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Pathogenic variants in the CDKL5 gene result in CDKL5 deficiency disorder (CDD), which is characterized by early-onset epilepsy, severe developmental delay, and often, cortical visual impairment. Validated clinical outcome measures are needed for future clinical trials to be successful. This study aimed to adapt the Rett Syndrome Hand Function Scale for CDKL5 deficiency disorder and evaluate its feasibility, acceptability, content validity, and reliability. Consultation with a cortical visual impairment experienced specialist and the Consumer Reference Group informed modifications to the instructions of the Rett Syndrome Hand Function Scale for children with CDKL5 deficiency disorder (CDD-Hand). Eighty-six families registered with the International CDKL5 Disorder Database provided video clips of their child's hand function and provided feedback about the measure. Video data were coded by 2 researchers to evaluate intra- and interrater reliability. This study provides initial evidence of validation and reliability. The scale appears to be suitable for a range of ages and functional abilities for CDKL5 deficiency disorder. [ABSTRACT FROM AUTHOR]

CDKL5 deficiency disorder (CDD), a severe developmental and epileptic encephalopathy, is being diagnosed earlier with improved access to genetic testing, but this may also have unanticipated impacts on parents' experience receiving the diagnosis. This study explores the lived experience of parents receiving a diagnosis of CDD for their child using mixed methods. Thirty-seven semistructured interviews were conducted with parents of children with a diagnosis of CDD, which were coded and analyzed to identify themes. Grief was a nearly universal theme expressed among participants. Parents of younger children discussed grief in the context of receiving the diagnosis, whereas parents of older children indicated they were at different stages along the grieving journey when they received the diagnosis. Parents with less understanding of their child's prognosis (poorer prognostic awareness) connected their grief to receiving the diagnosis as this brought a clear understanding of the prognosis. Several themes suggested what providers did well to improve the diagnostic experience for parents, much of which aligns with existing literature around how to provide serious news. Additionally, parents identified long-term benefits of having a diagnosis for their child's medical problems. Although interview data were concordant with a survey of parents' diagnostic experience from a large international cohort, most participants in this study were relatively affluent, white mothers and further research is needed to better understand if other groups of parents have a different diagnostic experience. This study gives context of parental experience that providers should be aware of when conveying new genetic diagnoses to families. [ABSTRACT FROM AUTHOR]

CDKL5 deficiency disorder (CDD) results in early-onset seizures and severe developmental impairments. A CDD clinical severity assessment (CCSA) was previously developed with clinician and parent-report items to capture information on a range of domains. Consistent with US Food and Drug Administration (FDA) guidelines, content validation is the first step in evaluating the psychometric properties of an outcome measure. The aim of this study was to validate the content of the clinician-reported items in the CCSA (CCSA-Clinician). Eight neurologists leading the USA CDD Center of Excellence clinics were interviewed using the "think aloud" technique to critique 26 clinician-reported items. Common themes were aggregated, and a literature search of related assessments informed item modifications. The clinicians then participated in 2 consensus meetings to review themes and finalize the items. A consensus was achieved for the content of the CCSA-Clinician. Eight of the original items were omitted, 11 items were added, and the remaining 18 items were revised. The final 29 items were classified into 2 domains: functioning and neurologic impairments. This study enabled refinement of the CCSA-Clinician and provided evidence for its content validity. This preliminary validation is essential before field testing and further validation, in order to advance the instrument toward clinical trial readiness. [ABSTRACT FROM AUTHOR]

Background: Children and adolescents with intellectual disability are at risk of developing psychiatric symptoms and disorders; yet, the estimates reported in the literature have been inconsistent, presenting a potential barrier for service planning and delivery. Sources of variability could arise from differences in measurement instruments as well as subgroup membership by severity of intellectual disability, gender and age. This systematic review aimed to address these gaps. Method: MEDLINE and PsycINFO databases were searched from inception to 2018 and selected studies were reviewed. Studies were included if they reported point prevalence estimates of mental health symptomology or diagnoses in a general population of 6- to 21-year-old individuals with intellectual disability. The Joanna Briggs Institute Prevalence Critical Appraisal Checklist was applied to eligible papers to appraise their scientific strength. Pooled prevalence for mental health symptomology was determined using a random-effects meta-analysis. Results: A total of 19 studies were included, including 6151 children and adolescents. The pooled prevalence estimate captured by the Developmental Behaviour Checklist was 38% (95% confidence interval = [31, 46]), contrasting with 49% (95% confidence interval = [46, 51]) captured by the Child Behaviour Checklist; both rates were higher than a non-intellectual disability population. Severity of intellectual disability did not significantly influence the Developmental Behaviour Checklist risks. Insufficient data were available to conduct statistical analyses on the effects of age, gender and socioeconomic status. Of diagnosed psychiatric disorders, attention deficit/hyperactivity disorder (30%), conduct disorder (3–21%) and anxiety disorders (7–34%) were the most prevalent conditions. Conclusion: This review consists of the largest sample hitherto evaluated. In the intellectual disability population, mental health comorbidities could be better detected by a symptom phenotype than a psychiatric diagnostic phenotype. Crucially, future research needs to address the effect of measurement validity in the intellectual disability population. Estimated prevalence rates were high compared to the general population, indicating the importance of systematic screening, case detection and appropriate management. [ABSTRACT FROM AUTHOR]

