Experiences of social interaction in young women with Turner syndrome: A qualitative study.

BACKGROUND: Turner Syndrome (TS; 45,X) is a sex chromosome aneuploidy associated with deficits in social interaction, for which clinical care guidelines have recently recommended trialling a social skills training intervention. The present study aimed to gather preliminary evidence to support a training programme for young women. METHODS: Semi-structured interviews and psychometric questionnaires about social ability were administered to young women with TS aged 16 to 25 years old (n=17) and their parents (n=20). Interview transcripts were analysed using thematic analysis. RESULTS: Although young women with TS experienced a "wide range of social competencies," they attributed social challenges to "personal and contextual factors." The magnitude of these challenges to social integration intensified during adolescence. They felt increasingly "out of sync" with their peers. They also considered their social abilities to be better than their parents did; on a scale of autistic traits (rated by parents), half had mild to severe autistic traits. Most expressed interest in taking part in a social skills programme. CONCLUSION: Young women with TS are aware they experience difficulties in social communication, and they express interest in improving their social skills. Accordingly, social skills training during adolescence would be welcomed by them and their families. Any intervention should take account of their feelings of social dislocation arising from hearing difficulties together with limited recognition, and slow processing, of social cues.

Cognitive, behavioral, and neural consequences of sex chromosome aneuploidy.

The X chromosome has played a critical role in the development of sexually selected characteristics for over 300 million years, and during that time it has accumulated a disproportionate number of genes concerned with mental functions. There are relatively specific effects of X-linked genes on social cognition, language, emotional regulation, visuospatial, and numerical skills. Many human X-linked genes outside the X-Y pairing pseudoautosomal regions escape X-inactivation. Dosage differences in the expression of such genes (which constitute at least 15% of the total) are likely to play an important role in male-female neural differentiation, and in cognitive deficits and behavioral characteristics, particularly in the realm of social communication, that are associated with sex chromosome aneuploidies. © 2016 Wiley Periodicals, Inc.

Rare neurodevelopmental conditions and parents' mental health - how and when does genetic diagnosis matter?

BACKGROUND: Parents of individuals with rare neurodevelopmental conditions and intellectual disabilities (ID) are vulnerable to mental health difficulties, which vary between parents and within parents over time. The underlying cause of a child's condition can influence parents' mental health, via uncertain pathways and within unknown time-windows. RESULTS: We analysed baseline data from the IMAGINE-ID cohort, comprising 2655 parents of children and young people with ID of known genetic origin. First, we conducted a factor analysis of the SDQ Impact scale to isolate specific pathways from genetic aetiology to parents' mental health. This suggested a two-factor structure for the SDQ Impact scale, with a "home & distress" dimension and a "participation" dimension. Second, we tested via structural equation modelling (SEM) whether genetic diagnosis affects Impact and mental health directly, or indirectly via children's characteristics. This analysis identified an indirect pathway linking genetic aetiology to parents' mental health, serially through child characteristics (physical disabilities, emotional and behavioural difficulties) and Impact: home & distress. Third, we conducted moderation analysis to explore the influence of time elapsed since genetic diagnosis. This showed that the serial mediation model was moderated by time since diagnosis, with strongest mediating effects among recently diagnosed cases. CONCLUSIONS: There are multiple steps on the pathway from ID-associated genetic diagnoses to parents' mental health. Pathway links are strongest within 5 years of receiving a genetic diagnosis, highlighting opportunities for better post-diagnostic support. Recognition and enhanced support for children's physical and behavioural needs might reduce impact on family life, ameliorating parents' vulnerabilities to mental health difficulties.

Irritability in young people with copy number variants associated with neurodevelopmental disorders (ND-CNVs).

A range of rare mutations involving micro-deletion or -duplication of genetic material (copy number variants (CNVs)) have been associated with high neurodevelopmental and psychiatric risk (ND-CNVs). Irritability is frequently observed in childhood neurodevelopmental conditions, yet its aetiology is largely unknown. Genetic variation may play a role, but there is a sparsity of studies investigating the presentation of irritability in young people with ND-CNVs. This study aimed to investigate whether there is a difference in irritability in young people with rare ND-CNVs compared to those without ND-CNVs, and to what extent irritability is associated with psychiatric diagnoses and cognitive ability (IQ). Irritability and broader psychopathology were assessed in 485 young people with ND-CNVs and 164 sibling controls, using the child and adolescent psychiatric assessment. Autism was assessed using the social communication questionnaire, and intelligence quotient (IQ) by the Wechsler abbreviated scale of intelligence. Fifty four percent of young people with ND-CNVs met the threshold for irritability; significantly more than controls (OR = 3.77, CI = 3.07-7.90, p = 5.31 × 10-11). When controlling for the presence of other psychiatric comorbidities, ND-CNV status was still associated with irritability. There was no evidence for a relationship between irritability and IQ. Irritability is an important aspect of the clinical picture in young people with ND-CNVs. This work shows that genetic variation is associated with irritability in young people with ND-CNVs, independent of psychiatric comorbidities or IQ impairment. Clinicians should be aware of this increased risk to inform management and interventions.

