Dr Joanna Moss

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.

Introduction: The current study aimed to answer the following questions: (1) What factor structures emerge to responses to the brief-COPE in a post-pandemic population of caregivers of children under 18 in the UK? (2) What differences, if any, are there in coping between parents of children with and without Learning Disabilities during COVID-19 restrictions? Method: An exploratory factor analysis was conducted across a sample of parents of children with and without learning disabilities. Following this, differences between responses on each factor were assessed with Mann Whitney U tests. Results: The analysis recovered 6 factors across the whole sample: External support-seeking, emotion-focused disengagement, positive cognitive reframing, substance use, religion, and problem-focused disengagement. These structures are largely in line with previous findings. Significant differences were found between groups on the emotion-focused disengagement factor, with parents of children with Learning Disabilities scoring significantly higher on measures of self-blame, denial and one venting item. Conclusion: These findings suggest some consistency in recovered factor structures of the Brief-COPE. Further work exploring the role of emotion-focused disengagement in caregivers of children with Learning Disabilities could provide further insight into what support may need to be made available in this group.

Background Relatively little is known about social cognition in people with intellectual disability (ID), and how this may support understanding of co-occurring autism. A limitation of previous research is that traditional social-cognitive tasks place a demand on domain-general cognition and language abilities. These tasks are not suitable for people with ID and lack the sensitivity to detect subtle social-cognitive processes. In autism research, eye-tracking technology has ofered an efective method of evaluating social cognition—indicating associations between visual social attention and autism characteristics. The present systematic review synthesised research which has used eye-tracking technology to study social cognition in ID. A meta-analysis was used to explore whether visual attention on socially salient regions (SSRs) of stimuli during these tasks correlated with degree of autism characteristics presented on clinical assessment tools. Method Searches were conducted using four databases, research mailing lists, and citation tracking. Following indepth screening and exclusion of studies with low methodological quality, 49 articles were included in the review. A correlational meta-analysis was run on Pearson’s r values obtained from twelve studies, reporting the relationship between visual attention on SSRs and autism characteristics. Results and conclusions Eye-tracking technology was used to measure diferent social-cognitive abilities across a range of syndromic and non-syndromic ID groups. Restricted scan paths and eye-region avoidance appeared to impact people’s ability to make explicit inferences about mental states and social cues. Readiness to attend to social stimuli also varied depending on social content and degree of familiarity. A meta-analysis using a random efects model revealed a signifcant negative correlation (r = −.28, [95% CI −.47, −.08]) between visual attention on SSRs and autism characteristics across ID groups. Together, these fndings highlight how eye-tracking can be used as an accessible tool to measure more subtle social-cognitive processes, which appear to refect variability in observable behaviour. Further research is needed to be able to explore additional covariates (e.g. ID severity, ADHD, anxiety) which may be related to visual attention on SSRs, to diferent degrees within syndromic and non-syndromic ID groups, in order to determine the specifcity of the association with autism characteristics. Keywords Eye-tracking, Social cognition, Intellectual disability, Genetic syndromes, Autism

Funder: Cerebra Funder: Cornelia de Lange Syndrome Foundation, UK & Ireland Funder: Research Autism Funder: Newlife the Charity for Disabled Children; doi: http://dx.doi.org/10.13039/100016187 Funder: Baily Thomas Charitable Fund; doi: http://dx.doi.org/10.13039/501100001262 BACKGROUND: Phenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of > 1500 individuals with rare genetic syndromes. METHODS: Profiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n = 154, Cri du Chat n = 75, Cornelia de Lange n = 199, fragile X n = 297, Prader-Willi n = 278, Lowe n = 89, Smith-Magenis n = 54, Down n = 135, Sotos n = 40, Rubinstein-Taybi n = 102, 1p36 deletion n = 41, tuberous sclerosis complex n = 83 and Phelan-McDermid n = 35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n = 254). Self-help skills were included as an additional predictor. RESULTS: Genetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader-Willi, Rubinstein-Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith-Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy. LIMITATIONS: The key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups. CONCLUSIONS: These findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID.

Funder: Cerebra Funder: Cornelia de Lange Syndrome Foundation, UK & Ireland Funder: Research Autism Funder: Newlife the Charity for Disabled Children; doi: http://dx.doi.org/10.13039/100016187 Funder: Baily Thomas Charitable Fund; doi: http://dx.doi.org/10.13039/501100001262 BACKGROUND: Phenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of > 1500 individuals with rare genetic syndromes. METHODS: Profiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n = 154, Cri du Chat n = 75, Cornelia de Lange n = 199, fragile X n = 297, Prader-Willi n = 278, Lowe n = 89, Smith-Magenis n = 54, Down n = 135, Sotos n = 40, Rubinstein-Taybi n = 102, 1p36 deletion n = 41, tuberous sclerosis complex n = 83 and Phelan-McDermid n = 35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n = 254). Self-help skills were included as an additional predictor. RESULTS: Genetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader-Willi, Rubinstein-Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith-Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy. LIMITATIONS: The key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups. CONCLUSIONS: These findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID.

People with intellectual disability are underrepresented and often actively excluded from autism research. A better understanding of autism requires inclusive research approaches that accurately represent the broad heterogeneity of the autistic population.

Research shows that questionable research practices (QRPs) are present in undergraduate final-year dissertation projects. One entry-level Open Science practice proposed to mitigate QRPs is “study preregistration,” through which researchers outline their research questions, design, method, and analysis plans before data collection and/or analysis. In this study, we aimed to empirically test the effectiveness of preregistration as a pedagogic tool in undergraduate dissertations using a quasi-experimental design. A total of 89 UK psychology students were recruited, including students who preregistered their empirical quantitative dissertation (n = 52; experimental group) and students who did not (n = 37; control group). Attitudes toward statistics, acceptance of QRPs, and perceived understanding of Open Science were measured both before and after dissertation completion. Exploratory measures included capability, opportunity, and motivation to engage with preregistration, measured at Time 1 only. This study was conducted as a Registered Report; Stage 1 protocol: https://osf.io/9hjbw (date of in-principle acceptance: September 21, 2021). Study preregistration did not significantly affect attitudes toward statistics or acceptance of QRPs. However, students who preregistered reported greater perceived understanding of Open Science concepts from Time 1 to Time 2 compared with students who did not preregister. Exploratory analyses indicated that students who preregistered reported significantly greater capability, opportunity, and motivation to preregister. Qualitative responses revealed that preregistration was perceived to improve clarity and organization of the dissertation, prevent QRPs, and promote rigor. Disadvantages and barriers included time, perceived rigidity, and need for training. These results contribute to discussions surrounding embedding Open Science principles into research training.

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.

Background: Hyperactivity and repetitive behaviour are characteristic features of fragile X syndrome (FXS). However, little is known about the influence of autism symptomatology on how these characteristics develop over time. We investigate the profiles and developmental trajectories of overactivity, impulsivity and repetitive behaviour, in males with FXS over three time points spanning 8 years. Method: Participants formed two subgroups, those who displayed elevated symptoms of autism at Time 1 (n = 37; Mage = 16.32; age range = 6.61-43.51) and those who did not (n = 32; Mage = 8.43; age range = 8.94-47.49). Results: Participants without elevated symptoms of autism showed a reduction in impulsivity and repetitive questioning over time, whereas those with elevated symptoms of autism did not. Differences between the two subgroups in several topographies of repetitive behaviour emerged at Time 3 only. Conclusions: These results further understanding of the relationship between autistic phenomenology and behavioural characteristics in FXS.

A systematic retrospective case note review was undertaken to investigate autism diagnostic factors in 124 individuals with Sturge-Weber syndrome (SWS). Social Responsiveness Scale questionnaires were then analysed to explore the severity and profile of autism characteristics in 70 participants. Thirty-two to forty percent of participants had a clinical diagnosis of autism and half of those without a diagnosis showed significant social communication difficulties. Children had a relative strength in social awareness and social motivation, which are typically much reduced in people with autism. This finding may explain why, to date, the diagnosis has often been overlooked in this population. The research therefore suggests that children with Sturge-Weber should be screened to identify social communications difficulties and provided with timely support.

