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In individuals with Down syndrome (DS), an additional HSA21 chromosome copy leads to the overexpression of a myriad of HSA21 genes, disrupting the transcription of the entire genome. This dysregulation in transcription and post-transcriptional modifications contributes to abnormal phenotypes across nearly all tissues and organs in DS individuals. The array of severe clinical symptoms associated with trisomy 21 poses a considerable challenge in the quest for a cure for DS. Fortunately, a wealth of research suggests that chromosome therapy, hinging on cutting-edge genome editing technologies, can potentially eliminate the extra copy of the human chromosome 21. Genome editing tools have demonstrated their efficacy in restoring trisomy to a normal diploid state in vitro DS cell models. Furthermore, we delve into the noteworthy findings in cellular therapy for DS, with recent studies showcasing the increasing feasibility of strategies involving stem cells and CAR T-cells to address corresponding clinical phenotypes., Competing Interests: Declaration of competing interest The authors report no conflict of interest concerning the material or methods used in this study or the findings specified in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

Introduction: The aims of this systematic review and meta-analysis are to synthesise quality of life (QOL) of family caregivers of children and young adults with Down syndrome (DS) and determine factors affecting their QOL., Method: This review was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Key search terms were "quality of life", "down syndrome" and "trisomy 21". Meta-analysis using random effect model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532)., Results: Eighteen studies with 1956 caregivers were included. Of the 10 studies utilising the World Health Organization Quality of Life Instrument-Brief Version, 5 were included in the meta-analysis. Psychosocial domain had the highest score with mean (95% confidence interval [CI]) of 63.18 (39.10-87.25). Scores were poorer in physical, environmental and social domains: 59.36 (28.24-90.48), 59.82 (19.57-100.07) and 59.83 (44.24-75.41), respectively. Studies were heterogenous with I 2 values ranging from 99-100% ( P <0.01). The remaining 8 studies used 6 other instruments. Qualitative synthesis revealed that caregivers' QOL was adversely affected by child-related factors, such as level of functional independence, developmental delay, presence of multiple comorbidities, impaired activities of daily living and poor sleep quality. Environmental factors that adversely affected caregivers' QOL included number of children, housing and support from the family. Personal factors that affected caregivers' QOL included age, being a single mother, low education and low income., Conclusion: QOL of caregivers of children with DS was lower than population reference data. Understand-ing the factors that influence family caregivers' QOL is an essential step towards improving the QOL of caregivers and their children with DS.

This review article aims to bridge the knowledge gap in providing comprehensive care to adults with Down syndrome (DS) in primary care settings. Despite the increasing prevalence of adults with DS, there is a significant lack of familiarity and comprehensive guidelines for their health care among primary care physicians. This often results in subpar health promotion, preventive screenings, and individualized care. This article attempts to provide guidance for healthcare providers on previsit preparation, clinic visit characteristics, testing and screening considerations, and decision making/guardianship for adults with DS. By emphasizing a patient-centered approach, this review aims to enhance the quality of care, reduce associated morbidity and mortality, and ultimately improve the health outcomes of adults with DS.

Background and Aim . Down syndrome (DS) is the most common reason for disabilities caused by genetic disorders. Due to the special nature of this disease and the special needs of children with Down syndrome, they are required to receive their families' support. Therefore, the recognition of their problems and needs and also the alternatives for resolving them and promoting their life quality are very useful. Also, since very limited qualitative studies have been conducted, it seems necessary to design a qualitative study. Method . This qualitative study was conducted by the content analysis method and through purposeful sampling method with the participation of 26 participants including 15 mothers, 6 fathers, 3 sisters, and 2 brothers of DS children in 2022-2023. The data were collected through semi-structured interviews. Findings . Using the content analysis method of Graneheim and Lundman (2004), the main theme was "Family self-supporting in protecting Down syndrome children." The subthemes were seven including "trying to find information-support resources," "Giving importance to child's health," "religious beliefs of the family," "child moral education, helping to child's relative self-support," "developing familial support," and "developing child's social interactions." Conclusion and Recommendations . The findings of this study showed that family is the main source of fulfilling the needs of children and their life challenges through using efficient self-support methods. This study introduced family self-support methods in terms of DS children in a way that other families can also manage the problems of their children more efficiently. The present study can be used by trustees of DS to support them and their families. Considering the existence of many problems in children with Down syndrome and the involvement of families, it is suggested that policymakers and community health managers provide the basis for receiving services and social support. For example, it is possible to strengthen the screening systems in the country to diagnose the disease on time and take quick action to solve this problem. Also, by increasing the health insurance coverage and fair distribution of the support resources needed by these people, it promoted the quality of life for them and their families. Also, health policymakers in Iran can take action to increase life expectancy and reduce deaths caused by DS by improving the equitable distribution of health resources and services. Also, public policies should enhance supportive intermediation for prevention and life quality promotion and also decrease health challenges. They are also supposed to lessen the costs of health care. Furthermore, to support social organizations, health service providers and researchers should consider the development of intermediations for the health enhancing and life quality promoting of DS children., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Farzaneh Noroozi et al.)

Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS). Adenoidectomy and/or tonsillectomy are the usual first interventions employed to treat OSA in children with DS but sometimes do not achieve adequate resolution of clinical signs. Positive airway pressure treatment is often used next, but this treatment is poorly tolerated by this population. Persistent OSA can adversely affect a child's health and cognitive development. Hypoglossal nerve stimulation (HGNS), previously shown to be safe and effective in adults with OSA, has been used in children as young as 10 years old with DS and has achieved measurable neurocognitive benefits. The US Food and Drug Administration recently lowered the age for HGNS implantation to 13 years for children with DS. However, questions remain regarding treatment of refractory OSA in younger children. Here, we report the case of a 4-year-old boy with DS and treatment-refractory OSA who underwent successful HGNS implantation. The decision to proceed with HGNS implantation in such a young child involved discussions about anatomic feasibility and potential neurocognitive benefits. The device was implanted without complication and with minimal postoperative bulk. This case suggests a possible treatment option that can be discussed in the course of shared decision-making between clinicians and families of young children with DS and treatment-refractory OSA., (Copyright © 2024 by the American Academy of Pediatrics.)

