Rett Syndrome Behaviour Questionnaire in Children and Adults With Rett Syndrome: Psychometric Characterization and Revised Factor Structure.

Rett syndrome (RTT) is a severe neurodevelopmental disorder associated with multiple neurobehavioral abnormalities. The Rett Syndrome Behaviour Questionnaire (RSBQ) was developed for pediatric RTT observational studies. Because its application has expanded to adult and interventional studies, we evaluated the RSBQ's psychometric properties in six pediatric (n = 323) and five adult (n = 309) datasets. Total and General Mood subscale scores had good reliability. Clinical severity had no influence on RSBQ scores. Exploratory and confirmatory factor analyses yielded 6 pediatric and 7 adult clinically relevant and psychometrically strong factors including the original Breathing Problems and Fear/Anxiety subscales and the novel Emotional and Disruptive Behavior subscale composed of items from the original General Mood and Nighttime Behaviours subscales. The present findings support additional evaluations and improvements of an important RTT behavioral measure.

Neonatal hypoxic-ischaemic encephalopathy: Motor impairment beyond cerebral palsy.

BACKGROUND: Research investigating neuromotor function in the absence of cerebral palsy (CP) for children who had neonatal HIE is limited. AIMS: To investigate school-age neurological and neuromotor function, and correlations with attention, neonatal Magnetic Resonance Imaging (MRI), and neuromotor assessments at toddler age. METHODS: Twenty-seven children with neonatal HIE without CP who underwent hypothermia treatment and a comparison group of 20 children were assessed at age 5-7 years for Minor Neurological Dysfunction (MND; simplified Touwen), motor skills (Movement Assessment Battery for Children-2; MABC-2), parental concern over motor function (MABC Checklist), general cognition (Wechsler Preschool and Primary Scale of Intelligence-IV, WPPSI), and attention (DuPaul ADHD Rating Scale). Neurological examination and motor development, using Bayley-3 scales, at age 24-months was extracted from the clinical database. Clinical neonatal MRI was assessed for hypoxic-ischaemic injury. RESULTS: In the HIE group, MND was more prevalent (p = 0.026) and M-ABC performance (total score p = 0.006; balance subtest p = 0.008) was worse; parents were more concerned about children's motor function (p = 0.011). HIE group inattention scores were higher (p = 0.032), which correlated with lower MABC-2 scores (rs = -0.590, p = 0.004). Neurological examination at 24-months correlated with MND (rs = 0.437, p = 0.033); Bayley-3 motor scores did not correlate with M-ABC-2 scores (rs = 368, p = 0.133). Neonatal MRI findings were not associated with school-age MND (rs = 0.140, p = 0.523) or MABC-2 (rs = 0.300, p = 0.165). CONCLUSIONS: Children with neonatal HIE, without CP, treated with hypothermia may be more likely to develop MND and motor difficulties than typically developing peers. Inattention may contribute to motor performance. In the absence of CP, neonatal MRI and toddler age assessment of motor development have limited predictive value for school-age outcome. Since this was an exploratory study with a small sample size, findings should be confirmed by a definite larger study.

Children with neonatal Hypoxic Ischaemic Encephalopathy (HIE) treated with therapeutic hypothermia are not as school ready as their peers.

AIM: We aimed to determine whether children with neonatal Hypoxic Ischaemic Encephalopathy (HIE) treated with therapeutic hypothermia (TH) differ from their peers on measures of fine motor skills, executive function, language and general cognitive abilities, factors that are important for school readiness. METHODS: We compared school readiness in 31children with HIE treated with TH (without Cerebral Palsy; mean age 5 years 4 months) with 20 typically developing children without HIE (mean age 5 years 6 months). RESULTS: Children with HIE scored significantly lower than typically developing children on fine motor skills, executive functions, memory and language. CONCLUSION: While general cognitive abilities and attainment were in the normal range, our findings suggest those scores mask specific underlying difficulties identified by more focussed assessments. Children with HIE treated with TH may not be as 'school ready' as their typically developing classmates and may benefit from long-term follow-up until starting school.

Minor neurological signs and behavioural function at age 2 years in neonatal hypoxic ischaemic encephalopathy (HIE).

