Down Syndrome
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2021 ◽  
Vol 118 (39) ◽  
pp. e2022442118
Luqiang Guo ◽  
Yichun Wu ◽  
Haishuang Chang ◽  
Ze Zhang ◽  
Hua Tang ◽  

The Down syndrome cell adhesion molecule (DSCAM) belongs to the immunoglobulin superfamily (IgSF) and plays important roles in neural development. It has a large ectodomain, including 10 Ig-like domains and 6 fibronectin III (FnIII) domains. Previous data have shown that DSCAM can mediate cell adhesion by forming homophilic dimers between cells and contributes to self-avoidance of neurites or neuronal tiling, which is important for neural network formation. However, the organization and assembly of DSCAM at cell adhesion interfaces has not been fully understood. Here we combine electron microscopy and other biophysical methods to characterize the structure of the DSCAM-mediated cell adhesion and generate three-dimensional views of the adhesion interfaces of DSCAM by electron tomography. The results show that mouse DSCAM forms a regular pattern at the adhesion interfaces. The Ig-like domains contribute to both trans homophilic interactions and cis assembly of the pattern, and the FnIII domains are crucial for the cis pattern formation as well as the interaction with the cell membrane. By contrast, no obvious assembly pattern is observed at the adhesion interfaces mediated by mouse DSCAML1 or Drosophila DSCAMs, suggesting the different structural roles and mechanisms of DSCAMs in mediating cell adhesion and neural network formation.

2021 ◽  
Vol 13 ◽  
Md. Mahiuddin Ahmed ◽  
Noah R. Johnson ◽  
Timothy D. Boyd ◽  
Christina Coughlan ◽  
Heidi J. Chial ◽  

Innate immune system activation and inflammation are associated with and may contribute to clinical outcomes in people with Down syndrome (DS), neurodegenerative diseases such as Alzheimer’s disease (AD), and normal aging. In addition to serving as potential diagnostic biomarkers, innate immune system activation and inflammation may play a contributing or causal role in these conditions, leading to the hypothesis that effective therapies should seek to dampen their effects. However, recent intervention studies with the innate immune system activator granulocyte-macrophage colony-stimulating factor (GM-CSF) in animal models of DS, AD, and normal aging, and in an AD clinical trial suggest that activating the innate immune system and inflammation may instead be therapeutic. We consider evidence that DS, AD, and normal aging are accompanied by innate immune system activation and inflammation and discuss whether and when during the disease process it may be therapeutically beneficial to suppress or promote such activation.

2021 ◽  
Vol 11 (9) ◽  
pp. 1216
Robyn P. Thom ◽  
Michelle L. Palumbo ◽  
Claire Thompson ◽  
Christopher J. McDougle ◽  
Caitlin T. Ravichandran

Background: Depression is a common psychiatric comorbidity in individuals with Down syndrome (DS), particularly adults, with an estimated lifetime prevalence of at least 10%. The current literature on the treatment of depression in adults with DS is limited to case series published more than two decades ago, prior to the widespread use of modern antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs). The purpose of this retrospective chart review study was to examine the effectiveness, tolerability, and safety of SSRIs for depression in adults with DS. Methods: Medical records of 11 adults with DS and depression were reviewed. Assignment of scores for severity (S) of symptoms of depression and improvement (I) of symptoms with treatment with an SSRI was made retrospectively using the Clinical Global Impression Scale (CGI). Demographic and clinical characteristics of the study population, SSRI name, dose, and duration of treatment; and adverse effects were also recorded. Results: All 11 patients (7 male, 4 female; mean age = 27.2 years, range 18–46 years) completed a 12-week treatment course with an SSRI. The median duration of time after initiation of the SSRI covered by record review was 2.1 years, with a range of 24 weeks to 6.7 years. Nine of the 11 patients (82%; 95% CI 52%, 95%) were judged responders to SSRIs based on a rating of “much improved” or “very much improved” on the CGI-I after 12 weeks of treatment (median time of follow-up was 14.4 weeks, with a range of 12.0–33.0 weeks). Adverse effects occurred in four patients (36%). The most common adverse effects were daytime sedation and anger. Conclusions: In this preliminary retrospective study, the majority of patients responded to a 12-week course of SSRI treatment and some tolerated long-term use. Controlled studies are needed to further assess the efficacy, tolerability, and safety of SSRIs for the treatment of depression in adults with DS.

