BACKGROUND:Autism spectrum disorder (ASD) is common in individuals with Down syndrome (DS), with an estimated prevalence of 16%-18%. However, receiving a dual diagnosis of Down syndrome and ASD (DS + ASD) is often delayed. Little evidence exists on the path to ASD diagnosis nor interventions to support individuals with DS + ASD. Barriers to diagnosis and treatment for this unique patient population have yet to be described. This study explores clinicians' practices and perceptions regarding the diagnosis and treatment DS + ASD, and the barriers their patients face in connecting to recommended evaluations and services. METHODS:The study used an anonymous web-based survey developed by a group of physicians, psychologists and researchers who work with individuals with DS, ASD and DS + ASD. The survey queried clinicians from various specialties about their practice patterns regarding assessment of suspected ASD in individuals with DS. The survey inquired about treatment recommendations for DS + ASD and perceived barriers to connecting families with evaluations and services. Data analysis involved descriptive statistics and Mann-Whitney U tests. RESULTS:Most respondents believe diagnosing ASD in individuals with DS significantly impacts management. Challenges were reported in accessing diagnostic evaluations, with heavy reliance on highly specialised DS and ASD clinics. Communication impairment (n = 64, 65%), aggressive behaviours (n = 38, 39%), self-injurious behaviours (n = 33, 34%) and adaptive skills (n = 27, 28%) are priority targets for intervention, and applied behavioural analysis (ABA) (n = 80, 82%), speech therapy through insurance (n = 60, 61%), augmentative and alternative communication evaluation through insurance (n = 59, 60%), and occupational therapy through insurance (n = 57, 58%) are the most frequent referrals following a diagnosis of DS + ASD. All respondents identified multiple barriers to care for individuals with DS + ASD, including waitlists, insurance networks and requirements, lack of experienced providers and high turnover. CONCLUSION:This study highlighted the complexity of caring for individuals with DS + ASD, revealed the heterogeneity of practice patterns among providers, and reported multiple barriers to care for this underserved patient population. Results should prompt work aimed at redressing barriers to care and additional research in the field of effective interventions for individuals with DS + ASD.

Abstract Down syndrome (DS) is the most common genetic cause of intellectual disability, yet age-related cortical maturation patterns that contribute to developmental delays remain poorly understood. We analyzed longitudinal resting-state EEG and developmental data from 86 children with DS and 154 typically developing (TD) children between 12 and 81 months of age. Linear mixed-effect models tested age-related trajectories of aperiodic and periodic spectral features, and manifold learning was used to characterize multivariate EEG profiles associated with age and developmental ability. Children with DS showed altered maturation across multiple EEG features. Aperiodic exponent decreased with age in DS, but not TD children, indicating possible altered maturation of cortical excitability. While TD children showed expected age-related increases in theta-alpha peak frequency and amplitude, children with DS exhibited limited alpha maturation and greater persistence of theta-only and theta+alpha peak profiles. We next asked whether multivariate EEG organization reflected chronological maturation or individual differences in developmental ability. A spectral dimension associated with chronological age in TD children was not similarly age-associated in DS. Instead, a second spectral dimension was associated with verbal developmental quotient in children with DS, independent of chronological age and nonverbal developmental ability. This language-associated profile included features considered atypical relative to TD maturation, including increased aperiodic activity and continued presence of theta activity. These findings suggest that in DS there is an altered relationship between cortical spectral organization, chronological age, and language development, extending beyond a uniform delay in typical maturation. Significance Statement Brain development in children with Down syndrome is often interpreted as delayed progression along a typical developmental path. Using longitudinal EEG across early childhood, we found that cortical spectral activity changed differently with age in Down syndrome. Moreover, spectral features that appeared less mature relative to typical development were associated with stronger language abilities within Down syndrome. These findings indicate that neural differences in Down syndrome do not solely reflect delay along a typical developmental timetable but may also represent distinct patterns of brain organization associated with developmental progress. Distinguishing altered organization from maturational delay is important for interpreting neural measures in Down syndrome and may help explain why developmental outcomes vary substantially among children with the same genetic condition.

