Down Syndrome Patients Research Articles

Periodontal Condition and Subgingival Microbiota Characterization in Subjects with Down Syndrome

The aim was to study the subgingival microbiota in subjects with Down syndrome (DS) with different periodontal health status, using cultural and molecular microbiological methods. In this cross-sectional study, DS subjects were selected among those attending educational or occupational therapy centers in Galicia (Spain). Medical histories, intraoral and periodontal examinations and microbiological sampling were performed. Samples were processed by means of culture and quantitative polymerase chain reaction (qPCR). Microbiological data were compared, by one-way ANOVA or Kruskal-Wallis and chi-square or Fisher tests, according to their periodontal status. 124 subjects were included, 62 with a healthy periodontium, 34 with gingivitis and 28 with periodontitis. Patients with periodontitis were older (p < 0.01) and showed lower prevalence of hypothyroidism and levothyroxine intake (p = 0.01), presented significantly deeper pockets and more attachment loss (p ≤ 0.01). Both gingivitis and periodontitis subjects showed higher levels of bleeding and dental plaque. PCR counts of T. forsythia and culture counts of E. corrodens and total anaerobic counts were significantly higher in periodontitis patients. Relevant differences were observed in the subgingival microbiota of DS patients with periodontitis, showing higher levels of anaerobic bacteria, T. forsythia and E. corrodens, when compared with periodontally healthy and gingivitis subjects. Moreover, periodontitis subjects were older, had lower frequency of hypothyroidism and higher levels of dental plaque.

Clinical features of 35 Down syndrome patients with transient abnormal myelopoiesis at a single institution

Transient abnormal myelopoiesis (TAM) is a unique clonal myeloproliferation characterized by immature megakaryoblasts that occurs in 5-10% of neonates with Down syndrome (DS). Although TAM regresses spontaneously in most patients, approximately 20% of TAM cases result in early death, and approximately 20% of survivors develop acute megakaryoblastic leukemia (AMKL). We retrospectively reviewed records of 35 DS patients with TAM to determine the correlation between clinical characteristics and blast percentage. Thirteen of the 35 patients were classified as low blast percentage TAM (LBP-TAM), defined as TAM with a peak peripheral blast percentage ≤ 10%. Although no patient with LBP-TAM experienced systemic edema, disseminated intravascular coagulation, or early death, eight patients had elevated direct bilirubin levels (> 2mg/dl) and one developed AMKL. All patients with LBP-TAM had serum markers of liver fibrosis that exceeded the normal limits, and two patients underwent liver biopsy to clarify the etiology of pathological jaundice. Taken together, our results suggest that patients with LBP-TAM may be at risk of liver fibrosis and liver failure, similarly to patients with classical TAM. Although these patients generally have a good prognosis, they should be carefully monitored for potential development of liver disease and leukemia.

Altered pro-inflammatory and anti-inflammatory plasma cytokines levels in children with Down's syndrome: A meta-analysis.

Background:Down syndrome (DS) is the commonest chromosomal anomalies at birth. DS is portrayed by the event of extra complete/deficient duplicate of chromosome number 21 (trisomy 21). Around the world, this disordered influencing roughly 1 out of 1000 infants. Pro-inflammatory and anti-inflammatory cytokines engaged with a few physiological procedures involving the guideline of inflammatory reactions. In DS kids, the creation of few important inflammatory and anti-inflammatory cytokines is altered. Different investigations shows that the cytokines are dysregulated in patients with DS. In this study, we led a meta-analysis to evaluate the connections of pro-inflammatory and anti-inflammatory cytokine changes in youngsters with DS patients.Methodology:We searched PubMed, Google and Web of Science for studies in exploring the association of pro-inflammatory and anti-inflammatory serum level with DS patients. Total 10 studies were included in the meta-analysis. The random effects were used to analyze the pooled data. All statistical tests were two-sided.Results:High circulating level of serum MCP-1 was significantly associated with DS [Cohen's d = 143.91 95% confidence interval (CI) =110.38-177.43]. However, the other circulating cytokines IL-2 and IL-17 level were lower whereas IL-13 level was higher but not significantly different in DS as contrasted to healthy controls. The heterogeneity level was higher in IL-2, IL-13 and IL-17 cytokines.Conclusion:This meta-analysis shows that the higher circulating level of MCP-1 was associated with DS.

