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Due to improvements in recognition and management of their multisystem disease, the long‐term survival of infants, children, and adolescents with trisomy 21 and congenital heart disease now matches children with congenital heart disease and no genetic condition in many scenarios. Although this improved survival is a triumph, individuals with trisomy 21 and congenital heart disease have unique and complex care needs in the domains of physical, developmental, and psychosocial health, which affect functional status and quality of life. Pulmonary hypertension and single ventricle heart disease are 2 known cardiovascular conditions that reduce life expectancy in individuals with trisomy 21. Multisystem involvement with respiratory, endocrine, gastrointestinal, hematological, neurological, and sensory systems can interact with cardiovascular health concerns to amplify adverse effects. Neurodevelopmental, psychological, and functional challenges can also affect quality of life. A highly coordinated interdisciplinary care team model, or medical home, can help address these complex and interactive conditions from infancy through the transition to adult care settings. The purpose of this Scientific Statement is to identify ongoing cardiovascular and multisystem, developmental, and psychosocial health concerns for children with trisomy 21 and congenital heart disease from birth through adolescence and to provide a framework for monitoring and management to optimize quality of life and functional status.

Abstract INTRODUCTION Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision‐makers for individuals with and without DS. METHODS We performed analyses using data from two registries: the University of California, Irvine Consent‐to‐Contact (C2C) Registry and DS‐Connect. The former represented a sample of non‐DS decision‐makers (N = 4818), while for the latter, we excluded individuals with DS, leaving a population of DS family decision‐makers (N = 976). We assessed scores on the Research Attitudes Questionnaire (RAQ) between DS and non‐DS decision‐makers. We compared total RAQ scores using linear regression and assessed item‐level RAQ differences using proportional odds regression. RESULTS Mean total RAQ scores were not statistically different between decision‐makers in the two registries, after adjusting for age, sex, race and ethnicity, education, and the coronavirus disease 2019 (COVID‐19) time frame (Est. Diff = 0.11, 95% confidence interval [CI]: ‐0.22, 0.43; p = 0.531). However, in a pre‐specified analysis, we did find evidence of differential attitudes on item‐level RAQ scores. Specifically, decision‐makers for participants with DS had increased odds of a more favorable response to the question of responsibility to help others (DS vs. non‐DS: odds ratio [OR] = 1.26, 95% CI: 1.08, 1.48) and decreased odds of a more favorable response to the question regarding the belief that medical research would find cures for major diseases during their lifetime (DS vs. non‐DS: OR = 0.77, 95% CI: 0.66, 0.90). DISCUSSION Our findings provide insights for researchers to develop strategies for recruiting individuals with and without DS into clinical research. The observed item‐level differences warrant further investigation to instruct precise recruitment strategies. Highlights Research attitudes between decision‐makers for individuals with Down syndrome (DS) and decision‐makers without DS were observed to be similar on average. Item‐level differences in research attitudes were observed to differ for DS and non‐DS decision‐makers. These results can help facilitate precise recruitment strategies for populations with DS.

Key Clinical Message Down syndrome (DS), characterized by trisomy 21, significantly increases susceptibility to leukemia, although the occurrence of multiple myeloma (MM) in DS is exceedingly rare. This report details the case of a 45‐year‐old female with DS who was diagnosed with MM, highlighting diagnostic and therapeutic complexities. It emphasizes the importance of tailored therapeutic strategies for treating MM in individuals with DS and the need for specialized approaches in these cases.

Abstract Down syndrome (DS) is caused by a third copy of chromosome 21. Alzheimer's disease (AD) is a neurodegenerative condition characterized by the deposition of amyloid‐beta (Aβ) plaques and neurofibrillary tangles in the brain. Both disorders have elevated Aβ, tau, dysregulated immune response, and inflammation. In people with DS, Hsa21 genes like APP and DYRK1A are overexpressed, causing an accumulation of amyloid and neurofibrillary tangles, and potentially contributing to an increased risk of AD. As a result, people with DS are a key demographic for research into AD therapeutics and prevention. The molecular links between DS and AD shed insights into the underlying causes of both diseases and highlight potential therapeutic targets. Also, using biomarkers for early diagnosis and treatment monitoring is an active area of research, and genetic screening for high‐risk individuals may enable earlier intervention. Finally, the fundamental mechanistic parallels between DS and AD emphasize the necessity for continued research into effective treatments and prevention measures for DS patients at risk for AD. Genetic screening with customized therapy approaches may help the DS population in current clinical studies and future biomarkers.

Abstract Introduction Down syndrome (DS) is associated with multiple comorbid conditions and chronic immune dysfunction. Persons with DS who contract COVID‐19 are at high risk for complications and have a poor prognosis. We aimed to study the clinical symptoms, laboratory and biochemical profiles, radiologic findings, treatment, and outcomes of patients with DS and COVID‐19. Method We systematically searched PubMed, MEDLINE, Web of Science, Scopus, and the Cochrane Library using the keywords COVID‐19 or coronavirus or SARS‐CoV‐2 and DS or trisomy 21. Seventeen articles were identified: eight case reports and nine case series published from December 2019 through March 2022, with a total of 55 cases. Results Patients averaged 24.8 years (26 days to 60 years); 29 of the patients were male. The most common symptoms were fever, dyspnea, and cough. Gastrointestinal and upper respiratory tract symptoms were commonly reported for pediatric patients. The most common comorbidities present in patients with DS were obesity (49.0%), hypothyroidism (21.6%) and obstructive sleep apnea (15.6%). The patients were hospitalized for a mean of 14.8 days. When the patients were compared with the general COVID‐19 population, the mean number of hospitalized days was higher. Most patients had leukopenia, lymphopenia, and elevated inflammatory markers (d‐dimer and C‐reactive protein). Bilateral infiltrations and bilateral ground‐glass opacifications were frequently seen in chest radiographs and chest computed tomographic imaging. Most of the patients were treated with methylprednisolone, macrolides, and hydroxychloroquine. Of the 55 patients, 22 died. The mean age of the patients who died was 42.8 years. Mortality rate was higher in individuals with DS over 40 years of age. Conclusion More studies are needed to better understand COVID‐19 infections among persons with DS. In addition, the study was limited by a lack of statistical analyses and a specific comparison group.