Background:This study examined the association between caregiving demands and depression symptoms among caregivers of individuals with Down syndrome during the COVID-19 pandemic. Method:We conducted an online survey of 200 caregivers of children and adults with Down syndrome, including demographic data, the Patient Health Questionnaire-8 (PHQ-8), and questions about lack of childcare and taking over instruction during the pandemic. A multiple linear regression analysis identified predictors of caregiver depression symptoms. Results:Household income (B = -3.45, p < .001) and having to take over instruction (B = 2.24, p < .001) were significant predictors of PHQ-8 scores. Child age, caregiver gender, difficulty paying for health insurance, and lack of childcare were not significant predictors. Conclusions:Lower income and instructional caregiving demands were associated with higher depression symptoms among caregivers of individuals with Down syndrome, suggesting potential targets for policy and intervention during future public health emergencies.

ABSTRACT Objective Children with Down syndrome follow distinct developmental trajectories that require specialized monitoring and counseling. We aimed to provide updated estimates of developmental milestone attainment using a nonparametric approach and to compare these results with previously reported generalized linear mixed‐effects model (GLMM) estimates. Methods We reanalyzed developmental data from 842 children with Down syndrome (ages 2 months to 24 years). For each milestone, achievement rates were calculated within overlapping 0.5‐year time windows, and shape‐constrained additive models were used to derive monotonic regression curves. Results Compared with GLMM‐based estimates, the nonparametric approach predicted milestone attainment at least 1 year earlier for 17 of 25 milestones at the highest comparable percentile. Early gross motor milestones showed consistent achievement patterns across methods, whereas more complex adaptive, language, and academic skills demonstrated greater variability and were more sensitive to modeling assumptions. Females achieved 17 of 25 milestones at least 1 year earlier than males. Conclusions These findings highlight substantial developmental heterogeneity and support the potential for continued skill acquisition throughout childhood and adolescence in individuals with Down syndrome. The updated estimates provide clinically relevant reference points to guide individualized monitoring, anticipatory guidance, and family counseling.

Abstract The efficient and safe transfection of hematopoietic cells is a major hurdle that limits efficacy of therapeutic approaches like RNA-interference. We therefore used our modular EL ectrostatic A ntibody si R NA T argeted therapy platform (ELART) to develop nanocarriers decorated with antibodies for delivery of siRNA into hematopoietic CD20-, CD22-, or CD33-positive cells. To analyze internalization efficacy into tumor cells, we applied nanocarriers loaded with Cy3- or Cy5-labeled siRNA and reached nearly all target cells within 1–4 h. Exposure to Cy5-labeled non-functional siRNAs resulted in reduction of the mitochondrial membrane potential and reduced viability, as detected in tetramethylrhodamine methyl ester (TMRM) and CellTiter-Glo (CTG) assays. We concluded that with our modular nanocarrier system, we can transport cytotoxic agents such as cyanine dyes when bound to siRNA, as ELART nanocarriers safely complex anionic siRNA electrostatically and releases it intracellularly within the target cell. This proof-of-concept study shows that ELART nanocarriers can transport anti-cancer agents utilizing siRNA as carrier substance.

Although individuals with Down syndrome (DS) remain highly vulnerable to severe infections, vaccination remains underutilized. Here we review, specific to people with DS, the safety and efficacy of vaccination, drivers of susceptibility to infection, and existing and emerging opportunities to improve vaccine response. We find that vaccines are generally safe and immunogenic in individuals with DS, although continued research is essential to improve vaccine efficacy and health outcomes.

PURPOSE:Independent locomotion has cascading impacts on overall infant development. Although infants with Down syndrome (DS) attain locomotor milestones later, it is unknown how they use emerging skills (e.g., creeping and walking) in everyday play. METHODS:This longitudinal observational study used behavioral coding to investigate locomotion quantity and type during play in infants with DS (n = 13), and changes with the acquisition of new motor skills. The amount of time locomoting was compared with 25 typically developing infants. RESULTS:Infants with DS spent less time locomoting than typically developing infants, and their locomotion time changed less with age and motor skill level. Infants with DS also continued to rely on floor mobility skills even after attaining upright locomotor skills. CONCLUSIONS:Detailed behavioral coding identified differences in real-world locomotion used by infants with DS with potential implications for motor skill learning and development.

