Analysis Of Down Syndrome Research Articles

Clinical and neuropathological analysis of Down syndrome over 7 decades of life.

Clinical and neuropathological analysis of Down syndrome over 7 decades of life.

Empowering Lives: Navigating the Landscape of Down Syndrome Support in Saudi Arabia

This study offers an in-depth analysis of Down syndrome (DS) in Saudi Arabia, encompassing healthcare, societal integration, and policy frameworks. It assesses DS prevalence within the Saudi population against global rates and underscores the progress in prenatal diagnostics and screening for early detection. The significance of neonatal care and early intervention programs in the comprehensive development of children with DS is highlighted. The paper explores societal perceptions and efforts to increase public awareness and reduce stigma, with a particular focus on media and educational initiatives. It reviews the educational landscape for individuals with DS, touching on inclusive policies and specialized programs, and evaluates the effectiveness and obstacles of these approaches. The study also compares Saudi policies and legal protections for individuals with DS to international standards, illustrating the country’s advancements toward global norms. It examines support systems, including contributions from nonprofits, community programs, and family services, and concludes with an identification of ongoing challenges and recommendations for future enhancements. This comprehensive overview underlines the importance of a multifaceted approach to supporting individuals with DS in Saudi Arabia, aiming to enhance their quality of life and ensure their full integration into society.

Pathological Analysis of down Syndrome and Its Nursing Care

Down Syndrome sounds like a rare case that can only be found in biology courses that are unrelated to normal peoples life. However, it occurs once every 1200 people according to CDC. Scientifically, Down syndrome is a genetic disease caused by trisomy 21 that cannot be cured by direct means of surgery or drugs. People must study the biochemical pathway Down Syndrome interferes with human body development, symptoms usually exhibit in patients, and Down Syndromes relationship with other diseases like Alzheimers in-depth and provide advanced detection for parents inclined to have Down Syndrome babies. Due to patients intellectual disability, someone must make important decisions for them so that they can receive needed treatments, Nursing patients with it not only requires extensive medical care but also patient emotional support. Well-trained nursing is required to protect this vulnerable group, not only to bring patients the chance to live a normal life but also to help their families avoid living in conflicts.

Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19

SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes. In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we identified the genes associated with the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We then analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) and created a DS-SARS-CoV-2 network. We detected COVID-19 protective and risk factors among HSA21 genes and interactors and/or DS deregulated genes that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome. Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells. However, as the anti-viral interferon I signaling is also upregulated in DS, this might increase the initial anti-viral response, inhibiting viral genome release, viral replication and viral assembly. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.

Missed Down Syndrome Cases after First Trimester False-Negative Screening-Lessons to be Learned.

Background and Objectives: Here, we performed a descriptive analysis of Down syndrome (DS) cases that were misdiagnosed and/or false-negative diagnosed after first trimester traditional screening via risk evaluation using ultrasound, biochemical markers, and different software programs. Our objective was to demonstrate the clear need to improve the application of prenatal DS screening programs using standardized ultrasound measurements, accurate pregnancy dating, analytical immunoassay performance, and properly selected medians. Materials and Methods: We performed a database search for the period 2010–2015 to analyze DS cases that were false-negative diagnosed after the first trimester of pregnancy, before the introduction of cell free fetal DNA-based tests by Romanian laboratories in 2015. First-trimester screening was performed using two software programs for prenatal DS risk calculation: Astraia and Prisca. The rationale for using both software programs was to assess the full risk using the maternal age combined test (based on nuchal translucency thickness, nasal bone, ductus venosus flow, tricuspid flow, free beta-human chorionic gonadotropin level, and serum pregnancy-associated plasma protein-A) and, in some cases, the triple test. Results: We identified seven DS cases that exhibited low risk for trisomy 21, and 6540 cases with a low risk for trisomy 21 and euploid fetus in the first trimester. Using Astraia software, 14 cases were diagnosed, and three cases were missed after risk calculation. Using Prisca software, four cases were missed. Additionally, one neonate had a missed prenatal diagnosis of atrio-ventricular canal defect. Conclusion: In Romania, the evaluation of DS risk depends on patient choice (without knowing the accuracy of the utilized tests) and on the operators’ skills. Both Astraia and Prisca software were developed by experts, who can prove their performance in DS screening. However, even in an ideal situation, false-negative results are possible. The application of first and second-trimester combined screening based on biochemical markers could be improved by the implementation of standardized protocols, professional guidelines for test application, and audit control.

Analysis of Down syndrome failed to be diagnosed after prenatal screening: A multicenter study.

