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CDKL5 Deficiency Disorder (CDD) is a rare genetic disorder with symptoms of epilepsy, developmental impairments, and other comorbidities. Currently, there are no outcome measures for CDD with comprehensive evidence of validation. This study aimed to evaluate the psychometric properties of the Quality of Life Inventory-Disability (QI-Disability) in CDD. Quality of Life Inventory-Disability was administered to 152 parent caregivers registered with the International CDKL5 Disorder Database (ICDD). Confirmatory factor analysis was conducted and the goodness of fit of the factor structure was assessed. Fixed-effects linear regression models examined the responsiveness of QI-Disability to reported changes in child health. A subset of parent caregivers (n = 56) completed QI-Disability, as well as additional health-related questions, on two occasions separated by four weeks to evaluate test-retest reliability. Test-retest reliability was assessed using intra-class correlations (ICCs) calculated from QI-Disability scores. Based upon adjustments for changes in child health, ICCs were recalculated to estimate responsiveness to change. Confirmatory factor analysis, internal consistency, and divergent validity were mostly satisfactory, except divergent validity was not satisfactory for the Social Interactions and Independence domains. The Physical Health, Social Interactions, Leisure, and Total scores responded to changes in the child's Physical health, and the Negative Emotions and Leisure domains responded to changes in the child's behavior. Unadjusted and adjusted ICC values were above 0.8 for the Positive Emotions, Negative Emotions, Social Interactions, Leisure, Independence domains and Total score, and above 0.6 for the Physical Health domain. Findings suggest that QI-Disability is suitable to assess the quality of life of children and adults with CDD and could be of value for upcoming clinical trials., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Helen Leonard: Consultancy for Marinus, Newron, Anavex, GW Pharmaceuticals, Orion and AveXis; Clinical Trials with Newron and Anavex; All remuneration has been made to her department. Tim A. Benke: Consultancy for AveXis, Ovid, GW Pharmaceuticals, International Rett Syndrome Foundation, Takeda, Neurogene, Ultragenyx, Zogenix, GrinTherapeutics, Alcyone, and Marinus; Clinical Trials with Acadia, Ovid, GW Pharmaceuticals, Marinus, and RSRT; All remuneration has been made to his department. Scott Demarest: Consultancy for Biomarin, Neurogene, Marinus, Tysha, Ultragenyx, and Ovid Therapeutics. He has funding from the NIH, project 8P, and Mila's Miracle Foundation. He also serves on the advisory board for the non-profit foundations SLC6A1 Connect, Project 8P, Ring14 USA, and FamilieSCN2A. Eric Marsh: Consultancy for Stoke therapeutics, Cipla pharmaceuticals. Clinical trials with Acadia, GW pharma, Marinus, RSRT, Biopharm, Stoke therapeutics, and Zogenix Pharmaceuticals. Jenny Downs: Consultancy for Marinus, Newron, Ultragenyx, AveXis, Orion, and Taysha; Clinical Trials with Newron and Anavex; All remuneration has been made to her department. Peter Jacoby and Jacinta Saldaris report no disclosures or conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To compare quality of life (QOL) across diagnoses associated with intellectual disability, construct QOL profiles and evaluate membership by diagnostic group, function and comorbidities., Method: Primary caregivers of 526 children with intellectual disability (age 5-18 years) and a diagnosis of cerebral palsy, autism spectrum disorder, Down syndrome, CDKL5 deficiency disorder or Rett syndrome completed the Quality of Life Inventory-Disability (QI-Disability) questionnaire. Latent profile analysis of the QI-Disability domain scores was conducted., Results: The mean (SD) total QOL score was 67.8 (13.4), ranging from 60.3 (14.6) for CDD to 77.5 (11.7) for Down syndrome. Three classes describing domain scores were identified: Class 1 was characterised by higher domain scores overall but poorer negative emotions scores; Class 2 by average to high scores for most domains but low independence scores; and Class 3 was characterised by low positive emotions, social interaction, and leisure and the outdoors scores, and extremely low independence scores. The majority of individuals with autism spectrum disorder and Down syndrome belonged to Class 1 and the majority with CDKL5 deficiency disorder belonged to Class 3. Those with better functional abilities (verbal communication and independent walking were predominately members of Class 1 and those with frequent seizures were more often members of Class 2 and 3., Conclusion: The profiles illustrated variation in QOL across a diverse group of children. QOL evaluations illustrate areas where interventions could improve QOL and provide advice to families as to where efforts may be best directed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to devise an evidence-based missing data rule for the Quality of Life Inventory-Disability (QI-Disability) questionnaire specifying how many missing items are permissible for domain and total scores to be calculated using simple imputation. We sought a straightforward rule that can be used in both research and clinical monitoring settings., Method: A simulation study was conducted involving random selection of missing items from a complete data set of questionnaire responses. This comprised 520 children with intellectual disability from 5 diagnostic groups. We applied a simple imputation scheme, and the simulated distribution of errors induced by imputation was compared with the previously estimated standard error of measurement (SEM) for each domain., Results: Using a stringent criterion, which requires that the 95th percentile of absolute error be less than the SEM, 1 missing item should be permitted for 2 of the 6 QI-Disability subdomain scores to be calculated and 1 missing item per domain for the total score to be calculated. Other, less stringent criteria would allow up to 2 missing items per domain., Conclusion: Empirical evidence about the impact of imputing missing questionnaire responses can be gathered using simulation methods applied to a complete data set. We recommend that such evidence be used in devising a rule that specifies how many items can be imputed for a valid score to be calculated., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The study investigated the effect of seizure and medication burden at initial contact with the International CDKL5 Disorder Database on subsequent development and clinical severity and compared quality of life among those whose development progressed, remained stable, or regressed between baseline and follow-up., Methods: The effects of seizure and medication burden at baseline (high or low) on the CDKL5 Disorder Severity Scores and CDKL5 Developmental Score (CDS) at follow-up were assessed using linear and negative binomial regressions, respectively, with adjustment for age at baseline, gender, and follow-up duration with and without genotype. Seizure and medication burden were defined by average daily seizure count (high, ≥5/day; low, <5/day) and number of antiseizure medications (high, ≥3/day; low, <3/day), respectively. The effects of change in CDS over time (improved, stable, or deteriorated) on Quality of Life Inventory-Disability (QI-Disability) total and domain scores at follow-up were assessed in those aged at least 3 years at follow-up using linear regression models with adjustment for baseline CDS, gender, and follow-up duration., Results: The expected follow-up CDS was lower for individuals with high compared to low seizure burden at baseline (β = -.49, 95% confidence interval [CI] = -.84 to -.13). The average total QI-Disability score was 5.6 (95% CI = -.2 to 11.5) points higher among those with improved compared with stable or deteriorating CDS and 8.5 (95% CI = 3.1-13.8) points lower for those with deteriorating compared to stable or improved CDS., Significance: Our finding that later development showed slight improvement in those with better earlier seizure control even after adjustment for genotype suggests that the trajectory for an individual child is not necessarily predetermined and could possibly be influenced by optimal seizure management. This has implications for children's quality of life., (© 2021 International League Against Epilepsy.)

