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Clinical Pediatrics May 2024Pulmonary disease, lower respiratory tract infection, and pneumonia are the largest causes of morbidity and mortality in individuals with Down syndrome (DS), but whether...
Pulmonary disease, lower respiratory tract infection, and pneumonia are the largest causes of morbidity and mortality in individuals with Down syndrome (DS), but whether pulmonary diagnoses in children with DS are common and occur independently of cardiac disease and pulmonary hypertension (PH) is unknown. Cardiopulmonary phenotypes were examined in a cohort of 1248 children with DS. Aptamer-based proteomic analysis of blood was performed in a subset (n = 120) of these children. By the age of 10 years, half of the patients in this cohort (n = 634, 50.8%) had co-occurring pulmonary diagnoses. That proteins and related pathways were distinct between children with pulmonary diagnoses and those with cardiac disease and/or PH may indicate that pulmonary diagnoses appear to occur independently of cardiac disease and PH. Heparin sulfate-glycosaminoglycandegradation, nicotinate metabolism, and elastic fiber formation were ranked highest in the group with pulmonary diagnoses.
Topics: Child; Humans; Down Syndrome; Proteomics; Heart; Hypertension, Pulmonary; Heart Diseases
PubMed: 37306037
DOI: 10.1177/00099228231179453 -
Placenta Jan 2020Down syndrome (DS) is the most common genetic disorder leading to developmental disability. The phenotypes associated with DS are complex and vary between affected... (Review)
Review
Down syndrome (DS) is the most common genetic disorder leading to developmental disability. The phenotypes associated with DS are complex and vary between affected individuals. Placental abnormalities in DS include differences in cytotrophoblast fusion that affect subsequent conversion to syncytiotrophoblast, atypical oxidative stress/antioxidant balance, and increased expression of genes that are also upregulated in the brains of individuals with Alzheimer's disease. Placentas in DS are prematurely senescent, showing atypical evidence of mineralization. Fetuses with DS are especially susceptible to adverse obstetric outcomes, including early in utero demise, stillbirth and growth restriction, all of which are related to placental function. The placenta, therefore, may provide key insights towards understanding the phenotypic variability observed in individuals with DS and aid in identifying biomarkers that can be used to evaluate phenotypic severity and prenatal treatments in real time. To address these issues, many different mouse models of DS have been generated to identify the mechanisms underlying developmental changes in many organ systems. Little is known, however, regarding placental development in the currently available mouse models of DS. Based upon the relative paucity of data on placental development in preclinical mouse models of DS, we recommend that future evaluation of new and existing models routinely include histologic and functional assessments of the placenta. In this paper we summarize studies performed in the placentas of both humans and mouse models with DS, highlighting gaps in knowledge and suggesting directions for future research.
Topics: Animals; Disease Models, Animal; Down Syndrome; Female; Mice; Oxidative Stress; Placenta; Placentation; Pregnancy
PubMed: 31683073
DOI: 10.1016/j.placenta.2019.10.002 -
Research in Developmental Disabilities Jan 2020Research conducted with typically developing (TD) infants and children generally indicates that better habitual sleep and sleep after learning are related to enhanced...
BACKGROUND
Research conducted with typically developing (TD) infants and children generally indicates that better habitual sleep and sleep after learning are related to enhanced memory. Less is known, however, about associations between sleep and recall memory in children with Down syndrome (DS).
AIMS
The present study was conducted to determine whether parent-reported sleep problems were differentially associated with encoding, 1-month delayed recall memory, and forgetting over time in children with DS and those who were TD.
METHODS AND PROCEDURES
Ten children with DS (mean age = 33 months, 5 days) and 10 TD children (mean age = 21 months, 6 days) participated in a two-session study. At each session, recall memory was assessed using an elicited imitation paradigm. Immediate imitation was permitted at the first session as an index of encoding, and delayed recall was assessed 1 month later. In addition, parents provided demographic information and reported on child sleep problems.
OUTCOMES AND RESULTS
Although parents did not report more frequent sleep problems for children with DS relative to TD children, regression-based moderation analyses revealed that more frequent sleep problems were associated with increased forgetting of individual target actions and their order by children with DS. Evidence of moderation was not found when examining encoding or delayed recall.
CONCLUSIONS AND IMPLICATIONS
Although group differences were not found when considering parent-reported sleep problems, more frequent sleep problems were positively associated with increased forgetting by children with DS relative to those who were TD. Although future experimental work is needed to determine causality, these results suggest that improved sleep in children with DS might reduce forgetting, ultimately improving long-term recall memory.
Topics: Case-Control Studies; Child, Preschool; Down Syndrome; Female; Humans; Infant; Male; Memory Consolidation; Mental Recall; Sleep Wake Disorders
PubMed: 31743853
DOI: 10.1016/j.ridd.2019.103512 -
Emerging Infectious Diseases Jan 2023Down syndrome is the most common human chromosomal disorder. Whether Down syndrome is a risk factor for severe COVID-19 outcomes in pediatric patients remains unclear,...