Prevalence of congenital heart disease among patients with down syndrome in Southwestern Saudi Arabia.

Background:There is a paucity of data on the prevalence and pattern of congenital heart disease (CHD) among patients with Down syndrome (DS) in Bisha, Saudi Arabia. The aim of the study was to determine the prevalence and patterns of CHD in patients with DS and explore the association of participants’ sex with CHD in DS patients.Methodology:A total of 42 patients with confirmed DS were enrolled in the study. Relevant data were obtained from the patients’ records. The spectrum of CHD was analyzed and classified accordingly. Pearson's Chi-square was used to determine the association of gender with CHD.Results:Approximately 81% of the study participants had CHD. The most common CHD was atrial septal defect (28.5%), followed by ventricular septal defect (25%), patent ductus arteriosus (16%), and atrioventricular septal defect (14.3%). No significant association was found between CHDs and sex.Conclusion:The prevalence of CHD in the study group was consistent with reports from other regions of Saudi Arabia and globally. Participants’ sex was not associated with the occurrence of CHD in DS patients in this study.

Assessment of cluster of differentiation 4 and 8 among children with trisomy 21

Background Down syndrome (DS) is the most common genetic disorder with more probability of recurrent infections. Aim This study aimed to determine the differences in lymphocyte subgroups (CD4 and CD8) between DS children and to study the pattern and likelihood for recurrent infections and hospital admission due to infection. Patients and methods This study was carried out in the Genetic Unit of Alexandria University Children’s Hospital, Egypt. The study enrolled 61 individuals with DS. They were assessed for recurrent infections [including otitis media, pneumonia, upper respiratory tract infections (URTIs), and gastroenteritis] and hospital admission due to infections. All patients were subjected to complete blood count and flow cytometric analysis for expression markers of T lymphocytes (CD4 and CD8). Results The authors found a statistically significant increase in the frequency of URTIs. In terms of the type of recurrent infection in DS, it was the highest for URTIs. A statistically significant decrease was found in CD4 in the DS patients. Nonsignificant correlations were found between CD markers and hospital admission. Conclusion An increase in the incidence and the recurrence of infections among children with DS, especially URTI, pneumonia and gastroenteritis, was reported in the present work. Children with DS showed decreased absolute CD4 and CD4/CD8 ratio less than normal values of similar children younger than 6 years of age. Also, normal or even increased levels of absolute CD8 were evident in children with DS.

Investigating the impact of Down syndrome on methylation and glycomics with two-stage PO2PLS.

Down syndrome (DS) is a condition that leads to precocious and accelerated aging in affected subjects. Several alterations in DS cases have been reported at a molecular level, particularly in methylation and glycosylation. Investigating the relation between methylation, glycomics and DS can lead to new insights underlying the atypical aging. We consider a data integration approach, where we investigate how DS affects the parts of glycomics and methylation which are correlated, and which CpG sites and glycans are relevant. Our motivating datasets consist of methylation and glycomics data, measured on 29 DS patients and their unaffected siblings and mothers. The family-based case-control design needs to be taken into account when studying the relationship between methylation, glycomics and DS. We propose a two-stage approach to first integrate methylation and glycomics data, and then link the joint information to Down syndrome. For the data integration step, we consider probabilistic two-way orthogonal partial least squares (PO2PLS). PO2PLS models two omics datasets in terms of low-dimensional joint and omic-specific latent components, and takes into account heterogeneity across the omics data. The relationship between the omics data can be statistically tested. The joint components represent the joint information in methylation and glycomics. In the second stage, we apply a linear mixed model to the relationship between DS and the joint methylation and glycomics components. For the components that are significantly as sociated with DS, we identify the most important CpG sites and glycans. A simulation study is conducted to evaluate the performance of our approach. The results showed that the effects of DS on the omics data can be detected in a large sample size, and the accuracy of the feature selection was high in both small and large sample sizes. Our approach is applied to the DS datasets, a significant effect of DS on the joint components is found. The identified CpG sites and glycans appeared to be related to DS. Our proposed method that jointly analyzes multiple omics data with an outcome variable may provide new insight into the molecular implications of DS at different omics levels.

Distinctive Demography, Biology, and Outcome of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Children With Down Syndrome: Children's Cancer Group Studies 2861 and 2891

AbstractIn recent pediatric trials of acute myeloid leukemia (AML), children with Down syndrome (DS) have had significantly more megakaryoblastic leukemia and have experienced better outcome than other children. To further characterize AML in DS, Children's Cancer Group Studies 2861 and 2891 prospectively studied demography, biology, and response in AML and myelodysplastic syndrome (MDS) of children with and without DS. These studies evaluated timing of induction therapy and compared postremission chemotherapy with marrow transplantation in 1,206 children. One-hundred eighteen (9.8%) had DS, a fourfold increase in 20 years. DS patients were younger, had lower white blood cell and platelet counts, more antecedent MDS, acute megakaryoblastic leukemia or undifferentiated AML, and an under-representation of chromosomal translocations (P < .001 for each variable). Four-year event-free survival in DS was 69% versus 35% in others (P < .001). Intensively timed induction conferred significantly higher mortality in DS patients; bone marrow transplantation offered no advantage. Conventional induction followed by chemotherapy achieved an 88%, 4-year, disease-free survival in DS patients versus 42% in others (P < .001). Megakaryoblastic leukemia was unfavorable in others but prognostically neutral in DS. AML in DS is demographically and biologically distinct from AML in other children. It is singularly responsive to conventional chemotherapy and may warrant even less therapy. The increasing proportion of DS patients with AML most likely reflects changes in attitudes about entering DS patients on AML trials and possibly increasing ability to distinguish megakaryoblastic leukemia from lymphoid leukemia.

Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21

AbstractPatients with Down syndrome (DS) frequently develop 2 kinds of clonal megakaryocytosis: a common, congenital, spontaneously resolving, transient myeloproliferative disorder (TMD) and, less commonly, childhood acute megakaryoblastic leukemia (AMKL). Recently, acquired mutations in exon 2 of GATA1, an X-linked gene encoding a transcription factor that promotes megakaryocytic differentiation, were described in 6 DS patients with AMKL. The mutations prevent the synthesis of the full-length GATA1, but allow the synthesis of a shorter GATA1 protein (GATA1s) that lacks the transactivation domain. To test whether mutated GATA1 is involved in the initiation of clonal megakaryoblastic proliferation or in the progression to AMKL, we screened 35 DS patients with either AMKL or TMD and 7 non-DS children with AMKL for mutations in exon 2 of GATA1. Mutations were identified in 16 of 18 DS patients with AMKL, in 16 of 17 DS patients with TMD, and in 2 identical twins with AMKL and acquired trisomy 21. Analysis revealed various types of mutations in GATA1, including deletion/insertions, splice mutations, and nonsense and missense point mutations, all of which prevent the generation of full-length GATA1, but preserve the translation of GATA1s. We also show that the likely mechanism of generation of GATA1 isoforms is alternative splicing of exon 2 rather than, or in addition to, alternative translation initiation, as was proposed before. These findings suggest that acquired intrauterine inactivating mutations in GATA1 and generation of GATA1s cooperate frequently with trisomy 21 in initiating megakaryoblastic proliferation, but are insufficient for progression to AMKL.