2021 ◽  
Katharina Lambert ◽  
Keagan G. Moo ◽  
Azlann Arnett ◽  
Gautam Goel ◽  
Kaitlin J. Flynn ◽  

People with Down syndrome show cellular and clinical features of dysregulated aging of the immune system, including naive-memory shift in the T cell compartment and increased incidence of autoimmunity. However, a quantitative understanding of how various immune compartments change with age in Down syndrome remains lacking. Here we performed deep immunophenotyping of a cohort of individuals with Down syndrome across the lifespan, selecting for individuals not affected by autoimmunity. We simultaneously interrogated age- and sex-matched healthy neurotypical controls and people with type 1 diabetes, as a representative autoimmune disease. We built a new analytical software, IMPACD, that enabled us to rapidly identify many features of immune dysregulation in Down syndrome that are recapitulated in other autoimmune diseases. We found significant quantitative and qualitative dysregulation of naive CD4+ and CD8+ T cells in Down syndrome and identified IL-6 as a candidate driver of some of these changes, thus extending the consideration of immunopathologic cytokines in Down syndrome beyond interferons. Notably, we successfully used immune cellular composition to generate three quantitative models of aging (i.e. immune clocks) trained on control subjects. All three immune clocks demonstrated significantly advanced immune aging in people with Down syndrome. Notably, one of these clocks, informed by Down syndrome-relevant biology, also showed advanced immune aging in people with type 1 diabetes. Together, our findings demonstrate a novel approach to studying immune aging in Down syndrome which may have implications in the context of other autoimmune diseases.

2021 ◽  
pp. 174462952110327
Beatriz Helena Brugnaro ◽  
Olaf Kraus de Camargo ◽  
Carolina Corsi ◽  
Ana Carolina de Campos ◽  
Gesica Fernandes ◽  

Purpose: To compare functioning and environmental aspects before and during physical distancing (DPD) and to determine which social, physical, behavioral and functioning aspects of DPD are correlated. Methods: Sixteen parents of children/adolescents with Down syndrome (11.38 ± 3.00 years) were surveyed before and DPD. Paired t-tests were used to compare functioning and environmental aspects before and DPD and chi-square tests were used to test associations. Results: There were increases in the frequency (p < 0.001) and involvement (p = 0.01) in home participation and on the impact, noticed by the parents, of the possibility of child to participate in daily activities (p = 0.036), as well as a reduction in social supports perceived by caregivers (p = 0.049). An association was found between the child’s socio-emotional difficulties symptoms and practice of physical activity (p = 0.043) and with parents’ satisfaction with the level of child’s home participation (p = 0.042). Conclusion: Functioning can be affected in either positive or negative ways.

Frederike E.C.M. Mulder ◽  
Levinus A. Bok ◽  
Florens Q.M.P. van Douveren ◽  
Hans E.H. Pruijs ◽  
Adelgunde V.C.M. Zeegers

Purpose The aim of this study was to retrospectively analyze the effect of the Sharrard procedure on hip instability in children with Down syndrome (DS), as measured by the migration index. Methods In total, 17 children (21 hips) were included from six hospitals in the Netherlands between 2003 and 2019. The primary outcome, hip instability, was assessed with the Reimers’ migration index on preoperative and postoperative plain anteroposterior pelvic radiographs. The mean age at surgery was 8.1 years, the majority of children were male (64.7%) and the mean follow-up time was 7.3 years. Results The mean preoperative migration index was 46% (sd 23.5) and the mean postoperative migration index was 37% (sd 28.4). The mean Delta migration index (the difference in pre-operative migration index and most recent post-operative migration index) showed an improvement of 9.3% (sd 22.7). An improvement in migration index was observed in 52%, no change in 29% and deterioration in 19% of hips. No (re)dislocations occurred in 91% of the hips. No major complications were observed during the follow-up period. Conclusion Early intervention is warranted in children with DS showing hip instability or hip migration, in order to succeed with less complex procedures. The Sharrard procedure should be considered in children with DS showing hip instability or hip migration, since it aims to rebalance the muscles of the hip joint, is less complex than bony procedures of the femur and acetabulum, surgery time is often shorter, there are fewer major complications and the rehabilitation period is shorter. Level of Evidence IV - retrospective case series

