"It's Really Complicated": Engaging Key Stakeholders to Inform a Novel Parent-led Sexual Health Education Program for Autistic Youth.

Autistic adolescents frequently encounter difficulties in managing changes associated with puberty, sexuality, and relationships, and parents may be a useful source of sexual and reproductive health education (SRE) for this population. Despite this, few evidence-based programs exist to support parents in this role. Thus, there is a need for the development of such programs, particularly those incorporating the lived experiences of key stakeholders. The present qualitative investigation aimed to determine the SRE needs of autistic youth and to inform a novel, parent-led SRE program. Data were collected through semi-structured interviews conducted with two rounds of focus groups with two stakeholder groups: parents of autistic children (N = 4) and adult autistic self-advocates (N = 4). Focus groups were recorded and transcribed verbatim. The research team conducted rapid qualitative analysis on all four transcripts, and major findings were summarized and triangulated across groups. Four overarching themes were identified: "Empower parents as educators," "Individualize supports and education," "Consider cultural and intersecting identities," and "Prioritize safety." Parents can serve a primary role in providing SRE to autistic youth and would likely benefit from participating in a tailored program that prioritizes safety and considers the influence of culture and other aspects of identity on content delivery. Future research on the implementation of such a program is needed.

Understanding Community-Specific Health Behaviors to Prevent Type 2 Diabetes and Depression in Rural Adolescents: A Qualitative Study.

BACKGROUND: Type 2 diabetes (T2D) and depression co-occur, and rates are on the rise in adolescents, disproportionately affecting teenagers in rural communities and those who identify as members of historically disadvantaged racial/ethnic groups. Addressing the promotion of health behaviors is important for prevention of these comorbid health concerns; however, disparities in their prevalence highlight that a healthy lifestyle is not equally accessible for all individuals. Thus, holistic and multi-level approaches that address structural inequities, leverage cultural and family assets, and are effectively integrated into the community are critically needed. This project is an initial phase of a broader community-academic collaboration that aims to address preventable chronic diseases and mental health in adolescents living in the rural Mountain West by tailoring an evidence-based health behavior and lifestyle intervention for these communities. METHOD: Interviewers conducted semi-structured interviews with N = 19 individuals (n = 11 adolescents, 11-17 years, n = 8 mothers) who lived in neighboring counties in the rural Mountain Western USA and had a family history of T2D. Interview schedules were developed by an interdisciplinary team, with community input, and covered topics such as food and staying active, stress, T2D risk, and community and culture. Using thematic analysis, data were reduced through coding, categorization, and development of themes. RESULTS: Data revealed three major themes: "Families Face Systemic Barriers to Health," "Family Routines Support Health," and "Connection is Crucial to Holistic Health." CONCLUSION: Findings reveal opportunities for addressing health inequities and developing effective, integrated T2D and depression prevention strategies within this specific community. They also potentially contain insights that may be applicable to others interested in adapting interventions for diverse groups.

Quantifying the Spectrum of Early Motor and Language Milestones in Sex Chromosome Trisomy.

Background and objectives: Sex chromosome trisomy (SCT) is a common chromosomal abnormality associated with increased risks for early developmental delays and neurodevelopmental disorders later in childhood. Our objective was to quantify the spectrum of early developmental milestones in SCT. We hypothesized later milestone achievement in SCT than the general population. Methods: Data were collected as part of the eXtraordinarY Babies Study, a prospective natural history of developmental and health trajectories in a prenatally identified sample of infants with SCT. Parent reported, clinician-validated, early motor and language milestones were collected at 2, 6, 12, 18, 24, and 36-months. Age distributions of milestone achievement were compared with normative data. Results: In all SCT conditions, compared with normative data, there was increased variability and a later median age of skill development across multiple gross motor and expressive language milestones. Results also show a significant amount of overlap with the general pediatric population, suggesting that for many children with prenatally identified SCT, early milestones present within, or close to, the expected timeline. Conclusions: As increasing numbers of infants with prenatal SCT diagnoses present at pediatric practices, we provide an evidence-based schedule of milestone achievement in SCT as a tool for pediatricians and families. Detailed data on SCT milestones can support clinical interpretation of milestone achievement. Increased variability and later median age of milestone acquisition in SCT compared to norms support consideration of all infants with SCT as high risk.