Down syndrome (DS) is associated with an increased risk for an inflammatory arthritis termed Down syndrome-associated arthritis (DA). Clinical awareness of DA may prevent morbidity, but there is currently no consensus approach to screen for DA. A DS musculoskeletal (DS-MSK) screening tool was developed and piloted in clinics to identify inflammatory arthritis in individuals with DS. The prevalence of DA and the feasibility of the DS-MSK screening tool were also evaluated. Through a non-randomized, cross-sectional, multicenter study, patients with DS were enrolled by eight institutions that provide specialized comprehensive care to individuals with DS. A novel tool was developed to screen all patients for DA through DS-MSK history and DS-physical exam. Feasibility was assessed through the assessment of additional time the screening tool added to clinical visits. Of the 1111 participants with an average age of 10 years (SD 6.7), there were 1019 pediatric patients and 92 adult patients. There were 62 (6%) positive screens; of those, 21 (34%) were diagnosed with DA by a rheumatologist. Reports of joint swelling, redness, warmth, and stiffness were most associated with a diagnosis of DA. DA is an important consideration in the comprehensive care of individuals with DS. The condition can be aggressive and debilitating if misdiagnosed. We developed a simple, feasible DS-MSK screening tool that can identify DA. Future studies should focus on a shorter, less time-consuming tool that maintains positive predictive value for diagnosing DA that can easily be implemented into routine care for people with DS.

We designed and synthesised an anionic small-molecular photosensitizer (aPSM-Cy3.5) for incorporation into electrostatic antibody targeted (ELART) vesicles, consisting of a protamine-coupled antibody as targeting unit, free protamine and aPSM-Cy3.5. These nanocarriers specifically internalize into different solid tumour cell lines. Upon illumination, the aPSM component initiates the production of reactive oxygen species (ROS). Tumour cells from lung, colorectal and pancreatic cancer with internalized aPSM show decreased growth in colony forming assay. This supports the development of systemically applicable anionic ROS inducers capable of specifically targeting tumour cells.

Independent mobility is a key driver of infant exploration, communication, and caregiver interactions that support overall development. Infants with Down syndrome (DS) have significant motor delays and have difficulty leveraging mobility for these purposes. Cost-effective, caregiver-implemented interventions that enhance independent mobility are needed to address DS infants' developmental delays. The PUMA body-weight support harness (Enlighten LLC) shows promise in facilitating mobility for infants with motor delays. However, it lacks systematic evidence supporting home-based use, specifically for infants with DS. Our ongoing feasibility study aims to address two critical questions for clinical trial development: (1) Is the PUMA device feasible and desirable for home use for infants with DS? and (2) Which observational and developmental outcome measures are useful for assessing intervention efficacy in the home? To date, eight families (target n = 15), have completed 68 virtual and 30 in-person home data collections. Sessions included infant-caregiver play, capturing observational outcomes (locomotion, object exploration, communication), and standardized developmental assessments. Families also assembled the harness and completed a feasibility survey. Initial feedback indicates all caregivers find the PUMA enjoyable for their infants and foresee its potential to enhance mobility and foster new experiences. Most feel confident in independently using the device at home, with seven willing to commit to at least 30 minutes daily. Ongoing analyses include comparison of virtual and in-person observational outcome measures and monitoring developmental changes over time. The results set the stage for developing the first clinical trial of a home-based mobility intervention tailored for infants with DS.

Down syndrome (DS) is a prevalent neurogenetic condition that impacts thousands of individuals, their families, and their communities each year. Due to the relatively high prevalence of DS and co-occurring conditions associated with this diagnosis, it is increasingly becoming the focus of clinical trials. In an effort to review the scope of interventions for this population across time, we reviewed ClinicalTrials.gov for clinical trials being conducted in DS. The goal was to evaluate the targets of clinical trials with individuals with DS, describe changes with the onset of the INCLUDE project, and identify gaps in clinical trial targets with individuals with DS. Across 138 clinical trials related to DS registered on ClinicalTrials.gov, the following target condition emerged (with some trials targeting more than one condition): motor functioning (n = 46), cognition (n = 24), Alzheimer's disease (n = 17), sleep (n = 12), adaptive daily living skills (n = 11), leukemia (n = 10), communication (n = 7), prenatal (n = 4), dental (n = 3), Attention Deficit Hyperactivity Disorder (n = 3), and other (n = 13; any category with <3 registered trials). Collectively, across these conditions, the number and variety in clinical trials in DS have increased substantially post-INCLUDE. Implications and future directions across each area of research are discussed.

