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Physiological Research 2014Oxidative stress is a phenomenon associated with imbalance between production of free radicals and reactive metabolites (e.g. superoxide and hydrogen peroxide) and the... (Review)
Review
Oxidative stress is a phenomenon associated with imbalance between production of free radicals and reactive metabolites (e.g. superoxide and hydrogen peroxide) and the antioxidant defences. Oxidative stress in individuals with Down syndrome (DS) has been associated with trisomy of the 21st chromosome resulting in DS phenotype as well as with various morphological abnormalities, immune disorders, intellectual disability, premature aging and other biochemical abnormalities. Trisomy 21 in patients with DS results in increased activity of an important antioxidant enzyme Cu/Zn superoxide dismutase (SOD) which gene is located on the 21st chromosome along with other proteins such as transcription factor Ets-2, stress inducing factors (DSCR1) and precursor of beta-amyloid protein responsible for the formation of amyloid plaques in Alzheimer disease. Mentioned proteins are involved in the management of mitochondrial function, thereby promoting mitochondrial theory of aging also in people with DS. In defence against toxic effects of free radicals and their metabolites organism has built antioxidant defence systems. Their lack and reduced function increases oxidative stress resulting in disruption of the structure of important biomolecules, such as proteins, lipids and nucleic acids. This leads to their dysfunctions affecting pathophysiology of organs and the whole organism. This paper examines the impact of antioxidant interventions as well as positive effect of physical exercise on cognitive and learning disabilities of individuals with DS. Potential therapeutic targets on the molecular level (oxidative stress markers, gene for DYRK1A, neutrophic factor BDNF) after intervention of natural polyphenols are also discussed.
Topics: Antioxidants; Brain; Cognition; Down Syndrome; Exercise; Genetic Predisposition to Disease; Humans; Learning; Oxidative Stress; Phenotype; Treatment Outcome
PubMed: 24908086
DOI: 10.33549/physiolres.932722 -
British Medical Bulletin Dec 2016Down syndrome (DS), caused by human trisomy 21 (Ts21), can be considered as a prototypical model for understanding the effects of chromosomal aneuploidies in other... (Review)
Review
INTRODUCTION
Down syndrome (DS), caused by human trisomy 21 (Ts21), can be considered as a prototypical model for understanding the effects of chromosomal aneuploidies in other diseases. Human chromosome 21 (Hsa21) is syntenically conserved with three regions in the mouse genome.
SOURCES OF DATA
A review of recent advances in genetic modeling and analysis of DS. Using Cre/loxP-mediated chromosome engineering, a substantial number of new mouse models of DS have recently been generated, which facilitates better understanding of disease mechanisms in DS.
AREAS OF AGREEMENT
Based on evolutionary conservation, Ts21 can be modeled by engineered triplication of Hsa21 syntenic regions in mice. The validity of the models is supported by the exhibition of DS-related phenotypes.
AREAS OF CONTROVERSY
Although substantial progress has been made, it remains a challenge to unravel the relative importance of specific candidate genes and molecular mechanisms underlying the various clinical phenotypes.
GROWING POINTS
Further understanding of mechanisms based on data from mouse models, in parallel with human studies, may lead to novel therapies for clinical manifestations of Ts21 and insights to the roles of aneuploidies in other developmental disorders and cancers.
Topics: Animals; Chromosome Mapping; Developmental Disabilities; Disease Models, Animal; Down Syndrome; Genetic Engineering; Mice
PubMed: 27789459
DOI: 10.1093/bmb/ldw040 -
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 -
Scientific Reports Feb 2022The Down syndrome (DS) phenotype is usually characterized by relative strengths in non-verbal skills and deficits in verbal processing, but high interindividual...
