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European Journal of Human Genetics :... May 2023Antenatal screening and diagnostic testing for Down syndrome has greatly advanced over the past 30 years. The goal of this manuscript is to provide a review of the... (Review)
Review
Antenatal screening and diagnostic testing for Down syndrome has greatly advanced over the past 30 years. The goal of this manuscript is to provide a review of the availability and accessibility of prenatal services and selective termination policies across Europe, Australia, New Zealand, and the United States for the period 1990-2021. We collected data from academic peer-reviewed journals, governmental documents, not-for-profit organizations, correspondence with experts, and other online sources without language restrictions. Prenatal screening services from 1990-2021 became increasingly available across countries, enabling expectant couples the opportunity to gain more accurate information earlier in the pregnancy before assuming the risk associated with more invasive techniques like CVS or amniocentesis. Many countries also began adopting prenatal screening as a qualification for prenatal diagnosis. As of 2021, at least 76.9% of countries offered full coverage for diagnostic testing for Down syndrome from government funding. Abortion coverage for a Down syndrome diagnosis was covered fully by government funding in 52.4% of countries in 1990, increasing to 73.8% in 2021. Understanding the changing landscape of prenatal services builds the foundation for future investigation into social policies that affect the prevalence of Down syndrome.
Topics: Pregnancy; Female; Humans; United States; Down Syndrome; New Zealand; Prenatal Diagnosis; Europe; Australia
PubMed: 36922634
DOI: 10.1038/s41431-023-01330-y -
The Lancet. Public Health Nov 2023
Topics: Humans; Down Syndrome; Racial Groups; Socioeconomic Factors
PubMed: 37898515
DOI: 10.1016/S2468-2667(23)00213-X -
International Journal of Molecular... Apr 2020Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of... (Review)
Review
Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of apoptosis and calcium levels, and other metabolic tasks, all closely linked to cell viability. Functionality of mitochondria appears to depend upon their network architecture that may dynamically pass from an interconnected structure with long tubular units, to a fragmented one with short separate fragments. A decline in mitochondrial quality, which presents itself as an altered structural organization and a function of mitochondria, has been observed in Down syndrome (DS), as well as in aging and in age-related pathologies. This review provides a basic overview of mitochondrial dynamics, from fission/fusion mechanisms to mitochondrial homeostasis. Molecular mechanisms determining the disruption of the mitochondrial phenotype in DS and aging are discussed. The impaired activity of the transcriptional co-activator PGC-1α/PPARGC1A and the hyperactivation of the mammalian target of rapamycin (mTOR) kinase are emerging as molecular underlying causes of these mitochondrial alterations. It is, therefore, likely that either stimulating the PGC-1α activity or inhibiting mTOR signaling could reverse mitochondrial dysfunction. Evidence is summarized suggesting that drugs targeting either these pathways or other factors affecting the mitochondrial network may represent therapeutic approaches to improve and/or prevent the effects of altered mitochondrial function. Overall, from all these studies it emerges that the implementation of such strategies may exert protective effects in DS and age-related diseases.
Topics: Aging; Animals; Biomarkers; Disease Susceptibility; Down Syndrome; Homeostasis; Humans; Mitochondria; Mitochondrial Dynamics; Molecular Targeted Therapy; Signal Transduction
PubMed: 32365535
DOI: 10.3390/ijms21093134 -
The Pan African Medical Journal 2023
Topics: Humans; Down Syndrome; Diabetes Mellitus, Type 1; Cataract
PubMed: 37013217
DOI: 10.11604/pamj.2023.44.13.37833 -
Free Radical Biology & Medicine Jan 2018Alzheimer's disease (AD) may affect in excess of 90% of individuals with Down syndrome (DS) after age 60, due to duplication of the APP gene in trisomy of chromosome 21,... (Review)
Review
Alzheimer's disease (AD) may affect in excess of 90% of individuals with Down syndrome (DS) after age 60, due to duplication of the APP gene in trisomy of chromosome 21, with neuropathology that is comparable to Sporadic AD and Familial AD (FAD). Previous literature suggested some unique features in clinical presentation of dementia in DS (DSd), which might be due to diagnostic difficulties, or represent a real difference compared to SAD or FAD. We review current knowledge on clinical diagnosis and presentation of dementia in DS in comparison with FAD due to APP mutations and APP duplication. We suggest that the clinical presentation in DS (prominent memory decline and behavioral symptoms, and early development of myoclonus and seizures) are similar to the clinical features associated with APP mutations that is known to have an increased Aβ42/ Aβ40 ratio, and highlight the relative lack of vascular complications associated with cerebral amyloid angiopathy in DS in comparison with those rare individuals with FAD due to duplication APP. We consider the biomarker evidence associated with DS and DSd with reference to Aβ peptide levels and oxidative stress, and suggest future directions for research to explore the potential mechanisms associated with the clinical presentation of DSd.