Background: Rett syndrome is a genetically caused neurodevelopmental disorder associated with functional deficits and comorbidities. This study investigated relationships between genotype, functional abilities and comorbidities and quality of life in Rett syndrome., Methods: The International Rett Syndrome Database, InterRett, was used as a sampling frame for this observational study. Information was collected to describe functional abilities (walking and feeding), health (Sleep Disorder Scale for Children, the Rett Syndrome Behavioural Questionnaire), parental health (12-item Short Form Health Survey) sociodemographic factors (parental employment and education) and quality of life (Quality of Life Inventory-Disability) for 210 individuals with Rett syndrome. Univariate and multivariate regressions were used to analyse the relationships between the independent variables and quality of life., Results: Compared with individuals with the p.Arg270* mutation, those with the p.Arg294* mutation type had the poorest quality of life (coeff -12.81, 95% CI -23.49 to 2.12), despite this being recognised as a clinically milder genotype. Overall better walking and feeding skills and seizure parameters were more associated with better quality of life and poor sleep and behavioural difficulties with poorer quality of life., Conclusions: These findings suggest that genotype, functioning and health each have implications for quality of life and should be considered when counselling families and planning clinical and support management strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many children with intellectual disability live with medical comorbidities. This study examined the impacts of comorbidities on quality of life (QOL) of children with intellectual disabilities and whether impacts varied with caregiver perceptions that medical needs had been met., Methods: Primary caregivers of 447 children (aged 5-19 years) with an intellectual disability reported on their child's medical comorbidities and the extent to which they perceived their child's medical needs had been met in a cross-sectional observational study. The Quality of Life Inventory-Disability was used to measure QOL on a 100-point scale. Linear regression models including interaction terms were used to evaluate their associations., Results: Parent-reported recurrent child pain (-4.97, 95% CI -8.21, -1.72), night-time sleep disturbances (-4.98, 95% CI -7.23, -2.73), daytime somnolence (-8.71, 95% CI -11.30, -2.73), seizures that occurred at least weekly (-7.59, 95% CI -13.50, -1.68) and conservatively managed severe scoliosis (-7.39, 95% CI -12.97, -1.81) were negatively associated with child QOL. Despite the majority of parents (~70%) perceiving that their child's medical needs had been met to a great extent, this did not significantly moderate the association between any comorbidities and QOL., Conclusions: Comorbidities were common and had marked associations with QOL. Evaluation and management of pain and sleep disturbance continue to be high priorities in improving QOL of young people with intellectual disabilities. Further research on the optimal methods of managing these comorbidities is warranted., (© 2021 John Wiley & Sons Ltd.)

Aims: To investigate associations between functioning, community participation, and quality of life (QoL) and identify whether participation mediates the effects of functioning on QoL., Method: The caregivers of 435 children (211 females, 224 males; mean age 12y; SD 3y 11mo; age range 5-18y) with intellectual disability and autism spectrum disorder, cerebral palsy, Down syndrome, or Rett syndrome reported on their child's functioning (dependence for managing personal needs, mobility, communication, eye contact when speaking), frequency of participation, and QoL. Linear regression and mediation analyses were used to evaluate the relationships between child functioning, participation, and QoL., Results: Children with greater dependency for managing personal needs and limited eye contact when speaking experienced poorer QoL. Less impaired functioning was associated with more frequent participation, which, in turn, was associated with a 3-point gain in QoL for each additional point in frequency of participation (coefficient=2.67, 95% confidence interval 1.56-3.78). The effect of impaired functioning on QoL was partially mediated by participation in children with greater dependency in managing personal needs and those with mildly impaired communication., Interpretation: Greater levels of impairments with poorer functioning, notably a high level of dependence, were associated with poorer QoL. Poorer QoL can be partly explained by less frequent community participation., (© 2020 Mac Keith Press.)

Purpose: Rett syndrome (RTT) is a rare neurodevelopmental disorder mainly affecting females and is caused by a mutation in the MECP2 gene. Recent research identified the domains of quality of life (QOL) important for children with RTT but there has been no investigation of domains important for adults. This qualitative study explored QOL in adults with RTT and compared domains with those previously identified for children. Methods: The sample comprised parents and/or primary caregivers of 20 adults, aged 18-38 years, who were registered with the Australian Rett Syndrome Database. Semi-structured telephone interviews were conducted to investigate aspects of life that were observed to be satisfying or challenging. Data were analyzed using directed content analysis, based on existing QOL domains for children with RTT that related to health and wellbeing, daily activities, and community immersion and services. Results: Each of the domains identified for children with RTT was represented in the adult dataset, with no new domains emerging. Conclusion: This is the first study to identify QOL domains important for adults with RTT. Health and therapy needs are ongoing during adulthood but services may be limited. Findings will guide choice of an appropriate QOL measure for this group.IMPLICATIONS FOR REHABILITATIONKnowing the important domains of quality of life enables clinicians and service providers to systematically review and address key management issues.Despite a high level of dependency and sometimes poor health, parent caregivers perceive potential for strong quality of life in adulthood.Services that maintain functional skills and health throughout the lifespan are valued for their support of quality of life in adults with Rett syndrome.

