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Nature Reviews. Disease Primers Feb 2020Trisomy 21, the presence of a supernumerary chromosome 21, results in a collection of clinical features commonly known as Down syndrome (DS). DS is among the most... (Review)
Review
Trisomy 21, the presence of a supernumerary chromosome 21, results in a collection of clinical features commonly known as Down syndrome (DS). DS is among the most genetically complex of the conditions that are compatible with human survival post-term, and the most frequent survivable autosomal aneuploidy. Mouse models of DS, involving trisomy of all or part of human chromosome 21 or orthologous mouse genomic regions, are providing valuable insights into the contribution of triplicated genes or groups of genes to the many clinical manifestations in DS. This endeavour is challenging, as there are >200 protein-coding genes on chromosome 21 and they can have direct and indirect effects on homeostasis in cells, tissues, organs and systems. Although this complexity poses formidable challenges to understanding the underlying molecular basis for each of the many clinical features of DS, it also provides opportunities for improving understanding of genetic mechanisms underlying the development and function of many cell types, tissues, organs and systems. Since the first description of trisomy 21, we have learned much about intellectual disability and genetic risk factors for congenital heart disease. The lower occurrence of solid tumours in individuals with DS supports the identification of chromosome 21 genes that protect against cancer when overexpressed. The universal occurrence of the histopathology of Alzheimer disease and the high prevalence of dementia in DS are providing insights into the pathology and treatment of Alzheimer disease. Clinical trials to ameliorate intellectual disability in DS signal a new era in which therapeutic interventions based on knowledge of the molecular pathophysiology of DS can now be explored; these efforts provide reasonable hope for the future.
Topics: Down Syndrome; Humans; Risk Factors
PubMed: 32029743
DOI: 10.1038/s41572-019-0143-7 -
The Lancet. Neurology Nov 2021Adults with Down syndrome develop the neuropathological hallmarks of Alzheimer's disease and are at very high risk of developing early-onset dementia, which is now the... (Review)
Review
Adults with Down syndrome develop the neuropathological hallmarks of Alzheimer's disease and are at very high risk of developing early-onset dementia, which is now the leading cause of death in this population. Diagnosis of dementia remains a clinical challenge because of the lack of validated diagnostic criteria in this population, and because symptoms are overshadowed by the intellectual disability associated with Down syndrome. In people with Down syndrome, fluid and imaging biomarkers have shown good diagnostic performances and a strikingly similar temporality of changes with respect to sporadic and autosomal dominant Alzheimer's disease. Most importantly, there are no treatments to prevent Alzheimer's disease, even though adults with Down syndrome could be an optimal population in whom to conduct Alzheimer's disease prevention trials. Unprecedented research activity in Down syndrome is rapidly changing this bleak scenario that will translate into disease-modifying therapies that could benefit other populations.
Topics: Adult; Alzheimer Disease; Biomarkers; Down Syndrome; Humans; Intellectual Disability
PubMed: 34687637
DOI: 10.1016/S1474-4422(21)00245-3 -
Circulation Jan 2023Cardiovascular disease is a leading cause of morbidity and mortality in individuals with Down syndrome. Congenital heart disease is the most common cardiovascular... (Review)
Review
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.
Topics: Pregnancy; Female; Humans; Cardiovascular Diseases; Down Syndrome; Consensus; Cardiovascular System; Heart Defects, Congenital
PubMed: 36716257
DOI: 10.1161/CIRCULATIONAHA.122.059706 -
Journal of Intellectual Disability... Aug 2019Down syndrome is the most common chromosomal abnormality, with a worldwide incidence of around 0.1% in live births. It is related to several conditions in which the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Down syndrome is the most common chromosomal abnormality, with a worldwide incidence of around 0.1% in live births. It is related to several conditions in which the physical therapy could take action-preventing co-morbidities. This study aims to evaluate the effectiveness of physical therapy in Down syndrome, to know and compare the effectiveness of different physical therapy interventions in this population.
METHODS
A systematic review and a meta-analysis of randomised controlled trials were conducted. The search was performed during June 2018 in the following databases: PubMed, Web of Science, Physiotherapy Evidence Database and Scopus. The studies were selected using predefined inclusion and exclusion criteria. The Physiotherapy Evidence Database scale evaluated the quality of the methods used in the studies. Subsequently, the data were extracted, and statistical analysis was performed when possible.