Can we distinguish the consequences of early maltreatment on child behaviour from idiopathic autism?

OBJECTIVE: To identify clinical features that could distinguish children presenting with autistic-like features and a history of severe early maltreatment from children with idiopathic autism spectrum disorders (ASDs). DESIGN: Matched-comparison study. SETTING: Great Ormond Street Hospital, UK. PARTICIPANTS: 46 children with a history of early maltreatment, mean (SD) age 10.6 (3.3) years and 47 children with an ASD, mean (SD) age 10.4 (2.9) years. MAIN OUTCOME MEASURES: A range of standardised interview and observational measures that are designed to quantify autistic traits. Caregiver and teacher reports were obtained on broader aspects of behavioural and emotional adjustment. RESULTS: Both groups had normal range IQ and were predominantly male. On the basis of autistic traits alone, caregiver interview and structured observation concurred that over 60% of the formerly maltreated children met criteria for an ASD. Autistic symptom profiles were very similar in both groups, although children with idiopathic ASD had significantly more marked repetitive and stereotyped behaviours. Teacher and caregiver reports indicated that children from both groups had an increased and broadly similar prevalence of emotional and behavioural disorders. CONCLUSION: Children presenting with a history of early maltreatment, who show autistic traits of behaviour, have a high risk of meeting diagnostic criteria for ASD. Their symptom profiles are virtually indistinguishable from children with idiopathic autism.

Mental health impact of autism on families of children with intellectual and developmental disabilities of genetic origin.

Background: Many children with an intellectual or developmental disability (IDD) have associated autism spectrum disorders (ASD), as well as an increased risk of mental health difficulties. In a cohort with IDD of genetic aetiology, we tested the hypothesis that excess risk attached to those with ASD + IDD, in terms of both children's mental health and parental psychological distress. Methods: Participants with a copy number variant or single nucleotide variant (5-19 years) were recruited via UK National Health Service. 1904 caregivers competed an online assessment of child mental health and reported on their own psychological wellbeing. We used regression to examine the association between IDD with and without co-occurring ASD, and co-occurring mental health difficulties, as well as with parental psychological distress. We adjusted for children's sex, developmental level, physical health, and socio-economic deprivation. Results: Of the 1904 participants with IDD, 701 (36.8%) had co-occurring ASD. Children with both IDD and ASD were at higher risk of associated disorders than those with IDD alone (ADHD: OR = 1.84, 95% confidence interval [CI] 1.46-2.32, p < 0.0001; emotional disorders: OR = 1.85, 95%CI 1.36-2.5, p < 0.0001; disruptive behaviour disorders: OR = 1.79, 95%CI 1.36-2.37, p < 0.0001). The severity of associated symptoms was also greater in those with ASD (hyperactivity: B = 0.25, 95%CI 0.07-0.34, p = 0.006; emotional difficulties: B = 0.91, 95%CI 0.67 to 1.14, p < 0.0001; conduct problems: B = 0.25, 95%CI 0.05 to 0.46, p = 0.013). Parents of children with IDD and ASD also reported greater psychological distress than those with IDD alone (ß = 0.1, 95% CI 0.85 to 2.21, p < 0.0001). Specifically, in those with ASD, symptoms of hyperactivity (ß = 0.13, 95% CI 0.29-0.63, p < 0.0001), emotional difficulties (ß = 0.15, 95% CI 0.26-0.51, p < 0.0001) and conduct difficulties (ß = 0.07, 95% CI 0.07-0.37, p < 0.004) all significantly contributed to parental psychological distress. Conclusions: Among children with IDD of genetic aetiology, one third have co-occurring ASD. Not only do those with co-occurring ASD present with a wider range of associated mental health disorders and more severe mental health difficulties than those with IDD alone, but their parents also experience more psychological distress. Our findings suggest that the additional mental health and behavioural symptoms in those with ASD contributed to the degree of parental psychological distress.

Irritability in young people with copy number variants associated with neurodevelopmental disorders (ND-CNVs).