Integrative Analysis Extracts a Core ceRNA Network of the Fetal Hippocampus With Down Syndrome.

Accumulating evidence suggests that circular RNAs (circRNAs)—miRNA–mRNA ceRNA regulatory network—may play an important role in neurological disorders, such as Alzheimer’s disease (AD). Interestingly, neuropathological changes that closely resemble AD have been found in nearly all Down syndrome (DS) cases > 35 years. However, few studies have reported circRNA transcriptional profiling in DS cases, which is caused by a chromosomal aberration of trisomy 21. Here, we characterized the expression profiles of circRNAs in the fetal hippocampus of DS patients (n = 8) and controls (n = 6) by using microarray. MiRNA, mRNA expression profiling of DS from our previous study and scRNA-seq data describing normal fetal hippocampus development (GEO) were also integrated into the analysis. The similarity between circRNAs/genes with traits/cell-types was calculated by weighted correlation network analysis (WGCNA). miRanda and miRWalk2 were used to predict ceRNA network interactions. We identified a total of 7,078 significantly differentially expressed (DE) circRNAs, including 2,637 upregulated and 4,441 downregulated genes, respectively. WGCNA obtained 15 hub circRNAs and 6 modules with cell type–specific expression patterns among scRNA-seq data. Finally, a core ceRNA network was constructed by 14 hub circRNAs, 17 DE miRNA targets and 245 DE mRNA targets with a cell type–specific expression pattern annotation. Known functional molecules in DS or neurodegeneration (e.g., miR-138, OLIG1, and TPM2) were also included in this network. Our findings are the first to delineate the landscape of circRNAs in DS and the first to effectively integrate ceRNA regulation with scRNA-seq data. These data may provide a valuable resource for further research on the molecular mechanisms or therapeutic targets underlying DS neuropathy.

Down's syndrome and COVID-19: risk or protection factor against infection? A molecular and genetic approach.

Down syndrome (DS) is the most common genetic cause of learning difficulties and intellectual disabilities. DS patients often present with several congenital defects and chronic diseases, including immunity disorders. Elevated levels of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) have been seen, which appear to vary with age. At birth, patients present with combined immunodeficiency, with frequent infections that decrease with age. Furthermore, high levels of IL-4 and IL-10 with anti-inflammatory properties and low levels of IL-6 and TNF-α are described in children. The immune system is believed to play an essential role in SARS-CoV-2 pathogenesis, and it has been associated with elevated levels of pro-inflammatory cytokines and an exaggerated cytokine release syndrome (CRS) that may eventually trigger a severe situation called cytokine storm. On the other hand, genetic features seem to be involved in the predisposition to illness and its severity. Overexpression of DSCR1 and ZAKI-4 inhibits the translocation of activated T lymphocyte nuclear factor (NF-AT) to the nucleus, a main step in the inflammatory responsiveness. We discuss here the possible role of immunology and genetic features of DS in the infection and prognosis in COVID-19.

Dermatoglyphics of the Digits and Inter-digit Areas in Down Syndrome Patients of a Sampled Nigeria Population

This study was carried out to determine the possible differences between the dermatoglyphic characteristics of the digit and inter-digit areas of Down Syndrome (DS) patients and healthy Nigerians. The dermatoglyphic prints of the digit and inter-digit areas were obtained by using the improvise digital method. Parameters evaluated were the digit patterns, inter-digit patterns and single flexion crease of the fifth digit. Comparison of dermal patterns in DS patients and normal ones was done using Chi-square test at a significant level of P = .05. The result of the digit patterns showed that the total mean percentage frequency for arch, radial loop, ulnar loop and whorl were 5.28%, 0.34%, 75.94% and 18.45% in DS patients and 9.55%, 1.11%, 60.11% and 29.22% in normal subjects respectively. The distribution of dermal ridge differ significantly in digits I, II and III of the right hand and digits II and III of the left hand in patients and normal subjects at P = .05 level. Down syndrome patients had more of open fields in all the inter-digit areas except in inter-digit C. The difference in patterns between DS patients and normal subjects was significant in inter-digit C and D of the left hand only. One normal subject had single flexion crease compared to four in Down syndrome patients. The findings of the study could be used as supplementary diagnostic aid for Down syndrome.

Treating acute myeloid leukemia among children with down syndrome

Abstract Background: Down Syndrome (DS) children with acute myeloid leukemia (AML) have unique differences in clinical features, epidemiologic nature, and biologic patterns of disease compared with AML in children without DS. Aims and Objective: AML in DS children should be considered distinct disorder from AML in Non DS population and treatment needs to be customized for this population. In this retrospective study spanning from 2014 to 2019 we present our experience of managing leukemia in children with DS. Materials and Methods: From 2014 and 2019, 72 children aged below 18 years were managed at our institute with acute myeloid leukemia (AML). Out of these 72 children with AML, 7 children were with DS which was confirmed by karyotyping. Majority of these children had M7 while M2 and M4 subtypes were seen in one child each. On conventional karyotyping in addition to trisomy 21 additional cytogenetic abnormalities were seen in 4 patients. Two children had trisomy 8. One child had deletion of 11 chromosomes and one had translocation between 8 and 21 chromosomes. Results: All 7 children were administered intensive chemotherapy with curative intent after informed parental consent. All 7 children achieved complete remission. Four out of 7 children had complications related to severe neutropenia. Conclusion: All patients of DS with AML should be offered chemotherapy with curative intent. Endeavour should be to give less aggressive chemotherapy protocol to bring down treatment related mortality.

Thyroid hormone and folinic acid in young children with Down syndrome: the phase 3 ACTHYF trial

This single center, randomized, double-blind, placebo-controlled phase 3 study investigated the effects of levothyroxine, folic acid, or both in combination over 12 months on global development in 143 infants with Down syndrome (DS). Over the last decades, treatment of DS associated co-morbidities has improved their life-expectancy. However, a therapy to improve mental development is still lacking. Folic acid as well as thyroxine are both crucial for normal neurodevelopment in utero and postnatally. Previously, two randomized controlled studies suggested beneficial effects of either folic acid especially in children treated with levothyroxine in an age group of 3–30 months [1] and levothyroxine alone started in the neonatal period [2], while a short-term cross-over study did not observe effects of levothyroxine on cognitive function in DS patients [3].

Progress of research on induced pluripotent stem cell models for Down syndrome

With an incidence of 1/800 - 1/600, Down syndrome (DS) is the most common chromosomal disorder in humans. Whilst most DS patients has trisomy 21, a small proportion may carry translocations or mosaicisms involving chromosome 21. The main characteristics of DS include mental retardation, peculiar facies, growth retardation, congenital heart disease, duodenal stenosis, Alzheimer's disease, leukemia, and immunodeficiency, which may be due to increased dosage of critical genes. Recent studies also showed that epigenetic changes may also occur in DS. For research on patients with DS or other trisomies have been restricted by ethical considerations, and commonly used mouse models cannot fully replicate the characteristic features of DS, pluripotent stem cells induced from fetal samples or biopsy tissues from DS patients may generate models with the same genetic content, which may provide idea materials for studying the pathogenesis of DS and customized cell and/or gene therapies.

Tomography-based definition of keratoconus for Down syndrome patients

BackgroundTo assess the diagnostic ability of Pentacam HR (Oculus Optikgeräte, GmbH, Wetzlar, Germany) tomographic indices in discriminating keratoconus (KC) and KC suspect (KCS) in 10- to 30-year-old patients with Down syndrome (DS).MethodsIn this study, DS patients were enrolled through special needs schools, the National Down Syndrome Society, and relevant non-profit organizations. Diagnoses were made independently by two experienced specialists. Forty Pentacam indices related to corneal thickness, volume, density, keratometry, power, shape, aberration, and elevation were extracted. For each index, the accuracy for KC and KCS diagnosis was evaluated using discriminant analysis and the area under receiver operating characteristic curve (AUROC). From each enrolled case, data from only one eye was entered in the analyses.ResultsAnalyses were performed on data from 25 KC, 46 KCS, and 154 non-ectatic DS eyes. The best discriminants for KC were anterior higher order aberrations (HOA) (cutoff > 0.643, AUROC = 0.879), posterior vertical coma (cutoff > 0.0702 μm, AUROC = 0.875), anterior vertical coma (cutoff > 0.4124 μm, AUROC = 0.868), and total HOA (cutoff > 0.608, AUROC = 0.867). The difference between AUROCs were not statistically significant (all P > 0.05). For KCS, the best discriminants were minimum corneal thickness (cutoff ≤ 480.0 μm, AUROC = 0.775), corneal volume (cutoff ≤ 55.3 μm, AUROC = 0.727) and Belin Ambrosio display-total deviation (BAD-D) (cutoff > 2.23, AUROC = 0.718) with no significant difference between AUROCs (all P > 0.05).ConclusionsIn this sample of DS patients, best KC discriminators were HOA and coma which showed good diagnostic ability. For KCS, best predictors were minimum corneal thickness, corneal volume, and BAD-D with relatively good diagnostic ability. Defining a new set of KC diagnostic criteria for DS patients is suggested.

Frequency of renal tubular acidosis in children with down syndrome

Background: Down syndrome (DS) is associated with various congenital diseases and malformations, including those of the kidneys and urinary tract. It has been thought that renal tubular acidosis (RTA) is more frequent in this population. The objective of this study was to assess the frequency of RTA and, secondarily, of other renal and urological disorders in persons with DS. Method: An observational, ambispective, descriptive and cross-sectional study of patients diagnosed with RTA, or suspected kidney or urological disorders, was carried out from July 2016 to September 2017 at the Down syndrome clinic of the Mexican National Institute of Paediatrics. Urinalysis was performed, along with analyses of venous blood gas, sodium, potassium, chlorine, calcium, phosphorus, albumin and creatinine. Those with any abnormal values were referred to nephrology for diagnostic evaluation. Results: Of a total of 700 patients seen at the clinic, 47 met the selection criteria. Of these, 32 had no RTA or other renal or urological alterations. The remaining 15 continued to the second phase of the study, where 6 were diagnosed with nephropathy or uropathy (RTA, systemic arterial hypertension, monosymptomatic familial haematuria, mild renal failure secondary to reflux nephropathy, urinary tract infection or right ureteropelvic stenosis). Four had mild metabolic acidosis without meeting the criteria for diagnosis of RTA. Conclusion: RTA is not more common in children with Down syndrome. Nephropathies and uropathies should be investigated in the evaluation of DS patients.

Normal Pressure Hydrocephalus in Down Syndrome: The Report of Two Cases

Down syndrome (DS) is the most common cause of intellectual disability in infants and has a well-known relationship with the Alzheimer's disease. The association between DS and the other pathologies of senescence, such as normal pressure hydrocephalus (NPH), has been poorly investigated. This series included two DS patients with NPH. In both cases, NPH symptoms were initially misdiagnosed as DS associated senescence. Patients were treated with ventricular-peritoneal shunt, showing a sustained improvement (1 and 4 years of follow-up). To our knowledge, this is the first description of the occurrence of NPH in adult patients with DS and surgical outcomes.

Salivary IgA as a Useful Biomarker for Dental Caries in Down's Syndrome Patients: A Systematic Review and Meta-analysis.