Abstract INTRODUCTION Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late‐onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. METHODS T1‐weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. RESULTS Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. DISCUSSION The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.

Abstract INTRODUCTION Alzheimer's disease (AD) affecting adults with Down syndrome (DS‐AD), like late‐onset AD (LOAD) in the neurotypical population, has preclinical, prodromal, and more advanced stages. Only tasks placing high demands on cognition are expected to be affected during the prodromal stage, with activities of daily living (ADLs) typically being spared. However, cognitive demands of ADLs could be high for adults with DS and may be affected during prodromal DS‐AD. METHODS Cognitively stable cases that subsequently developed prodromal DS‐AD were identified within a set of archived data from a previous longitudinal study. Measures of ADLs and multiple cognitive domains were examined over time. RESULTS Clear declines in ADLs accompanied cognitive declines with prodromal DS‐AD while stability in all measures was verified during preclinical DS‐AD. DISCUSSION Operationally defining prodromal DS‐AD is essential to disease staging in this high‐risk population and for informing treatment options and timing as new disease‐modifying drugs become available. Highlights Cognitive and functional stability were demonstrated prior to the onset of prodromal DS‐AD. ADL declines accompanied cognitive declines as adults with DS transitioned to prodromal AD. Declines in ADLs should be a defining feature of prodromal AD for adults with DS. Better characterization of prodromal DS‐AD can improve AD diagnosis and disease staging. Improvements in DS‐AD diagnosis and staging could also inform the timing of interventions.

Background Increasing survival among patients with congenital heart disease (CHD) has recently been reported. However, the impact of Down syndrome (DS) in patients with CHD is still debated. We aimed to estimate survival in patients with CHD with versus without DS compared with matched controls from the general population without CHD or DS. Methods and Results We linked data from Swedish health registries to identify patients with CHD born between 1970 and 2017. Data from the Total Population Register were used to match each patient with CHD by sex and birth year with 8 controls without CHD or DS. A Cox proportional regression model was used to estimate mortality risk, and Kaplan–Meier curves were analyzed for the survival analysis. We identified 3285 patients with CHD‐DS, 64 529 patients with CHD without DS, and 26 128 matched controls. The mortality risk was 25.1 times higher (95% CI, 21.3–29.5) in patients with CHD‐DS versus controls. The mortality rate was 2 times higher (95% CI, 1.94–2.31) for patients with CHD with versus without DS. Lower mortality was found during the second versus first birth periods in patients with CHD‐DS compared with controls; hazard ratio: 46.8 (95% CI, 29.5–74.0) and 17.7 (95% CI, 12.8–24.42) in those born between 1970 and 1989 versus 1990 and 2017, respectively. Conclusions In this retrospective cohort study, the mortality risk among patients with CHD‐DS was 25 times higher compared with matched controls and 2 times higher compared with patients with CHD without DS. Survival was higher in patients with CHD‐DS born after versus before 1990, coinciding with the modern era of congenital heart care.

Background Individuals with genetic syndromes can manifest both congenital heart disease (CHD) and cancer attributable to possible common underlying pathways. To date, reliable risk estimates of hematopoietic cancer (HC) among children with CHD based on large population‐based data remain scant. This study sought to quantify the risk of HC by the presence of genetic syndrome among children with CHD. Methods and Results Data sources were the Canadian CHD database, a nationwide database on CHD (1999–2017), and the CCR (Canadian Cancer Registry). Standardized incidence ratios were calculated for comparing HC incidences in children with CHD with the general pediatric population. A modified Kaplan‐Meier curve was used to estimate the cumulative incidence of HC with death as a competing risk. A total of 143 794 children (aged 0–17 years) with CHD were followed up from birth to age 18 years for 1 314 603 person‐years. Of them, 8.6% had genetic syndromes, and 898 HC cases were observed. Children with known syndromes had a substantially higher risk of incident HC than the general pediatric population (standardized incidence ratio, 13.4 [95% CI, 11.7–15.1]). The cumulative incidence of HC was 2.44% (95% CI, 2.11–2.76) among children with a syndrome and 0.79% (95% CI, 0.72–0.87) among children without a syndrome. Acute myeloid leukemia had a higher cumulative incidence during early childhood than acute lymphoblastic leukemia. Conclusions This is the first large population‐based analysis documenting that known genetic syndromes in children with CHD are a significant predictor of HC. The finding could be essential in informing risk‐stratified policy recommendations for cancer surveillance in children with CHD.

Abstract Introduction Down syndrome (DS) is the most common genetic cause of intellectual disability. Children and adults with DS show deficits in language performance and explicit memory. Here, we used magnetic resonance imaging (MRI) on children and adults with DS to characterize changes in the volume of specific brain structures involved in memory and language and their relationship to features of cognitive‐behavioral phenotypes. Methods Thirteen children and adults with the DS phenotype and 12 age‐ and gender‐matched healthy controls (age range 4–25) underwent an assessment by MRI and a psychological evaluation for language and cognitive abilities. Results The cognitive profile of people with DS showed deficits in different cognition and language domains correlating with reduced volumes of specific regional and subregional brain structures, confirming previous related studies. Interestingly, in our study, people with DS also showed more significant parahippocampal gyrus volumes, in agreement with the results found in earlier reports. Conclusions The memory functions and language skills affected in studied individuals with DS correlate significantly with the reduced volume of specific brain regions, allowing us to understand DS's cognitive‐behavioral phenotype. Our results provide an essential basis for early intervention and the design of rehabilitation management protocols.

Abstract Parental behaviours influence food acceptance in young children, but few studies have measured these behaviours using observational methods, especially among children with Down syndrome (CWDS). The overall goal of this study was to understand parent feeding practices used during snack time with young CWDS (N = 111, aged 11–58 months). A coding scheme was developed to focus on feeding practices used by parents of CWDS from a structured home‐use test involving tasting variously textured snack products. Behavioural coding was used to categorise parental feeding practices and quantify their frequencies (N = 212 video feeding sessions). A feeding prompt was coded as successful if the child ate the target food product or completed the prompt within 20 s of the prompt being given without a refusal behaviour. CWDS more frequently consumed the test foods and completed tasks in response to Autonomy‐Supportive Prompts to Eat (49.3%), than to Coercive‐Controlling Prompts to Eat (24.2%). By exploring the parent–CWDS relationship during feeding, we can identify potentially desirable parent practices to encourage successful feeding for CWDS. Future research should build upon the knowledge gained from this study to confirm longitudinal associations of parent practices with child behaviours during feeding.