Topics: Alzheimer Disease; Biomarkers; Down Syndrome; Humans; Mutation
PubMed: 28870521
DOI: 10.1016/j.freeradbiomed.2017.08.024 -
IUBMB Life Jan 2020Myeloid leukaemia of Down syndrome (ML-DS) is an acute megakaryoblastic/erythroid leukaemia uniquely found in children with Down syndrome (constitutive trisomy 21). It... (Review)
Review
Myeloid leukaemia of Down syndrome (ML-DS) is an acute megakaryoblastic/erythroid leukaemia uniquely found in children with Down syndrome (constitutive trisomy 21). It has a unique clinical course, being preceded by a pre-leukaemic condition known as transient abnormal myelopoiesis (TAM), and provides an excellent model to study multistep leukaemogenesis. Both TAM and ML-DS blasts carry acquired N-terminal truncating mutations in the erythro-megakaryocytic transcription factor GATA1. These result in exclusive production of a shorter isoform (GATA1s). The majority of TAM cases resolve spontaneously without the need for treatment; however, around 10% acquire additional cooperating mutations and transform to leukaemia, with differentiation block and clinically significant cytopenias. Transformation is driven by the acquisition of additional mutation(s), which cooperate with GATA1s to perturb normal haematopoiesis.
Topics: Down Syndrome; GATA1 Transcription Factor; Humans; Leukemia, Myeloid; Mutation
PubMed: 31769932
DOI: 10.1002/iub.2197 -
Neurological Sciences : Official... May 2021The aim of the current study was to determine whether COVID-19 is associated with a different presenting clinical picture or a more severe course of illness in people...
PURPOSE
The aim of the current study was to determine whether COVID-19 is associated with a different presenting clinical picture or a more severe course of illness in people with Down syndrome (DS).
METHODS
All consecutive patients who were admitted at healthcare facilities anywhere in Fars province (located in the south of Iran with a population of 4,851,000 people) from 19 February 2020 to 20 November 2020 were included. For every patient with DS, three age- and sex-matched patients with COVID-19 and without any underlying medical conditions were selected as controls.
RESULTS
During the study period, 37,968 patients were hospitalized with a diagnosis of COVID-19. Eighteen patients had DS. Patients with DS were significantly more likely to be intubated [7 patients (39%)] compared with those without DS [3 patients (6%)]; p = 0.002. Patients with DS significantly more often died of COVID-19 compared with the controls [8 (44.4%) vs. 1 (1.9%); odds ratio: 24.37; 95% confidence interval 2.39-247.94; p = 0.007].
CONCLUSION
Patients with DS are among the high-risk populations with respect to severe COVID-19 and should receive the vaccine as soon as possible. Furthermore, they should receive more intensive care if they get hospitalized with the illness.
Topics: COVID-19; Down Syndrome; Hospitalization; Humans; Iran; SARS-CoV-2
PubMed: 33523318
DOI: 10.1007/s10072-021-05091-8 -
The Lancet. Neurology Jan 2022
Topics: Down Syndrome; Humans
PubMed: 34942129
DOI: 10.1016/S1474-4422(21)00411-7 -
The Indian Journal of Medical Research Aug 2015Down syndrome (DS) is one of the most common chromosomal disorders, occurring in one out of 700-1000 live births, and the most common cause of mental retardation.... (Review)
Review
Down syndrome (DS) is one of the most common chromosomal disorders, occurring in one out of 700-1000 live births, and the most common cause of mental retardation. Thyroid dysfunction is the most typical endocrine abnormality in patients with DS. It is well known that thyroid dysfunction is highly prevalent in children and adults with DS and that both hypothyroidism and hyperthyroidism are more common in patients with DS than in the general population. Increasing evidence has shown that DS individuals are under unusual increased oxidative stress, which may be involved in the higher prevalence and severity of a number of pathologies associated with the syndrome, as well as the accelerated ageing observed in these individuals. The gene for Cu/Zn superoxide dismutase (SOD1) is coded on chromosome 21 and it is overexpressed (~50%) resulting in an increase of reactive oxygen species (ROS) due to overproduction of hydrogen peroxide (H 2 O 2 ). ROS leads to oxidative damage of DNA, proteins and lipids, therefore, oxidative stress may play an important role in the pathogenesis of DS.
Topics: Down Syndrome; Humans; Hypothyroidism; Oxidative Stress; Reactive Oxygen Species; Thyroid Diseases; Thyroid Gland
PubMed: 26354208
DOI: 10.4103/0971-5916.164218 -
American Journal of Alzheimer's Disease... Jun 2018People with Down syndrome (DS) enjoy a longer life expectancy now than they ever have before and are therefore at greater risk of developing conditions associated with... (Review)
Review
BACKGROUND
People with Down syndrome (DS) enjoy a longer life expectancy now than they ever have before and are therefore at greater risk of developing conditions associated with aging, including dementia.
OBJECTIVES
To explore the phenomenon of dementia in DS.
METHODS
Medline and Google Scholar searches were conducted for relevant articles, chapters, and books published until 2017. Search terms included Alzheimer's disease, cognitive impairment, dementia, DS, and trisomy 21. Publications found through this indexed search were reviewed for further references.
RESULTS AND CONCLUSIONS
Virtually, all subject aged 35 to 40 show key neuropathologic changes characteristic of Alzheimer's disease, but only a part of them show clinical signs of dementia, usually around the age of 50 years. Early signs of dementia in people with DS may be different from those experienced by the general population. Failure to recognize this can delay diagnosis and subsequent interventions.
Topics: Aging; Alzheimer Disease; Down Syndrome; Early Diagnosis; Humans
PubMed: 29504408
DOI: 10.1177/1533317518761093