Down syndrome is the most common human chromosomal disorder. Whether Down syndrome is a risk factor for severe COVID-19 outcomes in pediatric patients remains unclear, especially in low-to-middle income countries. We gathered data on patients <18 years of age with SARS-CoV-2 infection from a national registry in Brazil to assess the risk for severe outcomes among patients with Down syndrome. We included data from 14,684 hospitalized patients, 261 of whom had Down syndrome. After adjustments for sociodemographic and medical factors, patients with Down syndrome had 1.8 times higher odds of dying from COVID-19 (odds ratio 1.82, 95% CI 1.22-2.68) and 27% longer recovery times (hazard ratio 0.73, 95% CI 0.61-0.86) than patients without Down syndrome. We found Down syndrome was associated with increased risk for severe illness and death among COVID-19 patients. Guidelines for managing COVID-19 among pediatric patients with Down syndrome could improve outcomes for this population.
Topics: Humans; Child; COVID-19; SARS-CoV-2; Down Syndrome; Brazil; Risk Factors
PubMed: 36573520
DOI: 10.3201/eid2901.220530 -
Scientific Reports Feb 2021This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid...
This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid (UA), creatinine levels and MTHFR C677T genotype were analyzed in 147 subjects with DS. For 77 subjects, metabolite levels were correlated with cognitive tests. Griffiths-III test was administered to 28 subjects (3.08-6.16 years) and WPPSI-III test was administered to 49 subjects (7.08-16.08 years). Significant correlations were found among some metabolite levels and between homocysteine levels and MTHFR C677T genotype. Moreover, homocysteine, UA and creatinine levels resulted increased with age. We did not find any correlation between metabolites and cognitive test score in the younger group. Homocysteine showed statistically significant correlation with WPPSI-III subtest scores when its level is ≥ 7.35 µmol/L, remaining correlated in higher thresholds only for non-verbal area scores. Vitamin B12 showed correlations with all WPPSI-III subtest scores when its level is < 442 pg/mL. The relevance of the present findings is the detection of a specific metabolite threshold related with a better or worse cognitive score, suggesting that vitamin B12 and homocysteine may have a role in cognitive development in children with DS.
Topics: Biomarkers; Carbon; Child; Cognition; Down Syndrome; Energy Metabolism; Fasting; Female; Homocysteine; Humans; Male; Metabolic Networks and Pathways; Methylenetetrahydrofolate Reductase (NADPH2)
PubMed: 33608632
DOI: 10.1038/s41598-021-83379-7 -
The European Journal of Neuroscience Nov 2022Down's syndrome is associated with pathological ageing and a propensity for early-onset Alzheimer's disease. The early symptoms of dementia in people with Down's...
Down's syndrome is associated with pathological ageing and a propensity for early-onset Alzheimer's disease. The early symptoms of dementia in people with Down's syndrome may reflect frontal lobe vulnerability to amyloid deposition. Auditory predictive processes rely on the bilateral auditory cortices with the recruitment of frontal cortices and appear to be impaired in pathologies characterized by compromised frontal lobe. Hence, auditory predictive processes were investigated to assess Down's syndrome pathology and its relationship with pathological ageing. An auditory electroencephalography (EEG) global-local paradigm was presented to the participants, in which oddball stimuli could either violate local or higher level global rules. We characterised predictive processes in individuals with Down's syndrome and their relationship with pathological ageing, with a focus on the EEG event-related potential called Mismatch Negativity (MMN) and the P300. In Down's syndrome, we also evaluated the EEG components as predictor of cognitive decline 1 year later. We found that predictive processes of detection of auditory violations are overall preserved in Down's syndrome but also that the amplitude of the MMN to local deviancies decreases with age. However, the 1-year follow-up of Down's syndrome found that none of the ERPs measures predicted subsequent cognitive decline. The present study provides a novel characterization of electrophysiological markers of local and global predictive processes in Down's syndrome.
Topics: Adult; Humans; Down Syndrome; Alzheimer Disease; Aging; Electroencephalography
PubMed: 35799324
DOI: 10.1111/ejn.15762 -
American Journal on Intellectual and... Jan 2016Differences were examined between three groups of adults with Down syndrome in their behavioral presentation, social life/activities, health, and support needs. We...
Differences were examined between three groups of adults with Down syndrome in their behavioral presentation, social life/activities, health, and support needs. We compared those with comorbid dementia, with comorbid psychopathology, and with no comorbid conditions. Adults with comorbid dementia were more likely to be older, have lower functional abilities, have worse health and more health conditions, and need more support in self-care. Adults with comorbid psychopathology were more likely to exhibit more behavior problems and to be living at home with their families. Adults with no comorbidities were most likely to be involved in community employment. Differences in behavioral presentation can help facilitate clinical diagnoses in aging in Down syndrome, and implications for differential diagnosis and service supports are discussed.