The Down syndrome (DS) phenotype is usually characterized by relative strengths in non-verbal skills and deficits in verbal processing, but high interindividual variability has been registered in the syndrome. The goal of this study was to explore the cognitive profile, considering verbal and non-verbal intelligence, of children and adolescents with DS, also taking into account interindividual variability. We particularly aimed to investigate whether this variability means that we should envisage more than one cognitive profile in this population. The correlation between cognitive profile and medical conditions, parents' education levels and developmental milestones was also explored. Seventy-two children/adolescents with DS, aged 7-16 years, were assessed with the Wechsler Preschool and Primary Scale of Intelligence-III. Age-equivalent scores were adopted, and Verbal and Non-Verbal indices were obtained for each individual. The cognitive profile of the group as a whole was characterized by similar scores in the verbal and non-verbal domain. Cluster analysis revealed three different profiles, however: one group, with the lowest scores, had the typical profile associated with DS (with higher non-verbal than verbal intelligence); one, with intermediate scores, had greater verbal than non-verbal intelligence; and one, with the highest scores, fared equally well in the verbal and non-verbal domain. Three cognitive profiles emerged, suggesting that educational support for children and adolescents with DS may need to be more specific.
Topics: Adolescent; Adolescent Behavior; Adolescent Development; Age Factors; Biological Variation, Population; Child; Child Behavior; Child Development; Child Language; Cognition; Down Syndrome; Education of Intellectually Disabled; Educational Status; Female; Humans; Intelligence; Male; Persons with Mental Disabilities; Verbal Behavior; Vocabulary
PubMed: 35121796
DOI: 10.1038/s41598-022-05825-4 -
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 -
Down's Syndrome, Research and Practice... Oct 2008Animal models are extensively used in genetics, neuroscience and biomedical research. Recent studies illustrate the usefulness and the challenges of research utilising... (Review)
Review
Animal models are extensively used in genetics, neuroscience and biomedical research. Recent studies illustrate the usefulness and the challenges of research utilising genetically engineered mice to explore the developmental biology of Down syndrome. These studies highlight many of the issues at the centre of what we understand about Down syndrome, and may one day point to useful ways to improve quality of life for people living with Down syndrome.
Topics: Animals; Brain Chemistry; Disease Models, Animal; Down Syndrome; Gene Dosage; Humans; Mice
PubMed: 19026279
DOI: 10.3104/updates.2054 -
Turkish Journal of Ophthalmology Aug 2021To determine the prevalence of refractive errors and visual impairment in Down syndrome (DS) patients compared to normal controls.
OBJECTIVES
To determine the prevalence of refractive errors and visual impairment in Down syndrome (DS) patients compared to normal controls.
MATERIALS AND METHODS
Cycloplegic refraction was tested in 213 DS patients and 184 normal age- and gender-matched controls using autorefraction followed by retinoscopy. Data from the worse eye of each case were used in the analyses.
RESULTS
In the DS and control groups, respectively, mean age was 17.2±4.8 and 17.2±4.4 years (p=0.993) and 53.0% and 49.5% were male (p=0.473). In the DS and control groups, respectively, mean spherical equivalent (SE) was -5.13±4.47 and -4.15±3.04 diopters (D) in myopics (p=0.050) and 2.47±1.64 and 2.36±2.04 D in hyperopics (p=0.482), mean cylinder error was -2.17±1.39 and -2.05±1.57 D (p=0.451), mean J0 was -0.03±0.89 and 0.12±0.76 D (p=0.086), and mean J45 was 0.11±1.02 and -0.13±1.03 D (p=0.024). The prevalence of oblique astigmatism was higher in the DS group (20.4% vs. 6.1%) while against-the-rule astigmatism was more prevalent in the control group (84.0% vs. 71.6%) (p<0.001). The prevalence of anisometropia was not significantly different between the groups (19.4% vs. 13.8%). Visual impairment was detected in 11.7% of the DS and 0.5% of the control group (p<0.001). The prevalence of amblyopia was 36.3% and 3.8% in the DS and control groups, respectively (p<0.001). Based on the multiple model, only absolute SE inversely correlated with age and differed between males and females (all p<0.05).
CONCLUSION
In DS patients, the prevalence rates of refractive errors, amblyopia, and visual impairment are higher than those in non-DS individuals, and emmetropization appears to be either defective or slow. Cylinder error is stable in this age range, but the rotation of astigmatism axis is different from normal samples.