Cannabidiol for treatment of Irritability and Aggressive Behavior in Children and Adolescents with ASD: Background and Methods of the CAnnabidiol Study in Children with Autism Spectrum DisordEr (CASCADE) Study.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder commonly associated with behavioral challenges. There are few evidence based pharmacological interventions available for the treatment of behavioral symptoms associated with ASD. Cannabidiol (CBD), the non-psychoactive component of cannabis, has potential neuroprotective, antiepileptic, anxiolytic, and antipsychotic effects and may be useful in treating the behavioral symptoms of ASD. Methods: We describe the research methods of a 27-week double-blind placebo-controlled cross-over trial of cannabidiol for the treatment of irritability and aggression associated with ASD, utilizing the irritability subscale of the Aberrant Behavior Checklist-2nd edition (ABC-2) as the primary outcome measure. Adverse effects and safety monitoring protocols are included. Several secondary and exploratory outcomes measures also include anxiety, communication, repetitive behaviors, attention, hyperactivity, autism family experience, and telehealth functional behavior assessment. Conclusion: There is a significant need for clinical research exploring alternative medications for the treatment of behavioral symptoms of ASD. Cannabidiol (CBD) is being studied for the management of irritability, aggression, and other problem behaviors associated with ASD.

Mindfulness-based intervention for depression and insulin resistance in adolescents: Protocol for BREATHE, a multisite, pilot and feasibility randomized controlled trial.

BACKGROUND: Elevated depression symptoms have been associated with higher insulin resistance in adolescents, and consequently, greater risk for type 2 diabetes (T2D). Mindfulness-based intervention (MBI) may be suited for adolescents at risk for T2D given its potential to decrease depression and improve stress-related behavior/physiology underpinning insulin resistance. To prepare for a future multisite efficacy randomized controlled trial, a rigorous, multisite, pilot and feasibility study is needed to test this approach. The current paper describes the design and protocol for a multisite, pilot and feasibility randomized controlled trial of six-week MBI, cognitive-behavioral therapy (CBT), and health education (HealthEd) group interventions, to assess multisite fidelity, feasibility, and acceptability. METHODS: Participants are N = 120 adolescents ages 12-17, with body mass index (BMI) ≥85th percentile, elevated depression symptoms (20-item Center for Epidemiologic Studies-Depression Scale total score > 20), and family history of diabetes. Enrollment occurs across four United States (US) sites, two in Colorado, one in Washington, D·C., and one in Maryland. Group interventions are delivered virtually by trained psychologists and co-facilitators. Assessments occur at baseline, six-week follow-up, and one-year follow-up. RESULTS: Primary outcomes are intervention implementation fidelity, based upon expert ratings of audio-recorded sessions (≥80% adherence/competence), and recruitment feasibility, based upon percentage enrollment of eligible youth (≥80%). Secondary outcomes are intervention training fidelity/feasibility/acceptability, recruitment timeframe, and retention/assessment feasibility. CONCLUSION: Findings will inform optimization of training, recruitment, intervention delivery, retention, and assessment protocols for a multisite, efficacy randomized controlled trial evaluating MBI for decreasing depression and improving insulin resistance in adolescents at risk for developing T2D.

Anxiety in Turner syndrome: Engaging community to address barriers and facilitators to diagnosis and care.

Turner syndrome (TS), caused by complete or partial loss of the second sex chromosome, is associated with complex medical manifestations. The TS community identifies anxiety as a major contributor to reduced quality of life. The study aimed to improve understanding of anxiety symptomatology, diagnosis, and care in individuals with TS. A mixed methods design integrated community engagement, including community leaders as co-investigators and a community advisory board, an online survey (N = 135), and in-depth interviews (N = 10). The majority of respondents reported that anxiety symptoms occur two or more days per week, with self-advocates reporting more frequent symptoms than caregivers (p = 0.03). Self-advocates reported feeling anxious more often at school/work; both rater groups reported anxiety-related behaviors were most likely to be expressed at home. Insomnia was the most common symptom of anxiety endorsed across age and rater groups (>70%). Anxiety symptoms and triggers changed with age and often were undiagnosed or untreated during childhood. Therapy and medication were reported as helpful by most respondents who had tried these strategies. Qualitative themes included: 'Triggers for anxiety are related to TS', 'Anxiety impacts the whole family', and 'Opportunities for early identification and intervention'.

The emotional journey of adapting to prenatally identified trisomy X.

