Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics.

BACKGROUND: Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocephaly, and research indicates possibly increased rates of developmental delay and autism spectrum disorder (ASD) for people with germline mutations affecting PTEN. METHOD: A systematic review of literature reporting behavioural and psychological variables for people with constitutional PTEN mutations/PHTS was conducted using four databases. Following in-depth screening, 25 articles met the inclusion criteria and were used in the review. Fourteen papers reported the proportion of people with PTEN mutations/PTHS meeting criteria for or having characteristics of ASD and were thus used in a pooled prevalence meta-analysis. RESULTS: Meta-analysis using a random effects model estimated pooled prevalence of ASD characteristics at 25% (95% CI 16-33%), although this should be interpreted cautiously due to possible biases in existing literature. Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. Emotional difficulties and impaired cognitive functioning in specific domains were noted but assessed/reported less frequently. Methods of assessment of psychological/behavioural factors varied widely (with retrospective examination of medical records common). CONCLUSIONS: Existing research suggests approximately 25% of people with constitutional PTEN mutations may meet criteria for or have characteristics of ASD. Studies have also begun to establish a range of possible cognitive impairments in affected individuals, especially when ASD is also reported. However, further large-scale studies are needed to elucidate psychological/behavioural corollaries of this mutation, and how they may relate to physiological/physical characteristics.

The adaptive functioning profile of Pitt-Hopkins syndrome.

BACKGROUND: There are few cohort studies describing the adaptive functioning profile for Pitt-Hopkins syndrome (PTHS). In this study we examine the adaptive functioning profile for PTHS and compare it to Angelman syndrome (AS). METHOD: Caregivers of 14 individuals with PTHS, 33 with deletion AS and 23 with non-deletion AS, completed the Vineland Adaptive Behavior Scales-II. RESULTS: The profile of adaptive functioning in PTHS was characterised by strengths in socialisation, followed by motor skills, communication then daily living skills. The PTHS group scored significantly lower than the non-deletion AS group on all domains except socialisation and significantly lower than the deletion AS group, for motor skills only. CONCLUSIONS: An uneven adaptive behavior profile for individuals with PTHS mirrors that of AS, with implications for assessment and intervention.

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.

Influence of stereopsis on the ability to perform simulated microsurgery.

PURPOSE: To determine whether impaired or absent stereopsis affects the ability to perform simulated microsurgical tasks. SETTING: University of Edinburgh, United Kingdom. DESIGN: Prospective randomized cross-over study. METHODS: Visual acuity and stereoacuity were measured. A band-pass filter was placed over the nondominant eye to reduce stereoacuity to 150 seconds of an arc (partial stereopsis), or the nondominant eye was completely occluded (absent stereopsis). Participants completed a computerized surgical simulator task 3 times with a randomized testing order (normal stereopsis, absent stereopsis, and partial stereopsis). The task involved using forceps to grasp and position objects in the anterior chamber. Outcomes included area of ocular injury, time to task completion, and overall score. RESULTS: Ocular damage area was significantly worse with partial stereopsis (P = .002) and worse still when stereopsis was absent (P < .001 for normal vs absent stereopsis and P = .005 for partial vs absent stereopsis). The median ocular damage area was 3.55 mm (interquartile range [IQR], 1.21-5.88 mm) with normal stereopsis, increasing to 6.10 mm (IQR, 3.96-12.47 mm) with stereopsis reduced to 150 seconds of an arc and to 9.25 mm (IQR, 4.93-18.70 mm) with no stereopsis. Time taken to complete the task increased and overall score decreased as stereopsis was reduced. The overall score decreased from 53% (IQR, 22.5-82%) under normal stereopsis to 0% (IQR, 0-43.5%) with absent stereopsis. CONCLUSIONS: Impaired stereopsis was associated with worse microsurgical performance, which may have implications for surgical training. The absence of stereopsis resulted in worse performance than partial reduction in stereopsis.

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.