Key Clinical Message Non‐immune hydrops is a prenatal finding which can occur due to an underlying genetic diagnosis such as common chromosomal aneuploidy (Trisomy 21, Turner syndrome etc.). It is extremely rare to have more than one genetic cause of hydrops fetalis in a single pregnancy. This report describes a dichorionic diamniotic pregnancy for a consanguineous couple where noninvasive prenatal testing was “high risk” for Trisomy 21. Family declined amniocentesis and opted for postnatal genetic testing. The pregnancy was later complicated with severe hydrops fetalis leading to demise for one of the twins, and a premature delivery of the other twin who had remarkable collodion not in keeping with Trisomy 21. Postnatal genetic investigations confirmed both Trisomy 21 and prenatal lethal Gaucher disease in the survivor twin. This case report highlights some of the prenatal diagnostic challenges for a consanguineous couple where a rare cause of fetal hydrops was concealed in a setting of a common chromosomal aneuploidy. The prompt postnatal diagnosis of perinatal lethal Gaucher disease, confirmed with undetectable glucocerebrosidase enzyme activity, assisted the family in the decision of providing palliative care for their infant who was quickly deteriorating. The importance of postnatal genetic evaluation and its impact on immediate patient management in an NICU setting is emphasized. This dual diagnosis was significant for the couple as it explained pervious pregnancy losses and has important future recurrence risk implications.

Abstract Background Down syndrome (DS), which is characterized by various malfunctions, is the most common chromosomal disorder. As the DS population continues to grow and most of those with DS live beyond puberty, early‐onset health problems have become apparent. However, the cellular landscape and molecular alterations have not been thoroughly studied. Methods This study utilized single‐cell resolution techniques to examine DS in humans and mice, spanning seven distinct organs. A total of 71 934 mouse and 98 207 human cells were analyzed to uncover the molecular alterations occurring in different cell types and organs related to DS, specifically starting from the fetal stage. Additionally, SA‐β‐Gal staining, western blot, and histological study were employed to verify the alterations. Results In this study, we firstly established the transcriptomic profile of the mammalian DS, deciphering the cellular map and molecular mechanism. Our analysis indicated that DS cells across various types and organs experienced senescence stresses from as early as the fetal stage. This was marked by elevated SA‐β‐Gal activity, overexpression of cell cycle inhibitors, augmented inflammatory responses, and a loss of cellular identity. Furthermore, we found evidence of mitochondrial disturbance, an increase in ribosomal protein transcription, and heightened apoptosis in fetal DS cells. This investigation also unearthed a regulatory network driven by an HSA21 gene, which leads to genome‐wide expression changes. Conclusion The findings from this study offer significant insights into the molecular alterations that occur in DS, shedding light on the pathological processes underlying this disorder. These results can potentially guide future research and treatment development for DS.

Abstract Down syndrome (DS) is one of the common genetic disorders caused by the trisomy of human chromosome 21 (HSA21). Mitochondrial dysfunction and redox imbalance play important roles in DS pathology, and altered dopaminergic regulation has been demonstrated in the brain of individuals with DS. However, the pathological association of these elements is not yet fully understood. In this study, we analyzed dopaminergic neurons (DNs) differentiated from deciduous teeth‐derived stem cells of children with DS or healthy control children. As previously observed in the analysis of a single case of DS, compared to controls, patient‐derived DNs (DS‐DNs) displayed shorter neurite outgrowth and fewer branches, as well as downregulated vesicular monoamine transporter 2 and upregulated dopamine transporter 1, both of which are key regulators of dopamine homeostasis in DNs. In agreement with these expression profiles, DS‐DNs accumulated dopamine intracellularly and had increased levels of cellular and mitochondrial reactive oxygen species (ROS). DS‐DNs showed downregulation of non‐canonical Notch ligand, delta‐like 1, which may contribute to dopamine accumulation and increased ROS levels through DAT1 upregulation. Furthermore, DS‐DNs showed mitochondrial dysfunction in consistent with lower expression of peroxisome proliferator‐activated receptor‐gamma coactivator 1 alpha (PGC‐1α) and upregulation of a HSA21‐encoded negative regulator of PGC‐1α, nuclear receptor‐interacting protein 1. These results suggest that dysregulated dopamine homeostasis may participate in oxidative stress and mitochondrial dysfunction of the dopaminergic system in DS.

Abstract Patients with intellectual disabilities often fail to follow traditional tongue position instructions for panoramic radiographs resulting in missed pathology or unnecessary further radiation. This simple breathing technique is a new clinical instruction method for panoramic radiography developed to reduce the most common patient position error: patient failure to hold the tongue to the roof of the mouth. The technique is suitable for all patients including young patients and those with intellectual disabilities. The simple breathing technique uses ‘tell‐show‐do’ communication methods and does not mention the tongue but utilises the known tongue positions that occur during breathing and swallowing. This simple breathing technique instruction for panoramic radiography uses a demonstration of ‘breathe‐in, breathe‐out, swallow, lips closed and hold still’ to reduce the intensity of both the palatoglossal and pharyngeal airspaces on panoramic radiographs. This method, referred in this article as the simple breathing technique, can improve the diagnostic potential of panoramic radiographs and can be used with young children and patients with intellectual disabilities, and this slow breathing technique can help them further relax.

Abstract Introduction Adults with Down syndrome (DS) are at increased risk for Alzheimer's disease (AD) and vary in their age of transition from AD preclinical to prodromal or more advanced clinical stages. An empirically based method is needed to determine individual “estimated years from symptom onset (EYO),” the same construct used in studies of autosomal dominant AD . Methods Archived data from a previous study of > 600 adults with DS were examined using survival analysis methods. Age‐specific prevalence of prodromal AD or dementia, cumulative risk, and EYOs were determined. Results Individualized EYOs for adults with DS ranging in age from 30 to 70+ were determined, dependent upon chronological age and clinical status. Discussion EYOs can be a useful tool for studies focused on biomarker changes during AD progression in this and other populations at risk, studies that should contribute to improved methods for diagnosis, prediction of risk, and identification of promising treatment targets. HIGHLIGHTS Years from Alzheimer's disease (AD) onset (EYO) was estimated for adults with Down syndrome (DS). EYOs were informed by AD clinical status and age, ranging from 30 to > 70 years. Influences of biological sex and apolipoprotein E genotype on EYOs were examined. EYOs have advantages for predicting risk of AD‐related dementia compared to age. EYOs can be extremely informative in studies of preclinical AD progression.

