Trying to see, failing to focus: near visual impairment in Down syndrome.
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ABSTRACT:
SUBMITTER: Doyle L
PROVIDER: S-EPMC4742775 | biostudies-other | 2016 Feb
REPOSITORIES: biostudies-other
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Project description:This review summarizes research on disorders of speech production in Down syndrome (DS) for the purposes of informing clinical services and guiding future research.Review of the literature was based on searches using MEDLINE, Google Scholar, PsycINFO, and HighWire Press, as well as consideration of reference lists in retrieved documents (including online sources). Search terms emphasized functions related to voice, articulation, phonology, prosody, fluency, and intelligibility.The following conclusions pertain to four major areas of review: voice, speech sounds, fluency and prosody, and intelligibility. The first major area is voice. Although a number of studies have reported on vocal abnormalities in DS, major questions remain about the nature and frequency of the phonatory disorder. Results of perceptual and acoustic studies have been mixed, making it difficult to draw firm conclusions or even to identify sensitive measures for future study. The second major area is speech sounds. Articulatory and phonological studies show that speech patterns in DS are a combination of delayed development and errors not seen in typical development. Delayed (i.e., developmental) and disordered (i.e., nondevelopmental) patterns are evident by the age of about 3 years, although DS-related abnormalities possibly appear earlier, even in infant babbling. The third major area is fluency and prosody. Stuttering and/or cluttering occur in DS at rates of 10%-45%, compared with about 1% in the general population. Research also points to significant disturbances in prosody. The fourth major area is intelligibility. Studies consistently show marked limitations in this area, but only recently has the research gone beyond simple rating scales.
| S-EPMC3584188 | biostudies-other
Project description:BACKGROUND: Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. METHODS: Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1? plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. RESULTS: We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1? plasma levels and their progenitors had a reduced expression of SDF-1? encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. CONCLUSIONS: Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.
| S-EPMC2949777 | biostudies-literature
Project description:Down syndrome (DS) patients frequently develop organ-specific autoimmune disorders, particularly endocrinopathies and coeliac disease, as well as an increased susceptibility to mucosal candidiasis. These clinical features resemble APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy), a monogenic condition due to mutations in the AIRE gene, located on 21q22.3 and already described as down-regulated in 21 trisomy. Here we investigated AIRE expression and global gene expression profiles in surgically removed thymuses from 14 DS infants and children with congenital heart defects and from 42 age-matched individuals with cardiac defect as an isolated malformation. Immunohistochemistry revealed significantly reduced AIRE expression in DS thymuses (70.48M-BM-149.59 positive cells/mm2 in DS X 154.70M-BM-161.16 in controls, p<0.0001). qPCR confirmed the lower expression of AIRE in DS thymuses. Global thymic RNA profiles from DS patients and controls revealed 407 genes significantly hypoexpressed in DS. Network transcriptional analysis showed that hypoexpressed genes are related to biological processes such as antigen processing and presentation of endogenous antigen (ERAP2, CD1D), negative (PRDX2) and positive (CD3D, CD74) thymic T-cell selection and homeostasis of number of cells (PRDX2). Altogether these findings may explain the high prevalence of autoimmune phenomena in DS patients. Moreover, our data are in accordance with previous findings of thymic abnormal development in DS patients, characterized by lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation. Global gene profiles indicate that in DS patients, the trisomic imbalance probably leads to thymic hypofunction. In conclusion, lower AIRE expression and the impairment of other crucial pathways for central tolerance could well explain the high prevalence of organ-specific autoimmune disorders in DS. Among the 14 DS infants and 42 age-matched individuals with cardiac defect, only 4 from each group provided enough biological material (thymus fragments) for isolation of high-quality RNA to perform array analysis. Eight thymic samples were analyzed: C1, C2, C3 and C4 are controls, and D1, D2, D3 and D4 are from patients with Down syndrome.
2011-11-28 | E-GEOD-23910 | biostudies-arrayexpress
Project description:IntroductionDown syndrome (DS) is associated with a higher risk of dementia. We hypothesize that amyloid beta (Aβ) in specific brain regions differentiates mild cognitive impairment in DS (MCI-DS) and test these hypotheses using cross-sectional and longitudinal data.Methods18F-AV-45 (florbetapir) positron emission tomography (PET) data were collected to analyze amyloid burden in 58 participants clinically classified as cognitively stable (CS) or MCI-DS and 12 longitudinal CS participants.ResultsThe study confirmed our hypotheses of increased amyloid in inferior parietal, lateral occipital, and superior frontal regions as the main effects differentiating MCI-DS from the CS groups. The largest annualized amyloid increases in longitudinal CS data were in the rostral middle frontal, superior frontal, superior/middle temporal, and posterior cingulate cortices.DiscussionThis study helps us to understand amyloid in the MCI-DS transitional state between cognitively stable aging and frank dementia in DS. The spatial distribution of Aβ may be a reliable indicator of MCI-DS in DS.