2021 ◽  
Vol 12 ◽  
María C. Sánchez Gómez ◽  
Rocío Martín-Sevillano ◽  
María V. Martín-Cilleros ◽  
J. J. Mena Marcos ◽  
Francisco J. García-Peñalvo

Grandparents who have grandchildren with disabilities are an underrepresented group in existing research related to the field. This qualitative phenomenological study’s general purpose is to analyze, from a personal perspective, the situations and needs of grandparents who have grandchildren with Down syndrome. The participants’ ages range from 65 to 85, and the ages of their grandchildren with Down syndrome range from 3 to 21 years. All participants had one grandchild with a disability, except for two, who each had two. A sociodemographic questionnaire was administered, and individual interviews were conducted, using open questions, through phone and/or video calls. An analysis of the participants’ speech was carried out, which implied the development of a system of meta-categories and categories. This analysis was developed manually, given the COVID-19 environment. The results indicate a substantial change from negative feelings caused by the knowledge of the diagnosis to feelings related to positive experiences expressed currently. The participants see themselves as a fundamental source of support (informal, instrumental, practical, social, emotional, and economic) for their families and, mainly, for their grandchildren with Down syndrome. A need for information and training was observed when the grandparents talked about first being informed of the diagnosis and their concerns about the future of these grandchildren and their siblings. They made social demands, such as greater government involvement or more significant opportunities to access resources and rights for their grandchildren. The results are discussed, as are possible future research directions.

2021 ◽  
Vol 8 (9) ◽  
pp. 110
Suzanne J. A. Korporaal ◽  
Ronald J. van der Sluis ◽  
Miranda Van Eck ◽  
Menno Hoekstra

The genetic disorder Down syndrome is associated with a decreased susceptibility for atherosclerotic cardiovascular disease. Hematological and immune abnormalities occur frequently in Down syndrome patients. We evaluated, in a preclinical setting, the impact of a Down syndrome-like hematological / immune phenotype on atherosclerosis susceptibility. Hereto, hypercholesterolemic low-density lipoprotein receptor knockout mice were transplanted with bone marrow from either a trisomic Ts65Dn mouse or euploid wild-type control and subsequently fed a Western-type diet to induce the development of atherosclerotic lesions. T and B cell concentrations were markedly reduced in blood of Ts65Dn bone marrow recipients (p < 0.001). Expression levels of the pro-atherogenic scavenger receptor CD36 were respectively 37% and 59% lower (p < 0.001) in trisomic monocytes and macrophages. However, these combined effects did not translate into an altered atherosclerosis susceptibility. Notably, blood platelet numbers were elevated in Ts65Dn bone marrow recipients (+57%; p < 0.001), which was paralleled by higher platelet GPVI protein expression (+35%; p < 0.001) and an enhanced collagen-induced platelet activation (p < 0.001). In conclusion, we have shown that providing mice with a Down syndrome-like hematological profile does not change the susceptibility to atherosclerosis. Furthermore, our studies have uncovered a novel effect of the trisomy on platelet functionality that may be relevant in human clinical settings.

Leukemia ◽  
2021 ◽  
Austin C. Boucher ◽  
Kenneth J. Caldwell ◽  
John D. Crispino ◽  
Jamie E. Flerlage

Amanda Nicole White ◽  
Marly Chevette ◽  
Hampus Hillerstrom ◽  
Anna Esbensen

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