Abstract Introduction Alzheimer's disease (AD) occurs in aging adults with Down syndrome (DS) at a higher prevalence and an earlier age than in typical aging adults. As with the general aging adult population, there is an urgent need to understand the preclinical and early phases of AD progression in the adult population with DS. The aim of this scoping review was to synthesize the current state of the evidence and identify gaps in the literature regarding functional activity performance and falls and their significance to disease staging (i.e., mild, moderate, and severe defined staging criteria) in relation to Alzheimer's disease and related dementias (ADRD) in adults with DS. Methods This scoping review included six electronic databases (e.g., PsycInfo, Academic Search Complete, CINAHL, COCHRANE Library, MEDLINE, and PubMed). Eligible studies included participants with DS ≥25 years of age, studies with functional measures and/or outcomes (e.g., activities of daily living, balance, gait, motor control, speech, behavior, and cognition; falls; and fall risks), and studies that investigated AD pathology and implications. Results Fourteen eligible studies were included and categorized through a thematic analysis into the following themes: (1) physical activity and motor coordination (PAMC), (2) cognition, (3) behavior, and (4) sleep. The studies indicated how functional activity performance and engagement may contribute to early identification of those at risk of cognitive decline and AD development and/or progression. Discussion There is a need to expand the research regarding ADRD pathology relative to functional outcomes in adults with DS. Functional measures related to disease staging and cognitive impairment are essential to understanding how AD progression is characterized within real‐world settings. This scoping review identified the need for additional mixed‐methods research to examine the use of assessment and intervention related to function and its detection of cognitive decline and AD progression.

Objective: To examine the cost-effectiveness of hypoglossal nerve stimulation (HGNS) implantation at an early age in simulated pediatric cohorts with Down Syndrome (DS) and severe obstructive sleep apnea (OSA)., Study Design: Cost-utility analysis., Setting: Hypothetical cohort., Methods: A Markov model simulated 3 pediatric cohorts with DS and OSA beginning at age 4 years until 21 years. Cohorts received HGNS implants in early childhood, late childhood, or adulthood at age 4, 13 (current FDA-approved age), or 18 years, respectively. Input model parameters were obtained from the literature and our institution. Outcomes were measured with an incremental cost-effectiveness ratio (ICER), measured in dollars per quality-adjusted life-year (QALY). Deterministic 1-way sensitivity analyses were conducted to evaluate the effects of parameter uncertainty., Results: Results (total costs; total QALYs) across the time horizon were determined for each cohort: early implantation ($83,300.35; 15.79), late ($48,319.09; 14.98), and adult ($38,721.07; 14.55). ICERs were $48,892.47 per QALY for early vs late implantation, $43,471.15 per QALY for early vs adult implantation, and $30,959.58 per QALY for late vs adult implantation. All ICERs were below a willingness-to-pay threshold of $50,000 per QALY. Varying the discount rate and utility expectedly varied the ICERs and cost-effectiveness. Threshold analysis showed early implantation to be cost-effective for a HGNS implantation cost up to $62,230 compared to late implantation., Conclusion: The current study suggests HGNS is a cost-effective treatment strategy for pediatric patients with DS and severe OSA. Our findings also suggest cost-effectiveness at ages younger than 13, the current age of FDA approval., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Introduction: The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS., Material and Methods: Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000-2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression., Results: A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70)., Conclusions: The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background and Objective: As the population and life expectancy of people with Down syndrome increases, identifying common skin conditions throughout the lifespan will help inform clinical care and research. We sought to evaluate dermatologic conditions diagnosed in pediatric and adult patients with Down syndrome., Methods: This multicenter retrospective study analyzed demographic and outpatient visit International Classification of Diseases codes of patients with Down syndrome evaluated at outpatient dermatology clinics in the United States or Canada between 2011 and 2021., Results: A total of 1529 patients with Down syndrome were identified from eight academic medical centers: 50.8% were children (0-12 years), 25.2% were adolescents (13-17 years), and 24% were adults (18 years and older). Eczematous dermatitis was the most common diagnosis overall (26%), followed by folliculitis (19.3%) and seborrheic dermatitis (15.6%). Other notable diagnoses included dermatophyte infections (13%), alopecia areata (11.6%), and psoriasis (6.7%). About 4.3% of visits included a code for high-risk medication use. Eczematous dermatitis, alopecia areata, and folliculitis were the most common diagnoses observed in children; folliculitis, hidradenitis suppurativa, and eczematous dermatitis in adolescents; and seborrheic dermatitis, eczematous dermatitis, and folliculitis in adults., Conclusions: Dermatologic conditions in patients with Down syndrome vary by age, but are most often eczematous, adnexal, and cutaneous autoimmune disorders. This multicenter retrospective review identifies skin diseases that should be prioritized for clinical care guideline development and research in the Down syndrome community., (© 2024 Wiley Periodicals LLC.)