Neonatal acute myeloid leukemias (AML) occurred within the first 28 days of life and constitute only a small proportion of all AL. They are distinguished from leukemias of older children by their clinical presentation, which frequently includes cutaneous localizations ("blueberry muffin rash syndrome") and a leukocytosis above 50 ×10 9 /L. This proliferation may be transient, causing a transient leukemoid reaction in a background of constitutional trisomy 21 ("Transient Abnormal Myelopoieseis" or TAM) or Infantile Myeloproliferative Disease in the absence of constitutional trisomy 21 ("Infantile Myeloproliferative Disease" or IMD). In cases of true neonatal AML, the prognosis of patients is poor. Overall survival is around 35 % in the largest historical series. This poor prognosis is mainly due to the period of onset of this pathology making the use of chemotherapy more limited and involving many considerations, both ethical and therapeutic. The objective of this work is to review this rare pathology by addressing the clinical, biological, therapeutic and ethical particularities of patients with true neonatal AML or transient leukemoid reactions occurring in a constitutional trisomy 21 (true TAM) or somatic background (IMD)., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: People with intellectual disabilities may experience frailty earlier than the general population. This scoping review aimed to investigate how frailty is defined, assessed, and managed in adults with an intellectual disability; factors associated with frailty; and the potential impact of COVID-19 on frailty identification and management., Method: Databases were searched from January 2016 to July 2023 for studies that investigated frailty in individuals with intellectual disabilities., Results: Twenty studies met the inclusion criteria. Frailty prevalence varied between 9% and 84%. Greater severity of intellectual disability, presence of Down syndrome, older age, polypharmacy, and group home living were associated with frailty. Multiagency working, trusted relationships and provision of evidence-based information may all be beneficial in frailty management., Conclusion: Frailty is common for people with intellectual disabilities and is best identified with measures specifically designed for this population. Future research should evaluate interventions to manage frailty and improve lives., (© 2024 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)

Background: Individuals with Down syndrome (DS) require more time to develop motor and/or cognitive skills. Neuromodulation is used to assist in this development. However, there is a gap in the literature on neurophysiological changes that may occur in the primary motor cortex in individuals with DS following neuromodulation., Objective: Our objective was to investigate possible neurophysiological changes in brain wave behavior of the primary motor cortex following the administration of anodal transcranial direct current stimulation combined with sensorimotor training., Methods: The study involved 12 participants with DS. EEG equipment was used to investigate brain activity. The participants received neuromodulation involving anodal tDCS for 20 minutes with a current of 1 mA combined with virtual reality (VR) training three times a week for a total of ten sessions. We analyzed EGG signals and 3D movement during a reaching movement of the dominant upper limb before and after the ten-session protocol., Results: Significant differences in event-related desynchronization and event-related synchronization of the alpha and beta rhythms were found throughout the evaluations. Brain mapping revealed reductions in power and frequency, demonstrating changes in the patterns of these rhythms in the cerebral cortex. Revealed reorganization of the behavior of alpha and beta waves, as demonstrated by distribution of synchronization and desynchronization of these waves among the regions of the brain., Conclusion: The results suggest that anodal tDCS promotes the reorganization of brain impulses, redirecting these impulses to the required regions more efficiently and contributing to better motor planning.

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., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The Pediatric Integrated Care Survey (PICS) is validated for use to measure the caregiver reported experience of integration and efficiency of all the aspects of their child. We began using the PICS survey to track changes in the patient experience, including throughout changing models of care during the COVID-19 pandemic. From February 2019 to June 2023, 62 responses from caregivers of individuals seen in the Massachusetts General Hospital Down Syndrome Program completed the PICS. Responses were scored using the standardized PICS user manual, and descriptive statistics were completed. The raw scores and composite monthly scores of the PICs were graphed in statistical process control charts. The average PICS score was 12.0 (range 2-19) out of a maximum score of 19; no shifts or trends were seen. Items with lowest scores indicated greatest opportunities for improvement related to: advice from other care team members, impact of decisions on the whole family, things causing stress or making it hard because of child's health, and offering opportunities to connect with other families. Studying the PICS in a specialty clinic for Down syndrome for the first time has established a baseline for future quality improvement work and interventions to increase care integration., (© 2023 Wiley Periodicals LLC.)

Children with Down syndrome (DS) have a 10- to 20-fold greater predisposition to develop acute leukemia compared to the general population, with a skew towards myeloid leukemia (ML-DS). While ML-DS is known to be a subtype with good outcome, patients who relapse face a dismal prognosis. Acute lymphocytic leukemia in DS (DS-ALL) is considered to have poor prognosis. The relapse rate is high in DS-ALL compared to their non-DS counterparts. We have a better understanding about the mutational spectrum of DS leukemia. Studies using animal, embryonic stem cell- and induced pluripotent stem cell-based models have shed light on the mechanism by which these mutations contribute to disease initiation and progression. In this review, we list the currently available treatment strategies for DS-leukemias along with their outcome with emphasis on challenges with chemotherapy-related toxicities in children with DS. We focus on the mechanisms of initiation and progression of leukemia in children with DS and highlight the novel molecular targets with greater success in preclinical trials that have the potential to progress to the clinic., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Abstract Trisomy of chromosome 21 (TS21) is the most common autosomal aneuploidy compatible with postnatal survival with a prevalence of 1 in 700 newborns. Its phenotype is highly complex with constant features, such as mental retardation, dysmorphic traits and hypotonia, and variable features including heart defects, susceptibility to Alzheimer’s disease (AD), type 2 diabetes, obesity and immune disorders. Overexpression of genes on chromosome-21 (Hsa21) is responsible for the pathogenesis of Down syndrome (DS) phenotypic features either in a direct or in an indirect manner since many Hsa21 genes can affect the expression of other genes mapping to different chromosomes. Many of these genes are involved in mitochondrial function and energy conversion, and play a central role in the mitochondrial dysfunction and chronic oxidative stress, consistently observed in DS subjects. Recent studies highlight the deep interconnections between mitochondrial dysfunction and DS phenotype. In this short review we first provide a basic overview of mitochondrial phenotype in DS cells and tissues. We then discuss how specific Hsa21 genes may be involved in determining the disruption of mitochondrial DS phenotype and biogenesis. Finally we briefly focus on drugs that affect mitochondrial function and mitochondrial network suggesting possible therapeutic approaches to improve and/or prevent some aspects of the DS phenotype.

