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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 -
The New England Journal of Medicine Jun 2020
Review
Topics: Behavior Therapy; Cell-Free Nucleic Acids; Down Syndrome; Female; Heart Defects, Congenital; Humans; Karyotype; Male; Phenotype; Pregnancy; Prenatal Diagnosis
PubMed: 32521135
DOI: 10.1056/NEJMra1706537 -
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 -
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 -
American Journal of Medical Genetics.... Jan 2015The clinical and cytogenetic findings associated with mosaicism for trisomy 21/Down syndrome are the focus of this review. The primary topics discussed in this overview... (Review)
Review
The clinical and cytogenetic findings associated with mosaicism for trisomy 21/Down syndrome are the focus of this review. The primary topics discussed in this overview of the extant literature include the history of this condition and its diagnosis, the incidence of mosaicism, the meiotic and/or mitotic chromosomal malsegregation events resulting in mosaicism, the observation of mosaicism in the parents of children with the non-mosaic form of Down syndrome, and the variation in phenotypic outcome for both constitutional and acquired traits present in people with mosaicism for trisomy 21/Down syndrome, including cognition, fertility, and overall phenotypic findings. Additional topics reviewed include the social conditions of people with mosaicism, as well as age-related and epigenetic alterations observed in people with mosaicism for trisomy 21/Down syndrome. .
Topics: Down Syndrome; Genetic Testing; History, 19th Century; Humans; Meiosis; Mosaicism; Nondisjunction, Genetic; Phenotype
PubMed: 25412855
DOI: 10.1002/ajmg.a.36861 -
American Journal of Medical Genetics.... Jun 2015Individuals with Down syndrome (DS) commonly possess unique neurocognitive and neurobehavioral profiles that emerge within specific developmental periods. These profiles... (Review)
Review
Individuals with Down syndrome (DS) commonly possess unique neurocognitive and neurobehavioral profiles that emerge within specific developmental periods. These profiles are distinct relative to others with similar intellectual disability (ID) and reflect underlying neuroanatomic findings, providing support for a distinctive phenotypic profile. This review updates what is known about the cognitive and behavioral phenotypes associated with DS across the lifespan. In early childhood, mild deviations from neurotypically developing trajectories emerge. By school-age, delays become pronounced. Nonverbal skills remain on trajectory for mental age, whereas verbal deficits emerge and persist. Nonverbal learning and memory are strengths relative to verbal skills. Expressive language is delayed relative to comprehension. Aspects of language skills continue to develop throughout adolescence, although language skills remain compromised in adulthood. Deficits in attention/executive functions are present in childhood and become more pronounced with age. Characteristic features associated with DS (cheerful, social nature) are personality assets. Children are at a lower risk for psychopathology compared to other children with ID; families report lower levels of stress and a more positive outlook. In youth, externalizing behaviors may be problematic, whereas a shift toward internalizing behaviors emerges with maturity. Changes in emotional/behavioral functioning in adulthood are typically associated with neurodegeneration and individuals with DS are higher risk for dementia of the Alzheimer's type. Individuals with DS possess many unique strengths and weaknesses that should be appreciated as they develop across the lifespan. Awareness of this profile by professionals and caregivers can promote early detection and support cognitive and behavioral development.
Topics: Adult; Attention; Child; Child, Preschool; Cognition; Down Syndrome; Emotions; Executive Function; Genotype; Humans; Neuropsychological Tests; Phenotype; Social Support; Speech
PubMed: 25989505
DOI: 10.1002/ajmg.c.31439