Introduction: This study aimed to report the screening performance of cell-free DNA (cfDNA) testing for chromosomal abnormalities in twins, triplets, and vanishing twin pregnancies., Material and Methods: Data were obtained from pregnant women with a multiple pregnancy or a vanishing twin pregnancy at ≥10 weeks' gestation who requested self-financed cfDNA testing between May 2015 and December 2021. Those that had positive screening results had diagnostic confirmatory procedures after counseling and consent. The performance of screening of the cfDNA test was determined by calculating confirmation rate and combined false-positive rate (cFPR)., Results: Data from 292 women were included after exclusion of those lost to follow-up, with no-result on cfDNA testing, or had reductions. Of the 292 pregnancies, 10 (3.4%) were triplets, including no cases of trisomy 21 and trisomy 18; 249 (85.3%) were twins, including 3 cases of trisomy 21 and no cases of trisomy 18 and 13; and 33 (11.3%) were vanishing twins, including 3 cases of trisomy 21 and 1 case of trisomy 18. The median (IQR) maternal age was 34 years (31-37). For triplet pregnancies, the initial no-result rate was 10.3% (95% confidence interval [CI] 3.6-26.4), all with results after redraw. For twin pregnancies, the initial no-result rate was 12.9% (95% CI 9.6-17.0), and the no-result rate after redraw was 1.6% (95% CI 0.7-3.6). For vanishing twins, there were no cases with no-result. All triplets had low-risk cfDNA results. The confirmation rate for trisomy 21 was 100% with a FPR at 0% due to the small number of positive cases for twins. For vanishing twins, one high-risk case for trisomy 21 and the only high-risk case for trisomy 18 were confirmed with a cFPR of 8.3% (n = 2/24; 95% CI 2.3-25.9)., Conclusions: cfDNA testing in twin pregnancies has sufficient screening performance for trisomy 21 but the number of affected cases for other conditions is limited to draw any meaningful conclusion. The use of cfDNA testing in triplet pregnancies and vanishing twins remains an area for further research., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

ABSTRACT Background Ketotic hypoglycemia (KH) without an identifiable underlying metabolic or hormonal disease is historically named idiopathic KH. The prevalence is unknown, but idiopathic KH is considered the most frequent cause of hypoglycemia beyond the neonatal period. KH in Down syndrome (DS) has not been reported. Methods We conducted a web‐based survey on KH in DS through the non‐profit patient organization Ketotic Hypoglycemia International. The responses were evaluated for consistency with KH by two authors. Two DS patient histories with documented KH were shared in more details. Results Survey data on 139 DS patients were obtained. After validation, 10 patients (7.2%) had reported episodes of documented hypoglycemia, ketosis, and/or symptoms compatible with KH beyond the neonatal period. Glucose concentrations ranged 1.2‐2.9 mmol/L; betahydroxybutyrate was up to 5.5 mmol/L during hypoglycemia. One girl had trisomy 21 with no response to i.m. glucagon also had a heterozygous Xp22.23 deletion including GYG2, which protein, glycogenin 2, is a substrate for glycogen synthase. Treatment with extended release cornstarch was effective. Conclusion This is the first demonstration of a possible high prevalence of KH in DS. Even though this finding needs to be confirmed in other research settings, identification of KH in DS could have a dramatic impact, as simple treatments with cornstarch, protein and frequent meals may prevent KH attacks and, analogous to other conditions with KH, improve growth, stamina and prevent overeating and obesity. GYG2 deletion may contribute to KH in DS, resembling glycogen storage disease type 0.

Abstract Viruses that induce pulmonary difficulties and auto‐inflammation are more common in people with Down syndrome. They also have a higher number of comorbidities associated with a worse prognosis than the overall population. Adult patients with acute COVID‐19 are increasingly being diagnosed with Long COVID. However, patients with Down syndrome with later long COVID‐19 are the first example documented in Bangladesh.

Abstract Background Down syndrome (DS) is the most common chromosomal survival aneuploidy. The increase in DS life expectancy further heightens the risk of dementia, principally early‐onset Alzheimer's disease (AD). AD risk in DS is higher, considering that this population may also develop metabolic diseases such as obesity, dyslipidemias, and diabetes mellitus. The extra genetic material that characterizes DS causes an imbalance in the genetic dosage, including over‐expression of AD's key pathophysiological molecules and the gene expression regulators, the microRNAs (miRNAs). Two miRNAs, chromosome 21‐encoded, miR‐155, and let‐7c, are associated with cognitive impairment and dementia in adults; but, expression dynamics and relationship with clinical variables during the DS's lifespan had remained hitherto unexplored. Methods The anthropometric, clinical, biochemical, and profile expression of circulating miR‐155 and let‐7c were analyzed in a population of 52 control and 50 DS subjects divided into the young group (Aged ≤20 years) and the adult group (Aged ≥21 years). Results The expression changes for miR‐155 were not significant; nevertheless, a negative correlation with HDL‐Cholesterol concentrations was observed. Notably, let‐7c was over‐expressed in DS from young and old ages. Conclusion Overall, our results suggest that let‐7c plays a role from the early stages of DS's cognitive impairment while overexpression of miR‐155 may be related to lipid metabolism changes. Further studies of both miRNAs will shed light on their potential as therapeutic targets to prevent or delay DS's cognitive impairment.

Abstract DS‐ALL has a higher rate of relapse and treatment‐related mortality. The newer immunotherapies are potentially better options. Relapsed ALL with positive MRD has a poor prognosis. Transient long‐term remission after ALL relapse due to partial chemotherapy combined severe infection is rare.

Abstract Transient abnormal myelopoiesis is common among Down syndrome patients. Although no therapeutic measures are required, close monitoring of comorbidities such as gastrointestinal bleeding is required. Long‐term follow‐up is promising for a healthy future and reduced requirement of unnecessary therapeutic measures including chemotherapy and remission of the pathology.

Abstract Children with Down syndrome and severe intellectual disability have difficulties in learning a language. Enhanced learning procedure, including mora segmentation is beneficial to understand letter–sound correspondence in such children.

Abstract Unexplained regression in Down syndrome (URDS) has become a significant issue in clinical practice and research. This report illustrates the case of a patient with URDS treated with psychological treatment using Dohsa‐hou, in addition to medication. Although psychological treatment may be helpful, monitoring potential risks of acute aggression is necessary.

Abstract Background Subclinical hypothyroidism (SCH) is the commonest thyroid abnormality in patients with Down syndrome (DS). The purpose of this study was to determine the prevalence and types of thyroid abnormalities, to assess the age at diagnosis, and to examine the screening practice in children with DS in a resource limited setting. Methodology A retrospective study was conducted in children with DS seen at endocrine follow‐up clinic. Data were collected from patients' registration book and medical records. Result A total of 115 patients with DS were included in the study out of which 64 (59.8%) were males. Their median age at diagnosis was 9 months (range 4–15 years). Thyroid function test (TFT) was done at least once for 107 (93%) patients. Abnormal thyroid function was observed in 51 (47.7%) patients. The commonest thyroid abnormality was SCH (30/107, 28%) followed by congenital hypothyroidism (11/107, 10.3%), overt hypothyroidism (9/107, 8.4%) and hyperthyroidism (1/107, 0.9%). Most of the patients (86/107, 80.4%) were tested initially in the first 2 years of life. From those who were tested between the age of 2–6 months (n = 22 patients), seven (31.8%) patients had thyroid abnormalities. Conclusion Thyroid abnormalities were seen in a remarkable proportion of DS patients. The detection of abnormalities in the patients with age range of 2–6 months demands the need for additional TFT in this age category apart from the standard recommendation. Early diagnosis and management of thyroid abnormalities are important to decrease further impairment of cognition function in children with DS.