Background: A range of rare mutations involving micro-deletion or -duplication of genetic material (copy number variants (CNVs)) have been associated with high neurodevelopmental and psychiatric risk (ND-CNVs). Irritability is frequently observed in childhood neurodevelopmental conditions, yet its aetiology is largely unknown. Genetic variation may play a role, but there is a sparsity of studies investigating presentation of irritability in young people with ND-CNVs. Aims: This study aimed to investigate whether there is a difference in irritability in young people with rare ND-CNVs compared to those without ND-CNVs, and to what extent irritability is associated with psychiatric diagnoses and cognitive ability (IQ). Methods: Irritability and broader psychopathology was assessed in 485 young people with ND-CNVs and 164 sibling controls, using the child and adolescent psychiatric assessment (CAPA). Autism was assessed using the Social Communication Questionnaire (SCQ), and Intelligence Quotient (IQ) by the Wechsler Abbreviated Scale of Intelligence (WASI). Results: 54% of young people with ND-CNVs met the threshold for irritability; significantly more than controls (OR = 3.77, CI = 3.07-7.90, p= 5.31 × 10-11). When controlling for the presence of other psychiatric comorbidities, ND-CNV status was still associated with irritability. There was no evidence for a relationship between irritability and IQ. Conclusions: Irritability is an important aspect of the clinical picture in young people with ND-CNVs. This work shows that genetic variation is associated with irritability in young people with ND-CNVs, independent of psychiatric comorbidities or IQ impairment. Clinicians should be aware of this increased risk to inform management and interventions.

Mental health and neurodevelopment in children and adolescents with Turner syndrome.

OBJECTIVES: Turner syndrome (TS) is a rare sex chromosome aneuploidy, with an incidence of four in 10,000 new-born girls. TS is often associated with impaired social communication skills, but the extent to which these are attributable to Autism Spectrum Disorders (ASD) is uncertain. We made standardized assessments of the mental health and associated neurodevelopmental disorders in children and adolescents with TS and report on the prevalence of concurrent conditions. METHODS: Our sample comprised 127 girls with TS, 5-19 years of age. We obtained reports of their mental health from a combination of diagnostic interview (the Development and Wellbeing Assessment (DAWBA)), from the Strengths and Difficulties Questionnaire (SDQ) and from the Social Responsiveness Scale (SRS-2). Sources of information included parents, teachers and self-reports. The prevalence of mental health disorders in this sample was compared with age/sex matched national English data from typical controls. RESULTS: Most individuals with TS (83%) had experienced significant social communication difficulties and nearly one in four (23%) met diagnostic criteria for ASD on the DAWBA. One-third (34%) had at least one mental health or neurodevelopmental condition, and those girls with an ASD were at a greater risk of a co-occurring emotional disorder and/or attention deficit hyperactivity disorder (ADHD). CONCLUSION: Children and adolescents with TS are substantially more likely to meet criteria for ASD than their typically developing peers. Our finding has clinical implications for appropriate behavioural management from preschool through to adolescence.

Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE, a UK national cohort study.

BACKGROUND: Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population. METHODS: IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4-19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ. FINDINGS: We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9-36·5), ADHD RR 13·5 (95% CI 11·1-16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV. INTERPRETATION: Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services. FUNDING: UK Medical Research Council and Medical Research Foundation.

'We have been in lockdown since he was born': a mixed methods exploration of the experiences of families caring for children with intellectual disability during the COVID-19 pandemic in the UK.

OBJECTIVES: This study aimed to explore the experiences of parents caring for children with intellectual and developmental disabilities (IDD) during the UK national lockdown in spring 2020, resulting from the COVID-19 pandemic. DESIGN: Participants were identified using opportunity sampling from the IMAGINE-ID national (UK) cohort and completed an online survey followed by a semistructured interview. Interviews were analysed using thematic analysis. SETTING: Interviews were conducted over the telephone in July 2020 as the first UK lockdown was ending. PARTICIPANTS: 23 mothers of children with intellectual and developmental disabilities aged 5-15 years were recruited. RESULTS: Themes reported by parents included: managing pre-existing challenges during a time of extreme change, having mixed emotions about the benefits and difficulties that arose during the lockdown and the need for appropriate, individualised support. CONCLUSIONS: Our findings confirm observations previously found in UK parents of children with IDD and provide new insights on the use of technology during the pandemic for schooling and healthcare, as well as the need for regular check-ins.

New approaches to social skills training: Blended group interventions for girls with social communication difficulties.