BACKGROUND: Neurodevelopmental follow-up in Neonatal Hypoxic Ischaemic Encephalopathy (HIE) typically focusses on major neuromotor (cerebral palsy, CP) and severe cognitive impairment. Outcomes in those without major neuromotor impairment are less well explored. OBJECTIVES: To examine behavioural, cognitive and neurological outcomes after neonatal HIE, in a clinical cohort of children without CP, at age 2 years. METHODS: Clinical routine outcome data from children admitted to a tertiary centre with neonatal HIE for hypothermia treatment between 05/08/09-30/05/2016. Children were assessed for neuromotor status - particularly minor neurological signs (MNS), with Bayley Scales of Infant and Toddler Development III (Bayley III) or Ages and Stages Questionnaire-3 (ASQ), Child Behavior Checklist 1.5-5 (CBCL), Quantitative Checklist for Autism in Toddlers (Q-CHAT). RESULTS: Of 107 children, 75.5% had normal neurology, 12.1% CP, 12.1% MNS. Children with CP were excluded from analyses. For those without CP, Bayley-III scores were in the average range for the majority; mild cognitive delay observed in 5%, 4.2% language, 1.3% motor development; severe delay in 1.3% for cognitive, 4.2% for language. More than in the normative population scored in clinical ranges for CBCL externalising, sleep, and other problems. No significant difference was seen for Q-CHAT. Children with MNS were significantly more likely to have impaired Bayley-III scores, parent-reported internalising, sleep, and other problems. CONCLUSIONS: In this clinical cohort, the majority of children had favourable outcome at 2 years. However, children with MNS were at risk for cognitive and behavioural difficulties and will benefit from enhanced clinical follow-up and support.

Using Bayesian methodology to explore the profile of mental health and well-being in 646 mothers of children with 13 rare genetic syndromes in relation to mothers of children with autism.

BACKGROUND: It is well documented that mothers of children with intellectual disabilities or autism experience elevated stress, with mental health compromised. However, comparatively little is known about mothers of children with rare genetic syndromes. This study describes mental health and well-being in mothers of children with 13 rare genetic syndromes and contrasts the results with mothers of children with autism. METHODS: Mothers of children with 13 genetic syndromes (n = 646; Angelman, Cornelia de Lange, Down, Fragile-X, Phelan McDermid, Prader-Willi, Rett, Rubenstein Taybi, Smith Magenis, Soto, Tuberous Sclerosis Complex, 1p36 deletion and 8p23 deletion syndromes) and mothers of children with autism (n = 66) completed measures of positive mental health, stress and depression. Using Bayesian methodology, the influence of syndrome, child ability, and mother and child age were explored in relation to each outcome. Bayesian Model Averaging was used to explore maternal depression, positive gain and positive affect, and maternal stress was tested using an ordinal probit regression model. RESULTS: Different child and mother factors influenced different aspects of mental well-being, and critically, the importance of these factors differed between syndromes. Maternal depression was influenced by child ability in only four syndromes, with the other syndromes reporting elevated or lower levels of maternal depression regardless of child factors. Maternal stress showed a more complex pattern of interaction with child ability, and for some groups, child age. Within positive mental health, mother and child age were more influential than child ability. Some syndromes reported comparable levels of depression (SMS, 1p36, CdLS) and stress (SMS, AS) to mothers of children with autism. CONCLUSIONS: Bayesian methodology was used in a novel manner to explore factors that explain variability in mental health amongst mothers of children with rare genetic disorders. Significant proportions of mothers of children with specific genetic syndromes experienced levels of depression and stress similar to those reported by mothers of children with autism. Identifying such high-risk mothers allows for potential early intervention and the implementation of support structures.

Change over a 16-month period in the psychological well-being of mothers of girls and women with Rett syndrome.

PURPOSE: There is an emerging research literature on the experiences of family members of girls and women with Rett syndrome (RTT), but a lack of longitudinal data. METHODS: Fifty mothers whose daughters had RTT were surveyed 16-17 months after an earlier cross-sectional study. Measures completed at both time points focused on maternal positive and negative psychological well-being and their daughters' behavioral and emotional problems and RTT behavioral phenotype severity. RESULTS: Maternal stress, anxiety, and depression demonstrated at least moderate levels of stability. Maternal positive perceptions were also moderately stable over 16-17 months. Longitudinal analyses suggested that their daughters' behavioral and emotional problems rather than RTT behavioral phenotype severity predicted later maternal well-being. CONCLUSION: Mothers with RTT daughters experience chronic stress (persisting over time) but also ongoing positive perceptions. Practitioners should recognize positive perceptions and also consider targeted behavioral parent training to reduce behavior problems in individuals with RTT.

