BACKGROUND: Individuals with intellectual disability, including people with Down syndrome (DS), often exhibit restricted and repetitive behaviours (RRBs). However, RRBs have not been deeply characterised in children and adolescents with DS.
METHODS: The study encompassed a cohort of 151 participants aged 4 to 18 years with DS. RRBs were assessed utilising the Repetitive Behaviour Scale-Revised. Additionally, data pertaining to cognitive and adaptive functioning, linguistic abilities, sleep patterns and emotional/behavioural issues were gathered.
RESULTS: Self-injurious behaviours were reported less frequently whereas parents most commonly endorsed items related to behaviours associated with the need for sameness and ritualistic behaviours. We observed very few gender differences, whereas some age-related differences emerged, with adolescents exhibiting higher scores in items related with higher-level RRBs. The analysis of the association between RRBs and clinical features revealed that RRBs were associated with parent-reported sleep difficulties, as well as with internalising and externalising problems. We also observed a negative correlation with IQ whereas associations with adaptive skills emerged mainly for lower-level RRBs, such as motor stereotypies. Finally, RRBs were negatively associated with linguistic abilities, both expressive and receptive.
CONCLUSIONS: RRBs in children and adolescents with DS are of significant clinical interest due to their associations with various clinical dimensions. Therefore, psychological and neuropsychiatric assessment should include an accurate evaluation of RRBs for young people with DS.

BACKGROUND: SYNGAP1- related intellectual disability (SYNGAP1-ID) is a rare genetic disorder presenting with intellectual disability (ID), epilepsy, maladaptive behaviours and communication challenges. To date, few studies have assessed the context in which these maladaptive behaviours occur. This study aims to investigate the prevalence of problem behaviours, characterise the behavioural phenotype and use well-validated measures to explore variables that maintain the behaviours.
METHODS: Our sample includes 19 individuals diagnosed with SYNGAP1-ID and their parents. Parents provided information on behaviours that their children engage in, as well as their general behavioural dispositions. Well-validated measures (e.g., the Repetitive Behaviour Scale-Revised, Sensory Profile-2 and Vineland Adaptive Behaviour Scale) were used. A subset of individuals underwent further direct experimental assessment of their problem behaviour to identify the variables maintaining those problem behaviours. Parental reports were analysed using nonparametric statistical analysis; the direct assessments of individuals\' problem behaviour were analysed using visual analysis and validated supplemental measures.
RESULTS: All 19 individuals engaged in some form of maladaptive problem behaviour. Ratings of ritualistic, sameness and restricted behaviours measured by the RBS-R were commensurate with individuals diagnosed with idiopathic autism spectrum disorder (ASD) while self-injurious behaviours were endorsed at a higher level in SYNGAP1-ID when compared with idiopathic ASD. The problem behaviours in our cohort of patients with SYNGAP1-ID were maintained by automatic reinforcement and social attention and are positively correlated with atypical sensory responses.
CONCLUSIONS: Individuals with SYNGAP1-ID engage in problem behaviours commensurate with other populations (e.g., those with ASD), they exhibit atypical response to sensory stimuli. Problem behaviours were frequently maintained by automatic reinforcement, which may result from a dysregulated sensory system. Children with SYNGAP1-ID may benefit from strategies used in persons with ASD.

Epidemiological evidence has shown that maternal infection is a notable risk factor for developmental psychiatric disorders. Animal models have corroborated this link and demonstrated that maternal immune activation (MIA) induces long-term behavioural deficits and neuroimmunological responses to subsequent immune stress in offspring. However, it is unclear whether MIA offspring are more sensitive or more tolerant to immunological challenges from postnatal infections. Pregnant mice were weighed and injected with a single dose of polyinosinic-polycytidylic acid (poly I:C) or saline at gestational day 9.5, and their male offspring were exposed to poly I:C or saline again during adolescence, adulthood, and middle life. After a two-week recovery from the last exposure to poly I:C, the mice underwent behavioural and neuroendophenotypic evaluations. Finally, the mice were sacrificed, and the expression levels of inflammatory factors and the activation levels of glial cells in the cerebral cortex and hippocampus were evaluated. We found MIA mice have lifelong behavioural deficits and glial activation abnormalities. Postpartum infection exposure at different ages has different consequences. Adolescent and middle life exposure prevents sensorimotor gating deficiency, but adult exposure leads to increased sensitivity to MK-801. Moreover, MIA imposed a lasting impact on the neuroimmune profile, resulting in an enhanced cytokine-associated response and diminished microglial reactivity to postnatal infection. Our results reveal an intricate interplay between prenatal and postpartum infection in neuropsychiatric phenotypes, which identify potential windows where preventive or mitigating measures could be applied.