The objective of this systematic review and meta-analysis is to critically analyze and summarize studies reporting association of salivary immunoglobulin A (IgA) levels as a biomarker for dental caries in Down syndrome (DS) patients. Using the keywords salivary [All Fields] AND IgA [All Fields] AND (“down syndrome” [MeSH Terms] OR (“down”[All Fields] AND “syndrome” [All Fields]) OR “down syndrome” [All Fields]), an electronic search was conducted via PubMed and Scopus databases by two authors, H. H. and Z. K. independently. Retrieved studies were screened against the predefined exclusion and inclusion criteria. To estimate the risk of bias, quality assessment of included studies was carried using the Newcastle–Ottawa quality assessment scale for observational studies. Primary search resulted in 10 articles from PubMed and 13 articles from Scopus. Ten studies fulfilled the defined selection criteria and evaluated the salivary IgA (sIgA) level in DS patients with dental caries. Five articles were further analyzed in a quantitative synthesis presented in the meta-analysis. Due to a modified lifestyle and compromised oral hygiene in DS patients, understandably, it is still postulated in the literature that the presence of sIgA can have a protective effect on the occurrence of dental caries as compared with healthy counterparts. As indicated by the present meta-analysis, no conclusions can be drawn as to definitively label sIgA as a biomarker for dental caries. Further, well-designed longitudinal clinical studies and translational research are therefore required before the benchmarking of sIgA as a useful biomarker for dental caries in DS patients with preferable molecular insights.

Obstructive sleep apnea in adults with Down syndrome.

Patients with Down syndrome (DS) often have a high occurrence of obstructive sleep apnea-hypopnea (OSA) syndrome. We studied a large cohort of adults with DS attended due to clinical suspicion of OSA. A standardized questionnaire and full medical assessment were conducted, including a sleep study. One hundred and fifty-seven DS individuals were studied, with a mean ± SD age of 36 ± 10 years, 40.7% women, BMI 29.4 ± 5.6 kg/m2 . The main clinical symptom was daytime sleepiness (64.9%). A sleep study was conducted in 114 patients. All 114 DS patients were diagnosed with OSA, with a predominance of obstructive and hypopnea events, (apnea-hypopnoea index, AHI, 35.0 ± 26.6), with an oxygen desaturation index of 32.9, and a Tc90% of 24.7%. Continuous positive airway pressure (CPAP) treatment was implemented in 75 (65.8%) of subjects. Tolerance was considered good in 75% of them, with a high compliance of 79.2% >4 hr/day (mean 7.1 hr/day), resulting in a symptomatic improvement in 58.7% of them. Obstructive sleep apnea is frequently confirmed in patients with DS when it clinically suspected. Treatment with CPAP in DS is feasible, and with higher adherence than in adults with normal cognitive functioning.

Down syndrome iPSC model: endothelial perspective on tumor development.

Trisomy 21 (T21), known as Down syndrome (DS), is a widely studied chromosomal abnormality. Previous studies have shown that DS individuals have a unique cancer profile. While exhibiting low solid tumor prevalence, DS patients are at risk for hematologic cancers, such as acute megakaryocytic leukemia and acute lymphoblastic leukemia. We speculated that endothelial cells are active players in this clinical background. To this end, we hypothesized that impaired DS endothelial development and functionality, impacted by genome-wide T21 alterations, potentially results in a suboptimal endothelial microenvironment with the capability to prevent solid tumor growth.To test this hypothesis, we assessed molecular and phenotypic differences of endothelial cells differentiated from Down syndrome and euploid iPS cells. Microarray, RNA-Seq, and bioinformatic analyses revealed that most significantly expressed genes belong to angiogenic, cytoskeletal rearrangement, extracellular matrix remodeling, and inflammatory pathways. Interestingly, the majority of these genes are not located on Chromosome 21. To substantiate these findings, we carried out functional assays. The obtained phenotypic results correlated with the molecular data and showed that Down syndrome endothelial cells exhibit decreased proliferation, reduced migration, and a weak TNF-α inflammatory response. Based on this data, we provide a set of genes potentially associated with Down syndrome’s elevated leukemic incidence and its unfavorable solid tumor microenvironment—highlighting the potential use of these genes as therapeutic targets in translational cancer research.