Exploring an objective measure of overactivity in children with rare genetic syndromes.

BACKGROUND: Overactivity is prevalent in several rare genetic neurodevelopmental syndromes, including Smith-Magenis syndrome, Angelman syndrome, and tuberous sclerosis complex, although has been predominantly assessed using questionnaire techniques. Threats to the precision and validity of questionnaire data may undermine existing insights into this behaviour. Previous research indicates objective measures, namely actigraphy, can effectively differentiate non-overactive children from those with attention-deficit hyperactivity disorder. This study is the first to examine the sensitivity of actigraphy to overactivity across rare genetic syndromes associated with intellectual disability, through comparisons with typically-developing peers and questionnaire overactivity estimates. METHODS: A secondary analysis of actigraphy data and overactivity estimates from The Activity Questionnaire (TAQ) was conducted for children aged 4-15 years with Smith-Magenis syndrome (N=20), Angelman syndrome (N=26), tuberous sclerosis complex (N=16), and typically-developing children (N=61). Actigraphy data were summarized using the M10 non-parametric circadian rhythm variable, and 24-hour activity profiles were modelled via functional linear modelling. Associations between actigraphy data and TAQ overactivity estimates were explored. Differences in actigraphy-defined activity were also examined between syndrome and typically-developing groups, and between children with high and low TAQ overactivity scores within syndromes. RESULTS: M10 and TAQ overactivity scores were strongly positively correlated for children with Angelman syndrome and Smith-Magenis syndrome. M10 did not substantially differ between the syndrome and typically-developing groups. Higher early morning activity and lower evening activity was observed across all syndrome groups relative to typically-developing peers. High and low TAQ group comparisons revealed syndrome-specific profiles of overactivity, persisting throughout the day in Angelman syndrome, occurring during the early morning and early afternoon in Smith-Magenis syndrome, and manifesting briefly in the evening in tuberous sclerosis complex. DISCUSSION: These findings provide some support for the sensitivity of actigraphy to overactivity in children with rare genetic syndromes, and offer syndrome-specific temporal descriptions of overactivity. The findings advance existing descriptions of overactivity, provided by questionnaire techniques, in children with rare genetic syndromes and have implications for the measurement of overactivity. Future studies should examine the impact of syndrome-related characteristics on actigraphy-defined activity and overactivity estimates from actigraphy and questionnaire techniques.

International consensus recommendations for the identification and treatment of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND).

BACKGROUND: Tuberous sclerosis complex (TSC) is associated with a wide range of physical manifestations for which international clinical recommendations for diagnosis and management have been established. TSC is, however, also associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND) that are typically under-identified and under-treated yet associated with a profound burden of disease. The contemporary evidence base for the identification and treatment of TAND is much more limited and, to date, consensus recommendations for the diagnosis and management of TAND have also been limited and non-specific. METHODS: The TANDem project was launched with an international, interdisciplinary, and participatory consortium of 24 individuals, including TSC family representatives, from all World Health Organization (WHO) regions but one. One of the aims of the TANDem project was to generate consensus recommendations for the identification and treatment of TAND. At the time of this project, no internationally adopted standard methodology and methodological checklists existed for the generation of clinical practice recommendations. We therefore developed our own systematic procedure for evidence review and consensus-building to generate evidence-informed consensus recommendations of relevance to the global TSC community. RESULTS: At the heart of the consensus recommendations are ten core principles surrounded by cluster-specific recommendations for each of the seven natural TAND clusters identified in the literature (autism-like, dysregulated behavior, eat/sleep, mood/anxiety, neuropsychological, overactive/impulsive, and scholastic) and a set of wraparound psychosocial cluster recommendations. The overarching recommendation is to "screen" for TAND at least annually, to "act" using appropriate next steps for evaluation and treatment, and to "repeat" the process to ensure early identification and early intervention with the most appropriate biological, psychological, and social evidence-informed approaches to support individuals with TSC and their families. CONCLUSIONS: The consensus recommendations should provide a systematic framework to approach the identification and treatment of TAND for health, educational, social care teams and families who live with TSC. To ensure global dissemination and implementation of these recommendations, partnerships with the international TSC community will be important. One of these steps will include the generation of a "TAND toolkit" of "what to seek" and "what to do" when difficulties are identified in TAND clusters.