Purpose: Toddlers with Down syndrome (DS) showcase comparable or higher rates of gestures than chronological age-and language-matched toddlers without DS. Little is known about how gesture use in toddlers with DS relates to multiple domains of development, including motor, pragmatics, language, and visual reception (VR) skills. Unexplored is whether gesture use is a good marker of social communication skills in DS or if gesture development might be more reliably a marker of motor, language, pragmatics, or VR skills. This study examined the concurrent association of gesture use on other areas of development and investigated the association of autistic traits with gesture use in toddlers with DS. Method: Thirty toddlers with DS (15 females; M = 26.12 months, SD = 6.42 months) completed the Mullen Scales of Early Learning (MSEL) and the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). Parents completed the MacArthur-Bates Communicative Development Inventories Words and Gestures form and the Language Use Inventory (LUI; pragmatic language) about their child. Results: Controlling for child chronological age and sex, total gestures was strongly positively associated with the LUI total score (pragmatic language) and MSEL language (receptive, expressive) raw scores, moderately positively associated with motor (fine, gross) raw scores, but not significantly associated with VR raw scores. Higher ADOS social affect (SA) calibrated severity scores was strongly negatively associated with total gestures but not significantly associated with restricted and repetitive behaviors. Conclusions: Gestures track together with language, pragmatics, and motor skills. Higher ADOS SA calibrated severity scores were associated with fewer gestures in toddlers with DS. Clinicians can consider each child's developmental profile (e.g., motor, pragmatics, language, social communication skills) to better understand their gesture development. Supplemental Material: https://doi.org/10.23641/asha.28169186

BACKGROUND:Obtaining information about individual's abilities in specific areas of development can be used to monitor early developmental progress in young children with Down syndrome (DS). Two commonly used measures which assess specific areas of development are the Mullen Scales of Early Learning (MSEL) and the Vineland Adaptive Behavior Scales-3rd Edition (VABS-3 parent interview). In DS, previous work found a positive association and moderate agreement between overall composite scores of these two measures. No study has explored the comparability of overlapping domains between the MSEL and VABS-3 parent interview in young children with DS. AIM:This study examined the concurrent validity between overlapping language and motor domains from two sources of information, parent report (VABS-3 interview) and direct assessment (MSEL) in young children with DS. METHODS AND PROCEDURES:Twenty-three young children with DS (14 males; mean age = 34.52, SD = 10.12, 13-48 months) completed the MSEL, which was administered by a trained examiner. Parents completed the VABS-3 interview remotely. Overlapping areas include language (receptive language; RL and expressive language; EL) and motor skills (fine motor; FM and gross motor; GM). OUTCOMES AND RESULTS:Median age equivalent (AE) scores were similar when comparing overlapping domains. Across all four domains, MSEL and VABS-3 AE scores were strongly to very strongly positively associated (rs range: 0.82-0.94; all p values < 0.0001). The level of agreement between the MSEL and VABS-3 parent interview AE scores by domain ranged from moderate (FM, GM, and RL) to substantial (EL) agreement. CONCLUSIONS AND IMPLICATIONS:At a young age, the MSEL and VABS-3 parent interview provide a coherent portrait of age-level functioning in language and motor domains. Findings can help inform clinicians and researchers in selecting assessment tools to monitor developmental progress in growing hybrid in-person and telehealth care models. WHAT THIS PAPER ADDS?: Given the recent growth in hybrid clinical and research models that combine in-person and telemedicine visits, it is essential to better understand how direct in-person measures and remote/indirect parent report measures assessing language and motor skills relate to each other in young children with DS. This study evaluates concurrent validity using two different methods: parent report (Vineland Adaptive Behavior Scales-3rd Edition; VABS-3 interview) and direct assessment (Mullen Scales of Early Learning; MSEL), when measuring child developmental status in four overlapping domains (receptive language, expressive language, gross motor, and fine motor skills) in young children with DS. Findings suggest that for young children with DS, the VABS-3 parent interview provides similar age equivalent scores and developmental progress monitoring compared to the direct MSEL assessment.