Purpose: Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019., Methods: We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials., Results: Patients with DS exhibited more frequent minimal residual disease (MRD) ≥0.01% at end induction (30.8% v 21.5%; P < .001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P < .0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P < .0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P < .0001), and within NCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 × 10 3 /μL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P = .0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P < .0001), and induction death (3.4% v 0.8%; P < .0001). Mucositis, infections, and hyperglycemia were significantly more frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P = .005)., Conclusion: Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.

Introduction: This cross-sectional study aimed to (1) compare family management between families of children with autism spectrum disorder (ASD) or Down syndrome and (2) evaluate the contribution of the child (ASD behaviors, feeding difficulties, sleep disturbances), caregiver (mental health) and family (social support) factors to the caregiver's perceived condition management ability and effort., Method: Eighty-five caregivers (56 ASD, 29 Down syndrome) completed quantitative instruments online. Data analysis included independent samples t-tests and multiple linear regression., Results: There were no significant differences in the dimensions of family management between groups. More ASD behaviors were associated with lower condition management ability and higher condition management effort. Lower perceived social support and higher caregiver age were associated with lower condition management ability., Discussion: Integrating care into family life may be more challenging when the child has more social differences and behavioral rigidity. Nursing care should include an assessment of family social support., Competing Interests: CONFLICTS OF INTEREST None to report., (Copyright © 2023 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Background: A comprehensive multidisciplinary medical guideline for adults with Down syndrome is lacking in the Netherlands. In this study, we aim to explore parents' views on multidisciplinary care and identify which aspects of health care they find most important in the context of developing such a guideline., Method: This qualitative study used semi-structured interviews. Nineteen interviews were conducted with parents of adults with Down syndrome. The main themes and subthemes were identified from the transcripts by using the framework method., Results: Four main themes were identified which should be addressed in the guideline according to the parents: parents' support in medical care, patient-centred care, important medical topics and the organisation of medical care., Conclusions: This study provides insights into parents' opinions about medical care for adults with Down syndrome. These insights are used in the construction of a guideline to improve medical care for adults with Down syndrome., (© 2023 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)

Background: Periodontal diseases (PDs) have been documented to be significantly more prevalent and severe in patients with Down syndrome (DS). Different immunological and microbiological factors contributed to predisposing these patients to progressive and recurrent PDs., Aim: The aim of this review was to investigate the altered immunological responses and oral microbiota disorders as well as focus on adjunctive non-surgical methods for the treatment of PDs and its applicability in patients with DS., Material and Methods: A literature review was conducted addressing the following topics: (1) the altered immunological responses, (2) orofacial disorders related to DS patients, (3) oral microbiota changing, and (4) adjunctive non-surgical treatment and its efficacy in patients with DS., Results: Due to the early onset of PDs in children with DS, the need for prompt and effective treatment in these patients is essential., Discussion and Conclusion: So, investigating underlying factors may open a new window to better understand the pathology of PDs in DS people and thus, find better strategies for treatment in such group. Although non-surgical treatments such as photodynamic therapy and probiotic consumption represented acceptable outcomes in different examined patients without DS, data about the application of these convenience and no need for local anesthesia methods in patients with DS is limited., (© 2024 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

This study aiming to compare the effectiveness of Cognitive Orientation to Daily Occupational Performance (CO-OP) and Conductive Education (CE) approaches on motor skills, activity limitation and participation restrictions in children with Down Syndrome (DS). Twelwe children were randomly assigned into two groups. Twelve-week CO-OP or CE intervention (period-1) followed by a 12-week washout period. Same interventions were crossed over for another 12 weeks (period-2). The Performance Quality Rating Scale (PQRS), Canadian Occupational Performance Measure (COPM) and the Bruininks Oseretsky Test of Motor Proficiency Second Edition-Brief Form (BOT2-BF) were used for outcome measurements. CO-OP was effective in the improvement of task-specific activity performance, while both approaches have similar effects on the improvement of perceived performance, satisfaction, and motor skills performance., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Outcomes are extremely poor in Down syndrome-associated acute lymphocytic leukemia, particularly in recurrent cases. A 2-year-old boy with Down syndrome-associated acute lymphocytic leukemia achieved complete remission after standard chemotherapy. However, he experienced recurrence twice in the bone marrow and central nervous system. Salvage treatments included whole-brain/whole-spine irradiation. Thereafter, the patient received a second cord blood transplantation after the reduced-intensity conditioning. The graft was characterized by killer cell immunoglobulin-like receptor ligands mismatch. The patient has subsequently survived for 6.5 years without recurrence. We speculate that killer cell immunoglobulin-like receptor ligand-mismatched cord blood transplantation enhanced the graft-versus-leukemia effect through natural killer cells, and conferred long-term remission., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Therapeutic exercise exerts positive effects by mitigating or reducing the motor or cognitive changes that people with Down syndrome undergo throughout their life. There are no updated systematic reviews that integrate the evidence available in a way that facilitates decision-making for physical rehabilitation teams. This study therefore aimed to consolidate the information available and compare the effects of different types of physical exercise on the motor function of adults with DS. We conducted a systematic review and meta-analysis of randomized clinical trials and quasi-experimental studies. The literature search was performed between January 2023 and February 2023 using the PubMed, SCIELO, Epistemonikos, and Lilacs databases. Studies were selected according to pre-determined inclusion and exclusion criteria. The risk-of-bias assessment was performed using the risk-of-bias rating tool for randomized clinical trial (RoB) and the risk of bias of non-randomized comparative studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. Risk-of-bias assessment and meta-analyses were performed using the RevMan software package. Sixteen studies met the eligibility criteria for the qualitative synthesis and 4 were included in the meta-analyses. Combined exercise significantly increased muscle strength both in the upper limbs (SMD = 0.74 [95% CI 0.25-1.22]) and lower limbs (SMD = 0.56[95% CI 0.08-1.04]). Aerobic exercise improved spatiotemporal gait parameters. Aerobic exercise showed significant improvements in dynamic balance while combined exercise significantly increased dynamic and static balance. The certainty of the evidence was low to moderate for all outcomes. There was low and moderate certainty of evidence for the outcomes proposed in this review. However, therapeutic exercise could be effective in improving muscle strength and gait functionality., (© 2023. The Author(s).)