Objective: Children with intellectual disability and marked feeding difficulties may undergo gastrostomy insertion to assist with their nutritional and medication needs. Use has increased recently for younger children, and it is intended to provide long-term support. This study explored the perceived value of gastrostomy for the quality of life (QOL) of children with intellectual disabilities and their families., Methods: Twenty-one primary caregivers of children with intellectual disability aged 2-18 years participated in semistructured telephone interviews. Data were analysed using directed content analysis, and data were coded to existing QOL domains relevant to children with intellectual disability and their families., Results: Benefits in each of the child and family QOL domains were represented in the interview data. For children, the impacts of gastrostomy for the physical health domain were predominant, supplemented by experiences of value for emotional well-being, social interactions, leisure activities and independence. For families, gastrostomy was integrated into multiple aspects of QOL relating to family interactions, parenting, resources and supports, health and safety, and advocacy support for disability. Shortcomings related to difficulties with equipment and complications., Conclusions: Our comprehensive overview of the value of gastrostomy for children with intellectual disability and their families was classified within a QOL framework. Gastrostomy was mainly supportive over long time periods across many QOL domains. Findings will be of use to patient counselling and education and the development of family support resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess responsiveness and reproducibility using the estimates of test-retest reliability for the Quality of Life Inventory-Disability (QI-Disability), accounting for changes in child health and parental stress., Method: Quality of Life Inventory-Disability was administered twice over a 1-month period to a sample of 55 primary caregivers of children (aged 5-19 years) with intellectual disability. Caregivers also reported their child's physical and mental health and completed a 4-item Perceived Stress Scale to assess parental stress. Fixed-effects linear regression models examined responsiveness of QI-Disability to the reported change in child health and parental stress. Reliability was then assessed using intraclass correlations (ICCs) calculated from QI-Disability scores adjusted for changes in child health and parental stress., Results: Five of 7 unadjusted ICC values indicated at least moderate agreement (>0.70), and 2 values indicated fair agreement. After accounting for changes in child health and parental stress, adjusted ICC values showed substantial agreement for the total QI-Disability score and 4 domain scores (adjusted ICC ≥ 0.80). Adjusted ICC scores indicated moderate agreement for the Physical Health domain (adjusted ICC = 0.68) and fair agreement for the Positive Emotions domain (adjusted ICC = 0.58). Improvements in a child's physical health rating were associated with higher total, Physical Health, and Positive Emotion domain scores, whereas improvements in mental health were associated with higher total and Negative Emotions domain scores, indicating better quality of life. Changes in parental stress did not have a statistically significant relationship with quality of life., Conclusion: Satisfactory test-retest reliability was shown. Preliminary evidence indicates that QI-Disability is responsive to changes in child health, but not to differing levels of parental stress.

Prader-Willi syndrome (PWS) is a rare genetic condition with multi-system involvement. The literature was reviewed to describe neurodevelopment and the behavioural phenotype, endocrine and metabolic disorders and respiratory and sleep functioning. Implications for child and family quality of life were explored. Challenging behaviours contribute to poorer well-being and quality of life for both the child and caregiver. Recent evidence indicates healthy outcomes of weight and height can be achieved with growth hormone therapy and dietary restriction and should be the current target for all individuals with PWS. Gaps in the literature included therapies to manage challenging behaviours, as well as understanding the effects of growth hormone on respiratory and sleep function. New knowledge regarding the transition of children and families from schooling and paediatric health services to employment, accommodation and adult health services is also needed. Developing a national population-based registry could address these knowledge gaps and inform advocacy for support services that improve the well-being of individuals with PWS and their families., (© 2019 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Focus is shifting to better understand the lived experiences of children with intellectual disability in relation to their quality of life (QOL). Yet no available QOL measures are grounded in the domains important for this population. We previously conducted qualitative parent caregiver interviews identifying QOL domains in children with intellectual disability to constitute a new measure of QOL. This study describes the content validity of the Quality of Life Inventory-Disability (QI-Disability), a parent-report measure developed for children with intellectual disability., Methods and Results: Questionnaire items were extracted from a qualitative dataset of 77 parent caregiver interviews. To establish content validation, a draft of QI-Disability was administered to 16 parent caregivers of children with intellectual disability (Down syndrome, Rett syndrome, cerebral palsy, or autism spectrum disorder). Parents participated in a cognitive interviewing procedure known as the "think-aloud" method. The process of item generation, cognitive debriefing, and refinement of QI-Disability prior to its pilot testing are described. A conceptual framework is presented., Conclusions: Satisfactory content validity is reported, where ongoing consumer feedback shaped the dataset from which the final items were selected. Use of QI-Disability for children with intellectual disability will allow for greater insight into service utility and targeted intervention., (© 2019 John Wiley & Sons Ltd.)