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually affecting females. It is associated with intellectual and multiple disabilities leading to a high level of dependency in all aspects of daily living including participation in physical activities. This study explored facilitators and barriers to "uptime" (non-sedentary) activities in Danish girls and women with RTT as perceived by parents and professionals using focus groups. Through thematic analysis, one central theme emerged: a constant balance to do the best thing for the girl or woman. Within the central theme, five subthemes of facilitators and barriers were identified relating to the individual and the physical, organizational, social, and attitudinal environments. Environmental barriers can be reduced through policy and management-level changes in health promotion and strong advocacy of physical activity by health professionals. Targeting both facilitators and barriers of "uptime" activities enables the planning and implementing of health-promoting interventions in individuals with RTT. [ABSTRACT FROM AUTHOR]

Domains of quality of life in children with autism spectrum disorder have not previously been explored and there has been no quality of life measure developed for this population. Our study investigated parent observations to identify the domains important to children with autism spectrum disorder who also had an intellectual disability. In all, 21 parents (19 mothers, 2 fathers) of children with autism spectrum disorder (aged 6–17 years) participated in a qualitative study to discuss their child's quality of life. Thematic analysis using a grounded theory framework was conducted and 10 domains emerged in relation to health and well-being, capacity to perform and develop skills in daily life, and connections with the community and environment. Unique aspects of quality of life included varying levels of social desire, consistency of routines, and time spent in nature and the outdoors, which are not comprehensively captured in existing measures. Parent observations provide an initial framework for understanding quality of life in autism spectrum disorder and support the development of a new measure for this population. [ABSTRACT FROM AUTHOR]

This study aimed to validate measures of sedentary time in individuals with Rett syndrome. Twenty-six individuals (median [IQR] age 16.0 (9.4-20.6) years) wore an activPAL accelerometer during video-taped activities and agreement was determined between sedentary time determined by the activPAL and observation. For 11 individuals (median [IQR] age 14.5 (11.5-25.6) years), linear regression was used to determine the relationship between sedentary time recorded on the modified Bouchard activity record diary card and measured using the activPAL. In comparison to observation, the activPAL accurately measured duration of sedentary time with a mean difference (limit of agreement) of -1.0 (6.3) minutes. The duration of Bouchard activity record downtime accounted for 73% of the variance of sedentary time measured by the activPAL (coefficient 0.762, 95% CI 0.413 to 1.111). These data provide clinicians and caregivers with capacity to investigate strategies that would aim to increase activity in the nonexercise component of the activity continuum. [ABSTRACT FROM AUTHOR]

Rett syndrome is a rare but severe neurological disorder typically associated with a mutation in the MECP2 gene. We describe change in gross motor function over 3 to 4 years for 70 subjects participating in the Australian Rett Syndrome Database. Linear regression was used to assess relationships with age, genotype, and general and complex gross motor skills scores measured on the Gross Motor Scale for Rett syndrome. Skills were slightly better or maintained in approximately 40% of subjects and slightly decreased in approximately 60%. Teenagers and women who walked in 2004 were less likely to lose complex skills than those younger. Girls with a p.R294X mutation were more likely to lose complex motor skills, otherwise skill changes were spread across the mutation categories. In conclusion, small changes were observed over this period with greater stability of skills in teenagers and women with the ability to walk. [ABSTRACT FROM AUTHOR]

The early developmental history prior to the manifestation of Rett syndrome features is of clinical interest. This study describes the attainment of gross developmental milestones and regression, and assesses the relationships between genotype and age at diagnosis. The Australian Rett Syndrome Database and International Rett Syndrome Phenotype Database were used to source a total of 293 confirmed female subjects. Most girls learned to sit, were able to babble or use words, and approximately half learned to walk. Altered milestone attainment was associated with earlier diagnosis. There was variation in the acquisition of milestones, the age of regression, and the age of diagnosis by genotype. Most parents expressed concerns about unusual behaviors or development during infancy, and a more subtle atypical development during infancy was reported for most girls. It is important for clinicians to be aware of variable early development in Rett syndrome and that timely genetic testing is not precluded on this account. [ABSTRACT FROM PUBLISHER]

Aim: To investigate developmental trajectories in early childhood and predictors of class assignment. Methods: Data were available for Gen2 infants at 12 (n = 2275), 24 (n = 1845) and 36 (n = 2110) months of age in the Raine Study. Latent growth class analysis was used to identify developmental trajectories based on the Ages and Stages Questionnaire. Multivariate logistic regression analyses were used to estimate associations between foetal growth restriction, gestational age, child biological sex, breast feeding, parental age, socioeconomic factors and developmental trajectories. Results: Two groups of infants were identified, one typically performing and one poorer performing. Being born early-term, pre-term and male were associated with poorer development. Not exposed to breastfeeding was associated with the lower trajectories in the adaptive and personal-social domains. Conclusions: Developmental surveillance and advice for early-term infants should be considered. Findings highlight the continued need to support and promote breastfeeding as a protective mechanism for child development. [ABSTRACT FROM AUTHOR]