The duplication of chromosome 21, as evidenced in Down Syndrome (DS), has been linked to contraindications to health, such as chronotropic and respiratory incompetence, neuromuscular conditions, and impaired cognitive functioning. The purpose of this study was to examine the effects of eight weeks of prescribed exercise and/or cognitive training on the physical and cognitive health of adults with DS. Eighty-three participants (age 27.1 ± 8.0 years) across five continents participated. Physical fitness was assessed using a modified version of the six-minute walk test (6MWT), while cognitive and executive functions were assessed using the Corsi block test, the Sustained-Attention-To-Response Task (SART), and the Stroop task (STROOP). All were completed pre- and post-intervention. Participants were assigned to eight weeks of either exercise (EXE), 3 × 30 min of walking/jogging per week, cognitive training (COG) 6 × ~20 min per week, a combined group (COM), and a control group (CON) engaging in no intervention. 6MWT distance increased by 11.4% for EXE and 9.9% for COM ( p < 0.05). For SART, there were positive significant interactions between the number of correct and incorrect responses from pre- to post-intervention when participants were asked to refrain from a response (NO-GO-trials) across all experimental groups ( p < 0.05). There were positive significant interactions in the number of correct, incorrect, and timeout incompatible responses for STROOP in EXE, COG, and COM ( p < 0.05). Walking generated a cognitive load attributed to heightened levels of vigilance and decision-making, suggesting that exercise should be adopted within the DS community to promote physical and cognitive well-being.

Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between year 2000 to 2021. Median time from diagnosis to relapse was 6.8 (range, 1.1-45.5) months. Three-year event-free survival (EFS) and overall survival (OS) were 20.9 ± 5.3% and 22.1 ± 5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (hazard ratio [HR], 0.28), duration of first complete remission (CR1) (HR, 0.31 for > 12 months) and attainment of remission after relapse (HR, 4.03). Patients who achieved complete remission (CR) before HSCT, had an improved OS and EFS of 56.0 ± 11.8% and 50.5 ± 11.9%, respectively compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0 ± 9.5%). Treatment failure after HSCT was predominantly because of disease recurrence (52%) followed by treatment-related mortality (10%). The prognosis of r/r ML-DS remains dismal even in the current treatment period and serve as a reference point for current prognostication and future interventional studies. Clinical trials aimed at improving the survival of patients with r/r ML-DS are needed., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Trisomy of chromosome 21 (TS21) is the most common autosomal aneuploidy compatible with postnatal survival with a prevalence of 1 in 700 newborns. Its phenotype is highly complex with constant features, such as mental retardation, dysmorphic traits and hypotonia and variable features including heart defects, susceptibility to Alzheimer's disease (AD), type 2 diabetes, obesity and immune disorders. Overexpression of genes on chromosome-21 (Hsa21) is responsible for the pathogenesis of Down syndrome (DS) phenotypic features either in a direct or in an indirect manner since many Hsa21 genes can affect the expression of other genes mapping to different chromosomes. Many of these genes are involved in mitochondrial function and energy conversion, and play a central role in the mitochondrial dysfunction and chronic oxidative stress, consistently observed in DS subjects. Recent studies highlight the deep interconnections between mitochondrial dysfunction and DS phenotype. In this short review we first provide a basic overview of mitochondrial phenotype in DS cells and tissues. We then discuss how specific Hsa21 genes may be involved in determining the disruption of mitochondrial DS phenotype and biogenesis. Finally we briefly focus on drugs that affect mitochondrial function and mitochondrial network suggesting possible therapeutic approaches to improve and/or prevent some aspects of the DS phenotype. [ABSTRACT FROM AUTHOR]

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9-12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ 2  = 11.82, P = 0.001), abnormal MRI (χ 2  = 7.78, P = 0.005), and abnormal LP (χ 2  = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD., (© 2023. Springer Nature Limited.)

Importance: Down syndrome is the leading genetic cause of intellectual disability and automatically qualifies individuals for Social Security Insurance. Therefore, Medicaid is the major health insurance provider for a population at high risk for dementia, obesity, and premature mortality. Despite the importance of Medicaid for adults with Down syndrome, little is known about how this population uses Medicaid., Objective: To describe enrollment in, health care use in, and cost to Medicaid for adults with Down syndrome compared with adults with intellectual disability and a random sample of adults enrolled in Medicaid., Design, Setting, and Participants: In this cohort study, the data are from a claims cohort of adults aged 18 years or older enrolled in Medicaid at any point between January 1, 2011, and December 31, 2019. Participants were enrollees with 1 or more inpatient claim or 2 or more other claims with an International Classification of Diseases, Ninth Revision code or an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code for Down syndrome or intellectual disability as well as a random sample of those without developmental disability. Analyses were conducted from June 2022 to February 2023., Main Outcomes and Measures: Data were linked across 2 data reporting systems. Main outcomes were enrollee demographic characteristics, enrollment characteristics, cost, and service use., Results: This cohort study included 123 024 individuals with Down syndrome (820 273 person-years of coverage; mean [SD] age, 35 [14.7] years; median age, 33 years [IQR, 21-48 years]; 51.6% men; 14.1% Black individuals; 16.7% Hispanic individuals; and 74.6% White individuals), 1 182 246 individuals with intellectual disability (mean [SD] age, 37.1 [16.8] years; median age, 33 years [IQR, 22-50 years]; 56.5% men; 22.0% Black individuals; 11.7% Hispanic individuals; and 69.5% White individuals), and 3 176 371 individuals with no developmental disabilities (mean [SD] age, 38 [18.6] years; median age, 33 years [IQR, 21-52 years]; 43.8% men; 23.7% Black individuals; 20.7% Hispanic individuals; and 61.3% White individuals). Median enrollment in Medicaid for a person with Down syndrome was 8.0 years (IQR, 5.0-9.0 years; mean [SD], 6.6 [2.6] years). Costs were higher for the Down syndrome group (median, $26 278 per person-year [IQR, $11 145-$55 928 per person-year]) relative to the group with no developmental disabilities (median, $6173 per person-year [IQR, $868-$58 390 per person-year]). Asian, Black, Hispanic, Native American, and Pacific Islander adults with Down syndrome had fewer costs and claims per person-year compared with White adults with Down syndrome., Conclusion and Relevance: This cohort study of individuals with Down syndrome enrolled in Medicaid found consistent enrollment and high use of health care in a population with high health care needs. Results were similar comparing individuals with Down syndrome and those with intellectual disability, with both groups differing from a sample of Medicaid enrollees with no developmental disabilities. Medicaid data are a useful tool for understanding the health and well-being of individuals with Down syndrome.