Purpose: Children with intellectual disability encounter daily challenges beyond those captured in current quality of life measures. This study evaluated a new parent-report measure for children with intellectual disability, the Quality of Life Inventory-Disability (QI-Disability)., Methods: QI-Disability was administered to 253 primary caregivers of children (aged 5-18 years) with intellectual disability across four diagnostic groups: Rett syndrome, Down syndrome, cerebral palsy or autism spectrum disorder. Exploratory and confirmatory factor analyses were conducted and goodness of fit of the factor structure assessed. Associations between QI-Disability scores, and diagnostic and age groups were examined with linear regression., Results: Six domains were identified: physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors, and independence. Goodness-of-fit statistics were satisfactory and similar for the whole sample and when the sample was split by ability to walk or talk. On 100 point scales and compared to Rett syndrome, children with Down syndrome had higher leisure and the outdoors (coefficient 10.6, 95% CI 3.4,17.8) and independence (coefficient 29.7, 95% CI 22.9, 36.5) scores, whereas children with autism spectrum disorder had lower social interaction scores (coefficient - 12.8, 95% CI - 19.3, - 6.4). Scores for positive emotions (coefficient - 6.1, 95% CI - 10.7, - 1.6) and leisure and the outdoors (coefficient 5.4, 95% CI - 10.6, - 0.1) were lower for adolescents compared with children., Conclusions: Initial evaluation suggests that QI-Disability is a reliable and valid measure of quality of life across the spectrum of intellectual disability. It has the potential to allow clearer identification of support needs and measure responsiveness to interventions.

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.

Background: Rett syndrome (RTT) is a rare neurodevelopmental disorder leading to multiple disabilities and high dependency on caregivers. This study aimed to: (1) describe the patterns of sedentary time and daily steps and (2) identify the association of individual and environmental characteristics with sedentary time., Methods: All Danish females with RTT older than 5 years of age and with a MECP2 mutation were invited to participate. The activPAL and StepWatch Activity Monitor (SAM) were worn by participants for at least four days. Sedentary time and step counts were plotted by time to examine daily activity patterns. Associations between sedentary time and individual and environmental covariates were assessed with linear regression models., Results: The median (interquartile range) age of participants was 22.0 (14.3-36.5) years. On average 83.3% (standard deviation 13.9%) of waking hours were spent in sedentary behaviours (n = 48) and the median (interquartile range) daily step count was 5128 (2829-7704) (n = 28). Females older than 33.5 years, and those unable to walk independently were more sedentary., Conclusions: This study demonstrated high levels of sedentary time and low daily step counts in a Danish population of females with RTT. Advancing age and lower walking skills were associated with higher levels of sedentary time. Implications for Rehabilitation Sedentary lifestyles in individuals with disabilities have a negative impact on health and quality of life. High levels of sedentary time and low daily step counts were demonstrated in a Danish population of females with Rett syndrome. Advancing age and inability to walk independently were strongly associated with higher levels of sedentary time in females with Rett syndrome. Understanding patterns of sedentary behaviour and physical activity can aid health care professionals in developing health-promoting physical activity interventions.

Background: Young people with Down syndrome experience varying abilities in activities of daily living, cognitive functioning, behaviour and social skills. The aim of this research was to investigate, from a carer's perspective, the factors that influenced the quality of life of these young people., Methods: Families of young people with Down syndrome (n = 197), aged 16-31 years, living in Western Australia, took part in a questionnaire study regarding young person daily functioning, family characteristics, medical background and quality of life measured by the Kidscreen 27-item scale. Kidscreen-10 total score was used as an outcome in the investigation of determinants with higher scores indicating better quality of life., Results: After adjustment for confounders including carer's mental health measured by the Depression and Anxiety Scale (DASS), global impact of illness as well as impact of mental health and bowel conditions were all negatively associated with the young person's quality of life. Young people who had three or more friends had better quality of life than those with no friends. Scores were lower (reflecting poor quality of life) in individuals who had more behavioural problems but these relationships were attenuated after adjustment for confounders and DASS., Conclusions: Overall, our findings revealed that quality of life of young people with Down syndrome was most negatively associated with burden of medical conditions, but also with lack of friendships. We were somewhat surprised to find the effect of medical problems on quality of life persisting into adolescence and adulthood where in general the burden of medical comorbidities is much less than in childhood., Competing Interests: The authors have declared that no competing interests exist.

Aim: To describe health-related quality of life of Australian children and adolescents with Down syndrome and compare it with norm-referenced data., Method: A cross-sectional survey was conducted with parents of 75 children and adolescents (43 males, 32 females) with Down syndrome aged 5 to 18 years (mean age 13y 2mo, SD 4y 8mo). The proxy-report KIDSCREEN-27 questionnaire was administered and five dimensions of health-related quality of life were measured. Data were analysed descriptively and compared with normative data., Results: Total group mean scores for psychological well-being, autonomy and parent relation, and school environment dimensions were within normal threshold values, whereas mean scores for physical well-being, and social support and peers dimensions, were poorer. For participants with Down syndrome aged 8 to 18 years, the difference with normative data for proxy-reported physical well-being, psychological well-being, and social support and peers dimensions favoured typically developing children. Adolescents (13-18y) with Down syndrome scored poorer on all dimensions than children (5-12y) with Down syndrome., Interpretation: Our findings assist a better understanding of the lived experiences of children and adolescents with Down syndrome, as perceived by their parents, and suggest aspects of health that could be influenced to optimize their quality of life., What This Paper Adds: Proxy-reported psychological well-being and autonomy were within the normal range for children with Down syndrome. Physical well-being and social support scores were significantly lower than normative data. Proxy-reported scores for adolescents with Down syndrome were consistently poorer than for children with Down syndrome and the differences were clinically important., (© 2018 Mac Keith Press.)

Objective: There are many challenges to health, functioning, and participation for children with Down syndrome; yet, the quality-of-life (QOL) domains important for this group have never been clearly articulated. This study investigated parental observations to identify QOL domains in children with Down syndrome and determined whether domains differed between children and adolescents., Methods: The sample comprised 17 families whose child with Down syndrome was aged 6 to 18 years. Primary caregivers took part in semistructured telephone interviews to explore aspects of their child's life that were satisfying or challenging. Qualitative thematic analysis was implemented using a grounded theory framework to identify domains. The coded data set was divided into 2 groups (childhood and adolescence) at 3 age cut points to observe whether differences existed between the coded domains and domain elements: (1) 6 to 11 years with 12 to 18 years; (2) 6 to 13 years with 14 to 18 years; and (3) 6 to 15 years with 16 to 18 years., Results: Eleven domains were identified: physical health, behavior and emotion, personal value, communication, movement and physical activity, routines and predictability, independence and autonomy, social connectedness and relationships, variety of activities, nature and outdoors, and access to services. No differences in domains and domain elements were identified across childhood and adolescence., Conclusion: Our data form a preliminary framework from which to design investigations of the child's perspectives on life quality and suggest a range of necessary supports and services., Competing Interests: The authors have no potential, perceived or real conflict of interest to report. The study sponsors have had no role in determining any aspects of the study design; the collection, analysis and interpretation of the data; the writing of this paper; or the decision to submit this manuscript for publication.