BACKGROUND: Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2).
METHODS: De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N = 2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N = 1098 (48%)] were identified to create longitudinal data for N = 204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention.
RESULTS: In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer\'s disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention.
CONCLUSIONS: Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

BACKGROUND: The characterisation of autism in fragile X syndrome (FXS) has been a source of controversy due to the complexity of disentangling autism traits from common features of the FXS phenotype. Autism in FXS is significantly underdiagnosed in the community, which may be partly due to insufficient clinical description of the social interaction profile of autism within the FXS phenotype. In this study, we applied a classic framework for characterising social interaction styles in autism to a sample of young adult males with FXS and co-occurring autism to enhance understanding of how the social challenges associated with autism manifest within FXS.
METHODS: Participants were 41 males (M age = 18 years) with FXS and co-occurring autism. Interaction samples were coded for expression of predominately \'active\' (characterised by a desire to make social approaches) or \'passive\' (characterised by lack of initiation of social approach towards others) interaction profiles. Differences in the expression of phenotypic features of FXS, including anxiety, attention-deficit/hyperactivity disorder, cognitive, adaptive and language impairments and autism symptom severity, were examined across those with passive and active interaction styles.
RESULTS: Approximately half of the sample was classified as active and half as passive, demonstrating diversity in the social phenotype of autism associated with FXS. The two subtypes did not differ in autism severity, anxiety or attention-deficit/hyperactivity disorder symptoms or in cognitive, adaptive or language abilities.
CONCLUSIONS: This study enhances understanding of FXS-associated autism by documenting phenotypic variability in the social interaction profile in this group, with active and passive social interaction styles represented. The two social interaction styles were not associated with differential expression of common phenotypic features of FXS, suggesting similar support needs.

BACKGROUND: SOX11 syndrome is a rare condition caused by deletions or de novo point mutations of the SOX11 gene. SOX11 is a transcription factor gene that plays an important role in brain development.
OBJECTIVE: The aim of this study was to quantitatively evaluate the behavioural profiles of individuals with SOX11 syndrome.
METHODS: The Vineland Adaptive Behaviour Scales 3 (VABS-3) and the Social Responsiveness Scale 2 (SRS-2) were completed by parents of 21 children and young adults with SOX11 syndrome.
RESULTS: Most were found to have borderline (33 %) or mild (39 %) impairment in adaptive behaviour, with more difficulties in communication and daily living than socialisation in the cohort overall. Most (90 %) were found to exhibit clinically relevant levels of autistic traits, with 62 % scoring in the \"severe\" range, though social motivation was observed to be a relative strength in the cohort overall.
CONCLUSIONS: This study presents the first standardised evaluation of adaptive behaviour and autistic traits of individuals with SOX11 syndrome. This will improve clinicians, educators and parents\' understanding of SOX11 syndrome.