Autism spectrum disorder (ASD) phenomenology is reported to be more common in individuals with some genetic syndromes than in the general population; however, no meta-analysis has provided prevalence data within and between syndromes. In this systematic review and meta-analysis, we aimed to synthesise data from a wide range of papers to provide accurate estimates about ASD phenomenology in genetic and metabolic syndromes. We identified syndromes reported as most likely to be associated with ASD. We searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, and PubMed Central for English-language papers published from database creation up to early 2014 with use of syndrome-specific keywords and a set of ASD keywords. We screened and extracted papers that had ASD prevalence data for ten or more people within a genetic syndrome. With use of a prespecified set of reliable criteria, we applied quality weighting to papers and estimated a quality-effects prevalence of ASD phenomenology for each syndrome. We then calculated relative risks to compare ASD between all syndromes and also calculated odds ratios to compare prevalence with the general population taking the current estimate of one in 68 people. We identified 168 papers reporting the prevalence of ASD phenomenology and found widely varying methods and quality of data. Quality-weighted effect prevalence estimates of ASD phenomenology were established for Rett's syndrome (female individuals only 61%), Cohen's syndrome (54%), Cornelia de Lange syndrome (43%), tuberous sclerosis complex (36%), Angelman's syndrome (34%), CHARGE syndrome (30%), fragile X syndrome (male individuals only 30%; mixed sex 22%), neurofibromatosis type 1 (18%), Down's syndrome (16%), Noonan's syndrome (15%), Williams' syndrome (12%), and 22q11.2 deletion syndrome (11%). Relative risks and the odds ratio compared with the general population were highest for Rett's syndrome and Cohen's syndrome. In all syndromes, odds ratios showed ASD phenomenology to be significantly more likely than in the general population. ASD phenomenology varied between syndromes, but was consistently more likely than in the general population. Further research is needed in these populations, including how ASD in genetic and metabolic syndromes differs from idiopathic autism and what that can tell us about the mechanisms underlying ASD. Cerebra.

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.

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

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.

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 1and 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.

SMC1A encodes one of the proteins of the cohesin complex. SMC1A Wvariants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.

We investigated the prevalence and phenomenology of repetitive behavior in genetic syndromes to detail profiles of behavior. The Repetitive Behaviour Questionnaire (RBQ) provides fine-grained identification of repetitive behaviors. The RBQ was employed to examine repetitive behavior in Angelman (N = 104), Cornelia de Lange (N = 101), Cri-du-Chat (N = 58), Fragile X (N = 191), Prader-Willi (N = 189), Lowe (N = 56) and Smith-Magenis (N = 42) syndromes and individuals with intellectual disability of heterogeneous aetiology (N = 56). Repetitive behavior was variable across syndromes. Fragile X syndrome scored highly on all subscales. Angelman syndrome demonstrated a significantly lowered probability for most behaviors. Prader-Willi, Cri-du-Chat and Smith-Magenis syndrome evidenced unique profiles of repetitive behavior. There is extreme heterogeneity of repetitive behavior across genetic syndromes, highlighting syndrome specific profiles.

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.

We evaluated the proportion of individuals with Down syndrome (DS: N = 108) who met criteria for autism spectrum disorder (ASD) on the Social Communication Questionnaire and the severity of ASD-related symptomatology in this group. The proportions of individuals with DS meeting the cut-off for ASD and autism in this sample were 19% and 8%, respectively. We then evaluated the behavioural profile of individuals with DS who scored above cut-off for ASD (DS+ASD; N = 17) compared with those with DS-only (N = 17) and individuals with idiopathic ASD (N = 17), matched for adaptive behaviour skills and ASD symptom severity (ASD group only). Individuals in the DS+ASD and ASD-only groups showed more stereotyped behaviour, repetitive language, overactivity and self-injury than the DS-only group (p < .001). Individuals in the DS+ASD and DS-only groups appeared less withdrawn from their surroundings than those with ASD (p < .004). These findings indicate differences in the behavioural and cognitive profile of individuals with DS+ASD compared with those with DS-only, when controlling for adaptive behaviour skills. Individuals with DS+ASD show broad similarities with individuals with idiopathic ASD with regard to ASD and behavioural characteristics but may also show some areas of subtle difference from this group.

BackgroundAggressive behaviours are common inpeople with neurodevelopmental conditions,contributing to poorer quality of life and placementbreakdown. However, there is limited empiricalresearch documenting the prevalence and persistenceof aggressive behaviours in autism. In thislongitudinal study, aggressive behaviours wereinvestigated in a sample of autistic individuals over10years.MethodsCaregivers of autistic individuals, both withand without intellectual disability, completedquestionnaires relating to the presence of aggressivebehaviours atT1[N=229, mean age in years11.8,standard deviation (SD)5.9],T2(T1+3years,N=81, mean age in years15.1,SD5.9) andT3(T1+10years,N=54, mean age in years24.5,SD8.1). Analyses examined the presence and persistenceof aggressive behaviours and the predictive value ofestablished correlates of aggression.ResultsAggressive behaviours were common atbaseline (61.6%) but only persistent in30% of thesample over10years. Higher composite scores ofoveractivity and impulsivity atT1were significantlyassociated with the persistence of aggressivebehaviours atT2(P=0.027) andT3(P=0.012) withmedium effect size.ConclusionsAggressive behaviours are common inautism, but reduce with age. Behavioural correlates ofattention deficit hyperactivity disorder(ADHD) predict the presence and persistence ofaggressive behaviour and as such may be usefulclinical indicators to direct proactive interventionresources to ameliorate aggressive behaviours.Keywordsaggressive behaviours, autism,impulsivity, overactivity, persistence, prevalenceBackgroundThe term‘aggressive behaviours’is a broad term thatencompasses behaviours that inflict social, emotionaland physical harm (Farmer & Aman2011). In thiscontext, the term is not intended to imply that theperson showing the behaviour is intending to hurtanother person, but simply that these kinds ofbehaviours have the potential to cause harm. Physicalaggression is common and predicts deleteriousoutcomes for individuals with neurodevelopmentalconditions such as autism (Fitzpatricket al.2016),including an increased likelihood of admission toresidential facilities, physical abuse from caregivers,caregiver burnout, isolation and lower quality of life(Lakin1983; Stormshaket al.1999; Stithet al.2009;1Correspondence: Dr Catherine Laverty, School of Psychology,University of Birmingham,52Pritchatts Road, Edgbaston,Birmingham B15 2TT, UK (e-mail:c.laverty@bham.ac.uk).Journal of Intellectual Disability Researchdoi: 10.1111/jir.13004VOLUME PART©2023The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of theScientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License,which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial andno modifications or adaptations are made.bs_bs_banner

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.

Difficulties in communication and social functioning are key diagnostic components of intellectual disability (ID), and negatively impact the wellbeing of those with ID. Communication and social difficulties are multifaceted and comprise a wide breadth of skills. Current approaches in research and intervention often do not include refined assessment of communicative and social functioning in those with ID. Yet, in-depth behavioral phenotyping in neurogenetic syndromes associated with ID indicates that aspects of communication and social functioning are dissociable and interact with one another culminating in a diverse range of unique behavioral profiles between and within these groups. Detailed assessment of such profiles contributes to refined understanding of the developmental mechanisms underlying distinct aspects of communication and social functioning, and thus the advancement of targeted and evidence-based intervention. We discuss insights gained from refined assessment in five neurogenetic syndromes with distinct profiles of social and communication skills: Angelman syndrome, Cornelia de Lange syndrome, Down syndrome, fragile X syndrome and tuberous sclerosis complex. Specifically, we compare findings and the improved knowledge derived from detailed assessments relative to broader measures that mask nuanced strengths and difficulties. We then consider how refined but practical assessment approaches may be applied in research and intervention in broader groups of people with ID with heterogeneous causes.

Background Whilst up to 60% of males with fragile X syndrome (FXS) meet criteria for autism spectrum disorder (ASD), the prevalence and nature of ASD in females with FXS remains unclear. Method A systematic literature search identified papers reporting ASD prevalence and/or symptomatology in females with FXS. Results and conclusion Meta-analysis suggested that rates of ASD for females with FXS are reliably higher than for females in the general population (a random effects model estimated weighted average prevalence at 14%, 95% CI 13-18%). Whilst papers highlighted a number of social and repetitive difficulties for females with FXS, characteristic profiles of impairment are not clear. Possible associations between ASD traits and IQ, and between ASD and levels of fragile X mental retardation protein, are suggested, but data are equivocal.

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.

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.