Topics: Adolescent; Adult; Anisometropia; Astigmatism; Child; Down Syndrome; Female; Humans; Male; Refraction, Ocular; Refractive Errors; Young Adult
PubMed: 34461695
DOI: 10.4274/tjo.galenos.2020.52959 -
Biochimica Et Biophysica Acta.... Jun 2022Down syndrome (DS) is caused by trisomy 21, and it is characterized by developmental brain disorders and neurological dysfunction. Clinical studies and basic research...
Down syndrome (DS) is caused by trisomy 21, and it is characterized by developmental brain disorders and neurological dysfunction. Clinical studies and basic research have revealed that defects in mitochondrial function contribute to the pathogenesis of DS. However, the underlying mechanisms of mitochondrial dysfunction in DS remain unclear. In this study, we first generated GABAergic interneurons and medial ganglionic eminence (MGE) organoids from DS patients and control induced pluripotent stem cells. The mitochondria were abnormally clustered in the perinuclear region of GABA neurons and cell in MGE organoids from DS patients, which exhibited impaired mitochondrial function as assessed by seahorse oxidative phosphorylation assay. Inhibition of the DSCAM-PAK1 pathway by gene editing or treatment with a small molecule corrected mitochondrial perinuclear aggregation in cells from DS patients. Therefore, our study provides insight into the potential mechanism of mitochondrial dysfunction in DS.
Topics: Down Syndrome; Humans; Induced Pluripotent Stem Cells; Interneurons; Mitochondria; Organoids
PubMed: 35301086
DOI: 10.1016/j.bbadis.2022.166388 -
Revista Chilena de Pediatria Oct 2020In Chile, Down syndrome has a prevalence of 2.5 in 1,000 live births. These patients present more congenital anomalies and comorbidities than the general population,...
INTRODUCTION
In Chile, Down syndrome has a prevalence of 2.5 in 1,000 live births. These patients present more congenital anomalies and comorbidities than the general population, increasing their hospitaliza tion rate.
OBJECTIVE
To describe congenital anomalies and comorbidities of neonates with Down syndrome born and/or hospitalized between 2008 and 2018.
PATIENTS AND METHOD
We conducted a retrospective review of patient's medical records born and/or hospitalized during their first 28 days of life between January 1st, 2008, and December 31st, 2018. For each patient, we recorded maternal age, familiar cases of Down Syndrome, pre and perinatal history, genetic study result, as well as age at admission, reason for hospitalization, comorbidities, length of stay, and death. Two patients that had more than 50% of incomplete medical records were excluded. We studied the associations between comorbidities, congenital anomalies, and death.
RESULTS
140 in 79,506 newborns (0.2%) were diagnosed at our center with Down Syndrome in their neonatal period. 24.7% were born preterm and 26.4% had low birth weight for gestational age. Morbidities and hospitalizations were present in 83.6% and 90%, of the study population, respectively. The main reason for hospitalization was polycythemia and the most frequent was hyperbilirubinemia. Four patients died (2.9%) and 70.7% presented at least one congenital anomaly, mainly heart disease. Median maternal age was 36 years and 57.1% of mothers were aged 35 or older.
CONCLUSIONS
This cohort of patients with Down Syndrome provides important information for the optimization of their perinatal management and follow-up.
Topics: Abnormalities, Multiple; Chile; Comorbidity; Down Syndrome; Female; Follow-Up Studies; Hospitalization; Humans; Infant, Newborn; Logistic Models; Male; Retrospective Studies
PubMed: 33399638
DOI: 10.32641/rchped.vi91i5.1518 -
The Journal of the Royal College of... Nov 1989People with Down's syndrome form a heterogeneous group sharing a single constant feature--an extra chromosome. This paper reviews the many clinical problems associated... (Review)
Review
People with Down's syndrome form a heterogeneous group sharing a single constant feature--an extra chromosome. This paper reviews the many clinical problems associated with Down's syndrome and emphasizes the prevention of secondary handicapping conditions. Current policies on antenatal screening for Down's syndrome are discussed. The review draws attention to the need for general practitioners to see themselves as part of a network of community services providing support to people with Down's syndrome and their families.
Topics: Adult; Down Syndrome; Humans; Middle Aged; Prognosis
PubMed: 2560050
DOI: No ID Found