To analyze the characters of Down syndrome (DS) who failed to be diagnosed after prenatal screening and hope to be able to improve the programs of prenatal screening and reduce the missed diagnosis of DS. In this multicenter study, we collected the missed cases from 3 prenatal diagnosis centers and analyzed their characters. A total of 126 DS babies failed to be diagnosed after prenatal screening. Their mothers accepted the prenatal screening in second trimester. We collected the mothers’ blood and detected the levels of alpha-fetoprotein (AFP) and the free beta subunit of human chorionic gonadotropin (fβhCG) by time-resolved fluoroimmunoassay. The values were also presented as multiples of the median (MoM) and determined the risk of carrying a fetus with DS by Wallace LifeCycle Elipse analysis software. Compared with normal control group, the level of fβhCG and hCG MoM were dramatically increased, while AFP and AFP MoM were decreased. The area under the receiver-operating-characteristic curve of trisomy 21 was 0.8387 for hCG-MoM and AFP-MoM testing. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.6%, 74.8%, 75.4%, and 83.6%, respectively. Meanwhile, the prediction mode was “0.39957 + 1.90897∗HCG-MOM −3.32713∗AFP-MOM”. It was worthwhile noting that the risk of 65.9% DS missed diagnosis group were higher than 1/1000, 92.9% higher than 1/3000. However, 72.5% cases in normal control group were lower than 1/3000. Only 9.2% mothers would be higher than the value of risk in 1/1000. The prediction mode of hCG MoM and AFP MoM might be able to help us reduce the missed diagnosis. It is also necessary to adjust more reasonable range of noninvasive prenatal testing with further clinical researches.

Mouse-based genetic modeling and analysis of Down syndrome.

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. 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. 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. 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. 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.

ASSA14-14-03 Clinical analysis of Down's syndrome with congenital heart diseases

Background To analyse congenital heart deformity and haemodynamic data of Down’s syndrome. Methods We diagnosed 36 patients of congenital heart disease patients with Down syndrome by transthoracic two-dimensional echocardiography, colour Doppler flow imaging and right heart catheterization or angiocardiography from July 2008 to October 2012. This article analysed 36 cases of clinical data of Down’s syndrome with congenital heart disease and its hemodynamics. Results Among 36 cases, including VSD 10 cases, AVSD 6 cases, PDA 6 cases, ASD 2 cases, ASD + PDA 2 cases, ASD + VSD 1 case, ASD + PDA + VSD 1 case, VSD + PDA 4 cases, PDA + BAV 1 case, TOF 2 cases, TOF + ASD 1 case in which 18 patients had pulmonary hypertension, including 5 cases of resistant pulmonary arterial hypertension. Conclusions In cardiovascular malformations with Down syndrome, VSD (28%), AVSD (17%) and PDA (17%) are most common and were often associated with ASD or TOF. In patients absent of pulmonary artery stenosis, there were half of them combined with pulmonary artery hypertension.

Quantitative proteomic analysis of Down syndrome in the umbilical cord blood using iTRAQ.

Down sydrome (DS) is a relatively frequent chromosomal disorder, which has no safe and effective method of prenatal diagnosis to date. The present study was designed to identify DS biomarkers. We quantified the changes in the umbilical cord blood protein levels between DS-affected and healthy (control) pregnant females using isobaric tags for relative and absolute quantification (iTRAQ) and Gene Ontology(GO) analysis. A total of 505 proteins were identified, and of these, five proteins showed significantly different concentrations between the DS and the control group. These proteins may thus be relevant to DS and constitute potential DS biomarkers.

Molecular genetic analysis of Down syndrome

Down syndrome (DS) is caused by trisomy of all or part of human chromosome 21 (HSA21) and is the most common genetic cause of significant intellectual disability. In addition to intellectual disability, many other health problems, such as congenital heart disease, Alzheimer's disease, leukemia, hypotonia, motor disorders, and various physical anomalies occur at an elevated frequency in people with DS. On the other hand, people with DS seem to be at a decreased risk of certain cancers and perhaps of atherosclerosis. There is wide variability in the phenotypes associated with DS. Although ultimately the phenotypes of DS must be due to trisomy of HSA21, the genetic mechanisms by which the phenotypes arise are not understood. The recent recognition that there are many genetically active elements that do not encode proteins makes the situation more complex. Additional complexity may exist due to possible epigenetic changes that may act differently in DS. Numerous mouse models with features reminiscent of those seen in individuals with DS have been produced and studied in some depth, and these have added considerable insight into possible genetic mechanisms behind some of the phenotypes. These mouse models allow experimental approaches, including attempts at therapy, that are not possible in humans. Progress in understanding the genetic mechanisms by which trisomy of HSA21 leads to DS is the subject of this review.