Topics: Adult; Aged; Aging; Comorbidity; Dementia; Down Syndrome; Female; Health Status; Humans; Male; Mental Disorders; Middle Aged
PubMed: 26701071
DOI: 10.1352/1944-7558-121.1.13 -
EMBO Reports Jan 2015Trisomy 21, the commonest constitutional aneuploidy in humans, causes profound perturbation of stem and progenitor cell growth, which is both cell context dependent and... (Review)
Review
Trisomy 21, the commonest constitutional aneuploidy in humans, causes profound perturbation of stem and progenitor cell growth, which is both cell context dependent and developmental stage specific and mediated by complex genetic mechanisms beyond increased Hsa21 gene dosage. While proliferation of fetal hematopoietic and testicular stem/progenitors is increased and may underlie increased susceptibility to childhood leukemia and testicular cancer, fetal stem/progenitor proliferation in other tissues is markedly impaired leading to the characteristic craniofacial, neurocognitive and cardiac features in individuals with Down syndrome. After birth, trisomy 21-mediated premature aging of stem/progenitor cells may contribute to the progressive multi-system deterioration, including development of Alzheimer's disease.
Topics: Animals; Disease Models, Animal; Down Syndrome; Hematopoiesis; Humans; Induced Pluripotent Stem Cells; Phenotype; Stem Cells; Trisomy
PubMed: 25520324
DOI: 10.15252/embr.201439583 -
International Journal of Environmental... Sep 2022: Children with Down Syndrome (C-DS) have language, cognitive and communication difficulties, in addition to consistent physical inactivity that contributes to poor...
: Children with Down Syndrome (C-DS) have language, cognitive and communication difficulties, in addition to consistent physical inactivity that contributes to poor health and higher-disability-adjusted life years. The purpose of this study was to determine the correlation between the use of electronic technology and levels of physical activity in C-DS in the Riyadh region of Saudi Arabia. : A cross-sectional study was conducted with 49 mothers, where each had a child (6-12 years of age) with Down Syndrome (DS), and who were recruited using purposive sampling from three DS centers in Riyadh, Saudi Arabia. The Children's Physical Activity Questionnaire and Research Questionnaire on the Impact of Technology on Children were used. Descriptive statistics were used to describe the demographics. Pearson's correlation, Student's -test and the Chi-square test were used to assess the association between technology use, physical activity levels and socio-demographic variables. : There was no significant correlation between physical activity and the use of technology by C-DS. However, there was a negative correlation between a high level of physical activity and technology use (R = -0.037). Although, no significant correlation between the mother's characteristics and technology use was found; there was a significantly positive correlation ( = 0.05) between the education level of mothers and the technology use by C-DS. Nonetheless, there was no association between the physical activity level and the gender of the child with DS. : This study found that no significant relationship exists between the use of electronic gadgets and the level of physical activity in C-DS.
Topics: Child; Cross-Sectional Studies; Down Syndrome; Exercise; Female; Humans; Mothers; Technology
PubMed: 36078678
DOI: 10.3390/ijerph191710958 -
Archivos de Cardiologia de Mexico Jul 2023Down syndrome is the most common chromosomal abnormality, it is associated with a wide variety of congenital heart defects, being considered as clinical elements of high...
BACKGROUND
Down syndrome is the most common chromosomal abnormality, it is associated with a wide variety of congenital heart defects, being considered as clinical elements of high infant morbidity and mortality. Objective.
OBJECTIVE
To describe the clinical outcomes of patients with Down syndrome undergoing surgery and interventionism as treatment for congenital heart disease at this Institution.
MATERIAL AND METHODS
368 patients with Down syndrome and associated congenital heart disease were diagnosed. The variables studied were weight, stature, sex, age, type of heart disease, corrective procedure, length of stay in the hospital and intensive care unit, morbidity and mortality.
RESULTS
368 pediatric patients underwent surgical or interventional correction. Of which 197 (54%) were female, the median age was 24 months (interquartile range [IQR]: 14-48) in the surgical group and 36 months (IQR: 17-85) in the interventional group. The most frequent congenital heart diseases were: PCA (31%), IVC (28%), CAV (20%), ASD (16%) and tetralogy of Fallot with 4% respectively. Hospital stay was 9 days (IQR: 7-15) in the surgical group and 3 days (IQR: 2-5) in the hemodynamic group. Morbidities were postoperative infection in 30 patients (14%) and complete atrioventricular block in 19 patients (9%). Overall mortality including both surgical and interventional was 2%.
CONCLUSIONS
The therapeutic, surgical and interventional results in children with Down syndrome and congenital heart disease have improved very satisfactorily. The lower prevalence of the atrioventricular canal in the Mexican population is noteworthy. It is essential to carry out a cardiological evaluation of children with Down syndrome and those with congenital heart disease to correct them in a timely manner to promote survival and quality of life.
Topics: Infant; Child; Humans; Female; Child, Preschool; Male; Down Syndrome; Quality of Life; Heart Defects, Congenital; Heart Septal Defects; Cardiac Surgical Procedures; Retrospective Studies
PubMed: 36634578
DOI: 10.24875/ACM.22000053