There is a paucity of research on the experiences of parents of children with trisomy X (47,XXX). Increased prenatal diagnoses associated with advances in noninvasive prenatal screening necessitate a better understanding of how trisomy X impacts family systems. This qualitative investigation aimed to describe the lived experience of parents of young daughters with prenatally identified trisomy X to guide genetic counseling. Semi-structured qualitative interviews were conducted via teleconferencing with parents (n = 11) of girls with trisomy X, ages 6-44 months. A descriptive phenomenological approach was used to code transcripts for significant statements and reduce data into themes describing the experience of receiving a diagnosis of trisomy X and the experience of early parenting in this population. Participants described an emotional journey of adapting to prenatally identified trisomy X. Four descriptive themes included two related, yet distinct, life stages: Negative Diagnostic Experience and a Hopeful Early Childhood, as well as two ongoing experiences: Persistent Ambiguity and Coping with and Adapting to Uncertainty. Results suggest providers should carefully consider word choice and timing in delivery of diagnosis, and genetic counseling should provide expectant parents with current research specific to trisomy X, facilitate connections with other parents of young girls with trisomy X, introduce developmental monitoring approaches, and be prepared to support families with a range of emotional responses to the diagnosis and decisions regarding disclosure.

Deviation scores: An innovative approach to interpreting cognitive test results for individuals with intellectual disabilities.

BACKGROUND: Students with Intellectual Disability undergo frequent cognitive testing. Testing with this population is limited by insensitivity to relative strengths and weaknesses due to floor effects. AIM: The study explored the utility of deviation scores via four case studies as a supplement to educational decision-making. METHODS: Four students with Intellectual Disability completed cognitive testing. Deviation scores were calculated using age dependent raw z-score transformations to determine deviation from the standardization sample norms. RESULTS: The application of deviation scores highlighted true relative strengths and weaknesses for students with Intellectual Disability rather than documenting previously known deficits. The four cases studies illustrated where deviation scores could, or could not, add value above and beyond traditional scoring. DISCUSSION: Deviation scores can supplement placement and service decisions for students. Practical and psychometric considerations are reviewed. CONCLUSION: The findings highlight the usefulness of deviation scores in providing meaningful information to school- and clinic-based practitioners.

Cognitive-behavioral therapy and exercise training in adolescent females with elevated depression symptoms and at-risk for type 2 diabetes: Protocol for a randomized controlled trial.

BACKGROUND: Adolescent-onset type 2 diabetes (T2D) is a major public health concern of growing proportions. Prevention, therefore, is critical. Unfortunately, standard-of-care treatment for T2D prevention (e.g., exercise training) show insufficient effectiveness and do not address key modifiable barriers (e.g., depression symptoms) to exercise engagement. Depression symptoms are associated with both poorer physical fitness and greater insulin resistance, the key risk factor in adolescent-onset T2D. Thus, a targeted prevention approach that addresses depression symptoms in combination with exercise training may offer a novel approach to mitigating T2D risk. METHODS: This manuscript describes the design and study protocol for a multi-site, four-arm randomized controlled trial comparing the efficacy of group cognitive-behavioral therapy, group exercise training, and their combinations for the targeted prevention of worsening insulin resistance in N = 300 adolescent females at-risk for T2D with BMI ≥85th percentile and elevated depression symptoms. All four intervention arms will run in parallel and meet weekly for 1 h per week for 6-week to 6-week segments (12 weeks total). Outcomes are assessed at baseline, 6-week mid-treatment, 12-week follow-up, and 1-year follow-up. RESULTS: The primary outcome is insulin resistance. Key secondary outcomes include insulin sensitivity, cardiorespiratory fitness, physical activity, depression symptoms, and body measurements. CONCLUSION: Study findings will guide the ideal sequencing of two brief T2D prevention interventions for ameliorating the course of insulin resistance and lessening T2D risk in vulnerable adolescents. These interventions will likely be cost-effective and scalable for dissemination, having the potential for significant public health impact on communities at risk for T2D.

The comparison of expressed emotion of parents of individuals with fragile X syndrome to other intellectual disabilities.