Background: Although research in this area remains sparse, raising a child with some genetic disorders has been shown to adversely impact maternal health and family quality of life. The aim of this study was to investigate such impacts in families with a child with the CDKL5 disorder, a newly recognised genetic disorder causing severe neurodevelopmental impairments and refractory epilepsy., Methods: Data were sourced from the International CDKL5 Disorder Database to which 192 families with a child with a pathogenic CDKL5 mutation had provided data by January 2016. The Short Form 12 Health Survey Version 2, yielding a Physical Component Summary and a Mental Component Summary score, was used to measure primary caregiver's wellbeing. The Beach Center Family Quality of Life Scale was used to measure family quality of life. Linear regression analyses were used to investigate relationships between child and family factors and the various subscale scores., Results: The median (range) age of the primary caregivers was 37.0 (24.6-63.7) years and of the children was 5.2 (0.2-34.1) years. The mean (SD) physical and mental component scores were 53.7 (8.6) and 41.9 (11.6), respectively. In mothers aged 25-54 years the mean mental but not the physical component score was lower than population norms. After covariate adjustment, caregivers with a tube-fed child had lower mean physical but higher mean mental component scores than those whose child fed orally (coefficient = -4.80 and 6.79; p = 0.009 and 0.012, respectively). Child sleep disturbances and financial hardship were negatively associated with the mental component score. The mean (SD) Beach Center Family Quality of Life score was 4.06 (0.66) and those who had used respite services had lower scores than those who had not across the subscales., Conclusions: Emotional wellbeing was considerably impaired in this caregiver population, and was particularly associated with increased severity of child sleep problems and family financial difficulties. Family quality of life was generally rated lowest in those using respite care extensively, suggesting that these families may be more burdened by daily caregiving.

Rett syndrome is a neurodevelopmental disorder mainly affecting females and associated with a mutation on the MECP2 gene. There has been no systematic evaluation of the domains of quality of life (QOL) in Rett syndrome. The aims of this study were to explore QOL in school-aged children with Rett syndrome and compare domains with those identified in other available QOL scales. The sample comprised 21 families registered with the Australian Rett Syndrome Database whose daughter with Rett syndrome was aged 6-18 years. Semi-structured telephone interviews were conducted with each parent caregiver (19 mothers, 2 fathers) to investigate aspects of their daughter's life that were satisfying or challenging to her. Qualitative thematic analysis using a grounded theory framework was conducted, and emerging domains compared with those in two generic and three disability parent-report child QOL measures. Ten domains were identified: physical health, body pain, and discomfort, behavioral and emotional well-being, communication skills, movement and mobility, social connectedness, variety of activities, provision of targeted services, stability of daily routines, and the natural environment. The two latter domains were newly identified and each domain contained elements not represented in the comparison measures. Our data articulated important aspects of life beyond the genetic diagnosis. Existing QOL scales for children in the general population or with other disabilities did not capture the QOL of children with Rett syndrome. Our findings support the construction of a new parent-report measure to enable measurement of QOL in this group., (© 2015 Wiley Periodicals, Inc.)

Background: The concept of disability is now understood as a result of the interaction between the individual, features related to impairment, and the physical and social environment. It is important to understand these environmental influences and how they affect social participation. The purpose of this study is to describe the social participation of young adults with Down syndrome and examine its relationship with the physical and social environment., Methods: Families ascertained from the Down syndrome 'Needs Opinion Wishes' database completed questionnaires during 2011. The questionnaires contained two parts, young person characteristics and family characteristics. Young adults' social participation was measured using the Assessment of Life Habits (LIFE-H) and the influences of environmental factors were measured by the Measure of the Quality of the Environment (MQE). The analysis involved descriptive statistics and linear and logistic regression., Results: Overall, participation in daily activities was higher (mean 6.45) than in social roles (mean 5.17) (range 0 to 9). When the physical and/or social environment was reported as a facilitator, compared to being no influence or a barrier, participation in social roles was greater (coef 0.89, 95%CI 0.28, 1.52, coef 0.83, 95%CI 0.17, 1.49, respectively). The relationships between participation and both the physical (coef 0.60, 95% CI -0.40, 1.24) and social (coef 0.20, 95%CI -0.47, 0.87) environments were reduced when age, gender, behavior and functioning in ADL were taken into account., Conclusion: We found that young adults' participation in social roles was influenced more by the physical environment than by the social environment, providing a potentially modifiable avenue for intervention.

Purpose: To explore relationships between family quality of life, day occupations and activities of daily living (ADL) of young persons with Down syndrome., Method: Data were collected from 150 families with a young person with Down syndrome aged 16-30 years participating in the Down syndrome "Needs Opinions Wishes" database. Data described the young person's characteristics (including functional abilities, behaviour and day occupations) and family characteristics (including income, family and community supports and quality of life)., Results: Compared to families of young people attending open employment, families of young people participating in sheltered employment tended to report poorer family quality of life, after adjusting for personal characteristics, behaviour and income (coeff -6.78, 95 % CI -14.38, 0.81). Family supports reduced this relationship (coeff -6.00, 95 % CI -12.76, 0.76). Families of young people with greater functioning in ADL reported better family quality of life regardless of personal and environmental factors (coeff 0.45, 95 % CI 0.05, 0.85) and inclusion of family factors such as family supports reduced this association (coeff 0.29, 95 % CI -0.10, 0.67)., Conclusions: Participation of young people with Down syndrome in open employment may positively influence family quality of life. Services that facilitate functioning in ADL and assist the families in accessing suitable family supports have the potential to positively influence family quality of life.