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

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

Development and Feasibility of the Self-Report Quantified Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders Checklist (TAND-SQ).

BACKGROUND: Tuberous sclerosis complex-associated neuropsychiatric disorders (TAND) are often present but underidentified and undertreated in individuals with tuberous sclerosis complex (TSC). The clinician-completed TAND-Lifetime Checklist (TAND-L) was developed to address this identification and treatment gap. Stakeholder engagement identified the need for a TAND Checklist that can (1) be completed by caregivers or individuals with TSC and (2) quantify TAND difficulties. The aim of this study was to develop a self-report quantified TAND Checklist (TAND-SQ) and conduct feasibility and acceptability testing. METHODS: This aim was addressed in three phases: (1) development of the TAND-SQ Checklist, (2) feasibility and acceptability testing of the "near-final" TAND-SQ Checklist, and (3) preparation of the final TAND-SQ Checklist. Participants included 23 technical experts from the TAND consortium in all phases and 58 lived experts (caregivers and individuals with TSC) in phase 2. All participants completed a TAND-SQ Checklist and a checklist feedback form. RESULTS: Phase 1 additions to the TAND-SQ, when compared with the TAND-L, included four new items and a quantification rating. Phase 2 showed high ratings for the "near-final" TAND-SQ Checklist on comprehensiveness, clarity, ease of use, and overall acceptability. In phase 3, questions on strengths, strategies, and a TAND Cluster Profile were added. CONCLUSION: The TAND-SQ Checklist is presented here for use by individuals with TSC and their caregivers. The next steps as part of the TANDem project include internal and external validation of the checklist and linking of TAND Cluster Profiles generated from the checklist to evidence-informed consensus recommendations within a smartphone application.

Concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions: A systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis is to delineate the concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions (NDCs). A systematic literature search identified 31 studies that compare objective and subjective estimates of sleep parameters in autism, ADHD or rare genetic syndromes associated with intellectual disability. The meta-analyses revealed smaller mean differences and larger correlations indicative of greater concordance for parameters associated with sleep scheduling compared to parameters associated with sleep duration and night awakenings. Relative to objective measures, subjective measures produced: 1) greater estimates of total sleep time, sleep efficiency and time in bed; and 2) lower estimates of wake after sleep onset and number of night awakenings. Subgroup analyses also revealed differences in concordance between measurement comparison types (e.g., stronger correlations between actigraphy and sleep diaries, compared to actigraphy and questionnaires) and NDC diagnostic groups. The results predominantly replicate concordance trends observed in typically-developing samples, although some NDC-specific patterns of concordance were identified. This indicates that objective and subjective sleep measures retain broadly similar properties across populations, although researchers and clinicians should be cautious of the impact of NDC-related characteristics on sleep parameter estimates. These findings should inform sleep assessment design and the interpretation of sleep parameter estimates in NDCs, increasing the rigour of sleep parameter description across research and clinical settings.

Profiles of autism characteristics in thirteen genetic syndromes: a machine learning approach.

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.

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

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

Empowering Families Through Technology: A Mobile-Health Project to Reduce the TAND Identification and Treatment Gap (TANDem).

Introduction: Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder with various TSC-Associated Neuropsychiatric Disorders (TAND) that significantly impact the mental health and wellbeing of individuals with TSC and their caregivers. TAND represents the number one concern to families worldwide, yet is highly under-identified and under-treated. The clinician-administered TAND-Checklist (Lifetime version, TAND-L) has improved identification of TAND in clinical settings. However, many individuals with TSC and their caregivers still have difficulty accessing suitable support for diagnosis and evidence-informed interventions. The TANDem study is a community-based participatory research project with a broad range of TSC stakeholders aimed at reducing the TAND identification and treatment gap. Objectives: Participatory research identified three priority next steps: 1) development and validation of a self-report, quantified version of the TAND Checklist (TAND-SQ) and building the TAND-SQ into a smartphone application, 2) generation of consensus clinical recommendations for the identification and treatment of TAND, to be incorporated as a TAND toolkit on the app, and 3) establishment of a global TAND consortium through networking, capacity-building and public engagement activities. Methods: TANDem is a four-year project, and includes 24 consortium members from 10 countries representing all World Health Organization regions. Collaborators represent five stakeholder groups (family representatives, technology experts, clinical experts, non-profit organisations and researchers). Here we outline the project study protocol in detail, describing the scientific rationale, the project aims and objectives, the methods involved in participant recruitment, multi-site and multi-phase data collection, data analysis, ethical considerations including informed consent, data protection, privacy and confidentiality considerations related to the European Union General Data Protection Regulation and the USA Health Insurance Portability and Accountability Act. The expected outcomes and potential impact on the TSC community, implementation and dissemination of results, as well as future scale-up and scale-out plans are also discussed. Conclusions: The TANDem project has the potential to transform the global TSC community by empowering families living with TSC through an easily accessible digital solution to allow them to document their own TAND needs linked to an evidence-informed toolkit to enhance personalised healthcare, and by providing healthcare professionals with consensus clinical recommendations to prevent, identify and manage TAND manifestations.