Abstract Objective To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses. Methods A multicenter, retrospective, case–control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10–30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities. Results In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD (p < 0.001, 95%CI: 2.18–7.63). T2/FLAIR signal abnormalities were not appreciated more frequently in individuals with DSRD (14%, 30/210) than in the control cohort (9%, 11/119) (p = 0.18, OR: 1.63, 95%CI: 0.79–3.40). SWI signal abnormalities were appreciated at a higher frequency in individuals with DSRD (24%, 51/210) compared to the control cohort (4%, 5/119) (p < 0.001, OR: 7.31, 95%CI: 2.83–18.90). T2/FLAIR signal abnormalities were localized to the frontal (40%, 12/30) and parietal lobes (37%, 11/30). SWI signal abnormalities were predominantly in the bilateral basal ganglia (94%, 49/52). Individuals with DSRD and the presence of T2/FLAIR and/or SWI signal abnormalities were much more likely to respond to immunotherapy (p < 0.001, OR: 8.42. 95%CI: 3.78–18.76) and less likely to respond to benzodiazepines (p = 0.01, OR: 0.45, 95%CI: 0.25–0.83), antipsychotics (p < 0.001, OR: 0.28, 95%CI: 0.11–0.55), or electroconvulsive therapy (p < 0.001, OR: 0.12; 95%CI: 0.02–0.78) compared to individuals without these neuroimaging abnormalities. Interpretation This study indicates that in individuals diagnosed with DSRD, T2/FLAIR, and SWI signal abnormalities are more common than previously thought and predict response to immunotherapy.

Objectives: Patterns of psychotropic medication use in children and adolescents with Down syndrome (DS) are largely unknown. Clinical decisions are often made from evidence and experience from individuals with autism spectrum disorder (ASD) or intellectual disability (ID).Methods: Longitudinal data from 670 children with DS who received care in a specialty DS clinic from March 2021 to February 2024 were collected. After each clinic visit, the clinician indicated the presence or absence of co-occurring neurodevelopmental (ND) or mental health (MH) diagnoses, as well as whether the individual was prescribed a psychopharmacological treatment. We used descriptive statistics and analyzed associations between psychotropic medication use, co-occurring ND/MH conditions, and demographic data.Results: 19.1% of patients were prescribed at least one psychotropic medication at their most recent clinical visit. Alpha-agonists were the most commonly prescribed medication class (30.8%), followed by stimulants (18.9%), and antidepressants (16.7%). There was a significant difference in psychotropic medication use by age, with older children having increased odds of being prescribed a psychotropic medication. There were no differences in psychotropic medication use across sex (p = 0.10), race (p = 0.10), or household income (p = 0.16).Conclusions: We found that one-fifth of patients with DS were prescribed psychotropic medications. Nearly every individual with DS who was prescribed a psychotropic medication had a co-occurring ND/MH condition, yet these rates were lower than what have been reported in children with ID, ASD, and attention deficit/hyperactivity disorder. Further research needs to include those with DS to further understand medication efficacy and safe dosing practices to ensure optimal outcomes.

BACKGROUND:Adults with intellectual disabilities have high rates of unemployment and underemployment. Despite benefits to employers and employees, some groups may be hesitant to implement inclusive employment programs due to lack of knowledge, absence of well-defined strategies, and limited exposure to successful examples. OBJECTIVE:To address this gap, the Down Syndrome Program (DSP) in a New England tertiary pediatric hospital established an inclusive employment program that supports and trains young adults with Down syndrome in the development of foundational job skills within a hospital-based clinic. METHODS:This case study examines strategies and lessons learned from the employment program's implementation and evolution. RESULTS:Successful implementation required iterative, tailored approaches to meet diverse needs. CONCLUSION:The DSP developed a framework and collection of best practices for other organizations to adopt for successful employment of individuals with disabilities under an inclusive employment model.

Down syndrome (DS) is a genetic disorder characterized by intellectual disability whose etiology includes an additional partial or full copy of chromosome 21. Brain surface morphometry analyses can potentially assist in providing a better understanding of structural brain differences, and may help characterize DS-specific neurodevelopment. We performed a retrospective surface morphometry study of 73 magnetic resonance imaging (MRI) examinations of DS patients (aged 1 day to 22 years) and compared them to a large cohort of 993 brain MRI examinations of neurotypical participants, aged 1 day to 32 years. Surface curvature measurements, absolute surface area measurements, and surface areas as a percentage of total brain surface area (%TBSA) were extracted from each brain region in each examination. Results demonstrate broad reductions in surface area and abnormalities of surface curvature measurements across the brain in DS. After adjusting our regional surface area measurements as %TBSA, abnormally increased presentation in DS relative to neurotypical controls was observed in the left precentral, bilateral entorhinal, left parahippocampal, and bilateral perirhinal cortices, as well as Brodmann’s area 44 (left), and the right temporal pole. Findings suggest the presence of developmental abnormalities of regional %TBSA in DS that can be characterized from clinical MRI examinations.