Purpose:  To describe leisure participation for school-aged children with Down syndrome and to investigate how factors, classified by the World Health Organisation's International Classification of Functioning, Disability and Health, influence their leisure participation., Method:  Families in Western Australia with a child aged 5-18 years with Down syndrome were surveyed in a population-based study (n = 208) in 2004., Results:  One-third of parents reported that their child with Down syndrome had no friends although half reported two or more friends. Factors affecting number of friendships included the child's functional ability, behavioural issues and parent's availability of time. Those children with higher functional independence scores in daily tasks were more likely to have two or more friends than those with lower functional independence scores (OR: 1.02, 95% CI 1.01-1.04 for a single point increase in WeeFIM score). All children participated in predominantly solitary and sedentary leisure activities., Conclusions:  Leisure participation was affected by complex factors both within and external to the child with Down syndrome. Further investigation of the relevance of these factors to leisure may enable more satisfying and meaningful participation in leisure for school-aged children with Down syndrome.

Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by neurodevelopmental delays, hyperphagia, difficulties with social communication and challenging behaviours. Individuals require intensive supervision from caregivers which may negatively affect caregiver quality of life. This study used data collected in the Australasian PWS Registry (n = 50, mean age 11.2 years) to evaluate associations between child behaviours and caregiver mental well-being. Symptoms of sleep-related breathing disorder, child depression and social difficulties were associated with poorer caregiver mental and physical well-being. Growth hormone therapy use was associated with better caregiver mental and physical well-being. Optimising management of problematic behaviours and sleep disturbances have the potential to support caregivers who are the most vital network of support for individuals affected by PWS.

Objective: To use a model of health learning to examine the role of health-learning capacity and the effect of a school-based oral health education intervention (Winning Smiles) on the health outcome, child oral health-related quality of life (COHRQoL). Setting: Primary schools, high social deprivation, Ireland/Northern Ireland. Design: Cluster randomised controlled trial. Method: A total of 383, 7- to 8-year-old children were invited to participate and randomly allocated into intervention and control conditions. Baseline and 12-month follow-up assessments of COHRQoL, self-esteem, toothbrushing-fluoride toothpaste knowledge and unstimulated saliva samples were made. An 18-hour post-brushing, saliva fluoride concentration was used to assess toothbrushing with fluoride toothpaste (behaviour). The data were entered onto SPSSv22. Structural equation modelling was applied using AMOSv22 to test for the role of health-learning capacity (baseline self-esteem and COHRQoL) and simultaneous effects of Winning Smiles upon knowledge, behaviour and COHRQoL (at follow-up). Results: A total of 238 children participated at baseline and follow-up. A partial latent hybrid model fitted the data reasonably well (X[superscript 2] = 65.6, df = 50, p = 0.07) as shown in addition by a Comparative Fit Index of 0.97 and a Root Mean Square Error of Approximation (RMSEA) value of 0.042 (90% confidence interval [CI]: 0.00, 0.06). The intervention had a significant effect on toothbrushing-fluoride toothpaste knowledge (p < 0.03) and an effect on COHRQoL at the 6% level (p < 0.06). Knowledge was strongly associated with saliva fluoride concentration (p < 0.002). The model of health-learning capacity assisted in explaining the effect of a school-based intervention upon knowledge, toothbrushing behaviour and tentatively on COHRQoL.

Summary: Cyclin‐dependent kinase‐like 5 (CDKL5) gene pathogenic variants result in CDKL5 deficiency disorder (CDD). Early onset intractable epilepsy and severe developmental delays are prominent symptoms of CDD. Comorbid sleep disturbances are a major concerning symptom for families. We aimed to explore the relationship between insomnia, daytime sleepiness, sleep medications and quality of life in children with CDD. Caregivers of 129 children with CDD in the International CDKL5 Disorder Database completed the Quality‐of‐Life Inventory‐Disability (QI‐Disability) questionnaire and "Disorders of Maintaining Sleep" (DIMS) and the "Disorders of Excessive Somnolence" (DOES) items of the Sleep Disturbance Scale for Children. Adjusting for covariates, a unit increase in DOES score was associated with reduced quality of life total (coefficient −3.06, 95% confidence interval [CI] 1.35–7.80), physical health (coefficient −7.20, 95% CI −10.64, −3.76) and negative emotions (coefficient −3.90, 95% CI −7.38, −0.42) scores. Adjusting for covariates, a unit increase in DIMS score was associated with reduced negative emotions (coefficient −6.02, 95% CI −10.18, −2.86). Use of sleep medications had small influences on the effect sizes. This study highlights the importance of sleep problems as a determinant of quality of life in children with CDD, consistent with effects observed for other groups of children with intellectual disability. Excessive daytime sleepiness was particularly associated with detrimental effects on quality of life. Further research in optimal behavioural and pharmaceutical management of sleep problems for this population is required. [ABSTRACT FROM AUTHOR]

The natural history of MECP2 duplication syndrome (MDS), a rare X-linked neurodevelopmental disorder with an estimated birth prevalence of 1/150,000 live births, is poorly understood due to a lack of clinical data collected for research. Such information is critical to the understanding of disease progression, therapeutic endpoints and outcome measures for clinical trials, as well as the development of therapies and orphan products. This clinical information can be systematically collected from caregivers through data collation efforts—yet, no such database has existed for MDS before now. Here, in this methodological study, we document the development, launch and management of the international MECP2 Duplication Database (MDBase). The MDBase consists of an extensive family questionnaire that collects information on general medical history, system-specific health problems, medication and hospitalisation records, developmental milestones and function, and quality of life (for individuals with MDS, and their caregivers). Launched in 2020, in its first two years of operation the MDBase has collected clinical data from 154 individuals from 26 countries—the largest sample size to date. The success of this methodology for the establishment and operation of the MDBase may provide insight and aid in the development of databases for other rare neurodevelopmental disorders. [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]