In the last decade, an important effort was made in the field of Down syndrome to find new interventions that improve cognition. These therapies have added to the traditional symptomatic treatments and to the drugs for treating Alzheimer disease in the general population repurposed for Down syndrome. Defining next-generation therapeutics will involve biomarker-based therapeutic decision-making, and preventive and multimodal interventions. However, translation of specific findings into effective therapeutic strategies has been disappointingly slow and has failed in many cases at the clinical level, leading to reduced credibility of mouse studies. This is aggravated by a tendency to favour large-magnitude effects and highly significant findings, leading to high expectations but also to a biased view of the complex pathophysiology of Down syndrome. Here, we review some of the most recent and promising strategies for ameliorating the cognitive state of individuals with Down syndrome. We studied the landscape of preclinical and clinical studies and conducted a thorough literature search on PubMed and ClinicalTrials.gov for articles published between June 2012 and August 2022 on therapies for ameliorating cognitive function in individuals with Down syndrome. We critically assess current therapeutic approaches, why therapies fail in clinical trials in Down syndrome, and what could be the path forward. We discuss some intrinsic difficulties for translational research, and the need for a framework that improves the detection of drug efficacy to avoid discarding compounds too early from the companies' pipelines., (© 2023 Mac Keith Press.)

Background: Individuals with Down syndrome (DS) exhibit deficits in static and dynamic balance abilities and maladaptive functions. This study aimed to determine the effectiveness of dance movement therapy (DMT) group intervention in individuals with DS., Methods: The 31 participating individuals with DS, aged 5-29 years, were randomly divided into intervention (n = 16) and control (n = 15) groups. Posturography was used for static balance measurement, timed up and go test for dynamic balance measurement and the Achenbach System of Empirically Based Assessment (ASEBA) questionnaire for adaptive function and behavioural problem measurement in participants before and after the DMT interventions. The intervention group underwent 60-min DMT intervention once a week for 10 times, while the control group had usual daily activities., Results: The results revealed a statistically significant difference and large effect sizes in dynamic balance [(f(1, 29) = 4.52, P = 0.04, η p   2 = 0.14)] in the intervention group compared with the control group. There were no statistically significant differences in static balance and ASEBA scores between the groups., Conclusions: This study found that the DMT interventions helped to improve the dynamic balance in individuals with DS., (© 2023 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Impaired muscle strength, proprioceptive and vestibular deficits, and orthopedic dysfunction are common disorders associated with Down syndrome (DS). Hippotherapy uses the horses' multidimensional movement to improve posture, balance, and overall function, both motor and sensory. Research evidence supports hippotherapy as an effective, medically recognized intervention for the rehabilitation of gross motor skills. The aim of this study was to determine the effect of hippotherapy on balance, functional mobility, and functional independence in children with DS. Thirty-four children with DS were randomly assigned to the experimental (hippotherapy) and control groups after the initial assessment. Both groups received physiotherapy including balance exercises, and the experimental group also received hippotherapy as an integrative therapy. Pediatric Balance Scale (PBS), Timed Up and Go Test (TUG), and Functional Independence Measure for Children (WeeFIM) were used before and after the intervention. Baseline outcome measures (PBS, TUG, WeeFIM) were statistically similar between groups (p > 0.05). After the intervention, PBS and TUG scores improved in both groups (p < 0.05). On the other hand, WeeFIM scores improved just in the hippotherapy group (p < 0.05).   Conclusion: Therefore, providing hippotherapy as an integrative therapy to physiotherapy will be more effective in improving the functional independence of children with DS.    Trial registration: NCT05297149 (March 2022, retrospectively registered). What is Known: • Hippotherapy has an improvement effect on balance and functional independence in different diseases and age groups, but the evidence is limited in DS. • There is limited evidence about the effect of hippotherapy on functional mobility in different diseases and age groups, but there is no evidence in DS. What is New: • Hippotherapy is a safe and effective approach to support improvement in functional independence in children with DS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

An essential part of the care of children with Down syndrome is secondary screening for comorbidity. It is well known that comorbidity frequently occurs in these children. A new update of the Dutch Down syndrome medical guideline was developed to create a sound evidence base for several of these conditions. We present the latest insights and recommendations from this Dutch medical guideline which are based on the most relevant literature currently available and developed with rigorous methodology. The main focus of this revision of the guideline was on obstructive sleep apnea and other airway problems and hematologic disorders, such as transient abnormal myelopoiesis, leukemia, and thyroid disorders. Conclusion: This is a short summary of the latest insights and recommendations from the updated Dutch medical guideline for children with Down syndrome., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Justification: The diagnosis of Down syndrome (DS) is easily made clinically but the management is multi-disciplinary and life-long. There is no standard protocol available for its management in India., Process: A committee was formed under the Indian Academy of Pediatrics (IAP) chapter of Neuro developmental pediatrics consisting of 20 experts working in the related field. The various aspects of the condition were discussed and allotted to the concerned experts related for preparing the guidelines. The material received was collated to form a set of guidelines, which were reviewed by the committee, and a consensus statement made. The guidelines were then approved by the chapter, and by the IAP., Objectives: To define the condition and to look into the various aspects of antenatal and postnatal diagnosis. To explain briefly about the involvement of the various systems that are involved and formulate recommendations for management. To recommend early and sustained interventional therapies to enable children with DS lead an independent life., Recommendations: The stress on bio-psycho-social strategy for the management of children with DS is reiterated, and the need for a medical, social and rights model is recommended after each section. The age-wise recommendations are also highlighted in addition to the recommendations under each system.