Background Gaze following difficulties are considered an early marker of autism, thought likely to cumulatively impact the development of social cognition, language and social skills. Subtle differences in gaze following abilities may contribute to the diverse range social and communicative autistic characteristics observed across people with genetic syndromes, such as Cornelia de Lange (CdLS) and fragile X (FXS) syndromes. Aims To compare profiles of 1) visual attention to the eye region at critical points of the attention direction process, 2) whether children follow the gaze cue to the object, and 3) participant looking time to the target object following the gaze cue between groups and conditions. Materials and Methods Children with CdLS (N=11) and FXS (N=8) and autistic (N=22) and neurotypical (N=22) children took part in a passive viewing paradigm adapted from Senju & Csibra (2008), in which videos of a central cue (ball/cartoon face/human face) directed attention towards one of two objects. Visual attention patterns were recorded via eye tracking technology. Results Neurotypical children were used as a reference group against which the autistic, CdLS and FXS groups were compared. Although autistic children looked at the eye region for significantly less time, they looked at the target object as frequently and for a similar duration as neurotypical children. Children with FXS looked at the target as frequently as neurotypical children but looked at it for comparatively less time. Both neurotypical children and children with CdLS frequently looked at the eye region, but children with CdLS were less likely to look at the target than neurotypical children. Conclusions Findings provide preliminary evidence of unique patterns of visual attention and gaze following strategies in children with CdLS, children with FXS and autistic children. These unique gaze following patterns may underpin the distinct profiles of social and communication autistic traits observed between these groups.

This study describes the profile of repetitive behaviour in individuals with Williams syndrome, utilising cross-syndrome comparisons with people with Prader-Willi and Down syndromes. The Repetitive Behaviour Questionnaire was administered to caregivers of adults with Williams (n = 96), Prader-Willi (n = 103) and Down (n = 78) syndromes. There were few group differences, although participants with Williams syndrome were more likely to show body stereotypies. Individuals with Williams syndrome also showed more hoarding and less tidying behaviours than those with Down syndrome. IQ and adaptive ability were negatively associated with repetitive questioning in people with Williams syndrome. The profile of repetitive behaviour amongst individuals with Williams syndrome was similar to the comparison syndromes. The cognitive mechanisms underlying these behaviours in genetic syndromes warrant further investigation.

Existing literature draws links between social attention and socio-behavioural profiles in neurodevelopmental disorders. Fragile X syndrome (FXS) is associated with a known socio-behavioural phenotype of social anxiety and social communication difficulties alongside high social motivation. However, studies investigating social attention in males with FXS are scarce. Using eye tracking, this study investigates social attention and its relationship with both anxiety and autism symptomatology in males with FXS. We compared dwell times to the background, body, and face regions of naturalistic social scenes in 11 males with FXS (M  = 26.29) and 11 typically developing (TD) children who were matched on gender and receptive language ability (M  = 6.28). Using informant-report measures, we then investigated the relationships between social scene scanning and anxiety, and social scene scanning and social communicative impairments. Males with FXS did not differ to TD children on overall dwell time to the background, body, or face regions of the naturalistic social scenes. Whilst males with FXS displayed developmentally 'typical' social attention, increased looking at faces was associated with both heightened anxiety and fewer social communication impairments in this group. These results offer novel insights into the mechanisms associated with social attention in FXS and provide evidence to suggest that anxiety and autism symptomatology, which are both heightened in FXS, have differential effects on social attention.

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.

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.

Background Self-injurious and aggressive behaviours are reported as components of some behavioural phenotypes but there are few studies comparing across syndrome groups. In this study we examined the prevalence of these behaviours and the associated person characteristics in seven genetic syndromes. Methods Questionnaire data on self-injury and aggression, mood, hyperactivity, autism spectrum disorder and repetitive behaviour were collected on Angelman (AS, n = 104), Cornelia de Lange (CdLS, 101), Cri du Chat (CdCS, 58), Fragile X (FXS, 191), Lowe (LS, 56), Prader-Willi (PWS, 189) and Smith-Magenis (SMS, 42) syndromes. Results A significantly higher prevalence of self-injury was evident in CdCS, CdLS, FXS, PWS, LS and SMS. The prevalence of aggression was significantly heightened in AS and SMS. Self-injury was associated with repetitive and impulsive behaviour in CdLS, FXS, PWS and LS. Impulsivity and overactivity were significantly higher in those showing aggression across all syndrome groups. Conclusions These data quantify the risk for self-injury and aggression in the syndromes studied with implications for early intervention. The associations between these behaviours and person characteristics both within and between syndromes warrant further research.

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.

The operant learning theory account of behaviors of clinical significance in people with intellectual disability (ID) has dominated the field for nearly 50 years. However, in the last two decades, there has been a substantial increase in published research that describes the behavioral phenotypes of genetic disorders and shows that behaviors such as self-injury and aggression are more common in some syndromes than might be expected given group characteristics. These cross-syndrome differences in prevalence warrant explanation, not least because this observation challenges an exclusively operant learning theory account. To explore this possible conflict between theoretical account and empirical observation, we describe the genetic cause and physical, social, cognitive and behavioral phenotypes of four disorders associated with ID (Angleman, Cornelia de Lange, Prader-Willi and Smith-Magenis syndromes) and focus on the behaviors of clinical significance in each syndrome. For each syndrome we then describe a model of the interactions between physical characteristics, cognitive and motivational endophenotypes and environmental factors (including operant reinforcement) to account for the resultant behavioral phenotype. In each syndrome it is possible to identify pathways from gene to physical phenotype to cognitive or motivational endophenotype to behavior to environment and back to behavior. We identify the implications of these models for responsive and early intervention and the challenges for research in this area. We identify a pressing need for meaningful dialog between different disciplines to construct better informed models that can incorporate all relevant and robust empirical evidence.

Little is known about the way in which the characteristics of autism spectrum disorder (ASD) develop and manifest across the age span in individuals with genetic syndromes. In this study we present findings from a two and a half year follow-up of the characteristics associated with ASD in three syndromes: Cornelia de Lange (CdLS), Fragile X (FXS), and Cri du Chat (CdCS). Parents and carers of 251 individuals (CdLS=67, CdCS=42, and FXS=142) completed the Social Communication Questionnaire (SCQ) at Time 1 (T1) and again two and a half years later (T2). The FXS and CdLS groups were more likely to meet the cut-offs for both autism and ASD and show greater severity of ASD related behaviors, at both T1 and T2, compared to the CdCS group. Older individuals (>15yrs) with CdLS were more likely to meet the cut off for ASD than younger individuals (15yrs) with the syndrome and more likely to show greater severity of social impairments. In FXS repetitive behaviors were found to become less prominent with age and in CdCS social impairments were reported to be more severe with age. There were no significant changes between T1 and T2 in the severity of ASD characteristics in the CdCS and CdLS groups. The FXS group showed significantly fewer repetitive behaviors and less severe impairments in social interaction over this time frame. The findings suggest that while there may be similarities in overall severity and presentation of ASD characteristics in CdLS and FXS, these characteristics have divergent patterns of development within these groups. (c) 2015 Wiley Periodicals, Inc.

Autism spectrum disorder characteristics have not been evaluated in Cornelia de Lange and Cri du Chat syndromes using robust assessments. The Autism Diagnostic Observation Schedule and Social Communication Questionnaire were administered to 34 participants with Cornelia de Lange syndrome and a comparison group of 23 participants with Cri du Chat syndrome (M ages 12.4 [SD = 3.8] and 10.3 years [SD = 3.6], respectively). Twenty-one participants with Cornelia de Lange syndrome (61.8%) scored above the autism cutoff on the Autism Diagnostic Observation Schedule compared to 9 with Cri du Chat syndrome (39.2%). Prevalence of autism spectrum disorder characteristics is heightened in Cornelia de Lange syndrome. The profile of characteristics is atypical to that of idiopathic autism.

Even though self-injury and aggression are common in tuberous sclerosis complex (TSC), understanding of these behaviours in adults with TSC and intellectual disability (ID) is limited. Little is known about their frequency in comparison to other ID-related genetic disorders or their association with other TSC-Associated Neuropsychiatric Disorders (TAND). This study determined the caregiver-reported frequency of self-injury and aggression in adults with TSC plus ID in comparison to Down syndrome (DS) and Angelman syndrome (AS), and assessed demographic and behavioural characteristics associated with the occurrence of each behaviour in TSC. Rates of self-injury and aggression in adults with TSC plus ID were 31% and 37.9% respectively. The odds of self-injury for adults with TSC were nearly twice as high as the odds for adults with DS, and the odds of aggression were over 2.5 times higher for adults with TSC than for adults with DS. When compared to adults with AS, odds of self-injury in TSC were around half those of the AS group, and odds of aggression were less than a third of those for adults with AS. These differences were not statistically significant. In adults with TSC, poorer communication and socialisation skills, gastric health problems and impulsivity were associated with self-injury; compulsive behaviour and impulsivity were associated with aggression. Caregivers and professionals should be alert to the likelihood of these behaviours in adults with TSC plus ID, and to characteristics associated with increased risk for their occurrence. We suggest assessment strategies to identify those at elevated risk. This paper adds specific examination of behavioural difficulties in adults with tuberous sclerosis complex who also have intellectual disability, a population at heightened risk of adverse behavioural outcomes which has received limited focussed examination to date. Findings support existing suggestions that there is relatively high risk for both self-injury and aggression, and provide novel insight into characteristics that may be associated with the presence of these behaviours.

Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated with unusual facial features, limb abnormalities, a wide range of health conditions, and intellectual disability. Mutations in five genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been identified in up to 70% of individuals. Genetic cause remains unknown for a proportion of individuals. There is substantial heterogeneity in all aspects of CdLS but very little is known about what predicts phenotypic heterogeneity. In this study, we evaluated genotype–phenotype associations in 34 individuals with CdLS. Participants with NIPBL mutations had significantly lower self help skills and were less likely to have verbal skills relative to those who were negative for the NIPBL mutation. No significant differences were identified between the groups in relation to repetitive behavior, mood, interest and pleasure, challenging behavior, activity, impulsivity, and characteristics of autism spectrum disorder whilst controlling differences in self help skills. Significant correlations indicating lower mood, interest and pleasure, and increased insistence on sameness with older age were identified for those who were NIPBL mutation positive. The findings suggest similarities in the behavioral phenotype between those with and without the NIPBL mutation once differences in self help skills are controlled for. However, there may be subtle differences in the developmental trajectory of these behaviors according to genetic mutation status in CdLS.

Background The current study focuses on mothers and fathers of children with three rare genetic syndromes that are relatively unexplored in terms of family experience: Angelman syndrome, Cornelia de Lange syndrome and Cri du Chat syndrome. Method Parents of children with Angelman syndrome (n = 15), Cornelia de Lange syndrome (n = 16) and Cri du Chat syndrome (n = 18), and a matched comparison group of parents of children with autism and intellectual disabilities (n = 20) completed questionnaires on both psychological distress (stress, anxiety, depression) and positive psychological functioning. Results Parents of children with Angelman syndrome consistently reported the highest levels of psychological distress, and parents of children with Cornelia de Lange syndrome the lowest, with parents of children with Cri du Chat syndrome and autism scoring between these two. Positive psychological functioning was similar across the four aetiology groups. Conclusions Parents of children with rare genetic syndromes are at risk for high levels of stress and mental health problems. Methodological issues and the practical applications of these results are discussed.

Studies of individuals with Cornelia de Lange syndrome (CdLS) have described changes in mood and behavior with age, although no empirical or longitudinal studies have been conducted. Caregivers of individuals with CdLS (N = 67), cri du chat syndrome (CdCS; N = 42), and Fragile X syndrome (FXS; N = 142) completed the Mood, Interest and Pleasure Questionnaire (MIPQ) at Time 1 and 2 years later (Time 2). Scores on the MIPQ were significantly lower in the CdLS group compared with the CdCS and FXS groups at Time 1 and Time 2. Lower MIPQ scores were characteristic of older adolescents (> 15 years) and adults with CdLS. However, there were no significant differences in MIPQ scores between Time 1 and Time 2. Age and insistence on sameness predicted MIPQ scores in CdLS.

The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important.

The experiences of mothers of adult offspring with Angelman, Cornelia de Lange, or Cri du Chat syndrome have not been previously explored in research. The current study focuses on experiences with social and medical services and the impact the rareness of an adult offspring's syndrome has on the experiences of mothers. Eight mothers of adults with Angelman, Cornelia de Lange, or Cri du Chat syndrome were interviewed. Thematic Content Analysis was used to interpret the interviews. Four themes emerged from the analysis: (i) The rarity of their offspring's syndrome, (ii) Uneven medical and social care service provision, (iii) The inertia of social care services, and (iv) Mothers as advocates. Mothers felt that the rareness of their offspring's syndrome did not affect experiences with social care services, but did affect access to medical services and some aspects of day-to-day living. Accessing appropriate social care services was reported to be a lengthy and complex process. These data may help inform care service providers about how best to support adults with rare genetic syndromes and their families.

Food-related behavior problems are well documented in Prader-Willi syndrome (PWS), with impaired satiety, preoccupation with food and negative food-related behaviors (such as taking and storing food) frequently reported as part of the behavioral phenotype of older children and adults. Food-related behavior problems in other genetic neurodevelopmental syndromes remain less well studied, including those seen in Angelman Syndrome (AS), the 'sister imprinted disorder' of PWS. Food-related behavior problems were assessed in 152 participants each with one of five genetic neurodevelopmental syndromes – PWS, AS, 1p36 deletion, Cornelia de Lange, and fragile X. Predictably, levels of food-related behavior problems reported in participants with PWS significantly exceeded those of at least one other groups in most areas (impaired satiety; preoccupation with food; taking and storing food; composite negative behavior). However, in some areas people with AS were reported to display food-related problems at least as severe as those with PWS, with the AS group reported to display significantly more food-related behavior problems than at least one comparison group on measures of taking and storing food, composite negative behaviors, impaired satiety and preoccupation with food. Over 50% of participants in the AS group scored above the median point of the distribution of PWS scores on a measure of taking and storing food. These findings indicate further investigation of eating problems in AS are warranted and have implications for current theoretical interpretations of the behavioral differences between AS and PWS.

Background Autism spectrum disorder (ASD) has been identified as a risk marker for self-injurious behaviour. In this study we aimed to describe the prevalence, topography and correlates of self-injury in individuals with ASD in contrast to individuals with Fragile X and Down syndromes and examine person characteristics associated with self-injury across and within these groups. Method Carers of individuals with ASD (n = 149; mean age = 9.98, SD = 4.86), Fragile X syndrome (n = 123; mean age = 15.32, SD = 8.74) and Down syndrome (n = 49; mean age = 15.84, SD = 12.59) completed questionnaires relating to the presence and topography of self-injury. Information was also gathered regarding demographic characteristics, affect, autistic behaviour, hyperactivity, impulsivity and repetitive behaviour. Results Self-injurious behaviour was displayed by 50% of the ASD sample: a significantly higher prevalence than in the Down syndrome group (18.4%) but broadly similar to the prevalence in Fragile X syndrome (54.5%). Self-injury was associated with significantly higher levels of autistic behaviour within the Down and Fragile X syndrome groups. Within the ASD group, the presence of self-injury was associated with significantly higher levels of impulsivity and hyperactivity, negative affect and significantly lower levels of ability and speech. Conclusions Self-injurious behaviour is prevalent in individuals with ASD and the presence of ASD phenomenology increases the risk of self-injury in individuals with known genetic disorders but without a diagnosis of idiopathic autism. Person characteristics associated with self-injury in ASD indicate a role for impaired behavioural inhibition, low levels of ability and negative affect in the development of self-injurious behaviour.

Purpose - Research into the communication skills of individuals with Cornelia de Lange syndrome (CdLS) is extremely limited. This paper aims to evaluate the nature of these skills and impairments in CdLS using a detailed informant assessment of pre-verbal communication skills. Design/methodology/approach - The study used the Pre-verbal Communication Schedule to evaluate communication skills in individuals with CdLS (n = 14), aged five to 14 years. The group was compared with a contrast group of individuals with Cri du Chat syndrome (CdCS; n = 14) who were matched for age and intellectual ability. Findings - A significant difference was identified in understanding non- vocal communication (p < 0.005), with the CdLS group showing a greater deficit. These findings indicate the presence of a syndrome-specific deficit in understanding non- verbal communication in individuals with CdLS and suggest that there may be a dissociation between the processing of verbal and non-verbal communication. Originality/value - The findings indicate that, in many ways, these two syndrome groups are not dissimilar in terms of their communication skills. However, individuals with CdLS show a syndrome-specific deficit in understanding non- vocal communication relative to the CdCS group.

Background: Existing literature suggests differences in face scanning in individuals with different socio-behavioural characteristics. Cornelia de Lange syndrome (CdLS) and Rubinstein-Taybi syndrome (RTS) are two genetically defined neurodevelopmental disorders with unique profiles of social behaviour. Methods: Here, we examine eye gaze to the eye and mouth regions of neutrally expressive faces, as well as the spontaneous visual preference for happy and disgusted facial expressions compared to neutral faces, in individuals with CdLS versus RTS. Results: Results indicate that the amount of time spent looking at the eye and mouth regions of faces was similar in 15 individuals with CdLS and 17 individuals with RTS. Both participant groups also showed a similar pattern of spontaneous visual preference for emotions. Conclusions: These results provide insight into two rare, genetically defined neurodevelopmental disorders that have been reported to exhibit contrasting socio-behavioural characteristics and suggest that differences in social behaviour may not be sufficient to predict attention to the eye region of faces. These results also suggest that differences in the social behaviours of these two groups may be cognitively mediated rather than subcortically mediated.

BACKGROUND: Recent research suggests that around 16% to 18% of children with Down syndrome (DS) also meet diagnostic criteria for autism spectrum disorder (ASD). However, there are indications that profiles of autism symptoms in this group may vary from those typically described in children with ASD. METHOD: Rates of autism symptoms and emotional and behavioural problems among children with DS who screened positive for ASD on the Social Communication Questionnaire (SCQ) (n = 183) were compared with a group of children with clinical diagnoses of ASD (n = 189) attending specialist schools in the UK. Groups were matched for age and approximate language level (use of phrase speech). RESULTS: Profiles of autistic symptoms in the two groups were generally similar, but children with DS meeting ASD cut-off on the SCQ tended to show fewer problems in reciprocal social interaction than those in the ASD group. They also showed slightly lower rates of emotional and peer-related problems. The results mostly confirm findings from a previous study in which the original validation sample for the SCQ was used as a comparison group. CONCLUSION: Findings suggest that children with DS who meet screening criteria for ASD show similar profiles of communication and repetitive behaviours to those typically described in autism. However, they tend to have relatively milder social difficulties. It is important that clinicians are aware of this difference if children with DS and ASD are to be correctly diagnosed and eligible for specialist intervention and education services.

Research on women with the fragile-X premutation (FX-p) has been underrepresented within the field of behavioural phenotypes. To understand whether the FX-p confers risk for autistic traits, depression and anxiety, independent of maternal status. In study 1, mothers of children with fragile-X syndrome (M-FXp; n = 51, mean age 43 years (s.d. = 5.80)) were compared with mothers of autistic children (M-ASD; n = 59, mean age 42 (s.d. = 5.80)), mothers of children with Smith-Magenis syndrome (M-SMS; n = 27, mean age 39 (s.d. = 7.20)) and mothers of typically developing children (M-TD; n = 44, mean age 40 (s.d. = 4.90)). In study 2, the M-FXp group were compared with non-mothers with the FX-p (NM-FXp; n = 17, mean age 32 (s.d. = 9.20)), typically developed non-mothers (NM-TD; n = 28, mean age 31 (s.d. = 6.80)) and the M-TD group. All participants completed an online survey, including measures of IQ, autistic traits, anxiety, depression and positive affect. In study 1: the M-FXp group reported more autistic traits than the M-TD group (P < 0.05, η2 = 0.046). Anxiety and parental stress were elevated in the M-FXp, M-SMS and M-ASD groups relative to the M-TD group (all P ≤ 0.003, η2 = 0.079-0.322). In study 2: a main effect of premutation status indicated that women with the FX-p report elevated autistic traits and anxiety (P ≤ 0.007, η2 = 0.055-0.060); this did not interact with maternal status. The findings indicate that women with the FX-p show an increased risk for autistic traits and anxiety. This risk is specific to the presence of the FX-p and is not fully accounted for by maternal status or the stress of caring for children with neurodevelopmental disorders.

Introduction: Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1A variants. Methods: We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour (SIB) are compared to those in individuals with CdLS caused by NIPBL variants. For Dutch participants with SMC1A variants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. Results: Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disability and more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. Conclusions: Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families.

A small number of recent papers have described individuals with intellectual disabilities and microdeletions in chromosome band 19p13.2. However, little is known about the behavioral characteristics of individuals with microdeletions in this area. The current study examines behavioral characteristics of a series of 10 participants ranging in age from 2 to 20 years with 19p13.2 microdeletions. Parents/caregivers completed a series of established behavioral measures which have aided the elucidation of the behavioral phenotypes of a number of genetic neurodevelopmental syndromes. All but the youngest two participants (aged 2 and 3 years) were verbal, ambulant, and classified as "partly able" or "able" with regard to self-help skills. Six of eight participants for whom a screening measure for autism spectrum disorders (ASD) could be deployed met criteria for an ASD. Six of the 10 participants had displayed self-injurious behavior in the month prior to assessment, eight had displayed destruction/disruption of property, and eight had shown physically aggressive behaviors. Repetitive behaviors were prevalent in the sample (with all participants displaying at least one repetitive behavior to a clinically relevant level), as were problems with sleep. Low mood was not prevalent in this group, and nor were overactivity or impulsivity. Full determination of a behavioral phenotype for this group would require a larger sample size, distinguishing between genetic subtypes. However, the current data suggest that ASD characteristics, repetitive, and challenging behaviors (such as aggression and self-injury) might be associated with 19p13.2 microdeletions, providing a basis for future investigation.

Few comparative studies have evaluated the heterogeneity of sociability across a range of neurodevelopmental disorders. The Sociability Questionnaire for People with Intellectual Disability (SQID) was completed by caregivers of individuals with Cornelia de Lange (n = 98), Angelman (n = 66), Fragile X (n = 142), Down (n = 117) and Rubinstein Taybi (n = 88) syndromes and autism spectrum disorder (ASD; n = 107). Between groups and age-band (18yrs) comparisons of SQID scores were conducted. Rates of behaviors indicative of selective mutism were also examined. Fragile X syndrome achieved the lowest SQID scores. Cornelia de Lange, ASD, and Fragile X groups scored significantly lower than Angelman, Down and Rubinstein Taybi groups. Selective mutism characteristics were highest in Cornelia de Lange (40%) followed by Fragile X (17.8%) and ASD (18.2%). Age-band differences were identified in Cornelia de Lange and Down syndrome.

Background Cornelia de Lange syndrsome (CdLS) is a rare genetic syndrome with notable impaired expressive communication characterised by reduced spoken language. We examined gesture use to refine the description of expressive communication impairments in CdLS. Methods During conversations, we compared gesture use in people with CdLS to peers with Down syndrome (DS) matched for receptive language and adaptive ability, and typically developing (TD) individuals of similar chronological age. Results As anticipated the DS and CdLS groups used fewer words during conversation than TD peers (P < .001). However, the CdLS group used twice the number of gestures per 100 words compared with the DS and TD groups (P = .003). Conclusions Individuals with CdLS have a significantly higher gesture rate than expected given their level of intellectual disability and chronological age. This result indicates the cause of reduced use of spoken language does not extend to all forms of expressive communication.

Children and adults with severe intellectual disability and complex needs often show behaviours and distress that carers and professionals find difficult to identify causes for, manage and decrease. The prevailing view is that these behaviours and distress are learned and consequently interventions focus on behavioural techniques. In this article we summarise the findings of research that indicate that behaviour and distress in this population are influenced by transient and stable characteristics or conditions that can interact with aspects of learning, be independent of learning, and interact with each other. These transient and stable characteristics or conditions are: pain and discomfort, sensory sensitivity, anxiety and low mood, sleep problems, atypical emotional regulation, specific cognitive difference, and differences in social behaviour. To aid carers and professionals, we present a checklist of the elements of an assessment process that covers these transient and stable characteristics or conditions and other relevant influences on behaviour and distress such as seizures, medication, learning and communication. We also draw attention to the benefit of identifying the cause of intellectual disability to inform the assessment process.

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. 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. 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. 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.

Previously, we have proposed that there are nine domains that warrant assessment when intervening to decrease challenging behavior and\or increase well-being in people with profound or severe intellectual disability and complex needs. These domains are: pain and discomfort, sensory sensitivity, anxiety and low mood, sleep, emotional dysregulation, cognitive difference, learned or functional behaviors, and expressive communication. In this article we: (1) identify specific challenging behaviors that might be influenced by these domains, (2) describe the relationship between these domains and the specified challenging behaviors, (3) identify assessments for each domain and (4) describe interactions between the domains. Our aim in this article is to provide practitioners with a framework for assessment and to stimulate debate about the domains that are demonstrably important when considering challenging behavior and well-being in people with profound or severe intellectual disability and complex needs.

Purpose of Review Elevated prevalence of autism characteristics is reported in genetic syndromes associated with intellectual disability. This review summarises recent evidence on the behavioural heterogeneity of autism in the following syndromes: Fragile X, Cornelia de Lange, Williams, Prader-Willi, Angelman, Down, Smith-Magenis, and tuberous sclerosis complex. Key considerations for assessment and support are discussed. Recent Findings The profile and developmental trajectory of autism-related behaviour in these syndromes indicate some degree of syndrome specificity which may interact with broader behavioural phenotypes (e.g. hypersociability), intellectual disability, and mental health (e.g. anxiety). Genetic subtype and co-occurring epilepsy within syndromes contribute to increased significance of autism characteristics. Autism-related strengths and challenges are likely to be overlooked or misunderstood using existing screening/diagnostic tools and criteria, which lack sensitivity and specificity within these populations. Summary Autism characteristics are highly heterogeneous across genetic syndromes and often distinguishable from non-syndromic autism. Autism diagnostic assessment practices in this population should be tailored to specific syndromes. Service provisions must begin to prioritise needs-led support.

Psychopathology is prevalent in Williams (WS), fragile X (FXS) and Prader-Willi (PWS) syndromes. However, little is known about the potential correlates of psychopathology in these groups. A questionnaire study was completed by 111 caregivers of individuals with WS (n = 35); FXS (n = 50) and PWS (n = 26). Mean age was 26 years (range 12-57 years); 74 (67%) were male. Multiple regression analyses indicated that higher rates of health problems and sensory impairments predicted higher psychopathology in WS (p

An atypical presentation of autism spectrum disorder is noted in Cornelia de Lange and Fragile X syndromes, but there are few detailed empirical descriptions. Participants in this study were individuals with Cornelia de Lange syndrome (n = 130, M age = 17.19), Fragile X syndrome (n 5 182, M age 5 16.94), and autism spectrum disorder (n = 142, M age = 15.19), who were comparable on chronological age. Using the Social Communication Questionnaire, the proportion meeting cutoff for autism spectrum disorder and autism was 78.6%, and 45.6%, respectively, in Cornelia de Lange syndrome and 83.6% and 48.6% in Fragile X syndrome. Domain and item analyses indicate differing, atypical autism spectrum disorder profiles in Fragile X and Cornelia de Lange syndromes. A limited association between adaptive behavior and autism spectrum disorder was identified in all groups. The findings have implications for intervention in genetic syndromes and conceptualization of autism spectrum disorder in the wider population.

Background: Extreme shyness and social anxiety is reported to be characteristic of adolescents and adults with Cornelia de Lange syndrome (CdLS); however, the nature of these characteristics is not well documented. In this study, we develop and apply an experimental assessment of social anxiety in a group of adolescents and adults with CdLS to determine the nature of the social difficulties and whether they are related to impairments in executive functioning. Methods: A familiar and unfamiliar examiner separately engaged in socially demanding tasks comprising three experimental conditions with a group of individuals with CdLS (n = 25; % male = 44; mean age = 22.16; SD = 8.81) and a comparable group of individuals with Down syndrome (DS; n = 20; % male = 35; mean age = 24.35; SD = 5.97). Behaviours indicative of social anxiety were coded. The Behavior Rating Inventory of Executive Function-Preschool version, an informant measure of executive function, was completed by participants' caregivers. Results: Significantly less verbalisation was observed in the CdLS group than the DS group in conditions requiring the initiation of speech. In the CdLS group, impairments in verbalisation were not associated with a greater degree of intellectual disability but were significantly correlated with impairments in both planning and working memory. This association was not evident in the DS group. Conclusions: Adolescents and adults with CdLS have a specific difficulty with the initiation of speech when social demands are placed upon them. This impairment in verbalisation may be underpinned by specific cognitive deficits, although further research is needed to investigate this fully.

Background Individuals with tuberous sclerosis complex (TSC) are at increased risk of developing self-injurious behaviour. The persistence of this deleterious behaviour over years is reported in aetiologically heterogeneous samples to be between 60% and 80% but is unknown for TSC. Method Results In this study, we determined the 3-year persistence of self-injury in a sample (n = 52) of children (with and without ID) and adults (with ID) with TSC and examined characteristics associated with persistence. Findings for self-injury were contrasted to those for aggression and property destruction to examine the specificity of results to this behaviour. Self-injury was persistent in 84.6% of those with TSC who showed this behaviour, in contrast to 66.7% both for aggression and destruction. Persistent self-injury was associated with poor self-help skills, greater overactivity/impulsivity and more behavioural indicators of pain. These latter two characteristics were also associated with persistent aggression. No characteristics were associated with persistence of property destruction. Conclusion These findings suggest that self-injurious behaviours in individuals with TSC, together with aggressive and destructive behaviours, are highly persistent and would benefit from targeted intervention. Poor adaptive skills, overactivity/impulsivity and painful health conditions may differentiate those at most risk for persistent self-injury or aggression.

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.

Background. Phenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of > 1500 individuals with rare genetic syndromes. Methods. Profiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n = 154, Cri du Chat n = 75, Cornelia de Lange n = 199, fragile X n = 297, Prader–Willi n = 278, Lowe n = 89, Smith–Magenis n = 54, Down n = 135, Sotos n = 40, Rubinstein–Taybi n = 102, 1p36 deletion n = 41, tuberous sclerosis complex n = 83 and Phelan–McDermid n = 35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n = 254). Self-help skills were included as an additional predictor. Results. Genetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader–Willi, Rubinstein–Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith–Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy. Limitations. The key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups. Conclusions. These findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID.

Background: There are few studies documenting the persistence of self-injury in individuals with autism spectrum disorder (ASD) and consequently limited data on behavioural and demographic characteristics associated with persistence. In this longitudinal study, we investigated self-injury in a cohort of individuals with ASD over 3 years to identify behavioural and demographic characteristics associated with persistence. Methods: Carers of 67 individuals with ASD (Median age of individuals with ASD in years = 13.5, Interquartile Range = 10.00-17.00), completed questionnaires relating to the presence and topography of self-injury at T-1 and three years later at T-2. Analyses were conducted to evaluate the persistence of self-injury and to evaluate the behavioural and demographic characteristics associated with persistence of self-injury. Results: At T-2 self-injurious behaviour had persisted in 77.8 % of individuals. Behavioural correlates of being non-verbal, having lower ability and higher levels of overactivity, impulsivity and repetitive behaviour, were associated with self-injury at both time points. Risk markers of impulsivity (p = 0.021) and deficits in social interaction (p = 0.026) at T-1 were associated with the persistence of self-injury over 3 years. Conclusions: Impulsivity and deficits in social interaction are associated with persistent self-injury in ASD and thus may act as behavioural risk markers. The identification of these risk markers evidences a role for behaviour dysregulation in the development and maintenance of self-injury. The findings have clinical implications for proactive intervention; these behavioural characteristics may be utilised to identify 'at risk' individuals for whom self-injury is likely to be persistent and therefore those individuals for whom early intervention may be most warranted.

We evaluated autism spectrum disorder (ASD) characteristics and social behavior in Angelman (AS; n = 19; mean age =10.35 years), Cornelia de Lange (CdLS; n = 15; mean age =12.40 years), and Cri du Chat (CdCS, also known as 5 p-syndrome; n = 19; mean age = 8.80 years) syndromes. The proportion of individuals meeting the ASD cutoff on the Social Communication Questionnaire was significantly higher in the AS and CdLS groups than in the CdCS group (p < .01). The groups demonstrated divergent social behavior profiles during social conditions in which adult availability, adult familiarity, and social demand were manipulated. Social enjoyment was significantly heightened in AS, whereas social approaches were heightened in individuals with CdCS. Social motivation, social communication, and enjoyment were significantly lower in CdLS. The findings highlight the importance of detailed observation when evaluating ASD and social behavior in genetic syndromes.

Background There are few well validated brief measures that can be used to assess the general progress of young children with autism spectrum disorders (ASD) over time. In the present study, the Autism Treatment Evaluation Checklist (ATEC) was used as part of a comprehensive assessment battery to monitor the progress of 22 school-aged children with ASD who had previously taken part in intensive home- or school-based intervention programmes in their pre-school years. Methods Parents completed the ATEC when the children were on average 5.5 years and then again 5-6 years later (mean age 10.4 years). Standardised measures were also used to assess cognitive, language and adaptive behaviour skills and severity of autism symptoms over the same period. Results The ATEC had high internal consistency at both time points. ATEC total and sub-scale scores remained relatively stable over time and were highly and significantly correlated with cognitive, language and adaptive behaviour skills and severity of autism symptoms at both assessment points. Initial ATEC total scores predicted 64% of the variance in scores at the subsequent follow-up. However, there was also considerable variation in the patterns of scores shown by individual children over time. Conclusions This study provides some preliminary evidence of the ATEC's potential value for monitoring progress of children with ASD over time. Its advantages and limitations are discussed in the context of the need systematically to monitor the progress of children with ASD over time or in response to intervention.

Recent research shows that a significant minority of children with Down's syndrome (DS) also meet diagnostic criteria for an autism spectrum disorder (ASD). The present study investigated what proportion of children aged 6-15 years with a confirmed diagnosis of DS in England and Wales display autistic-type behaviours, and explored the characteristics of this group of children. The Social Communication Questionnaire (SCQ) was used to screen for autism characteristics and the Strengths and Difficulties Questionnaire (SDQ) to explore behavioural difficulties. The proportion of children who met the cut-off score for ASD on the SCQ (total score >= 15) was 37.7% (95% CI: 33.4-42.0%); for autism (total score >= 22) the proportion was 16.5% (95% CI: 13.2-19.8%). Children who met the cut-off for ASD were significantly more likely to be reported as having emotional symptoms, conduct problems and hyperactivity on the SDQ than children who scored well below cut-off (total score < 10). However, the profile of their autism characteristics on the SCQ was atypical compared with individuals with idiopathic ASD. The pervasiveness of ASD in children with DS in England and Wales is substantially higher than in the general population. These children also experience significantly greater behavioural problems than children with DS only. Early detection of autism characteristics is important for appropriate intervention. However, the unusual profile of autism characteristics in this group may affect the recognition of the disorder and hinder the implementation of appropriate interventions. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc.

Background: The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in Cornelia de Lange syndrome (CdLS). However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. In this study we examine the ASD profile in CdLS in comparison to a matched group of individuals with ASD. Method: The Autism Diagnostic Observation Schedule (ADOS) was administered to 20 individuals with CdLS (mean age = 11.34; range = 613 years) and 20 individuals with idiopathic ASD (mean age = 10.42; range = 811 years). Participants were matched according to adaptive behaviour and receptive language skills. Results: Sixty-five percent (N = 13) of individuals with CdLS met the cut-off score for autism on the total ADOS score. Further analysis at domain and item level indicated that individuals with CdLS showed significantly less repetitive behaviour, (specifically sensory interests); more eye contact, more gestures and less stereotyped speech than the ASD group. The CdLS group also showed higher levels of anxiety. Conclusions: The comparison between CdLS and idiopathic ASD indicates subtle group differences in the profile of ASD symptomatology that are not accounted for by degree of intellectual disability or receptive language skills. These differences may not be evident when relying solely upon clinical and domain level scores, but may be distinguishing features of the ASD presentations in the two disorders. The findings have implications for the conceptualisation and assessment of ASD in individuals with genetic syndromes.

There are few long-term follow-up studies of children with Autism Spectrum Disorders (ASD) who attended intensive intervention programmes in their pre-school years. Thirty-six children with ASD enrolled in relatively intensive, specialist pre-school programmes (minimum of 15 h intervention per week for 2 years at a mean age of 3.4 years) were assessed after 2 years (mean age 5.5 years) and again after a further 5 years (mean age 10.3 years). Cognitive, language and adaptive behaviour skills and severity of autism symptoms were assessed at intake (Time 1) and subsequent follow-ups (Times 2 and 3). Children made significant increases in raw and age equivalent scores in most areas of development assessed, although mean standard scores remained stable or decreased over time. Time 1 IQ language and adaptive behaviour skills were predictive of outcome at Time 3. Although there were marked individual differences in the rate and patterns of change over time, many children continued to show increases in test scores over the course of the study. This study highlights that whilst overall group improvements may be evident, the rate and nature of these improvements is highly variable across individual children. Further investigation of the specific child characteristics that affect treatment effectiveness is required. (C) 2010 Elsevier Ltd. All rights reserved.

This study examined the stability of scores on the ADI-R from pre-school to elementary school age in children with autism spectrum disorders (ASD). Participants were 35 children who, at T1, all had a clinical diagnosis of ASD. On initial assessment (mean age 3.5 years; SD 0.6 years), all met ADI-R algorithm criteria for autism. ADI-R assessments were repeated at follow up (FU; mean age 10.5 years; SD 0.8 years). Changes in ADI-R total, domain and ADI-R algorithm item scores were assessed. Twenty-eight children continued to score above the ADI-R cut-off for autism at FU, although significant decreases in ADI-R domain and item scores were also found. In conclusion while classification of children according to ADI-R criteria generally remained stable between pre-school and elementary school age, many children demonstrated significant improvements in symptom severity.

Cornelia de Lange Syndrome (CdLS) is due to mutations in the genes for the structural and regulatory proteins that make up the cohesin complex, and is considered a cohesinopathy disorder or, more recently, a transcriptomopathy. New phenotypes have been recognized in this expanding field. There are multiple clinical issues facing individuals with all forms of CdLS, particularly in the neurodevelopmental system, but also gastrointestinal, cardiac, and musculoskeletal. Aspects of developmental and cell biology have found common endpoints in the biology of the cohesin complex, with improved understanding of the mechanisms, easier diagnostic tests, and the possibility of potential therapeutics, all major clinical implications for the individual with CdLS. The following abstracts are the presentations from the 7th Cornelia de Lange Syndrome Scientific and Educational Symposium, June 22-23, 2016, in Orlando, FL, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting. In addition to the scientific and clinical discussions, there were talks related to practical aspects of behavior including autism, transitions, communication, access to medical care, and databases. At the end of the symposium, a panel was held, which included several parents, affected individuals and genetic counselors, and discussed the greatest challenges in life and how this information can assist in guiding future research. The Research Committee of the CdLS Foundation organizes this meeting, reviews, and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board and publications. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD.

Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein-Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals reaching cut-off for autism spectrum disorder (N = 228). Total and matched group analyses were conducted. A phenotypic profile of repetitive behavior was found in RTS. The majority of behaviors in RTS were not associated with social-communication deficits or degree of disability. Repetitive behavior should be studied at a fine-grained level. A dissociation of the triad of impairments might be evident in RTS.

Background An emerging literature on behavioural phenotypes has highlighted apparent associations between autism spectrum disorders (ASDs) or ASD-related phenomenology and a number of different genetically determined syndromes. Method A systematic review of the current literature regarding the association with ASD and ASD characteristics was conducted in the following syndrome groups: Fragile X, Rett, Tuberous Sclerosis Complex, Down, Angelman, CHARGE and Phenylketonuria. Specific consideration was given to the role of intellectual disability in assessing the association between ASD and these syndrome groups. Results The review highlights that while formal diagnostic assessments may indicate an association between ASD and specific syndrome groups, detailed investigation has revealed subtle but qualitative differences in the presentation of ASD-like phenomenology in particular syndrome groups. The degree of ID of the individual clearly has a role to play with regard to the development and presentation of ASD-like characteristics, and caution should be taken when assessing ASD symptomatology in genetically determined syndromes associated with severe ID. However, degree of ID cannot solely account for the heightened prevalence of ASD characteristics in some specific syndrome groups. Conclusions There is a need for caution in interpreting the significance of superficial similarities between ASD and the behavioural phenotypes of certain genetically determined syndromes. However, recognition of ASD-like characteristics (even where a true diagnosis of ASD may not be relevant) in individuals with genetic syndromes is crucial in ensuring that individuals receive appropriate behavioural management and educational placement. Further research in this field requires fine-grained investigation of behavioural phenomenology within individual syndrome groups.

Background: Research reporting prevalence rates of self-injurious and aggressive behaviour in people with tuberous sclerosis complex (TSC) is limited. No studies have compared rates of these behaviours in TSC with those in other syndrome groups matched for degree of disability or investigated risk markers for these behaviours in TSC. Methods: Data from the Challenging Behaviour Questionnaire were collected for 37 children, aged 4 to 15 years, with TSC. Odds ratios were used to compare rates of self-injury and aggression in children with TSC with children with idiopathic autism spectrum disorder (ASD), fragile X, Cornelia de Lange and Down syndromes. Characteristics were measured using the Mood Interest and Pleasure Questionnaire, the Activity Questionnaire, the Social Communication Questionnaire, the Repetitive Behaviour Questionnaire, the Wessex Behaviour Schedule and the revised Non-communicating Children Pain Checklist. Mann-Whitney U analyses were used to compare characteristics between individuals with self-injury and aggression and those not showing these behaviours. Results: Rates of self-injury and aggression in TSC were 27% and 50%, respectively. These are high but not significantly different from rates in children with Down syndrome or other syndrome groups. Both self-injury and aggression were associated with stereotyped and pain-related behaviours, low mood, hyperactivity, impulsivity and repetitive use of language. Children who engaged in self-injury also had lower levels of interest and pleasure and showed a greater degree of `insistence on sameness' than children who did not self-injure. Aggression was associated with repetitive behaviour. The majority of these associations remained significant when the association with level of adaptive functioning was controlled for. Conclusions: Behavioural profiles can be used to identify those most at risk of developing self-injury and aggression. Further research is warranted to understand the influence of such internal factors as mood, ASD symptomatology and pain on challenging behaviour in people with intellectual disability.