To investigate modifiable child and caregiver factors influencing community participation among children with Down syndrome. Cross-sectional data from a study investigating quality of life of children with intellectual disability were analysed. Participants were caregivers of 89 children with Down syndrome (54 females; 83 school attenders) (mean age 11 y 1 mo; SD 4 y 1 mo). Components of participation (attendance, involvement) were measured using the Participation and Environment Measure for Children and Youth, community module. Caregiver factors were time, mood, transport, and disability funding. Child factors were sleep, behaviour, communication, and health. Multivariate linear regression analyses examined if (i) caregiver factors were associated with attendance and (ii) child factors were associated with involvement. Increased caregiver time availability was associated with higher frequency of attendance. Higher frequency of attendance was associated with greater child involvement, and having a sleep breathing disorder and less verbal communication ability was associated with less child involvement. These factors combined explained 21% of the variance. Children with Down syndrome who participated in the community more frequently enjoyed greater involvement. Supporting participation of children with poorer verbal communication and/or sleep breathing disorders could further the participation of children with Down syndrome. Children with Down syndrome who more frequently attended opportunities for participation were more likely to be involved in those experiences. Healthcare providers and educators could foster involvement in participation opportunities of children with poorer verbal ability by supporting the development of prerequisite communication strategies. Rehabilitation programs and policies pertaining to accessibility of community activities need to align with modifiable determinants of participation in children, including availability of caregivers' time. [ABSTRACT FROM AUTHOR]

Objective: To review the effectiveness of oral health education and oral health promotion interventions for children and adolescents with intellectual and developmental disabilities (IDD), in ensuring optimal gingival health, caries experience and oral health‐related quality of life, compared to no interventions or alternative interventions. Methods: A systematic review was conducted to identify published studies from four databases (Medline, PsycINFO, CINAHL and ERIC). Randomised or quasi‐randomised controlled trials were included. Two independent reviewers performed risk of bias and qualitative analysis. Meta‐analysis was performed as appropriate. Results: Eight treatment comparisons were identified. There was low certainty evidence that fluoride interventions provided long‐term reductions in caries in those with IDD; and there was some evidence that chlorhexidine albeit with low certainty provided short‐term and long‐term reductions in plaque and gingivitis. There was moderate certainty evidence for short‐term reductions in dental plaque from the use of modified toothbrushes, but not compelling evidence for powered toothbrushes. Conclusions: Most studies provided a low quality of evidence, and so any adaptations made to oral health practices of individuals with IDD need to consider their individual needs. PROSPERO registration: CRD42019145784. [ABSTRACT FROM AUTHOR]

Summary: Children with intellectual disabilities are more likely to experience sleep disorders of insomnia, excessive daytime sleepiness and sleep breathing disorders than typically developing children. The present study examined risk factors for these sleep disorders in 447 children (aged 5–18 years), diagnosed with an intellectual disability and comorbid autism spectrum disorder, cerebral palsy, Down syndrome or Rett syndrome. Primary caregivers reported on their child's sleep using the Sleep Disturbance Scale for Children (SDSC), as well as medical comorbidities and functional abilities. Multivariate linear and logistic regressions were used to examine the effects of these factors on SDSC t scores and a binary indicator, respectively for the relevant subscales. Receiving operating characteristic curves were generated for each logistic regression model to determine their ability to discriminate between poor and good sleep. Comorbidities rather than functional abilities were associated with poorer sleep. In particular, recurrent pain, frequent seizures, frequent coughing, constipation and prescription of sleep medications were associated with abnormal sleep across the entire sample, but predictors differed between diagnostic groups. The present study suggests that comorbidities are more strongly associated with quality of sleep than functional impairments. The present study provides new information on potential associations between frequent coughing, prescription sleep medications and sleep quality that should be further investigated. [ABSTRACT FROM AUTHOR]

The CDKL5 deficiency disorder (CDD) is a rare condition caused by spontaneous mutations on the cyclin‐dependent kinase‐like 5 (CDKL5) gene. It is a severe and complex disability that markedly affects the individual's health and wellbeing. This study aimed to identify the quality of life (QOL) domains important for individuals with CDD. Twenty‐five parents of individuals registered in the International CDKL5 Disorder Database participated in semi‐structured telephone interviews to explore areas that supported or challenged their child's QOL. Rett syndrome (RTT) is another severe genetically‐caused neurodevelopmental disorder but is generally less severe than CDD. Qualitative data were analysed using directed content analysis, based on previously identified QOL domains for RTT that related to health and wellbeing, daily activities and community immersion and services. Each of the domains identified for RTT was represented in the CDD dataset overall and when the dataset was divided into three age groups: 3–5 years old; 6–18 years old; and older than 18 years. This is the first study to conceptualise factors important for individuals with CDD. Findings from this study will guide health professionals and other service providers who support individuals with CDD and will offer insight into choosing appropriate QOL instruments when measuring outcomes for this group. [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]

Sleep disturbances are debilitating for individuals with Rett syndrome (RTT) and their families yet the evidence base for management is poor. We investigated management strategies and their relationships with sleep problems. Data were provided by 364/461 (79%) families with a child with RTT and registered with the International RTT Phenotype Database. Logistic regression models were used to investigate relationships between impacts of sleep problems on the child and family with age group, mutation type, medication type, and sleep hygiene score. Linear regression models were used to estimate the association of disorders of initiating and maintaining sleep (DIMS) with age group, mutation type, medication type, and sleep hygiene. Among those who ever had difficulty falling asleep or night waking, use of any medication was associated with higher odds of moderate/major impact sleep problems (relative to minor/no impact) for the affected child and the family, as well as higher DIMS scores, when compared with the no treatment/nonmedication group accounting for the effects of age, mutation type, and sleep hygiene score. Better use of sleep hygiene practices was associated with lower odds of moderate/major impact on the family (odds ratio 0.60, 95% confidence intervals [CIs] 0.37, 0.98) and lower DIMS scores (geometric mean ratio 0.86, 95%CI 0.80, 0.92) compared with poorer use after adjusting for covariates. Attention to sleep hygiene remains an important management strategy for sleep problems in RTT. Further prospective research is required to investigate efficacy of pharmaceutical treatments. [ABSTRACT FROM AUTHOR]