| S-EPMC7233421 | biostudies-literature
Project description:Perceptual learning is an important means for the brain to maintain its agility in a dynamic environment. Top-down focal attention, which selects task-relevant stimuli against competing ones in the background, is known to control and select what is learned in adults. Still unknown, is whether the adult brain is able to learn highly visible information beyond the focus of top-down attention. If it is, we should be able to reveal a purely stimulus-driven perceptual learning occurring in functions that are largely determined by the early cortical level, where top-down attention modulation is weak. Such an automatic, stimulus-driven learning mechanism is commonly assumed to operate only in the juvenile brain. We performed perceptual training to reduce sensory eye dominance (SED), a function that taps on the eye-of-origin information represented in the early visual cortex. Two retinal locations were simultaneously stimulated with suprathreshold, dichoptic orthogonal gratings. At each location, monocular cueing triggered perception of the grating images of the weak eye and suppression of the strong eye. Observers attended only to one location and performed orientation discrimination of the gratings seen by the weak eye, while ignoring the highly visible gratings at the second, unattended, location. We found SED was not only reduced at the attended location, but also at the unattended location. Furthermore, other untrained visual functions mediated by higher cortical levels improved. An automatic, stimulus-driven learning mechanism causes synaptic alterations in the early cortical level, with a far-reaching impact on the later cortical levels.
| S-EPMC3175289 | biostudies-literature
Project description:The presence of an extra whole or part of chromosome 21 in people with Down syndrome (DS) is associated with multiple neurological changes, including pathological aging that often meets the criteria for Alzheimer’s Disease (AD). While the mechanism underlying these changes is unknown, it has been hypothesized that the presence of the amyloid precursor protein (APP) on chromosome 21 may contribute to the phenotype. Genome-wide DNA methylation abnormalities have been shown in neural tissue of patients with AD, and cells may respond to changes in gene dosage with altered DNA methylation. We therefore examined whole-genome DNA methylation in buccal epithelial cells of adults with DS to determine whether patterns of DNA methylation correlated with DS and/or cognitive impairment. In addition we examined DNA methylation at the APP gene itself, to see whether there were changes in DNA methylation in this population. Using the Illumina 450K Human Methylation Array, we examined more than 485,000 CpG sites distributed across the genome in buccal epithelial cells. We found 297 CpGs to be differentially methylated between the groups, including 26 genes that were represented by more than one CpG. In addition, we found 331 probes that were correlated with cognitive function including 23 genes represented by more than one probe. We found no enrichment on chromosome 21 and targeted analysis of the APP gene revealed weak evidence for epigenetic impacts related to the AD phenotype. Overall, our results indicate that both Trisomy 21 and cognitive impairment are associated with distinct patterns of DNA methylation. This cohort consist of genomic DNA extracted from 20 buccal swabs, bisulphite converted and hybridized to the Illumina Infinium HumanMethylation450 Beadchip for genome wide DNA methylation profiling.
2014-01-02 | E-GEOD-50586 | biostudies-arrayexpress
Project description:Down syndrome (DS) patients frequently develop organ-specific autoimmune disorders, particularly endocrinopathies and coeliac disease, as well as an increased susceptibility to mucosal candidiasis. These clinical features resemble APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy), a monogenic condition due to mutations in the AIRE gene, located on 21q22.3 and already described as down-regulated in 21 trisomy. Here we investigated AIRE expression and global gene expression profiles in surgically removed thymuses from 14 DS infants and children with congenital heart defects and from 42 age-matched individuals with cardiac defect as an isolated malformation. Immunohistochemistry revealed significantly reduced AIRE expression in DS thymuses (70.48±49.59 positive cells/mm2 in DS X 154.70±61.16 in controls, p<0.0001). qPCR confirmed the lower expression of AIRE in DS thymuses. Global thymic RNA profiles from DS patients and controls revealed 407 genes significantly hypoexpressed in DS. Network transcriptional analysis showed that hypoexpressed genes are related to biological processes such as antigen processing and presentation of endogenous antigen (ERAP2, CD1D), negative (PRDX2) and positive (CD3D, CD74) thymic T-cell selection and homeostasis of number of cells (PRDX2). Altogether these findings may explain the high prevalence of autoimmune phenomena in DS patients. Moreover, our data are in accordance with previous findings of thymic abnormal development in DS patients, characterized by lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation. Global gene profiles indicate that in DS patients, the trisomic imbalance probably leads to thymic hypofunction. In conclusion, lower AIRE expression and the impairment of other crucial pathways for central tolerance could well explain the high prevalence of organ-specific autoimmune disorders in DS.
2011-11-28 | GSE23910 | GEO
Project description:Down syndrome (DS) is the most common non-lethal genetic condition that affects approximately 1 in 700 births in the United States of America. DS is characterized by complete or segmental chromosome 21 trisomy, which leads to variable intellectual disabilities, progressive memory loss, and accelerated neurodegeneration with age. During the last three decades, people with DS have experienced a doubling of life expectancy due to progress in treatment of medical comorbidities, which has allowed this population to reach the age when they develop early onset Alzheimer's disease (AD). Individuals with DS develop cognitive and pathological hallmarks of AD in their fourth or fifth decade, and are currently lacking successful prevention or treatment options for dementia. The profound memory deficits associated with DS-related AD (DS-AD) have been associated with degeneration of several neuronal populations, but mechanisms of neurodegeneration are largely unexplored. The most successful animal model for DS is the Ts65Dn mouse, but several new models have also been developed. In the current review, we discuss recent findings and potential treatment options for the management of memory loss and AD neuropathology in DS mouse models. We also review agerelated neuropathology, and recent findings from neuroimaging studies. The validation of appropriate DS mouse models that mimic neurodegeneration and memory loss in humans with DS can be valuable in the study of novel preventative and treatment interventions, and may be helpful in pinpointing gene-gene interactions as well as specific gene segments involved in neurodegeneration.
| S-EPMC5034871 | biostudies-literature
Project description:The presence of an extra whole or part of chromosome 21 in people with Down syndrome (DS) is associated with multiple neurological changes, including pathological aging that often meets the criteria for Alzheimer’s Disease (AD). While the mechanism underlying these changes is unknown, it has been hypothesized that the presence of the amyloid precursor protein (APP) on chromosome 21 may contribute to the phenotype. Genome-wide DNA methylation abnormalities have been shown in neural tissue of patients with AD, and cells may respond to changes in gene dosage with altered DNA methylation. We therefore examined whole-genome DNA methylation in buccal epithelial cells of adults with DS to determine whether patterns of DNA methylation correlated with DS and/or cognitive impairment. In addition we examined DNA methylation at the APP gene itself, to see whether there were changes in DNA methylation in this population. Using the Illumina 450K Human Methylation Array, we examined more than 485,000 CpG sites distributed across the genome in buccal epithelial cells. We found 297 CpGs to be differentially methylated between the groups, including 26 genes that were represented by more than one CpG. In addition, we found 331 probes that were correlated with cognitive function including 23 genes represented by more than one probe. We found no enrichment on chromosome 21 and targeted analysis of the APP gene revealed weak evidence for epigenetic impacts related to the AD phenotype. Overall, our results indicate that both Trisomy 21 and cognitive impairment are associated with distinct patterns of DNA methylation.
2014-01-02 | GSE50586 | GEO
Project description:BACKGROUND: The presence of an extra whole or part of chromosome 21 in people with Down syndrome (DS) is associated with multiple neurological changes, including pathological aging that often meets the criteria for Alzheimer's Disease (AD). In addition, trisomies have been shown to disrupt normal epigenetic marks across the genome, perhaps in response to changes in gene dosage. We hypothesized that trisomy 21 would result in global epigenetic changes across all participants, and that DS patients with cognitive impairment would show an additional epigenetic signature. METHODS: We therefore examined whole-genome DNA methylation in buccal epithelial cells of 10 adults with DS and 10 controls to determine whether patterns of DNA methylation were correlated with DS and/or cognitive impairment. In addition we examined DNA methylation at the APP gene itself, to see whether there were changes in DNA methylation in this population. Using the Illumina Infinium 450 K Human Methylation Array, we examined more than 485,000 CpG sites distributed across the genome in buccal epithelial cells. RESULTS: We found 3300 CpGs to be differentially methylated between the groups, including 495 CpGs that overlap with clusters of differentially methylated probes. In addition, we found 5 probes that were correlated with cognitive function including two probes in the TSC2 gene that has previously been associated with Alzheimer's disease pathology. We found no enrichment on chromosome 21 in either case, and targeted analysis of the APP gene revealed weak evidence for epigenetic impacts related to the AD phenotype. CONCLUSIONS: Overall, our results indicated that both Trisomy 21 and cognitive impairment were associated with distinct patterns of DNA methylation.
| S-EPMC3879645 | biostudies-literature