Background There is a need for assessments of psychological difference and disorder in people who have more severe intellectual disability (ID). Hyperactivity and impulsivity are two behavioural domains of importance as they are correlated with self-injury and aggression and this alludes to a shared cognitive correlate of compromised behavioural inhibition. Additionally, compromised behavioural inhibition is demonstrably related to repetitive behaviour and the latter might be expected to be associated with impulsivity and hyperactivity. Methods The Activity Questionnaire (TAQ) was developed for this study. Three sub-scales with high levels of face validity were supported by factor analysis of the scoring of 755 intellectually disabled participants on the TAQ items. These sub-scales mapped onto the constructs of Overactivity, Impulsivity and Impulsive Speech. Test-retest, inter-rater reliability and internal consistency were robust. TAQ scores and scores on the Repetitive Behaviour Questionnaire (RBQ) were collected for a sample of 136 participants with varying degrees of ID. Results Scores on the TAQ at sub-scale and full-scale level were not related to level of adaptive functioning. There were significant positive associations between overactivity (TAQ) and stereotyped behaviour (RBQ), impulsivity (TAQ) and restricted preferences (RBQ), and impulsive speech (TAQ) and repetitive speech (RBQ). Conclusions The TAQ is a reliable assessment of hyperactivity and impulsivity for people with ID with robust factor structure. Validity requires evaluation. The relationship between impulsivity and restricted preferences may result from a common cognitive impairment in inhibition, which may underpin these two classes of behaviour.

In this study we assessed the behavioral presentation of social anxiety in Cornelia de Lange syndrome (CdLS) using a contrast group of Cri du Chat syndrome (CdCS). Behaviors indicative of social anxiety were recorded in twelve children with CdLS (mean age = 11.00; SD = 5.15) and twelve children with CdCS (8.20; SD = 2.86) during social interaction. Lag sequential analysis revealed that participants with CdLS were significantly more likely to evidence behavior indicative of anxiety in close temporal proximity to the point at which they maintained eye contact or spoke. Individuals with CdLS demonstrate a heightened probability of anxiety related behavior during social interaction but only at the point at which social demand is high.

In this study we describe the levels of clinically significant behavior in participants with Sotos syndrome relative to three matched contrast groups in which the behavioral phenotype is well documented (Autism Spectrum Disorder, ASD; Prader-Willi, and Down syndromes). Parents and carers of 38 individuals with Sotos syndrome (mean age = 17.3; SD = 9.36), completed questionnaires regarding self-injury, aggression, repetitive behavior, autism spectrum phenomenology, overactivity, impulsivity and mood, interest and pleasure. Individuals with Sotos syndrome showed an increased risk of self-injurious behavior, physical aggression, and destruction of property relative to the Down syndrome group but not a greater risk of stereotyped behavior. Impulsivity and levels of activity were also significantly higher relative to those with Down syndrome and comparable to those with ASD. A large proportion of participants met the cut off score for ASD (70.3%) and Autism (32.4%) on the Social Communication Questionnaire. Social impairments were particularly prominent with repetitive behavior and communication impairments less characteristic of the syndrome. Interestingly, preference for routine and repetitive language were heightened in individuals with Sotos syndrome and the repetitive behavior profile was strikingly similar to that observed in individuals with Prader-Willi syndrome. These findings build upon previous research and provide further evidence of the behavioral phenotype associated with Sotos syndrome.

Objectives This study examined parental perceptions of behaviours that challenge (CB) in their adult children with intellectual disability (ID), and explored whether perceptions mediated associations between CB and parental psychological distress. Design A within‐group correlational design was employed. Methods Sixty‐five parents reported on individuals with genetic syndromes and ID who had chronic CB. Parents completed the Illness Perception Questionnaire‐Revised (IPQ‐R) adapted to measure perceptions of self‐injury, aggression or property destruction, alongside assessments of parental locus of control, attributions about behaviour, parental psychological distress, and CB. Results A high proportion of parents evidenced anxiety and depression at clinically significant levels (56.9% and 30.8%, respectively). Contrary to predictions, psychological distress was not significantly associated with CB. The perception that the adult with ID exerted control over the parent's life mediated the association between CB and parental psychological distress. Few parents endorsed operant reinforcement as a cause of CB (

The limited behavioural phenotype literature on Phelan-McDermid syndrome (PMS) indicates atypically high levels of activity, impulsivity and autism spectrum disorder (ASD) behaviours. Divergent profiles of ASD in PMS are also reported, with some studies demonstrating similarities to idiopathic ASD and others indicating an uneven profile of social and communication impairments and repetitive behaviours. An evaluation of the behavioural phenotype of PMS and the prevalence and phenomenology of ASD is warranted, particularly given the causal involvement of the SHANK3 gene in the aetiology of PMS. Carers of individuals with PMS (N = 30; mean age = 10.55, SD = 7.08) completed questionnaires relating to impulsivity, overactivity, mood, interest and pleasure, repetitive behaviour and ASD phenomenology. These data were compared to data from matched samples of individuals with fragile X and Down syndromes and idiopathic ASD. In order to evaluate the profile of ASD phenomenology in PMS, two comparisons were made: first, including the total sample with PMS, and second, including only those who met the threshold indicative of autism on an ASD screening measure. The results revealed lower mood in individuals with PMS, but no differences in impulsivity and overactivity. Compulsive and routine-driven repetitive behaviours were less common in the total sample with PMS; however, motor-based stereotyped behaviours were more common. ASD phenomenology was highly prevalent, with 87% of the sample meeting the cutoff score for ASD and 57% meeting the cutoff for autism. The profile of ASD phenomenology in the total sample with PMS differed from those with idiopathic ASD across impairments in communication and social interaction and repetitive behaviour. However, the profile of those who met the threshold for autism was commensurate to those with idiopathic ASD. ASD phenomenology is common within PMS. Whilst the total sample may display an atypical profile of ASD behaviour, the profile in those who met the threshold for autism was very similar to those with idiopathic ASD. These results are discussed in relation to the wider behavioural phenotype and the emerging evidence of an autism endophenotype in PMS.

Fragile X syndrome (FXS) and autism spectrum disorders (ASD) are characterized by impaired social functioning. We examined the spontaneous discrimination of happy and disgusted facial expressions, from neutral faces, in individuals with FXS (n = 13, M-age = 19.70) and ASD (n 5 15, M-age 5 11.00) matched on adaptive behavior and verbal abilities measured by the Vineland Adaptive Behavior Scale. Eye gaze to the eyes and mouth of neutral faces was also measured. Results suggest individuals with FXS and ASD distinguish facial expressions spontaneously in the same way. Individuals with FXS looked significantly less at the eye region of neutral faces than individuals with ASD. These results provide insight into similarities and differences in face processing in two neurodevelopmental disorders noted for their similarities in social behavior.

Background: Individuals with Cornelia de Lange syndrome (CdLS) have been reported to show comparatively high levels of flat and negative affect but there have been no empirical evaluations. In this study, we use an objective measure of facial expression to compare affect in CdLS with that seen in Cri du Chat syndrome (CDC) and a group of individuals with a mixed aetiology of intellectual disabilities (ID). Method: Observations of three groups of 14 children with CdLS, CDC and mixed aetiology of ID were undertaken when a one-to-one interaction was ongoing. Results: There was no significant difference between the groups in the duration of positive, negative or flat affect. However, the CdLS group displayed a significantly lower ratio of positive to negative affect than children in the other groups. Discussion: This difference partially confirms anecdotal observations and could be due to the expression of pain caused by health problems associated with CdLS or neurological expression of the CdLS gene in facial muscles related to expression of positive affect. However, further research is needed to directly test these possible associations.

We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD symptomatology was heightened in CdLS and FXS. High levels of impulsivity were seen in SMS, AS, CdCS, FXS and adults with CdLS. Negative affect was prominent in adults with CdLS, while positive affect was prominent in adults with AS and FXS. Heightened levels of overactivity and impulsivity were identified in FXS, AS and SMS while low levels were identified in PWS. These findings confirm and extend previously reported behavioral phenotypes.

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.