BACKGROUND: Parenting children and young adults with intellectual disabilities, including individuals with fragile X syndrome and Down syndrome, is challenging, joyful, and complicated. Exploring how parents talk about their children, and the quality of the parent/child relationship can provide insight into the home environment and interactional patterns of the family. METHOD: Expressed emotion (EE) is a measurement of a family's emotional climate based on a parent or caregiver's report of warmth, emotional overinvolvement, hostility, and criticism. The purpose of this study was to describe EE for a sample of parents of individuals with intellectual disabilities and to determine any differences in EE amongst individuals within subgroups. Based on previous research about fragile X syndrome and family systems, we hypothesized that there would be significant differences between the disability groups (higher EE in families with children/young adults with fragile X syndrome). RESULTS: Results showed relatively high proportions of EE across groups of individuals with intellectual disabilities, however, there were no significant differences between the subgroups. Null findings suggest that differences in EE may not relate directly to a child's specific genetic condition. Rather, increased EE in caregiver populations may simply reflect well-documented stressors related to stigma, caregiver burden, and limited community supports. Critical statements were infrequent, however, over half of the participants reported dissatisfaction with their situation, and many were categorized as having emotional overinvolvement, as measured by frequent statements of intense worry and self-sacrifice. CONCLUSION: Findings point to potential utility in family-level interventions focused on providing structured caregiver therapy to manage excessive worry and grief related to a diagnosis of intellectual disability, and respite care to encourage caregiver independence and pursuit of personal care.

Defining Treatment Response for Clinical Trials of Pediatric Acute Asthma.

BACKGROUND: An agreed-upon definition of treatment response for clinical trials of pediatric acute asthma does not exist, limiting meaningful comparisons among therapeutic interventions and advances in asthma management. OBJECTIVE: To develop a consensus definition of treatment response for clinical trials of pediatric acute asthma. METHODS: A multidisciplinary panel of 22 experts participated in a Web-based modified Delphi process to achieve consensus on a definition of treatment response. Round 1 consisted of closed- and open-ended questions in which panelists ranked measures of treatment response developed by literature review, suggested additional measures, and explained their responses. In rounds 2 and 3, panelists reviewed summary statistics of the panel's rating from prior rounds and reconsidered their rankings. In round 3, pairwise ranking was performed to determine the ranked importance of components. Consensus was defined as 70% or greater agreement among panelists choosing Likert-scale values of 1 to 6 (extremely unimportant to extremely important) and an interquartile range less than 2. RESULTS: Drawing on results from the expert panel, we developed a definition of treatment response that includes Clinical Severity Score, need for additional therapies, and hospitalization. Clinical Severity Score encompassed most ranked criteria (eg, respiratory distress, wheeze) for a treatment response definition. Panelists recommended that a valid and pragmatic severity score be used consistently across institutions. Panelists also achieved consensus on the top 10 criteria that appropriately classify need for hospitalization. CONCLUSIONS: This consensus definition of treatment response can be used in clinical trials of children with acute asthma to standardize outcome measurement and report meaningful outcomes.

Sensitivity of the NIH Toolbox to Detect Cognitive Change in Individuals With Intellectual and Developmental Disability.

BACKGROUND AND OBJECTIVE: Individuals with intellectual disability (ID) experience protracted cognitive development compared with typical youth. Sensitive measurement of cognitive change in this population is a critical need for clinical trials and other intervention studies, but well-validated outcome measures are scarce. This study's aim was to evaluate the sensitivity of the NIH Toolbox Cognition Battery (NIHTB-CB) to detect developmental changes in groups with ID-fragile X syndrome (FXS), Down syndrome (DS), and other ID (OID)-and to provide further support for its use as an outcome measure for treatment trials. METHODS: We administered the NIHTB-CB and a reference standard cross-validation measure (Stanford-Binet Intelligence Scales, Fifth Edition [SB5]) to 256 individuals with FXS, DS, and OID (ages 6-27 years). After 2 years of development, we retested 197 individuals. Group developmental changes in each cognitive domain of the NIHTB-CB and SB5 were assessed using latent change score models, and 2-year growth was evaluated at 3 age points (10, 16, and 22 years). RESULTS: Overall, effect sizes of growth measured by the NIHTB-CB tests were comparable with or exceeded those of the SB5. The NIHTB-CB showed significant gains in almost all domains in OID at younger ages (10 years), with continued gains at 16 years and stability in early adulthood (22 years). The FXS group showed delayed gains in attention and inhibitory control compared with OID. The DS group had delayed gains in receptive vocabulary compared with OID. Unlike the other groups, DS had significant growth in early adulthood in 2 domains (working memory and attention/inhibitory control). Notably, each group's pattern of NIHTB-CB growth across development corresponded to their respective pattern of SB5 growth. DISCUSSION: The NIHTB-CB is sensitive to developmental changes in individuals with ID. Comparison with levels and timing of growth on the cross-validation measure shows that the NIHTB-CB has potential to identify meaningful trajectories across cognitive domains and ID etiologies. Sensitivity to change within the context of treatment studies and delineation of clinically meaningful changes in NIHTB-CB scores, linked to daily functioning, must be established in future research to evaluate the battery more completely as a key outcome measure.