Space-time analysis of Down syndrome: results consistent with transient pre-disposing contagious agent

Whilst maternal age is an established risk factor for Patau syndrome (trisomy 13), Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), the aetiology and contribution of genetic and environmental factors remains unclear. We analysed for space-time clustering using high quality fully population-based data from a geographically defined region. The study included all cases of Patau, Edwards and Down syndrome, delivered during 1985-2003 and resident in the former Northern Region of England, including terminations of pregnancy for fetal anomaly. We applied the K-function test for space-time clustering with fixed thresholds of close in space and time using residential addresses at time of delivery. The Knox test was used to indicate the range over which the clustering effect occurred. Tests were repeated using nearest neighbour (NN) thresholds to adjust for variable population density. The study analysed 116 cases of Patau syndrome, 240 cases of Edwards syndrome and 1084 cases of Down syndrome. There was evidence of space-time clustering for Down syndrome (fixed threshold of close in space: P = 0.01, NN threshold: P = 0.02), but little or no clustering for Patau (P = 0.57, P = 0.19) or Edwards (P = 0.37, P = 0.06) syndromes. Clustering of Down syndrome was associated with cases from more densely populated areas and evidence of clustering persisted when cases were restricted to maternal age <40 years. The highly novel space-time clustering for Down syndrome suggests an aetiological role for transient environmental factors, such as infections.

ETS family of genes in leukemia and Down syndrome

The human ETS2 and ERG genes are members of the ETS gene family, with sequence homology to the viral ets gene of the avian erythroblastosis retrovirus, E26. These genes are located on chromosome 21 and molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 suggested that ETS2 may be a gene within the minimal DS genetic region. We have, in fact, been able to confirm the presence of the ETS2 gene dosage in triplicate occurring in occult human 21 chromosome abnormalities. It is known that ERG and ETS2 gene translocations occur in certain specific leukemias associated with defined chromosome rearrangements [e.g., t(8;21)]. Moreover, it is known that DS individuals are at greater risk for leukemic disease than their normal familial cohorts, implying that trisomy of that region of human chromosome 21 may play a role in the development of this type of neoplasia. The human ETS genes, first identified in our laboratory, are highly conserved, being found from lower organisms, like Drosophila and sea urchin, to humans. In mammals, the ETS genes are structurally distinct, located on separate chromosomes; they are transcriptionally active and differentially regulated. The ETS2 protein is phosphorylated and turns over with a half-life of approximately 20 min. After activation with the tumor promoter, TPA, the level of ETS2 elevates 5- to 20-fold. The properties of the ETS2 protein, such as nuclear localization, phosphorylation, rapid turnover, and response to protein kinase C, indicate that this protein belongs to a group of oncogene proteins thought to have regulatory functions in the nucleus. In the mouse thymus ets-1 and ets-2 are 8-10-fold higher, respectively, in the CD4+ subset than in other subsets examined, suggesting a role in T-cell development for these genes. Cells transfected with the cellular ets-2 gene, expressing higher levels of ets-2 products, showed a stimulated proliferation response, abolished their serum requirement and formed colonies in soft agar that could induce tumors in nude mice. Collectively, these data suggest that this family of genes might play a role in controlling specific steps of the signaling transduction pathway. Thus, the ETS genes, as other genes with homology to viral oncogenes, might be instrumental in regulating cellular growth and differentiation, as well as organismal development.

Isolation and Refined Regional Mapping of Expressed Sequences from Human Chromosome 21

To increase candidate genes from human chromosome 21 for the analysis of Down syndrome and other genetic diseases localized on this chromosome, we have isolated and studied 9 cDNA clones encoded by chromosome 21. For isolating cDNAs, single-copy microclones from a chromosome 21 microdissection library were used in direct screening of various cDNA libraries. Seven of the cDNA clones have been regionally mapped on chromosome 21 using a comprehensive hybrid mapping panel comprising 24 cell hybrids that divide the chromosome into 33 subregions. These cDNA clones with refined mapping positions should be useful for identification and cloning of genes responsible for the specific component phenotypes of Down syndrome and other diseases on chromosome 21, including progressive myoclonus epilepsy in 21q22.3.

Cytogenetic analysis of down syndrome in Libya

The frequency of Down syndrome in Libya was 1 in 516 live births. The mean age of Down mother was 35.62 years. Eighty two percent of the Down mothers were over 30 years of age as compared to 36% of the control Libyan mothers. As there was a greater percentage of late conceptions, the maternal age appears to be influential in the birth of Down syndrome in Libya. Cytogenetically 96% of the cases were that of trisomy 21. There was one case each of mosaic and 21/21 translocation, and four cases of 14/21 translocation as evidenced by Giemsa banding. Twenty two percent of the cases of Down syndrome also had other associated congenital abnormalities. The unique features involved in genetic counselling in this population are discussed. This study reflects the enormous problem of Down syndrome in the Arab world.

Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease.

The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease.