. The results highlight the importance of considering shared aetiology as well as syndrome-specific pathways in the development of outbursts., (© 2019 The Authors. Journal of Applied Research in Intellectual Disabilities Published by John Wiley & Sons Ltd.)

Self-injurious and aggressive behaviors are common in fragile X syndrome (FXS). However, little is known about the persistence of these behaviors and associated risk markers. We established the prevalence and persistence of self-injurious and aggressive behaviors over eight years in males with FXS, and associations with risk markers. Results showed 77% and 69% persistence rates for self-injurious and aggressive behavior, respectively. Baseline levels of repetitive behavior predicted persistent self-injurious behavior. Chronological age, impulsivity and overactivity were associated with persistent aggressive behavior but only impulsivity predicted persistence. This is the first study to document the persistence of self-injurious and aggressive behavior in FXS over the medium to long term and to identify behavioral risk markers that might facilitate targeted early intervention.

Purpose: Dosimetry of ionizing radiation in the presence of strong magnetic fields is gaining increased relevance in light of advances for MRI-guided radiation therapy. While the impact of strong magnetic fields on the overall response of ionization chambers has been simulated and measured before, this work investigates the local impact of the magnetic field on dose response in an ion chamber. High-resolution 1D and 2D response maps have been created for two small clinical thimble ionization chambers, the PinPoint chambers 31006 and 31014 (Physikalisch Technische Werkstaetten Freiburg, Germany)., Methods: Working on the Imaging and Medical Beam Line of the Australian Synchrotron an intense kilovoltage radiation beam with very low divergence, collimated to 0.1 mm was used to scan the chambers by moving them on a 2D motion platform. Measured current and beam position were correlated to create the response maps. Small neodymium magnets were used to create a field of about 0.25 T. Chamber axis, magnetic field, and beam direction were perpendicular to each other. Measurements were performed with both orientations of the magnetic field as well as without it. Chamber biases of 5 and 250 V in both polarities were used., Results: The local distribution of the response of small thimble-type ionization chambers was found to be impacted by a magnetic field. Depending on the orientation of the magnetic field, the chamber response near the stem was either enhanced or reduced with the response near the tip behaving the opposite way. Local changes were in the order of up to 40% compared to measurements without the magnetic field present. Bending of the central electrode was observed for the chamber with the steel electrode. The size of the volume of reduced collection near the guard electrode was impacted by the magnetic field. As the here investigated beam and field parameters differ from those of clinical systems, quantitatively different results would be expected for the latter. However, the gyroradii encountered here were similar to those of a 6-7 MV MRI linac with a 1.5 T magnet., Conclusions: Magnetic fields impact the performance of ionization chambers also on a local level. For practical measurements this might mean a change in the effective point of measurement, in addition to any global corrections. Further knowledge about the local response will help in selecting or constructing optimized chambers for use in magnetic fields., (© 2019 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast., Methods: A 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS (n = 44) and FXS (n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time 3 (7 years later)., Results: The CdLS group were lower in mood than the FXS group overall (p < .001). Interest and pleasure scores showed a significant decline over the lifespan for individuals with CdLS (p < .001) but not the FXS group. Lower level of ability at Time 1 was associated with lower mood at Time 1 and Time 3 in the FXS group only. Higher levels of ASD symptomology at Time 1 were associated with low mood and interest and pleasure in both syndrome groups at Time 1 and Time 3. Greater insistence on sameness at Time 1 was associated with lower mood at Time 1 in the FXS group and lower interest and pleasure at Time 1 and Time 3 in the CdLS group., Conclusions: Low affect in specific genetic syndromes may be associated with differing lifespan trajectories and behavioural profiles. Specifically, individuals with CdLS appear at risk for experiencing declines in levels of interest and pleasure whereas individuals with FXS show no significant change in the level of affect with age.

Age-related behavioural change in Cornelia de Lange syndrome is poorly understood. We report a 7 year follow-up study of adaptive behaviour, autism spectrum disorder symptomatology, language skills and behavioural characteristics in 30 individuals with Cornelia de Lange syndrome, compared with 18 individuals with Cri du Chat syndrome. The proportion of individuals with Cornelia de Lange syndrome meeting criteria for autism spectrum disorder on the Autism Diagnostic Observation Schedule increased, although patterns of change were complex. For both syndrome groups, absolute levels of adaptive ability were stable and receptive language improved, suggesting that changes over time do not result from an overall decline in ability. Reliable change index scores indicate heterogeneity within both groups in the occurrence of improvement or decline.

A diet rich in B-group vitamins is essential for optimal body and brain function, and insufficient amounts of such vitamins have been associated with higher levels of neural inflammation and oxidative stress, as marked by increased blood plasma homocysteine. Neural biomarkers of oxidative stress quantified through proton magnetic spectroscopy (1H-MRS) are not well understood, and the relationship between such neural and blood biomarkers is seldom studied. The current study addresses this gap by investigating the direct effect of 6-month high-dose B-group vitamin supplementation on neural and blood biomarkers of metabolism. Using a randomized, double-blind, placebo-controlled design, 32 healthy adults (20 female, 12 male) aged 30⁻65 years underwent blood tests (vitamin B6, vitamin B12, folate, and homocysteine levels) and 1H-MRS of the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) before and after supplementation. Results confirmed the supplement was effective in increasing vitamin B6 and vitamin B12 levels and reducing homocysteine, whereas there was no change in folate levels. There were significant relationships between vitamin B6 and N -acetylaspartate (NAA), choline, and creatine, as well as between vitamin B12 and creatine ( p s < 0.05), whereas NAA in the PCC increased, albeit not significantly ( p > 0.05). Together these data provide preliminary evidence for the efficacy of high-dose B-group supplementation in reducing oxidative stress and inflammation through increasing oxidative metabolism. It may also promote myelination, cellular metabolism, and energy storage.

Background: It is well documented that mothers of children with intellectual disabilities or autism experience elevated stress, with mental health compromised. However, comparatively little is known about mothers of children with rare genetic syndromes. This study describes mental health and well-being in mothers of children with 13 rare genetic syndromes and contrasts the results with mothers of children with autism., Methods: Mothers of children with 13 genetic syndromes (n = 646; Angelman, Cornelia de Lange, Down, Fragile-X, Phelan McDermid, Prader-Willi, Rett, Rubenstein Taybi, Smith Magenis, Soto, Tuberous Sclerosis Complex, 1p36 deletion and 8p23 deletion syndromes) and mothers of children with autism (n = 66) completed measures of positive mental health, stress and depression. Using Bayesian methodology, the influence of syndrome, child ability, and mother and child age were explored in relation to each outcome. Bayesian Model Averaging was used to explore maternal depression, positive gain and positive affect, and maternal stress was tested using an ordinal probit regression model., Results: Different child and mother factors influenced different aspects of mental well-being, and critically, the importance of these factors differed between syndromes. Maternal depression was influenced by child ability in only four syndromes, with the other syndromes reporting elevated or lower levels of maternal depression regardless of child factors. Maternal stress showed a more complex pattern of interaction with child ability, and for some groups, child age. Within positive mental health, mother and child age were more influential than child ability. Some syndromes reported comparable levels of depression (SMS, 1p36, CdLS) and stress (SMS, AS) to mothers of children with autism., Conclusions: Bayesian methodology was used in a novel manner to explore factors that explain variability in mental health amongst mothers of children with rare genetic disorders. Significant proportions of mothers of children with specific genetic syndromes experienced levels of depression and stress similar to those reported by mothers of children with autism. Identifying such high-risk mothers allows for potential early intervention and the implementation of support structures.

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

This study provides the first meta-analysis of the purported differences in sleep time and sleep quality between people with and without intellectual disabilities. Twenty-one papers were identified that compared sleep time and/or sleep quality in people with and without intellectual disabilities. The meta-analysis of sleep time revealed that people with an intellectual disability slept for 18 min less, on average, than people without an intellectual disability. This significant difference was limited to those studies that tested groups of people with an identified genetic syndrome or developmental disorder. The analysis of sleep quality also concluded that people with intellectual disabilities experienced poorer sleep: In 93% of comparisons between groups, sleep was found to be of poorer quality in the group of people with intellectual disabilities. There were no differences found between studies that measured sleep objectively and those that used diary or questionnaire measures. Notably, most samples were drawn from populations of people with specified genetic syndromes or developmental disorders, rather than intellectual disability of heterogeneous origin. Similarly, most studies investigated sleep in children, although there was no evidence that the differences between the groups reduced during adulthood. Most studies used highly-regarded objective measures of sleep, such as polysomnography or actigraphy, although methodological flaws were evident in the identification of samples and the measurement of intellectual disability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Mental health problems are more prevalent in people with than without intellectual disabilities, yet treatment options have received little attention. The aim of this study was to identify and evaluate the effectiveness of pharmacological and psychological interventions in the treatment of mental health problems in children and adults with severe and profound intellectual disabilities, given their difficulties in accessing standard mental health interventions, particularly talking therapies, and difficulties reporting drug side effects., Design: A systematic review using electronic searches of PsycINFO, PsycTESTS, EMBASE, MEDLINE, CINAHL, ERIC, ASSIA, Science Citation Index, Social Science Citation Index and CENTRAL was conducted to identify eligible intervention studies. Study selection, data extraction and quality appraisal were performed by two independent reviewers., Participants: Study samples included at least 70% children and/or adults with severe or profound intellectual disabilities or reported the outcomes of this subpopulation separate from participants with other levels of intellectual disabilities., Interventions: Eligible intervention studies evaluated a psychological or pharmacological intervention using a control condition or pre-post design., Outcomes: Symptom severity, frequency or other quantitative dimension (e.g., impact), as assessed with standardised measures of mental health problems., Results: We retrieved 41 232 records, reviewed 573 full-text articles and identified five studies eligible for inclusion: three studies evaluating pharmacological interventions, and two studies evaluating psychological interventions. Study designs ranged from double-blind placebo controlled crossover trials to single-case experimental reversal designs. Quality appraisals of this very limited literature base revealed good experimental control, poor reporting standards and a lack of follow-up data., Conclusions: Mental ill health requires vigorous treatment, yet the current evidence base is too limited to identify with precision effective treatments specifically for children or adults with severe and profound intellectual disabilities. Clinicians therefore must work on the basis of general population evidence, while researchers work to generate more precise evidence for people with severe and profound intellectual disabilities., Prospero Registration Number: CRD 42015024469., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