Noninvasive prenatal screening (NIPS) results for participants of the eXtraordinarY babies study: Screening, counseling, diagnosis, and discordance.

Sex chromosome aneuploidies (SCAs), including 47,XXY, 47,XXX, 47,XYY, and supernumerary variants, occur collectively in approximately one of 500 live births. Clinical phenotypes are highly variable resulting in previous ascertainment rates estimated to be only 10%-25% during a lifetime. Historically, prenatal SCA diagnoses were incidental findings, accounting for ≤10% of cases, with the majority of diagnoses occurring postnatally during evaluations for neurodevelopmental, medical, or infertility concerns. The initiation of noninvasive prenatal screening (NIPS) in 2012 and adoption into standardized obstetric care provides a unique opportunity to significantly increase prenatal ascertainment of SCAs. However, the impact NIPS has had on ascertainment of SCAs is understudied, particularly for those who may defer diagnostic testing until after birth. This study evaluates the timing of diagnostic testing following positive NIPS in 152 infants with SCAs and potential factors influencing this decision. Eighty-seven (57%) elected to defer diagnostic testing after a positive NIPS until birth, and 8% (7/87) of those confirmed after birth were found to have discordant results on postnatal diagnostic testing, most of which would have influenced genetic counseling.

Observable Symptoms of Anxiety in Individuals with Fragile X Syndrome: Parent and Caregiver Perspectives.

Caregiver reports, clinical observations, and diagnostic assessments indicate that most individuals with fragile X syndrome experience high levels of chronic anxiety. However, anxiety is a challenging endpoint for outcome measurement in FXS because most individuals cannot reliably report internal emotional or body states. A comprehensive survey of the presence, frequency, and duration of anxiety-related symptoms and questions to elicit open-ended responses was completed by caregivers of 456 individuals with FXS, ages 2-81 years (87 female, 369 male) and 24 female and 2 male FXS self-advocates ages 15-66 years. Caregivers reported classic behavioral indicators of anxiety, such as avoidance, irritability, motor agitation, and physiological symptoms, as well as behavioral features in FXS such as repetitive behavior, aggression, and self-injury. Self-advocate accounts largely paralleled caregiver data. Factor analyses yielded four factors: (1) increased irritability, aggression, and self-injury; (2) increased physical movement, nervous activity, and restlessness; (3) physical and physiological features of anxiety; and (4) internalizing and gastrointestinal symptoms. Caregivers are capable of observing and reporting behaviors that are valid indicators of anxious states that are usually reported in self-report standardized assessments. These results support the development of an anxiety measure for FXS that minimizes problems with rater inference.

Supporting students with sex chromosome aneuploidies in educational settings: Results of a nationwide survey.

Children with sex chromosome aneuploidies (SCAs) are at an increased risk for neurocognitive and behavioral disorders that may interfere with academic success, including early developmental delays, learning disabilities, executive function problems, and social communication deficits. The present national survey aimed to update and extend our understanding of school supports and educational outcomes for students with these increasingly common genetic diagnoses. Parents of children with a diagnosed SCA, birth to 21 years, living in the United States (N = 248), responded to an electronic survey with questions focused on school support plans, academic accommodations, educational therapies, school completion, and perceptions of educator awareness of SCAs. Results revealed high rates of delayed kindergarten, grade retention in primary years, and educational support plans (IEPs = 71%; Section 504 Plans = 26%). A majority (73%) of respondents with children over age 18 years (N = 41) reported their children successfully completed high school, and nearly half (46%) pursued post-secondary education opportunities. Many parents reported their children's educators had little to no knowledge of SCA conditions, justifying a need to train teachers and policy makers in the unique educational needs of children and adolescents with SCAs. School psychologists should be aware of the frequent need for accommodations and individualized support plans in this population so they can support children and families by advocating for early and comprehensive evaluations and intervention plans.