Background Children with Down syndrome (DS) have a high risk of cardiac disease that may prompt consideration for heart transplantation (HTx). However, transplantation in patients with DS is rarely reported. This project aimed to collect and describe waitlist and post– HTx outcomes in children with DS. Methods and Results This is a retrospective case series of children with DS listed for HTx. Pediatric HTx centers were identified by their participation in 2 international registries with centers reporting HTx in a patient with DS providing detailed demographic, medical, surgical, and posttransplant outcome data for analysis. A total of 26 patients with DS were listed for HTx from 1992 to 2020 (median age, 8.5 years; 46% male). High‐risk or failed repair of congenital heart disease was the most common indication for transplant (N=18, 69%). A total of 23 (88%) patients survived to transplant. All transplanted patients survived to hospital discharge with a median posttransplant length of stay of 22 days. At a median posttransplant follow‐up of 2.8 years, 20 (87%) patients were alive, 2 (9%) developed posttransplant lymphoproliferative disorder, and 8 (35%) were hospitalized for infection within the first year. Waitlist and posttransplant outcomes were similar in patients with and without DS (P=non‐significant for all). Conclusions Waitlist and post‐HTx outcomes in children with DS selected for transplant listing are comparable to pediatric HTx recipients overall. Given acceptable outcomes, the presence of DS alone should not be considered an absolute contraindication to HTx.

Abstract Less than one percent of individuals with Down syndrome exhibit mosaicism, a biological phenomenon that describes an individual who has two or more genetically distinct cell lines. The percentage of mosaicism in different tissues can impact the presence of clinical findings and hinder cytogenetic diagnosis. We report a case of mosaicism for trisomy 21 diagnosed after multi‐tissue cytogenetic analysis of peripheral blood and buccal mucosa, associated with significant intellectual disability, dysmorphic facial features, congenital heart defects, macropenis, and imperforate anus.

Abstract Background Children and adolescents with Down syndrome have a distinctive foot shape (such as wide and flat feet) that often leads to difficulty with footwear fitting. 3-dimensional (3D) scanning can accurately measure the foot dimensions of individuals with Down syndrome, which may assist shoe fit. However, the reproducibility of measuring foot dimensions using 3D scans in children and adolescents with Down syndrome is unknown. The aim of this study was to determine the intra- and inter-rater reproducibility of measuring foot dimensions of children and adolescents with Down syndrome using 3D scanning. Methods 3D foot scans of 30 participants with Down syndrome aged 5 to 17 years were obtained using the FotoScan 3D scanner. Foot dimensions assessed were foot length, ball of foot length, outside ball of foot length, diagonal foot width, horizontal foot width, heel width, ball girth, instep girth, first and fifth toe height, and instep height. Additionally, the Wesjflog Index and forefoot shape were determined. Measurements were completed by two raters independently on two separate occasions, 2 weeks apart. Intra- and inter-rater reliability were assessed using intra-class coefficients (ICCs) and Gwet’s AC1 statistics with 95% confidence intervals. Agreement was determined by calculating limits of agreement (LOA) and percentage agreement. Results Eighteen participants were female and 12 were male (mean age 10.6 [3.9] years). Intra-rater reproducibility (ICCs ranged from 0.74 to 0.99, 95% LOA from − 13.7 mm to 16.3 mm) and inter-rater reproducibility (ICCs ranging from 0.73 to 0.99, 95% LOA from − 18.8 mm to 12.7 mm) was good to excellent, although some measurements (ball of foot length, outside ball of foot length, heel width and girth measurements) displayed wider LOAs indicating relatively poorer agreement. Forefoot shape displayed substantial to almost perfect reliability (Gwet’s AC1 0.68 to 0.85) and percentage agreement ranged from 73 to 87%, indicating acceptable agreement. Conclusions The measurement of specific foot dimensions of children and adolescents with Down syndrome using 3D scans is reproducible. Findings of this study may be used to support future research measuring specific foot dimensions of children and adolescents with Down syndrome using 3D foot scans.

Abstract Introduction Retromer complex proteins are decreased in Down syndrome (DS) brains and correlate inversely with brain amyloidosis. However, whether retromer dysfunction contributes to the amyloid beta (Aβ) and tau neuropathology of DS remains unknown. Methods Human trisomic induced Pluripotent Stem Cells (iPSCs) and isogenic controls were differentiated into forebrain neurons, and changes in retromer proteins, tau phosphorylated epitopes, and Aβ levels were assessed in euploid and trisomic neurons using western blot and enzyme‐linked immunosorbent assay (ELISA). Genetic overexpression and pharmacological retromer stabilization were used to determine the functional role of the retromer complex system in modulating amyloid and tau pathology. Results Trisomic neurons developed age‐dependent retromer core protein deficiency associated with accumulation of Aβ peptides and phosphorylated tau isoforms. Enhancing retromer function through overexpression or pharmacological retromer stabilization reduced amyloid and tau pathology in trisomic neurons. However, the effect was greater using a pharmacological approach, suggesting that targeting the complex stability may be more effective in addressing this neuropathology in DS. Discussion Our results demonstrate that the retromer complex is directly involved in the development of the neuropathologic phenotype in DS, and that pharmacological stabilization of the complex should be considered as a novel therapeutic tool in people with DS.