3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric phenotypes. Mild to moderate intellectual disability (ID) is common in this population, and previous work by our team identified substantial deficits in adaptive behaviour. However, the full profile of adaptive function in 3q29del has not been described nor has it been compared with other genomic syndromes associated with elevated risk for neurodevelopmental and neuropsychiatric phenotypes.
Individuals with 3q29del (n = 32, 62.5% male) were evaluated using the Vineland Adaptive Behaviour Scales, Third Edition, Comprehensive Parent/Caregiver Form (Vineland-3). We explored the relationship between adaptive behaviour and cognitive function, executive function, and neurodevelopmental and neuropsychiatric comorbidities in our 3q29del study sample, and we compared subjects with 3q29del with published data on fragile X syndrome, 22q11.2 deletion syndrome and 16p11.2 deletion and duplication syndromes.
Individuals with 3q29del had global deficits in adaptive behaviour that were not driven by specific weaknesses in any given domain. Individual neurodevelopmental and neuropsychiatric diagnoses had a small effect on adaptive behaviour, and the cumulative number of comorbid diagnoses was significantly negatively associated with Vineland-3 performance. Both cognitive ability and executive function were significantly associated with adaptive behaviour, and executive function was a better predictor of Vineland-3 performance than cognitive ability. Finally, the severity of adaptive behaviour deficits in 3q29del was distinct from previously published data on comparable genomic disorders.
Individuals with 3q29del have significant deficits in adaptive behaviour, affecting all domains assessed by the Vineland-3. Executive function is a better predictor of adaptive behaviour than cognitive ability in this population and suggests that interventions targeting executive function may be an effective therapeutic strategy.

Different instruments were devised for assessing emotional development (ED) level in persons with an intellectual disability (ID), that is, the Scale of Emotional Development - Short (SED-S), the Scheme for Appraisal of Emotional Development (SAED), the Scale for Emotional Development - Second Revision (SED-R2 ) and the Schaal voor Emotionele Ontwikkeling - Lukas (SEO-Lukas). The aim of this study was to compare the level of emotional functioning as assessed with the SED-S with the SAED, SED-R2 and SEO-Lukas.
Emotional development was measured in adults with ID with the SED-S (N = 186) and the SAED (n = 85), the SED-R2 (n = 50) and the SEO-Lukas (n = 51). Correlation analysis and Cohen\'s kappas were calculated between the SED-S and the three respective scales. Internal consistencies (Cronbach\'s alpha) of the four scales were determined.
The SED-S results correlated most with the SEO-Lukas (γ = 1; кω = 0.936) followed by the SAED (γ = 0.809; кω = 0.343) and least by the SED-R2 (γ = 0.665; кω = 0.182). The stage of ED assessed with the SED-S was lower than the ED results measured with the SAED, but higher than with the SED-R2 and most similar to the SEO-Lukas. Cronbach\'s alphas were high, ranging from 0.853 to 0.975.
Given the respective differences between the scales, the SED-S may equalise the results as compared with previous versions.

Genomic conditions can be associated with developmental delay, intellectual disability, autism spectrum disorder, and physical and mental health symptoms. They are individually rare and highly variable in presentation, which limits the use of standard clinical guidelines for diagnosis and treatment. A simple screening tool to identify young people with genomic conditions associated with neurodevelopmental disorders (ND-GCs) who could benefit from further support would be of considerable value. We used machine learning approaches to address this question.
A total of 493 individuals were included: 389 with a ND-GC, mean age = 9.01, 66% male) and 104 siblings without known genomic conditions (controls, mean age = 10.23, 53% male). Primary carers completed assessments of behavioural, neurodevelopmental and psychiatric symptoms and physical health and development. Machine learning techniques (penalised logistic regression, random forests, support vector machines and artificial neural networks) were used to develop classifiers of ND-GC status and identified limited sets of variables that gave the best classification performance. Exploratory graph analysis was used to understand associations within the final variable set.
All machine learning methods identified variable sets giving high classification accuracy (AUROC between 0.883 and 0.915). We identified a subset of 30 variables best discriminating between individuals with ND-GCs and controls which formed 5 dimensions: conduct, separation anxiety, situational anxiety, communication and motor development.
This study used cross-sectional data from a cohort study which was imbalanced with respect to ND-GC status. Our model requires validation in independent datasets and with longitudinal follow-up data for validation before clinical application.
In this study, we developed models that identified a compact set of psychiatric and physical health measures that differentiate individuals with a ND-GC from controls and highlight higher-order structure within these measures. This work is a step towards developing a screening instrument to identify young people with ND-GCs who might benefit from further specialist assessment.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.