Objective: To address gaps in routine recommended care for children with Down syndrome, through quality improvement during the coronavirus disease 2019 (COVID-19) pandemic., Study Design: A retrospective chart review of patients with Down syndrome was conducted. Records of visits to the Massachusetts General Hospital Down Syndrome Program were assessed for adherence to 5 components of the 2011 American Academy of Pediatrics (AAP) Clinical Report, "Health Supervision for Children with Down Syndrome." The impact of 2 major changes was analyzed using statistical process control charts: a planned intervention of integrations to the electronic health record for routine health maintenance with age-based logic based on a diagnosis of Down syndrome, created and implemented in July 2020; and a natural disruption in care due to the COVID-19 pandemic, starting in March 2020., Results: From December 2018 to March 2022, 433 patients with Down syndrome had 940 visits. During the COVID-19 pandemic, adherence to the audiology component decreased (from 58% to 45%, P < .001); composite adherence decreased but later improved. Ophthalmology evaluation remained stable. Improvement in adherence to 3 components (thyroid-stimulating hormone, hemoglobin, sleep study ever) in July 2020 coincided with electronic health record integrations. Total adherence to the 5 AAP guideline components was greater for follow-up visits compared with new patient visits (69% and 61%, respectively; P < .01)., Conclusions: The COVID-19 pandemic influenced adherence to components of the AAP Health supervision for children with Down syndrome, but improvements in adherence coincided with implementation of our intervention and reopening after the COVID-19 pandemic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: Down syndrome regression disorder (DSRD) is a symptom cluster consisting of neuropsychiatric regression without cause. Although knowledge of this condition has accelerated over the last decade, prior studies have been limited by heterogenous nomenclature, diagnostic approaches and therapeutic interventions. This review highlights recent advances in the diagnosis and clinical approach to DSRD and reviews the most up-to-date literature on therapeutic interventions for this condition., Recent Findings: Several multicentre studies have reported exciting findings on the presence of neurodiagnostic study abnormalities and responses to a variety of therapeutics, including psychotropics (including benzodiazepines), electroconvulsive therapy and immunotherapy. Differential response rates have been observed in the presence and absence of a variety of clinical and diagnostic factors., Summary: Individuals with DSRD are responsive to a variety of psychiatric pharmacotherapy and immunotherapy underscoring this phenotype may have multiple causes. Multidisciplinary care is helpful in the evaluation and management of individuals with this condition., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Sex chromosome disorders severely compromise gametogenesis in both males and females. In oogenesis, the presence of an additional Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes 1-5 . Here we efficiently converted the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells. In addition, this chromosomal alteration successfully eradicated trisomy 16, a model of Down's syndrome, in PS cells. Artificially produced euploid XX PS cells differentiated into mature oocytes in culture with similar efficiency to native XX PS cells. Using this method, we differentiated induced pluripotent stem cells from the tail of a sexually mature male mouse into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could ameliorate infertility caused by sex chromosome or autosomal disorders, and opens the possibility of bipaternal reproduction., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Mitochondrial dysfunctions have been described in Down syndrome (DS) caused by either partial or full trisomy of chromosome 21 (HSA21). Mitochondria play a crucial role in various vital functions in eukaryotic cells, especially in energy production, calcium homeostasis and programmed cell death. The function of mitochondria is primarily regulated by genes encoded in the mitochondrion and nucleus. Many genes on HSA21 are involved in oxidative phosphorylation (OXPHOS) and regulation of mitochondrial functions. This review highlights the HSA21 dosage-sensitive nuclear-encoded mitochondrial genes associated with overexpression-related phenotypes seen in DS. This includes impaired mitochondrial dynamics, structural defects and dysregulated bioenergetic profiles such as OXPHOS deficiency and reduced ATP production. Various therapeutic approaches for modulating energy deficits in DS, effects and molecular mechanism of gene therapy and drugs that exert protective effects through modulation of mitochondrial function and attenuation of oxidative stress in DS cells were discussed. It is prudent that improving DS pathophysiological conditions or quality of life may be feasible by targeting something as simple as cellular mitochondrial biogenesis and function., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

Children with Down syndrome require services from different sectors over time to optimize health and development, however, there is little information on longitudinal, cross-sector service use. Parents of children with Down syndrome attending a Canadian children's hospital participated in semistructured interviews covering life-time multiple sector service use. Five key service patterns were identified: (1) primary care physicians playing a circumscribed role; (2) a marked shift in public habilitative service receipt from development agencies in the preschool years to exclusive school delivery after school entry; (3) families obtaining private services to address gaps from public sector services; (4) a prominent role for parents to identify additional services; and (5) service variability as a function of timing and severity of medical comorbidity., (©AAIDD.)

Cardiovascular disease is a leading cause of morbidity and mortality in individuals with Down syndrome. Congenital heart disease is the most common cardiovascular condition in this group, present in up to 50% of people with Down syndrome and contributing to poor outcomes. Additional factors contributing to cardiovascular outcomes include pulmonary hypertension; coexistent pulmonary, endocrine, and metabolic diseases; and risk factors for atherosclerotic disease. Moreover, disparities in the cardiovascular care of people with Down syndrome compared with the general population, which vary across different geographies and health care systems, further contribute to cardiovascular mortality; this issue is often overlooked by the wider medical community. This review focuses on the diagnosis, prevalence, and management of cardiovascular disease encountered in people with Down syndrome and summarizes available evidence in 10 key areas relating to Down syndrome and cardiac disease, from prenatal diagnosis to disparities in care in areas of differing resource availability. All specialists and nonspecialist clinicians providing care for people with Down syndrome should be aware of best clinical practice in all aspects of care of this distinct population.