Abstract Introduction By age 60, 60% of adults with Down syndrome (DS) have dementia. Detecting dementia in persons with intellectual disability (ID) can be challenging because their underlying cognitive impairment can confound presentation of dementia symptoms and because adults with ID may have difficulty reporting symptoms. The National Task Group Early Detection Screen for Dementia (NTG‐EDSD) was developed to aid detection of report of cognitive impairment in adults with ID. We implemented an educational curriculum using the NTG‐EDSD and evaluated the impact of the intervention on professional caregivers’ self‐assessed capacity to identify persons with ID and dementia. Methods We held five in‐person training sessions for professional caregivers of persons with ID, partnering with various managed care organizations and social services agencies. We assessed knowledge and attitudes at baseline; immediately after training; and 1 week, 1 month, and 6 months after training. Results A total of 154 direct care workers, case managers, health‐care providers, and other social services staff attended the trainings. Satisfaction with the NTG‐EDSD training was high; 94% of attendees agreed or strongly agreed that they could use the NTG‐EDSD with their clients. After training, attendees reported a marked increase in confidence in their ability to track various health circumstances and detect functional decline in their clients, although some gains were not sustained over time. As a result of the training, one managed care organization made the NTG‐EDSD a standard part of its assessment of adults with DS starting at age 40. Discussion Social services and health‐care professionals can learn to document signs of cognitive decline in adults with ID using the NTG‐EDSD. Attendees were highly satisfied with the training, experienced an increase in confidence in their care of persons with ID, and found the NTG‐ EDSD feasible to use. Because not all gains were sustained over time, booster trainings may be necessary.

Abstract Constipation and stercoral ulcer are risk factors associated with Hirschsprung's disease (HD); long‐term follow‐up is, thus, essential. In postoperative HD associated with Down syndrome (DS) with intellectual disability, vigilant follow‐up is required to avoid severe constipation because DS predisposes the patients to constipation and caregivers cannot easily understand the symptoms.

Objective: Obstructive sleep apnea is common in children with Down syndrome (DS). Tonsillectomy is recommended as the first-line approach in treating children with obstructive sleep apnea (OSA), however, there is limited data on the long-term outcomes in children with DS who undergo tonsillectomy. In this retrospective study, we examined the long-term polysomnographic and symptomatic outcomes in children with DS who underwent tonsillectomy with or without an adenoidectomy (T&A). We hypothesize that the success of T&A to treat OSA in children with DS will diminish with time., Study Design: A retrospective chart review of children with DS who underwent T&A between 2009 and 2015 was conducted. Inclusion criteria were children with at least 1 postoperative polysomnogram (PSG) within 6 months of T&A with an obstructive apnea/hypopnea index (OAHI) < 5. Outcomes were determined by subsequent clinic visits and postoperative polysomnograms: OAHI ≥ 5, snoring reported during clinic visit and time to reoccurrence., Setting: Childrens Hospital Colorado., Results: Of the 57 children with mild OSA at 1st (initial) PSG, 13/40 (33%) children had OAHI ≥ 5 at the 2nd postoperative PSG. Of the 18 patients who underwent a 3rd PSG, 4 (22%) progressed to moderate/severe OSA. A total of 17 patients out of the original 57 (30%) progressed to moderate/severe OSA with the median time for the additional post-op PSG's being 2.3 years., Conclusion: Children with DS who have at most mild OSA (OAHI < 5) following a T&A are at risk for progressing to at least moderate OSA within 2 years after their T&A. A surveillance PSG 2 years following surgery will identify these children., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

In 2011, the National Society of Genetic Counselors (NSGC) published practice resources about communicating a prenatal or postnatal diagnosis of Down syndrome (DS). However, the impact of GC adherence to those recommendations on patient experiences has been unknown. The objective of this analysis was to investigate perceived GC adherence to professional recommendations for delivering a DS diagnosis and the impact on parental diagnosis experiences and the information and support offered. Parents of children with DS born between 2016 and 2021 completed a survey distributed by 12 local DS organizations and the national DS Diagnosis Network to assess prenatal diagnosis experiences and the provision of support and information by health professionals. Participants were queried about whether their GC followed specific recommendations from the NSGC practice resource. Respondents were also invited to describe their diagnosis experience. An overall perceived adherence score was calculated (percentage of elements GC demonstrated/total number of elements). Open-ended responses were inductively coded by a GC and GC student to identify categories and to perform a sentiment analysis where 1 was completely negative, 2 was mixed/more negative, 3 was neutral, 4 was mixed/more positive, and 5 was completely positive. The GCs were blinded to participants' perceived adherence scores while performing the sentiment analysis. Of the 242 parents who completed the survey, 161 respondents answered questions about GC's perceived practice resource adherence. The median perceived adherence score was 42.9% (IQR 21.4-71.4)%. A total of 61 people provided an open-ended response about their prenatal diagnosis experience with a GC and were assigned a sentiment score. The median sentiment score was 3 (IQR 1-5). Kendall's Tau analysis showed that higher perceived practice resource adherence was associated with more positive sentiment scores. These results suggest that NSGC practice resource adherence may improve the prenatal diagnosis experiences of parents of children with DS and have the potential to improve counseling outcomes., (© 2024 National Society of Genetic Counselors.)

Down syndrome (DS) is associated with many dermatological conditions, including hidradenitis suppurativa, folliculitis, and alopecia areata. Despite the high incidence of skin conditions in this population, there are no quality of life (QoL) studies in the dermatology literature focused on patients with DS or their caregivers. The frequently used QoL assessment tool, the Dermatology Life Quality Index (DLQI), has yet to be studied in this population. This study addresses these disparities by capturing how various skin conditions affect the QoL of people with DS and their caregivers and assessing the utility of the DLQI., (© 2024 Wiley Periodicals LLC.)