It is well documented that mothers of children with challenging behavior (CB) experience elevated levels of stress and that this persists over time, but less is known about the experience of mothers of children with rare genetic syndromes. This article describes 2 studies, 1 cross-sectional and 1 longitudinal, comparing well-being in mothers of children with Angelman, Cornelia de Lange and Cri du Chat syndrome who have either shown chronic CB ( n = 18) or low/no CB ( n = 26) in the preceding 7 years. The presence of chronic, long-term CB increased maternal stress but not depression or anxiety, and did not influence positive well-being. Stress relating specifically to their child's genetic syndrome reduced with age, highlighting the need for further exploration in this area.

Background and Purpose: Independent dosimetry audits improve quality and safety of radiation therapy. This work reports on design and findings of a comprehensive 3D conformal radiotherapy (3D-CRT) Level III audit., Materials and Methods: The audit was conducted as onsite audit using an anthropomorphic thorax phantom in an end-to-end test by the Australian Clinical Dosimetry Service (ACDS). Absolute dose point measurements were performed with Farmer-type ionization chambers. The audited treatment plans included open and half blocked fields, wedges and lung inhomogeneities. Audit results were determined as Pass Optimal Level (deviations within 3.3%), Pass Action Level (greater than 3.3% but within 5%) and Out of Tolerance (beyond 5%), as well as Reported Not Scored (RNS). The audit has been performed between July 2012 and January 2018 on 94 occasions, covering approximately 90% of all Australian facilities., Results: The audit pass rate was 87% (53% optimal). Fifty recommendations were given, mainly related to planning system commissioning. Dose overestimation behind low density inhomogeneities by the analytical anisotropic algorithm (AAA) was identified across facilities and found to extend to beam setups which resemble a typical breast cancer treatment beam placement. RNS measurements inside lung showed a variation in the opposite direction: AAA under-dosed a target beyond lung and over-dosed the lung upstream and downstream of the target. Results also highlighted shortcomings of some superposition and convolution algorithms in modelling large angle wedges., Conclusions: This audit showed that 3D-CRT dosimetry audits remain relevant and can identify fundamental global and local problems that also affect advanced treatments., (Crown Copyright © 2018 Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Background: Potocki-Lupski syndrome (PTLS) and Smith-Magenis syndrome (SMS) are related genomic disorders, as duplication 17p11.2 (associated with PTLS) is the reciprocal recombination product of the SMS microdeletion. While SMS has a relatively well-delineated behavioural phenotype, the behavioural profile in PTLS is less well defined, despite purported associations with autism spectrum disorder (ASD) and the suggestion that some behaviours may be diametric to those seen in SMS., Methods: Caregivers of individuals with PTLS (N = 34; M age = 12.43, SD = 6.78) completed online behavioural questionnaires, including the Challenging Behaviour Questionnaire (CBQ), the Activity Questionnaire (TAQ), the Repetitive Behaviour Questionnaire (RBQ), the Mood, Interest and Pleasure Questionnaire-Short Form (MIPQ-S) and the Social Communication Questionnaire (SCQ), which assesses behaviours associated with ASD. Individuals with PTLS were matched on age and adaptive functioning to individuals with SMS (N = 31; M age = 13.61, SD = 6.85) and individuals with idiopathic ASD (N = 33; M age = 12.04, SD = 5.85) from an existing dataset., Results: Individuals with PTLS and SMS were less impaired than those with idiopathic ASD on the communication and reciprocal social interaction subscales of the SCQ, but neither syndrome group differed from idiopathic ASD on the restricted, repetitive and stereotyped behaviours subscale. On the repetitive behaviour measure, individuals with PTLS and idiopathic ASD scored higher than individuals with SMS on the compulsive behaviour subscale. Rates of self-injury and property destruction were significantly lower in PTLS and idiopathic ASD than in SMS. No between-syndrome differences were found in relation to overactivity or mood; however, impulsivity was greater in SMS than in PTLS., Conclusions: Findings suggest some overlap in the behavioural phenotype of PTLS and features of ASD symptomatology; however, the overall profile of behaviours in PTLS appears to be divergent from both idiopathic ASD and SMS. Relative to idiopathic ASD, PTLS is not characterised by communication or social interaction deficits. However, restricted and repetitive behaviours were evident in PTLS, and these may be characterised specifically by compulsive behaviours. While several behavioural differences were identified between PTLS and SMS, there was little evidence of diametric behavioural phenotypes, particularly in relation to social behaviour.