RESULTS
A total of 27 articles were included, of which nine contributed information to the meta-analysis. Statistical analysis showed favourable results for the strength of upper and lower limbs [standardised mean difference (SMD) = 1.46; 95% confidence interval (CI): (0.77-2.15); and SMD = 2.04; 95% CI: (1.07-3.01)] and mediolateral oscillations of balance [SMD = -3.30; 95% CI: (-5.34 to -1.26)].
CONCLUSIONS
The results show the potential benefit of certain types of physical therapy interventions, specifically in strength and balance, in people with Down syndrome. There are still many aspects to clarify and new lines of research.
Topics: Down Syndrome; Humans; Physical Therapy Modalities
PubMed: 30788876
DOI: 10.1111/jir.12606 -
Arquivos de Neuro-psiquiatria Jun 2022The diagnosis of autism spectrum disorder (ASD) in Down syndrome (DS) is underestimated because it is necessary to understand which aspects of the behavioral phenotype...
The diagnosis of autism spectrum disorder (ASD) in Down syndrome (DS) is underestimated because it is necessary to understand which aspects of the behavioral phenotype are related to DS and which are related to ASD. Objective: To conduct a systematic review of the literature on early identification and diagnosis of ASD in patients with DS. Data source: The VHL, MEDLINE, Cochrane, CINAHL, Scopus, Web of Science and Embase databases were searched and data were evaluated using PRISMA. Data synthesis: Out of 1,729 articles evaluated, 15 were selected. Although well studied, identification of ASD in DS can be difficult because of the need to understand which aspects of the behavioral phenotype are related to Down syndrome and which to autism. In this review, the prevalence of ASD was found to range from 12% to 41%. Early identification of autism risk in individuals with Down syndrome is still poorly studied, even though there are screening instruments for infants. Several instruments for diagnosing autism in individuals with Down syndrome were found, but a developmental approach is fundamental for making a clear diagnosis. Conclusions: Screening procedures are important for detecting early signs of autism risk in the first year of life. Careful evaluation methods are needed to establish the diagnosis, which include choosing appropriate tools for evaluation of development and cognition, and analysis of qualitative aspects of social interaction, among others. It has been indicated in the literature that early detection and timely accurate diagnosis, in association with an intervention, may benefit development, quality of life and social inclusion.
Topics: Autism Spectrum Disorder; Autistic Disorder; Down Syndrome; Early Diagnosis; Humans; Quality of Life
PubMed: 35946706
DOI: 10.1590/0004-282X-ANP-2021-0156 -
American Journal of Physiology. Lung... Nov 2021Down syndrome (DS) is one of the most prevalent chromosomal abnormalities worldwide, affecting 1 in 700 live births. Although multiple organ systems are affected by the... (Review)
Review
Down syndrome (DS) is one of the most prevalent chromosomal abnormalities worldwide, affecting 1 in 700 live births. Although multiple organ systems are affected by the chromosomal defects, respiratory failure and lung disease are the leading causes of morbidity and mortality observed in DS. Manifestations of DS in the respiratory system encompass the entire lung starting from the nasopharynx to the trachea/upper airways to the lower airways and alveolar spaces, as well as vascular and lymphatic defects. Most of our knowledge on respiratory illness in persons with DS arises from pediatric studies; however, many of these disorders present early in infancy, supporting developmental mechanisms. In this review, we will focus on the different lung phenotypes in DS, as well as the genetic and molecular pathways that may be contributing to these complications during development.
Topics: Child; Disease Progression; Down Syndrome; Humans; Lung; Lung Diseases; Phenotype
PubMed: 34469245
DOI: 10.1152/ajplung.00434.2020 -
Haematologica Oct 2023Children with Down syndrome (DS, trisomy 21) are at a significantly higher risk of developing acute leukemia compared to the overall population. Many studies... (Review)
Review
Children with Down syndrome (DS, trisomy 21) are at a significantly higher risk of developing acute leukemia compared to the overall population. Many studies investigating the link between trisomy 21 and leukemia initiation and progression have been conducted over the last two decades. Despite improved treatment regimens and significant progress in iden - tifying genes on chromosome 21 and the mechanisms by which they drive leukemogenesis, there is still much that is unknown. A focused group of scientists and clinicians with expertise in leukemia and DS met in October 2022 at the Jérôme Lejeune Foundation in Paris, France for the 1st International Symposium on Down Syndrome and Leukemia. This meeting was held to discuss the most recent advances in treatment regimens and the biology underlying the initiation, progression, and relapse of acute lymphoblastic leukemia and acute myeloid leukemia in children with DS. This review provides a summary of what is known in the field, challenges in the management of DS patients with leukemia, and key questions in the field.