Background: Down syndrome (DS) population has a very high prevalence of obstructive sleep apnoea (OSA), but this remains underdiagnosed. Hence, we aimed to evaluate caregiver's knowledge of OSA and related sociodemographic factors that could contribute to OSA screening patterns in this population., Methods: An online survey though the LuMind IDSC Foundation focused on OSA diagnosis, treatments and the number of sleep studies performed. Data were compared between subjects born before and after the American Academy of Pediatrics (AAP) recommendations for OSA screening., Results: Of the caregivers, 724 (parents 96.3%), responded to the survey. The median [interquartile (IQR)] age of the subjects with DS was 12 [20;7] years. The majority (84.3%) had sleep apnoea diagnosis, and half of them were initially referred for a sleep study due to disturbed sleep symptoms. Only 58.7% of the responders were aware of the AAP recommendations. This was linked to higher socioeconomic and/or educational level and to an earlier OSA diagnosis. The median (IQR) age of OSA diagnosis was lowered after the AAP guidelines publication compared with before its publication (3 [4;2] years vs. 10 [18;5] years, P < 0.000). Adenotonsillectomy (81.9%) and continuous positive airway pressure (61.5%) were the most commonly prescribed treatments. Few had discussed other new therapies such as hypoglossal nerve stimulation (16.0%). Only 16.0% of the subjects repeated the sleep study to monitor OSA with ageing, and 30.2% had to wait more than 4 years between studies., Conclusions: This study reinforces the need to improve OSA knowledge of caregivers and clinicians of individuals with DS to promote an earlier diagnosis and optimal treatment of OSA in this population., (© 2022 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Introduction: Care coordination is critical for the management of health care needs of children with Down syndrome by encompassing management of health information and linking of providers. This study was designed to identify caregiver and health care provider experiences of care coordination to inform the development of an m-health application., Method: In this mixed methods study, caregivers completed survey materials addressing the child's health care needs, m-health use, and care coordination experiences. A sample of caregivers and health care providers were interviewed to further understanding., Results: Most caregivers reported having a primary health care provider but wanted increased communication and help with care coordination. Interview data identified themes related to care coordination challenges, including information management, information sharing, use of health care guidelines, tracking health data, resources, technology use, previous application use, and coordination of schedules., Discussion: Qualitative themes were linked to desired features of an m-health application to aid in development., (Copyright © 2022 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Background: The emotional state of parents of babies with Down syndrome affects their babies' development and their parent-child bonding. The aim for this study was to conduct a pilot randomised controlled evaluation of the effect of infant massage on parents of babies with Down syndrome., Methods: This pilot study compared two groups (intervention and control), each with 16 parents of babies with Down syndrome. Indices of acceptance, engagement and awareness of influence were measured at two different time points (pre-test and after 5 weeks) using the 'This Is My Baby' Interview. The allocation of families to each group was randomised. The experimental group performed infant massage, applied by the parents, for 5 weeks, every day for at least 10 min. The massage protocol was based on the methodology created by Vimala McClure. Parents in the control group received the intervention after completion of the study., Results: The indices of acceptance, commitment and awareness of influence improved in the experimental group and in the control group. The 2 × 2 mixed-model analysis of variance indicates a statistically significant group-by-time interaction for all indices (P < 0.001), which was significantly higher in the experimental group than in the control group., Conclusions: The application of infant massage, by parents to their babies, improves the rates of acceptance, commitment and awareness of influence of parents of babies with Down syndrome in the short term., (© 2022 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background: While children are considered at low risk for COVID-19, little is known about the impact of SARS-CoV-2 on paediatric risk patients like children with Trisomy 21 (T21). As these children often need regular therapy and various medical appointments, this study aimed to investigate the possible impact of the COVID-19 pandemic on children with T21., Patients and Methods: Parents of children with T21 in the age of 0-12 years in Saxony-Anhalt were interviewed via phone in June 2021 regarding the health status and medical care of their children during the past 15 months of pandemic., Results: 37 children with mean age of 6.1 years (min 0; max 12) were included in the study. The majority did not have any additional congenital anomalies. Surveyed parents hardly reported adverse changes of health status during the pandemic, but rather improvements, such as decreased number of respiratory infections and more time spend with their children. Outpatient appointments and therapy were cancelled or postponed at the onset of the pandemic, but parents reported low impact on their child's health and development. The main concern seemed to be lack of childcare during school and day-care closures and uncertainty concerning possible health impacts of an infection on their children., Conclusion: There was low impact of the COVID-19 pandemic on health and medical care of children with T21 in our study population. Further research is needed to help weigh the child's individual risk of infection against the need for medical treatment and therapy when dealing with paediatric risk patients., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Exercise has the potential to reduce cognitive decline in people with Down syndrome by maximising their cognitive function. The aim of the study was to determine the effect of regular exercise on cognitive functioning in young people with Down syndrome., Method: People with Down syndrome were eligible if aged between 13 and 35 years and enrolled to participate in an exercise programme (called FitSkills). The intervention was a 12-week community-based exercise programme completed with a student mentor. Outcomes were assessed before (week 0) and immediately after (week 13) the intervention. Executive functioning (planning, response inhibition, attention shifting) was assessed using Tower of London, Sustained Attention to Response Task, CANTAB Intra-extra Dimensional Set Shift Test, Cognitive Scale for Down Syndrome, and Behaviour Rating Inventory of Executive Function (BRIEF). Working memory was assessed using the CANTAB Paired Associates Learning task, and information processing speed was assessed using the Motor Screening Task. Outcomes were analysed using ANCOVA with the baseline measure as the covariate., Results: Twenty participants (9 women; mean age 23.6 ± 6.6 years) enrolled. Between-group differences, in favour of the experimental group, were found for the global executive composite score of the BRIEF (mean difference -4.77 units, 95% CI -9.30 to -0.25). There were no between group differences for any other outcome measured., Conclusion: Participation in a 12-week exercise programme was effective in improving everyday executive functions in young people with Down syndrome. These preliminary findings need to be confirmed in future randomised controlled trials of community-based exercise with larger sample sizes., (© 2022 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background: Individuals with Down syndrome (DS) are increasingly eligible for clinical trial intervention, particularly for the treatment or prevention of Alzheimer disease (AD). Yet, little is known about research attitudes that may contribute to decisions regarding clinical trial enrollment for people with DS, a gap which is addressed in the current study., Methods: The Research Attitudes Questionnaire (RAQ) is a brief validated instrument that measures cultural and social factors which influence clinical trial enrollment decisions in the general population. Applied herein to a cohort of 1002 families who have an individual with DS, this survey was carried out through a national registry (DS-Connect). In addition to the RAQ, demographic data were collected., Results: The response rate to the survey was 49.9%. Respondents were asked to complete demographic information and to respond to the 7 question RAQ. The scores were stratified by a cut point assigned a priori into those more favorable toward research participation vs. those less favorably inclined. Within this sample, nearly 95% self-identified as the primary caretaker for the individual with DS. The RAQ score analyses generally indicated favorable respondent views toward research with particularly high favorability ratings from respondents who had previously participated in research and from those who were older (P = .01 to .001)., Conclusions: This is one of the first formal studies to evaluate research attitudes among relatives of individuals with DS and shows the feasibility of using this approach to answer important questions that will guide trialists developing treatments for AD in DS. Future research will require broadening the racial and ethnic mix of respondents and the role that a standardized assessment of research attitudes will have for clinical trial participation., (© 2022. The Author(s).)