Background: Feeding difficulty is widely recognized in patients with Down syndrome, and many patients require gastrostomy tube (G-tube) placement for nutrition. No reliable factors have been identified to predict the expected duration of G-tube feeds in patients with Down syndrome. This descriptive cohort study aimed to determine the factors affecting the duration of G-tube feeds. We also investigated change in body mass index (BMI) from G-tube placement to discontinuation., Methods: Medical records of patients with Down syndrome seen by a pediatric gastroenterologist at a tertiary care center between September 1986 and December 2021 were reviewed. Data collection included demographics, anthropometrics, comorbidities, and feeding route. Comparison was performed between patients who discontinued G-tube feeds and those who did not., Results: Two hundred twenty patients (45% female) were included. The median age at G-tube placement was 5 months (interquartile range [IQR]: 0.2-1.3 years). There were 113 (51%) patients who discontinued G-tube feeds, after a median duration of 31.6 months (IQR: 15.6-55.7 months). Tracheostomy was the only covariant associated with a longer duration of G-tube feeds (158 months vs 53 months; P = 0.002). Neither age at G-tube placement nor any comorbidities were associated with BMI status at discontinuation of G-tube., Conclusion: In our cohort of patients with Down syndrome, age at placement of G-tube did not impact the duration of G-tube feeds. Most patients who had a G-tube placed were likely to require enteral feeds for at least 1 year. Those who had a tracheostomy needed their G-tube for a longer time., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Background: Down syndrome (DS) is a neurodevelopmental disorder of genetic origin with a cognitive-behavioural profile that distinguishes it from other syndromes. Within this profile, language difficulties are particularly marked, having been more studied in childhood than in adulthood. More generally, there is a paucity of research on the prosodic skills of individuals with DS, despite the relevance of this linguistic component for effective communication., Aims: This study aimed to analyse, for the first time, the prosodic profile of Spanish-speaking teenagers and young adults with DS. We hypothesized that participants with DS would show significantly lower skills for the perception and production of prosodic functions and forms when compared to peers with intellectual disability (ID) of unknown origin. We also hypothesized that teenagers and young adults with DS would have better prosody perception than prosody production., Methods & Procedures: The final sample included in the study comprised 28 Spanish-speaking teenagers and young adults with DS and 29 teenagers and young adults with other ID matched on chronological age and nonverbal cognition. Their prosodic skills were tested by means of the Profiling Elements of Prosody for Speech and Communication battery. This battery allows for the separate evaluation of the comprehension and expression of the communicative functions of prosody and the discrimination and production of the forms that carry out such functions., Outcomes & Results: In the prosody function tasks, which are the most adaptive tasks for the communicative process, we found, as expected, significantly lower scores on the turn-end, chunking, and focus tasks in the group with DS. However, no significant between-group differences were found for the affect tasks. Participants with DS also had significantly lower scores on the prosodic form tasks than participants with other ID. The results of the comparison between prosodic perception and production skills showed that a generalization about a better profile in comprehension versus production is not possible and that there is a dependence on the demands of the prosodic task undertaken., Conclusions & Implications: The findings contribute to the ongoing development of the language profile of teenagers and young adults with DS and imply the need to design prosodic intervention programs based on their specific profile., What This Paper Adds: What is already known on the subject Prosody is a fundamental element of language, and its mastery affects the effectiveness of communication. However, research on prosody in Down syndrome (DS) that offers a holistic view from a psycholinguistic approach is still scarce. To date, studies focused on providing a detailed profile of prosodic skills in individuals with DS have been mainly conducted with a few English-speaking children. These studies have shown that the comprehension and production of prosody is severely impaired, especially when considering affect and focus production, as well as the perception and production of prosodic forms. During childhood, greater efficacy is found in prosody comprehension than in prosody expression. What this study adds This is the first study analysing the prosodic profile of a large group of Spanish-speaking teenagers and young adults with DS. Poorer performance in the perception and production of both prosodic functions and forms was observed in participants with DS compared to participants with intellectual disability of unknown origin matched on chronological age and nonverbal cognition. Unlike what has been previously found in children, teenagers and young adults with DS performed at the same level as the control group on the understanding and expression of affect through prosodic cues. Results also showed that a generalization about a better prosody profile in comprehension versus production is not possible. What are the clinical implications of this work? This study provides new data on the prosodic skills of Spanish-speaking teenagers and young adults with DS. Given the impact of prosody on effective communication and the pattern of difficulties found in this study, speech and language therapists working with individuals with DS should consider including prosodic skills in interventions not only in childhood but also in adolescence and adulthood. Therefore, the prosodic profile of strengths and weaknesses in individuals with DS found in this research has direct implications for clinical practice., (© 2023 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Abstract Adults with Down syndrome are more prone to develop intellectual, physical, and psychological disorders than their pediatric counterparts. It is pertinent to prevent the occurrence of severe complications in these patients. This case demonstrates the importance of support, regular follow‐up, and wound management in self‐care of adults with Down syndrome.

Abstract Pericardial effusion associated with transient abnormal myelopoiesis in Down's syndrome neonates needs to be diagnosed in a timely manner, and the comorbidities must be treated to prevent mortality. To our knowledge, the occurrence of basophilic/eosinophilic pericardial effusion without an increase of these cells in the peripheral blood and with no evidence of associated hypothyroidism is rare.

Abstract Myxedema is extremely rare in children, and guidelines are lacking. We treated a 12‐year‐old girl with myxedema and cardiogenic shock with initial low dose (0.3‐2.5 μg/kg body weight/day) of oral levothyroxine and intensive care. Oral administration may safely revert children's myxedema in a dosage resembling that for hypothyroidism.

Abstract Background Down syndrome (DS) is a chromosomal disorder that causes intellectual disability. Few studies have been conducted on functional connectivity using resting‐state fMRI (functional magnetic resonance imaging) signals or more specifically, on the relevant structure and density of the default mode network (DMN). Although data on this issue have been reported in adult DS individuals (age: >45 years), the DMN properties in young DS individuals have not been studied. The aim of this study was to describe the density and structure of the DMN network from fMRI signals in young DS (age:

Abstract Introduction Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre‐dementia stages. Methods We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria. Results There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted of memory, language/executive functioning, selective attention, orientation, and praxis tests. Discussion We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

Abstract Introduction People with Down syndrome (DS) are particularly susceptible to Alzheimer's disease (AD) due to the triplication of the amyloid precursor protein (APP) gene. In this cross‐sectional study, we hypothesized that choroidal thinning reported in sporadic AD (sAD) is mirrored in adults with DS. Methods The posterior pole of the eye for 24 adults with DS and 16 age‐matched controls (Ctrl) were imaged with optical coherence tomography. Choroidal thickness (ChT) was measured and analyzed in relation to cognitive status and cerebral amyloid beta (Aβ) load. Results ChT was increased in people with DS (pwDS) compared to Ctrl. This increase was associated with gender differences and positively correlated with cerebral Aβ load in a small subset. There was no significant correlation detected between ChT and age or cognitive status. Discussion In contrast to sAD this study found a significantly thicker choroid in pwDS. Whether these changes are related to Aβ pathology in DS needs further investigation.