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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 -
Roczniki Panstwowego Zakladu Higieny 2015Down syndrome (DS) is one of the more commonly occurring genetic disorders, where mental retardation is combined with nutritional diseases. It is caused by having a... (Review)
Review
Down syndrome (DS) is one of the more commonly occurring genetic disorders, where mental retardation is combined with nutritional diseases. It is caused by having a third copy of chromosome 21, and there exist 3 forms; Simple Trisomy 21, Translocation Trisomy and Mosaic Trisomy. Symptoms include intellectual disability/mental retardation, early onset of Alzheimer's disease and the appearance of various phenotypic features such as narrow slanted eyes, flat nose and short stature. In addition, there are other health problems throughout the body, consisting in part of cardiac defects and thyroid function abnormalities along with nutritional disorders (ie. overweight, obesity, hypercholesterolemia and deficiencies of vitamins and minerals). Those suffering DS have widespread body frame abnormalities and impaired brain development and function; the latter leading to impaired intellectual development. Many studies indicate excessive or deficient nutrient uptakes associated with making inappropriate foodstuff choices, food intolerance, (eg. celiac disease) or malabsorption. DS persons with overweight or obesity are linked with a slow metabolic rate, abnormal blood leptin concentrations and exhibit low levels of physical activity. Vitamin B group deficiencies and abnormal blood homocysteine levels decrease the rate of intellectual development in DS cases. Zinc deficiencies result in short stature, thyroid function disorders and an increased appetite caused by excessive supplementation. Scientific advances in the research and diagnosis of DS, as well as preventing any associated conditions, have significantly increased life expectancies of those with this genetic disorder. Early dietary interventions by parents or guardians of DS children afford an opportunity for decreasing the risk or delaying some of the DS associated conditions from appearing, thus beneficially impacting on their quality of life.
Topics: Chromosomes, Human, Pair 21; Dietary Supplements; Down Syndrome; Food Hypersensitivity; Humans; Nutritional Requirements; Nutritional Status; Trisomy
PubMed: 26400113
DOI: No ID Found -
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 -
Current Opinion in Endocrinology,... Feb 2018To summarize the recent developments in endocrine disorders associated with Down syndrome. (Review)
Review
PURPOSE OF REVIEW
To summarize the recent developments in endocrine disorders associated with Down syndrome.
RECENT FINDINGS
Current research regarding bone health and Down syndrome continues to show an increased prevalence of low bone mass and highlights the importance of considering short stature when interpreting dual energy x-ray absorptiometry. The underlying cause of low bone density is an area of active research and will shape treatment and preventive measures. Risk of thyroid disease is present throughout the life course in individuals with Down syndrome. New approaches and understanding of the pathophysiology and management of subclinical hypothyroidism continue to be explored. Individuals with Down syndrome are also at risk for other autoimmune conditions, with recent research revealing the role of the increased expression of the Autoimmune Regulatory gene on 21st chromosome. Lastly, Down-syndrome-specific growth charts were recently published and provide a better assessment of growth.
SUMMARY
Recent research confirms and expands on the previously known endocrinopathies in Down syndrome and provides more insight into potential underlying mechanisms.
Topics: Down Syndrome; Endocrine System Diseases; Female; Humans; Prevalence; Thyroid Diseases
PubMed: 29135488
DOI: 10.1097/MED.0000000000000382 -
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 -
Human Molecular Genetics Apr 2009Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and is associated with a number of deleterious phenotypes, including learning disability, heart defects,... (Review)
Review
Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and is associated with a number of deleterious phenotypes, including learning disability, heart defects, early-onset Alzheimer's disease and childhood leukaemia. Individuals with DS are affected by these phenotypes to a variable extent; understanding the cause of this variation is a key challenge. Here, we review recent research progress in DS, both in patients and relevant animal models. In particular, we highlight exciting advances in therapy to improve cognitive function in people with DS and the significant developments in understanding the gene content of Hsa21. Moreover, we discuss future research directions in light of new technologies. In particular, the use of chromosome engineering to generate new trisomic mouse models and large-scale studies of genotype-phenotype relationships in patients are likely to significantly contribute to the future understanding of DS.
Topics: Animals; Chromosomes, Human, Pair 21; Cognition; Down Syndrome; Humans
PubMed: 19297404
DOI: 10.1093/hmg/ddp010 -
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 -
Current Hematologic Malignancy Reports Oct 2016Children with constitutional trisomy 21 (Down syndrome (DS)) have a unique predisposition to develop myeloid leukaemia of Down syndrome (ML-DS). This disorder is... (Review)
Review
Children with constitutional trisomy 21 (Down syndrome (DS)) have a unique predisposition to develop myeloid leukaemia of Down syndrome (ML-DS). This disorder is preceded by a transient neonatal preleukaemic syndrome, transient abnormal myelopoiesis (TAM). TAM and ML-DS are caused by co-operation between trisomy 21, which itself perturbs fetal haematopoiesis and acquired mutations in the key haematopoietic transcription factor gene GATA1. These mutations are found in almost one third of DS neonates and are frequently clinically and haematologcially 'silent'. While the majority of cases of TAM undergo spontaneous remission, ∼10 % will progress to ML-DS by acquiring transforming mutations in additional oncogenes. Recent advances in the unique biological, cytogenetic and molecular characteristics of TAM and ML-DS are reviewed here.
Topics: Down Syndrome; GATA1 Transcription Factor; Humans; Leukemia, Myeloid, Acute; Leukemoid Reaction; Risk; Stem Cell Transplantation
PubMed: 27510823
DOI: 10.1007/s11899-016-0338-x -
BMC Pediatrics May 2018The use of technology to assist in the communication, socialization, language, and motor skills of children with Down's syndrome (DS) is required. The aim of this study...
BACKGROUND
The use of technology to assist in the communication, socialization, language, and motor skills of children with Down's syndrome (DS) is required. The aim of this study was to analyse research findings regarding the different instruments of 'augmentative and alternative communication' used in children with Down's syndrome.
METHODS
This is a systematic review of published articles available on PubMed, Web of Science, PsycInfo, and BVS using the following descriptors: assistive technology AND syndrome, assistive technology AND down syndrome, down syndrome AND augmentative and alternative communication. Studies published in English were selected if they met the following inclusion criteria: (1) study of children with a diagnosis of DS, and (2) assistive technology and/or augmentative and alternative communication analysis in this population.
RESULTS
A total of 1087 articles were identified. Thirteen articles met the inclusion criteria. The instruments most used by the studies were speech-generating devices (SGDs) and the Picture Exchange Communication System (PECS).
CONCLUSION
Twelve instruments that provided significant aid to the process of communication and socialization of children with DS were identified. These instruments increase the interaction between individuals among this population and their peers, contributing to their quality of life and self-esteem.
Topics: Child; Child Language; Communication Aids for Disabled; Down Syndrome; Humans; Motor Skills; Social Skills
PubMed: 29751828
DOI: 10.1186/s12887-018-1144-5