BackgroundPrior research has characterized neurodevelopmental phenotypes for Down syndrome (DS), but there is variability in age of milestone attainment and limited identification of early predictors of developmental trajectories. Additionally, less is known about receipt of education and services in relation to development.ObjectiveThis study describes the delivery of education and therapies in the setting of general developmental and behavioral needs in a large clinical cohort of children with DS seen in a specialized Down Syndrome Program (DSP).MethodThe clinically collected data included 814 patients with DS who were seen at a specialty DSP at a large, tertiary pediatric care center from March 2018 to January 2023. Data were collected through caregiver-and clinician-reported history at clinical visits to the program. Descriptive frequencies were utilized to describe participant demographics, skills and behaviors, and receipt of services, across age groups in childhood.ResultsDelays were present across all developmental domains; in particular delays in language, communication, and academic skills, and behavioral challenges were commonly reported. Almost all children received Early Intervention (EI) services, and many young children received non-public therapies after completing EI. Older participants demonstrated more impairments than younger age groups, yet received services at lower rates, particularly behavioral and speech language interventions.ConclusionA snapshot of developmental skill attainment in individuals with DS is provided. Therapies to support the levels of need were reported at much lower frequencies than the level of need reported to target aspects of development and behavior. Several gaps in therapies and educational services were identified. There is an important need for tailoring supports, based on developmental level, to meet individual needs. These findings may help to inform policy change related to developmental and educational services for individuals with DS.

IntroductionThe Neurodevelopmental Parent Report for Outcome Monitoring (ND-PROM), initially developed to monitor developmental and behavioral functions in children with autism spectrum disorder (ASD), assesses symptoms across a wide range of domains relevant in Down syndrome (DS).MethodsPsychometric properties of ND-PROM were assessed in 385 individuals with DS and 52 with a combined diagnosis of DS and ASD (DS+ASD), whose caregivers completed the ND-PROM questionnaire for a clinical visit in a specialized Down syndrome program at a tertiary pediatric hospital. Confirmatory factor analysis was conducted to evaluate the internal structure validity of the ND-PROM. Measurement invariance was assessed, with a comparison group of 246 individuals with ASD, and latent mean differences between the DS and ASD-only groups, as well as the combined DS+ASD groups, were assessed.ResultsFindings support the existence of the 12 clinically-derived factors in the DS population: Expressive Language, Receptive Language, Adaptive skills/Toileting, Social Emotional Understanding, Social Interaction, Independent Play, Sensory Processes, Challenging Behaviors, Impulse/ADHD, and Mental Health. Differences in response patterns of development and behaviors were observed between those with DS and those with ASD, including those with DS having higher abilities in nonverbal communication, social emotional understanding, and social interaction, and fewer restricted and repetitive behaviors and interests, impulsivity or ADHD symptoms, and mental health concerns compared to those with ASD. Individuals in the DS+ASD group had more difficulties with expressive and receptive language, nonverbal and social communication, social interaction, independent play, and adaptive skills than either the DS-only group or the ASD-only groups.DiscussionThe ND-PROM has a desirable factor structure and is a valid and clinically useful tool that captures a range of distinct and independent areas of developmental and behavioral functioning in DS, for individuals with and without an ASD diagnosis.

OBJECTIVES:The American Academy of Pediatrics recommends that children and adolescents with Down syndrome receive anticipatory guidance regarding development and behavior. However, few tools provide specific guidance on developmental norms for children with Down syndrome. Our objective was to estimate age ranges at which children and adolescents with Down syndrome achieve developmental milestones to facilitate developmental screening by pediatric practitioners. METHODS:We used standardized questionnaires to obtain information from clinicians and caregivers of children with Down syndrome who received care at the Boston Children's Hospital Down Syndrome Program between March 2018 and March 2023. Data included information from 2599 visits for 842 individuals with Down syndrome ages 2 months to 24 years. We used mixed-effects logistic regressions to predict the probability of achieving 25 specific developmental milestones with 15%, 30%, 45%, 60%, 75%, and 90% probability as a function of age. We further stratified results by individuals' sex. RESULTS:We present age norms for our study's population of people with Down syndrome for key milestones in academic, adaptive, language, and motor domains by calculating the ages at which milestone achievement was 75% probable. We then compare these norms to published norms for the general population. CONCLUSIONS:This study provides clinicians and families with age-based norms for achievement of key developmental milestones for children and adolescents with Down syndrome.