Background: Although research in this area remains sparse, raising a child with some genetic disorders has been shown to adversely impact maternal health and family quality of life. The aim of this study was to investigate such impacts in families with a child with the CDKL5 disorder, a newly recognised genetic disorder causing severe neurodevelopmental impairments and refractory epilepsy.Methods: Data were sourced from the International CDKL5 Disorder Database to which 192 families with a child with a pathogenic CDKL5 mutation had provided data by January 2016. The Short Form 12 Health Survey Version 2, yielding a Physical Component Summary and a Mental Component Summary score, was used to measure primary caregiver's wellbeing. The Beach Center Family Quality of Life Scale was used to measure family quality of life. Linear regression analyses were used to investigate relationships between child and family factors and the various subscale scores.Results: The median (range) age of the primary caregivers was 37.0 (24.6-63.7) years and of the children was 5.2 (0.2-34.1) years. The mean (SD) physical and mental component scores were 53.7 (8.6) and 41.9 (11.6), respectively. In mothers aged 25-54 years the mean mental but not the physical component score was lower than population norms. After covariate adjustment, caregivers with a tube-fed child had lower mean physical but higher mean mental component scores than those whose child fed orally (coefficient = -4.80 and 6.79; p = 0.009 and 0.012, respectively). Child sleep disturbances and financial hardship were negatively associated with the mental component score. The mean (SD) Beach Center Family Quality of Life score was 4.06 (0.66) and those who had used respite services had lower scores than those who had not across the subscales.Conclusions: Emotional wellbeing was considerably impaired in this caregiver population, and was particularly associated with increased severity of child sleep problems and family financial difficulties. Family quality of life was generally rated lowest in those using respite care extensively, suggesting that these families may be more burdened by daily caregiving. [ABSTRACT FROM AUTHOR]

Introduction: Mothers of children with intellectual disability or autism spectrum disorder (ASD) have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers. Methods: The study population comprised all mothers of live-born children in Western Australia from 1983–2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers. Results and Discussion: During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed. Conclusion: Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity. [ABSTRACT FROM AUTHOR]

Background The transition from school to adulthood for young adults with an intellectual disability involves movement from a generally secure and supported school environment to an emerging adult life that may be characterised by a wide variation in adoption of adult roles related to employment, independent living, friendships, and day activities. Method In this study, we investigated the perspectives of 18 mothers of young adults with either Down syndrome or Rett syndrome through qualitative semistructured interviews. The International Classification of Functioning, Disability and Health (ICF) framework was used as a conceptual basis. Results Themes that emerged included adult roles assumed during the day, accommodation, quality of life, living a 'good' life, and family impact. Conclusions In contrast with Rett syndrome, mothers of young adults with Down syndrome described more difficult pathways to attaining stability in adult roles. Environmental facilitators and barriers emerged in the area of support, relationships, services, systems, and policies. [ABSTRACT FROM AUTHOR]

The article presents guidelines for clinicians, family members and support workers in assessing and managing vitamin D status in people with intellectual disability (ID). It relates that Vitamin D insufficiency has been associated with osteoporosis, fractures and adverse health consequences, and is relatively common in people with ID. A study of 410 people with ID in Sydney, New South Wales indicates that 43% had vitamin D levels of less than 50 nanomole/liter. Moreover, it suggests that serum 25-Hydroxyvitamin D (OHD) levels should be rechecked after 3-4 moths if people are found to be vitamin D insufficient and are subsequently treated, or the dosage of an established treatment is altered.

• This is the first study of quality of life (QOL) in CDKL5 Deficiency Disorder. • A novel validated QOL scale was administered to families in the International CDKL5 Disorder Database. • Quality of life was adversely impacted by the severity of the functional impairment. • Individuals using only one anti-epileptic medication had better quality of life. CDKL5 Deficiency Disorder (CDD) is a rare genetic disorder caused by a mutation in the cyclin-dependent kinase-like 5 (CDKL5) gene. It is now considered to be a developmental and epileptic encephalopathy because of the early onset of seizures in association with severe global delay. Other features include cortical visual impairment, sleep and gastro-intestinal problems. Progress in clinical understanding, especially regarding the spectrum of functional ability, seizure patterns, and other comorbidities was initially slow but accelerated in 2012 with the establishment of the International CDKL5 Database (ICDD). Our aim was to use this data source to investigate quality of life (QOL) and associated factors in this disorder. A follow-up questionnaire was administered in 2018 to parents of children registered with the ICDD who had a pathogenic CDKL5 variant. QOL was assessed using QI Disability, an instrument, specifically developed to measure total and specific domains of QOL (physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors (leisure) and independence) in children with intellectual disability. Associations with functional abilities, physical health, mental health and family factors were investigated, initially using univariate analyses followed by multivariate analyses for each of these groups with a final composite model which included the important variables identified from previous models. Questionnaires were returned by 129/160 families with a child aged >3 years. Functional impairment, including lack of ability to sit, use hands and communicate had the greatest adverse impact on QOL. There were also some relationships with major genotype groupings. Individuals using three or more anti-epileptic medications had poorer QOL than those on one or no medication, particularly in the physical health domain. There was also variation by geographical region with those living in North America typically having the best QOL and those living in middle or lower income countries poorer QOL. Although lower functional abilities were associated with poorer quality of life further research is needed to understand how environmental supports might mitigate this deficit. Comprehensive care and support for both the child and family have important roles to play in helping families to thrive despite the severity of CDD. [ABSTRACT FROM AUTHOR]