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.

The developmental trajectory of sleep in children with Smith-Magenis syndrome compared to typically developing peers: a 3-year follow-up study.

Study Objectives: To determine the trajectory of: (i) objective sleep parameters and (ii) caregiver-reported sleep questionnaire scores over 3 years in children with Smith-Magenis syndrome (SMS) compared to age-matched typically developing (TD) controls. We also aimed to (iii) describe individual profiles of change in sleep parameters over time. Methods: Week-long, overnight actigraphy and questionnaire data from 13 children with SMS and 13 age-matched TD children were collected at Time 1 and Time 2 (3 years later). Independent samples t-tests, paired samples t-tests, and Bayesian analyses were used to compare sleep parameters and sleep questionnaire scores between groups at each time point and compare data within groups to assess change over time. Results: Sleep parameters were consistently more disrupted in the SMS group than the TD group, with significantly reduced sleep efficiency, increased wake after sleep onset and earlier get up times at both time points. This was mirrored in the questionnaire data, with children with SMS evidencing higher scores for overall sleep disturbance, night waking, and daytime sleepiness. While TD sleep parameters demonstrated expected developmental changes over 3 years, in the SMS group sleep parameters and variability between and within children remained largely stable. However, some children with SMS showed substantial variation in sleep parameters over time. Questionnaire scores remained stable over 3 years in both groups. Conclusions: Overall, sleep disturbance appears to be a stable feature of SMS, indicative of a divergent sleep trajectory compared to TD peers. Proactive intervention approaches should be considered for poor sleep in SMS.

Direct assessment of overnight parent-child proximity in children with behavioral insomnia: Extending models of operant and classical conditioning.

INTRODUCTION: Explanatory models of behavioral insomnia typically draw on operant learning theory with behavioral techniques focused on altering parent-child interactions to improve sleep. However, there are no data describing parent-child interactions overnight beyond parent report. In this study we used radio frequency identification technology to quantify parent-child proximity overnight in two groups at elevated risk of behavioral insomnia, Angelman syndrome (AS) and Smith-Magenis syndrome (SMS). MATERIALS AND METHODS: Nineteen children aged 4-15 years (8 with AS, 11 with SMS) participated in a week-long at-home assessment of sleep and overnight parent-child proximity. Sleep parameters were recorded using the Philips Actiwatch 2 and proximity data were recorded using custom-built radio frequency identification watches. RESULTS: Three patterns of proximity data between parent-child dyads overnight were evident: "checking" (six with AS, five with SMS), "co-sleeping" (four with SMS) and those who had "no proximity" overnight (two with AS, two with SMS). In the AS group, 25.45% of actigraphy-defined wakes resulted in a parent-child interaction. In the SMS group, 39.34% of wakes resulted in a parent-child interaction. Children who interacted with their parents when settling to sleep were not significantly more likely to interact at waking. DISCUSSION: The novel application of radio frequency identification technology is a feasible method for studying overnight parent-child proximity. Profiles of proximity between participants that are not closely aligned with operant models of behavioral insomnia were evident. These results have significant implications for the etiology of poor sleep and the application of behavioral sleep interventions.

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.

Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile.

BACKGROUND: Sleep disorders are common in people with intellectual disability (ID) and autism, with growing evidence of diverse sleep profiles across ID associated genetic syndromes. Documenting the prevalence and profile of specific sleep disorders in syndromes will quantify syndrome-driven 'risk', inform prognosis and enhance understanding of aetiology of sleep disorders. METHOD: Following PRISMA guidelines for meta-analysis, we searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, Web of Science and PubMed Central with use of syndrome-specific keywords and 60 sleep-related search terms. We screened and extracted papers that reported sleep disorder prevalence data for five or more individuals within a genetic syndrome, and applied quality criteria to produce a quality-effects prevalence model of six types of sleep disorder across nineteen syndromes. Relative risk estimates were calculated for the prevalence of each sleep disorder in each syndrome. RESULTS: Two hundred and seventy three papers were identified, generating 463 prevalence estimates for Angelman, CHARGE, Cornelia de Lange, Down, fragile X, Prader-Willi, Rett, Smith-Magenis and Williams syndromes, mucopolysaccharidoses (MPS disorders), neurofibromatosis and tuberous sclerosis complex. Prevalence estimates were higher in genetic syndromes than published equivalents for typically developing individuals, with few exceptions. Between-syndrome differences for some disorders were evident; sleep-disordered breathing was most prevalent in MPS disorders (72-77%), while excessive daytime sleepiness was highest in Smith-Magenis syndrome (60%). Conversely, insomnia, which was reported at a higher rate than TD estimates in all syndromes except fragile X, was not associated with specific genetic risk. This suggests insomnia could emerge because of the individual's environment or associated developmental delay, rather than any specific genetic syndromes. LIMITATIONS: Due to the broad scope of the meta-analysis, only syndromes previously identified as reporting preliminary sleep research were included. Other syndromes may also experience elevated prevalence rates of specific types of sleep disorder. Only English language papers were included. CONCLUSIONS: Differing prevalence rates between types of sleep disorder suggest differing causal mechanisms, such as cranio-facial morphology in Down and Prader-Willi syndromes and the build-up of mucopolysaccharides in MPS disorders. Priorities for clinical assessment and intervention for sleep disorders are discussed.

Sleep disorders in children with Angelman and Smith-Magenis syndromes: The assessment of potential causes of disrupted settling and night time waking.

BACKGROUND: Sleep problems are common in Smith-Magenis (SMS) and Angelman syndromes (AS). Effectiveness of interventions depends on appropriate assessment, complicated by compromised self-report and health and behaviour difficulties. Studying settling and waking in these syndromes could inform assessment. AIMS: To describe settling and waking behaviours in children at high-risk of sleep and health problems, using direct observation. METHODS AND PROCEDURES: Video and actigraphy data were collected for 12 participants with AS (Mean age = 8.02, SD = 2.81) and 11 with SMS (Mean age = 8.80, SD = 2.18). Settling (30 min prior to sleep onset) and night waking were coded for nineteen behaviours relating to pain, challenging behaviour and caregiver interaction. Lag sequential analyses were conducted for pain-related behaviours. OUTCOMES AND RESULTS: Percentage of time spent in behaviours was calculated. Parent-child interactions (0.00-9.93 %) and challenging behaviours (0 %) were rare at settling and waking in both groups. In the AS group, pain-related behaviours were more likely to occur before waking than by chance (p < 0.001). CONCLUSIONS AND IMPLICATIONS: Findings highlight the importance of considering pain as a cause of sleep problems in AS. The principle and methodology could be extended to individuals with ID experiencing sleep problems.