Social skills group interventions are increasing popular for children with social communication disorders but there is little evidence of their acceptability or effectiveness when delivered online. We report a feasibility study that adapted the Program for Education and Enrichment of Relational Skills (PEERS) to provide an intensive 8 week online delivery to female adolescents, blended with some face-to-face group meetings. A systematic multiple-case series design with case tracking was developed, comprising a 3-month baseline, a 2-month intervention and a 3-month follow-up period. Seven adolescents with Turner Syndrome and social communication difficulties (17-20 years) took part, together with their parents. Acceptability and feasibility were assessed by means of qualitative feedback and attendance rates. Changes in social adaptation were tracked using measures of social knowledge, social behaviour and autistic symptoms, plus anxiety and self-esteem. Attendance rates were consistently high and there were no dropouts. Qualitative feedback indicated the online format was acceptable to both the participants and their families. Objective outcome measures showed significant gains in social knowledge and improved social initiations from measures made during the pre-intervention baseline. This proof-of-principle pilot study demonstrated blended social skills interventions are both feasible and acceptable to adolescent females with social communication difficulties. LAY SUMMARY: Social skills groups are increasingly popular for children with social communication disorders, but there is little evidence for their use online. Psychological treatments that require weekly face-to-face sessions for both children and their parents are associated with practical difficulties, disrupting family life and school commitments. Our study, is the first to use a blended online and face-to-face social skills training program for adolescent girls with social communication difficulties. We showed that this new approach to treatment was acceptable to families and has a positive and significant impact on participant's social performance and social knowledge. This new treatment approach may increase the accessibility of treatment for adolescents and young adults, especially those with social communication difficulties. Autism Res 2021, 14: 1061-1072. © 2021 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4-BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature.

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4-BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers' cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.

Social skills and relationships in Turner syndrome.

PURPOSE OF REVIEW: Summarize the literature on the social skills and relationships of women with Turner syndrome and examine the biological and psychological factors that may contribute to social interaction difficulties. RECENT FINDINGS: Turner syndrome is often associated with impaired social-cognitive processing and executive function deficits. These cognitive abnormalities, together with a range of physical differences, may adversely affect social communication skills, which typically begin to impair quality of life during early adolescence. Parental accounts of their daughter's social skills frequently highlight interaction problems, both in the home and beyond; in contrast, self-reports are usually far more positive. At present, we do not know the extent to which such self-reports reflect a lack of social awareness, or a lack of concern about social difficulties. SUMMARY: Women with Turner syndrome are likely to experience social interaction challenges (especially in friendships and relationships) across the lifespan. Providing appropriate guidance and support to them demands a better understanding of their strengths and weaknesses.

Sex chromosome aneuploidies.

Sex chromosome aneuploidies comprise a relatively common group of chromosome disorders characterized by the loss or gain of one or more sex chromosomes. We discuss five of the better-known sex aneuploidies: Turner syndrome (XO), Klinefelter syndrome (XXY), trisomy X (XXX), XYY, and XXYY. Despite their prevalence in the general population, these disorders are underdiagnosed and the specific genetic mechanisms underlying their phenotypes are poorly understood. Although there is considerable variation between them in terms of associated functional impairment, each disorder has a characteristic physical, cognitive, and neurologic profile. The most common cause of sex chromosome aneuploidies is nondisjunction, which can occur during meiosis or during the early stages of postzygotic development. The loss or gain of genetic material can affect all daughter cells or it may be partial, leading to tissue mosaicism. In both typical and atypical sex chromosome karyotypes, there is random inactivation of all but one X chromosome. The mechanisms by which a phenotype results from sex chromosome aneuploidies are twofold: dosage imbalance arising from a small number of genes that escape inactivation, and their endocrinologic consequences.

Protocol: New approaches to managing the social deficits of Turner Syndrome using the PEERS program.

Turner Syndrome (TS) is a sex chromosome aneuploidy (45,X) associated with social skill difficulties. Recent clinical care guidelines recommend that the Program for the Education and Enrichment of Relational Skills (PEERS) social skills intervention programme be trialled in this population. PEERS has been successfully used in adolescents with autism spectrum conditions without intellectual disabilities. The PEERS program will be piloted with adolescents and young women with TS aged 16-20 using an uncontrolled study trial with a multiple-case series design. The program will be delivered face to face and online. The assessment battery is designed to measure social skills comprehensively from diverse informants (parent, teacher young person). It includes measures of social performance, social knowledge and social cognition. Parents and young people taking part in the intervention will also feedback on the acceptability and feasibility of the pilot. The outcomes of this small scale pilot (n=6-10) will be used to adapt the programme based on feedback and estimate the sample for a future randomised controlled trial.