Direct Observation of the Behaviour of Females with Rett Syndrome.

The aim was to observe the behaviour of a sample of females with RTT and explore how it was organized in relation to environmental events. Ten participants, all with a less severe form of classic (n = 9) or atypical (n = 1) Rett syndrome (RTT), were filmed at home and at school or day centre. Analysis used real-time data capture software. Observational categories distinguished engagement in social and non-social pursuits, hand stereotypies, self-injury and the receipt of attention from a parent, teacher or carer. Associations between participant behaviour and intake variables and receipt of attention were explored. Concurrent and lagged conditional probabilities between behavioural categories and receipt of attention were calculated. Receipt of adult attention was high. Engagement in activity using the hands was associated with a less severe condition and greater developmental age. Engagement in activity, whether using the hands or not, and social engagement were positively associated with receipt of support. The extent of hand stereotypies varied greatly across participants but was independent of environmental events. Six participants self-injured. There was some evidence that self-injury was related to adult attention. Participants appeared to experience a carer and attention rich environment and their levels of engagement seemed high as a result. As in the more general literature, engagement in activity was related to personal development and to social support. Self-injury contrasted with hand stereotypies in having possible environmental function.

Psychological Well-Being of Mothers and Siblings in Families of Girls and Women with Rett Syndrome.

Few published studies have reported on the psychological well-being of family members of individuals with Rett syndrome (RTT). Eighty-seven mothers of girls and women with RTT completed a questionnaire survey about their daughters' behavioral phenotype, current health, and behavior problems, and their own and a sibling's well-being. Mothers reported increased anxiety but similar levels of depression when compared to a normative sample. Across all problem domains on the Strengths and Difficulties Questionnaire, child and adolescent siblings (n = 39) were reported by mothers to have fewer difficulties than a normative sample. The severity of their daughters' RTT behavioral phenotype predicted increased anxiety and stress for mothers. Increased RTT daughters' current health problems predicted more maternal perceptions of positive gain.

A national survey of Rett syndrome: age, clinical characteristics, current abilities, and health.

As part of a wider study to investigate the behavioral phenotype of a national sample of girls and women with Rett syndrome (RTT) in comparison to a well-chosen contrast group and its relationship to parental well-being, the development, clinical severity, current abilities and health of 91 participants were analyzed in relation to diagnostic, clinical and genetic mutation categories. Early truncating mutations or large deletions were associated with greater severity. Early regression was also associated with greater severity. All three were associated with lower current abilities. Epilepsy and weight, gastrointestinal and bowel problems were common co-morbidities. Participants with classic RTT had greater health problems than those with atypical RTT. A substantial minority of respondents reported fairly frequent signs of possible pain experienced by their relative with RTT. Overall, the study provides new data on the current abilities and general health of people with RTT and adds to the evidence that the severity of the condition and variation of subsequent disability, albeit generally within the profound range, may be related to gene mutation. The presence of certain co-morbidities represents a substantial ongoing need for better health. The experience of pain requires further investigation.

A national survey of Rett syndrome: behavioural characteristics.

BACKGROUND: The aim was to gain a UK national sample of people with Rett syndrome (RTT) across the age range and compare their characteristics using a variety of relevant behavioural measures with a well-chosen contrast group. METHODS: The achieved sample was 91 girls and women, aged from 4 to 47 years, of whom 71 were known to be MECP2 positive. The contrast group (n = 66), matched for age, gender, language and self-help skills, comprised individuals with six other syndromes associated with intellectual disability. Parental questionnaire measures of RTT specific characteristics, impulsivity, overactivity, mood, interest and pleasure, repetitive behaviour and self-injury were administered. RESULTS: Hand stereotypies, breathing irregularities, night-time unrest and anxiety or inappropriate fear were commonly reported among the RTT sample. Problems of low mood were also reported as common. However, mood and interest and pleasure were no lower than found in the contrast group. In addition, self-injury was lower than in the contrast group and was associated with factors found to predict self-injury in other groups of people with severe intellectual disabilities. CONCLUSIONS: There is variability in the manifestation of problem behaviours potentially associated with the syndrome across individuals, with some more severely affected in most areas than others. Some of this variability appears to be underpinned by genetic mutation.