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

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

The research landscape of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)-a comprehensive scoping review.

BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) is an umbrella term for the behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations of TSC. Although TAND affects 90% of individuals with TSC during their lifetime, these manifestations are relatively under-assessed, under-treated and under-researched. We performed a comprehensive scoping review of all TAND research to date (a) to describe the existing TAND research landscape and (b) to identify knowledge gaps to guide future TAND research. METHODS: The study was conducted in accordance with stages outlined within the Arksey and O'Malley scoping review framework. Ten research questions relating to study characteristics, research design and research content of TAND levels and clusters were examined. RESULTS: Of the 2841 returned searches, 230 articles published between 1987 and 2020 were included (animal studies = 30, case studies = 47, cohort studies = 153), with more than half published since the term TAND was coined in 2012 (118/230; 51%). Cohort studies largely involved children and/or adolescents (63%) as opposed to older adults (16%). Studies were represented across 341 individual research sites from 45 countries, the majority from the USA (89/341; 26%) and the UK (50/341; 15%). Only 48 research sites (14%) were within low-middle income countries (LMICs). Animal studies and case studies were of relatively high/high quality, but cohort studies showed significant variability. Of the 153 cohort studies, only 16 (10%) included interventions. None of these were non-pharmacological, and only 13 employed remote methodologies (e.g. telephone interviews, online surveys). Of all TAND clusters, the autism spectrum disorder-like cluster was the most widely researched (138/230; 60%) and the scholastic cluster the least (53/200; 27%). CONCLUSIONS: Despite the recent increase in TAND research, studies that represent participants across the lifespan, LMIC research sites and non-pharmacological interventions were identified as future priorities. The quality of cohort studies requires improvement, to which the use of standardised direct behavioural assessments may contribute. In human studies, the academic level in particular warrants further investigation. Remote technologies could help to address many of the TAND knowledge gaps identified.

Sleep disruption in children and adolescents with epilepsy: A systematic review and meta-analysis.

This systematic review and meta-analysis aims to assess and quantify putative differences in sleep architecture, sleep efficiency, sleep timing and broadly-defined sleep difficulties between children with and without epilepsy. Databases were searched systematically, and studies identified in PubMed, EMBASE, PsychINFO and Medline. The meta-analysis included 19 studies comparing a total of 901 children with epilepsy to 1470 healthy children. Relative to healthy children, children with epilepsy experienced reduced sleep time, sleeping on average 34 mins less across self-report, actigraphy, 24-h video-EEG and polysomnography measures. They had more sleep difficulties specifically in the domains of night waking, parasomnias and sleep disordered breathing. The analysis also revealed a significantly increased percentage of N2 sleep and decreased sleep efficiency in children with epilepsy compared to healthy children. These results illustrate that children with epilepsy are vulnerable to more sleep difficulties compared to healthy children. This suggests that screening for sleep difficulties should be an integral part in a diagnosis of epilepsy to ensure that clinically relevant sleep difficulties are identified and treated. Such an approach may ultimately aid in the development of treatment strategies which can contribute to improvements in both developmental and diagnostic outcomes for children with epilepsy.

Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes.

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.

The behavioural phenotype of Potocki-Lupski syndrome: a cross-syndrome comparison.

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.