Topics: Child; Humans; Down Syndrome; Leukemia, Myeloid, Acute; Acute Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; France
PubMed: 37439336
DOI: 10.3324/haematol.2023.283225 -
Medicina 2021Cerebral palsy and Down syndrome are two conditions that present with a deficit in motor development. Treadmill interventions were found to improve this delay in...
Cerebral palsy and Down syndrome are two conditions that present with a deficit in motor development. Treadmill interventions were found to improve this delay in development. This work aimed to describe and analyze the methodological quality of studies that applied treadmill interventions alone or combined with other therapies to promote gait and balance in children under 12 years of age with cerebral palsy and Down syndrome. A systematic review was made in different databases: PubMed, PEDro, Cochrane and Science Direct. Only randomized clinical trials published to date were selected. The methodological quality of the identified studies was assessed using the PEDro scale. Of the 324 articles initially found, 10 were selected, which met the established inclusion criteria for qualitative analysis. The variables analyzed were gait and balance in both populations after the treadmill intervention, with and without suspension of body weight. The main conclusion was that the application of a treadmill alone is an effective intervention to promote the development of gait and balance in children under 12 years with cerebral palsy and Down syndrome.
Topics: Body Weight; Cerebral Palsy; Child; Down Syndrome; Exercise Test; Exercise Therapy; Gait; Humans
PubMed: 34137695
DOI: No ID Found -
International Journal of Environmental... Jul 2021The aim of this study was to estimate the influence of a 33-week swimming program on aerobic capacity, muscle strength, balance, flexibility, and body composition of... (Randomized Controlled Trial)
Randomized Controlled Trial
The aim of this study was to estimate the influence of a 33-week swimming program on aerobic capacity, muscle strength, balance, flexibility, and body composition of adolescents with Down syndrome (DS). Twenty-two adolescents diagnosed with DS were randomly allocated into the training group (T) and the control group (C). The T group participated in 33 weeks of water-based exercise and a swimming program while the control group maintained their normal daily activity. Following thirty-three weeks of swimming program, body mass, body fat, and BMI of the T group decreased significantly (from 56.8 ± 7.97 kg to 55.0 ± 7.11 kg, from 15.1 ± 4.47 kg to 13.2 ± 3.92 kg, and from 25.1 ± 2.37 to 24.0 ± 2.05, respectively) while a significant increase was recorded in C (from 57.3 ± 8.43 kg to 59.7 ± 8.29 kg, from 14.5 ± 2.76 kg to 16.0 ± 3.11 kg, and from 25.4 ± 2.46 to 26.0 ± 2.72, respectively). Moreover, significant improvement in aerobic capacity in the T group was noted; VOmax (mL/kg/min) increased by 16.3% in T and decreased by 4.8% in C. Improvement in static arm strength, trunk strength and endurance/functional strength were noted in T, while the parameters did not change in C. The speed of arm movement, balance and flexibility did not change following the intervention. Also, the aquatic skills improved significantly in the training group. Changes in C were not significant. The results of our study indicate that 33-week swimming program significantly improved health status and swimming skills in adolescents with DS.
Topics: Adolescent; Body Composition; Down Syndrome; Exercise Therapy; Humans; Muscle Strength; Swimming
PubMed: 34299891
DOI: 10.3390/ijerph18147441 -
Nature Oct 2021Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks...
Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).
Topics: B-Lymphocytes; Bone Marrow; Bone Marrow Cells; Dendritic Cells; Down Syndrome; Endothelial Cells; Eosinophils; Erythroid Cells; Fetus; Granulocytes; Hematopoiesis; Humans; Immune System; Immunity; Myeloid Cells; Stromal Cells
PubMed: 34588693
DOI: 10.1038/s41586-021-03929-x