Research to guide clinicians in the management of the devastating regression which can affect adolescents and young adults with Down syndrome is limited. A multi-site, international, longitudinal cohort of individuals with a clinical diagnosis of Unexplained Regression in Down syndrome (URDS) was collated through seven Down syndrome clinics. Tiered medical evaluation, a 28-item core symptom list, and interim management are described naturalistically. Improvement-defined by the percentage of baseline function on a Parent-reported Functional Score, overall improvement in symptoms on a Clinician-administered Functional Assessment, or report of management type being associated with improvement-was analyzed. Improvement rates using ECT, IVIG, and others were compared. Across seven clinics, 51 patients with URDS had regression at age 17.6 years, on average, and showed an average 14.1 out of 28 symptoms. Longitudinal improvement in function was achieved in many patients and the medical management, types of treatment, and their impact on function are described. Management with intravenous immunoglobulin (IVIG) was significantly associated with higher rate of improvement in symptoms at the next visit (p = 0.001). Our longitudinal data demonstrates that URDS is treatable, with various forms of clinical management and has a variable course. The data suggests that IVIG may be an effective treatment in some individuals. Our description of the management approaches used in this cohort lays the groundwork for future research, such as development of standardized objective outcome measure and creation of a clinical practice guideline for URDS., (© 2022 Wiley Periodicals LLC.)

Background: Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) are at increased risk of treatment-related morbidity and mortality compared to non-DS-ALL, requiring increased supportive care. We examined the healthcare utilization and costs in DS-ALL patients to inform future evaluations of novel therapies., Methods: A provincial registry identified all children (1-17 years) diagnosed with B-lineage ALL in Ontario, Canada between 2002 and 2012. Detailed demographic, disease, treatment, and outcome data were abstracted. Linkage to population-based health services databases identified all outpatient and emergency department (ED) visits, hospitalizations, and physician billings. Healthcare utilization costs were available for patients diagnosed during 2006-2012 using validated algorithms (2018 Canadian dollars). Healthcare utilization rates and costs were compared between DS and non-DS patients using regression models, adjusting for all covariates., Results: Of 711 patients, 28 (3.9%) had DS. Adjusting for all covariates, children with DS-ALL experienced substantially higher rates of ED visits (rate ratio [RR] 1.5, 95% confidence interval [95% CI]: 1.2-2.0; p = .001) and inpatient days (RR 2.5, 95% CI: 1.4-4.5; p = .002) compared to non-DS children. Outpatient visit rates were similar (RR 1.1, 95% CI: 0.9-1.3; p = .41). Among patients with available cost data (N = 533, DS = 19), median 5-year healthcare utilization cost was $247,700 among DS patients (interquartile range [IQR]: 200,900-354,500) and $196,200 among non-DS patients (IQR: 148,900-280,300; p = .02). In adjusted analyses, DS-associated costs were 50% higher (RR 1.5, 95% CI: 1.2-1.9; p < .002)., Conclusions: Healthcare utilization and treatment costs of DS-ALL patients are substantially higher than those of non-DS-ALL. Our data provide a baseline for future DS-specific cost-effectiveness studies., (© 2022 Wiley Periodicals LLC.)

A hormone enhances cognition in mouse models of Alzheimer's disease and Down syndrome.

The effects and the prescription parameters of therapeutic exercise are not clear. For this reason, is needed to determine the effect of neuromuscular exercise on balance, muscle strength and flexibility specifying the parameters and characteristics of effective interventions in children between 6 and 12 years and adolescent between 13 and 18 years with Down Syndrome. The present study is a systematic review of effectiveness outcomes balance, muscle strength and flexibility in this population. The databases of PubMed, PEDro, EMBASE, SCIELO, Lilacs, Cochrane library were searched from May to December 2021. We recruited randomized controlled trials (RCTs) which met the inclusion criteria in our study. Ten studies were included. The interventions included mechanotherapy, vibration, and use of different unstable surfaces. The exercise frequency ranged from 3 to 5 days a week, and the duration of each session was between six and 15 min. The frequency was between two and three times a week for 6 and 12 weeks and the intensity were between 60 and 80% of maximal voluntary contraction. Neuromuscular exercise in different modes of application was associated with increases in chest and lower limb muscle strength mean 8.51, CI [2.35-14.67] kg and (21.54 [1.64, 41.43]) kg. Balance also improved when the mode of application was isokinetic training and core stability exercises (- 0.20 [- 0.29, - 0.12]) evaluated with stability index. Neuromuscular exercise appears to be effective for the improvement of both lower limb and chest muscle strength and balance in children over 8 years. No evidence was found in children under 8 years., (© 2022. The Author(s).)

Background: Transitioning from paediatric medical care to adult care is a challenging process for children, parents and healthcare professionals. The aim of this study was to explore the experiences, concerns and needs of parents of children with Down syndrome and of professionals regarding this transition., Method: A qualitative study was performed using semi-structured interviews with 20 parents of children with Down syndrome and six healthcare professionals., Results: We showed that parents and professionals have concerns during each of the three distinct phases of transition (preparation, transfer and integration). Data disclose specific concerns regarding communication, continuity of care and rebuilding trust. We propose a framework for the transition to adult care., Conclusions: The transition in medical care for children with Down syndrome should be flexible, patient-centred and coordinated together with patients and parents. Only in ensuring continuity of care will individuals with Down syndrome not get lost in transition., (© 2022 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)