'I Wish the School Had a Better Understanding of the Diagnosis': parent perspectives on educational needs of students with sex chromosome aneuploidies.

Students with sex chromosome aneuploidies (SCAs) are at increased risk for learning disabilities and often require individualized supports in the school setting. Parents of students with rare disorders such as SCAs possess a unique understanding of their child's educational experiences and play a crucial role in the development of successful school support plans. This international survey study aimed to inductively capture parent perspectives on educational needs and supports for students with SCAs. Parents of youth with SCAs ages 5-21 years (n = 305) provided free-text responses to open-ended questions about their child's education. Qualitative content analysis using a bioecological systems framework resulted in three overarching themes. Overall, parents identified multiple factors related to the SCA diagnosis that act as barriers to learning, a strong need for school-based social and emotional supports, and elusive or incomplete educational support plans. Based on these findings, we recommend developing robust family-school partnerships, increased collaboration between the school and the child's medical team, and acknowledgement of the significant role the genetic condition plays in the educational experiences of students with SCAs. Specific suggestions for school support plans for students with SCAs are explored, such as providing school-based behavioral health supports and explicit teaching of executive function strategies.

Communication practices of parents and unaffected sibling needs in families impacted by a diagnosis of Angelman syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental condition affecting approximately 1 in 15,000 individuals. To date, limited research elucidates how parents communicate about AS with unaffected siblings and their needs. This study aimed to understand if, when, and what parents are communicating with unaffected siblings. The study also evaluated unaffected siblings' knowledge of AS and their perceptions of their siblings with AS. Recruitment took place through social media platforms and a multidisciplinary Chromosome 15 clinic. Families were eligible for the study if they had a child diagnosed with AS and at least one unaffected sibling age five years or older. Two novel surveys, one for the parent and one for each of the unaffected siblings, were created based on a detailed literature review and input from AS professionals. Eighty-two families met the criteria and completed the required surveys. The majority of parents (94%) discussed AS with the unaffected siblings, but despite these discussions 41% of unaffected siblings still had unanswered questions. This study highlights the need for improved communication between parents and the unaffected siblings and emphasizes the importance of educational materials for unaffected siblings.

Early neurodevelopmental and medical profile in children with sex chromosome trisomies: Background for the prospective eXtraordinarY babies study to identify early risk factors and targets for intervention.

Sex chromosome trisomies (SCT), including Klinefelter syndrome/XXY, Trisomy X, and XYY syndrome, occur in 1 of every 500 births. The past decades of research have resulted in a broadening of known associated medical comorbidities as well as advances in psychological research. This review summarizes what is known about early neurodevelopmental, behavioral, and medical manifestations in young children with SCT. We focus on recent research and unanswered questions related to the risk for neurodevelopmental disorders that commonly present in the first years of life and discuss the medical and endocrine manifestations of SCT at this young age. The increasing rate of prenatal SCT diagnoses provides the opportunity to address gaps in the existing literature in a new birth cohort, leading to development of the eXtraordinarY Babies Study. This study aims to better describe and compare the natural history of SCT conditions, identify predictors of positive and negative outcomes in SCT, evaluate developmental and autism screening measures commonly used in primary care practices for the SCT population, and build a rich data set linked to a bank of biological samples for future study. Results from this study and ongoing international research efforts will inform evidence-based care and improve health and neurodevelopmental outcomes.

Thriving with Down syndrome: A qualitative multiple case study.

BACKGROUND: Down syndrome (DS) is the most common genetic cause of intellectual disability. Prior research has primarily focused on associated medical problems and skill deficits. This study takes a novel positive psychology approach by examining critical individual characteristics and environmental factors that facilitate exceptional quality of life for people with DS. METHOD: A qualitative multiple case study design was used to document the lives of four adults thriving with DS. Thriving was defined as high subjective well-being coupled with continued personal development. RESULTS: Descriptive contexts were provided for each case along with four overarching themes: a supportive social ecology, high expectations for independence, advocacy, and strengths facilitating happiness. A new conceptual framework for understanding thriving with DS was proposed. CONCLUSIONS: These findings provide insight as to what is possible for people with DS, including ideas for future research and practice to promote thriving in the DS population.