31 research outputs found
Maladie coeliaque et trisomie 21 (où en sommes-nous ?)
No full textPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF
Deciphering the links between psychological stress, depression, and neurocognitive decline in patients with Down syndrome
No full textInternational audienceThe relationships between psychological stress and cognitive functions are still to be defined despite some recent progress. Clinically, we noticed that patients with Down syndrome (DS) may develop rapid neurocognitive decline and Alzheimer's disease (AD) earlier than expected, often shortly after a traumatic life event (bereavement over the leave of a primary caregiver, an assault, modification of lifestyle, or the loss of parents). Of course, individuals with DS are naturally prone to develop AD, given the triplication of chromosome 21. However, the relatively weak intensity of the stressful event and the rapid pace of cognitive decline after stress in these patients have to be noticed. It seems DS patients react to stress in a similar manner normal persons react to a very intense stress, and thereafter develop a state very much alike post-traumatic stress disorders. Unfortunately, only a few studies have studied stress-induced regression in patients with DS. Thus, we reviewed the biochemical events involved in psychological stress and found some possible links with cognitive impairment and AD. Interestingly, these links could probably be also applied to non-DS persons submitted to an intense stress. We believe these links should be further explored as a better understanding of the relationships between stress and cognition could help in many situations including individuals of the general population
Methylomic profiling in trisomy 21 identifies cognition- and Alzheimer's disease-related dysregulation
No full textBackground: Trisomy 21 (T21) is associated with intellectual disability that ranges from mild to profound with an average intellectual quotient of around 50. Furthermore, T21 patients have a high risk of developing Alzheimer's disease (AD) early in life, characterized by the presence of senile plaques of amyloid protein and neurofibrillary tangles, leading to neuronal loss and cognitive decline. We postulate that epigenetic factors contribute to the observed variability in intellectual disability, as well as at the level of neurodegeneration seen in T21 individuals.Materials and Methods: A genome-wide DNA methylation study was performed using Illumina Infinium (R) MethylationEPIC BeadChips on whole blood DNA of 3 male T21 patients with low IQ, 8 T21 patients with high IQ (4 males and 4 females), and 21 age- and sex-matched control samples (12 males and 9 females) in order to determine whether DNA methylation alterations could help explain variation in cognitive impairment between individuals with T21. In view of the increased risk of developing AD in T21 individuals, we additionally investigated the T21-associated sites in published blood DNA methylation data from the AgeCoDe cohort (German study on Ageing, Cognition, and Dementia). AgeCoDe represents a prospective longitudinal study including non-demented individuals at baseline of which a part develops AD dementia at follow-up.Results: Two thousand seven hundred sixteen differentially methylated sites and regions discriminating T21 and healthy individuals were identified. In the T21 high and low IQ comparison, a single CpG located in the promoter of PELI1 was differentially methylated after multiple testing adjustment. For the same contrast, 69 differentially methylated regions were identified. Performing a targeted association analysis for the significant T21-associated CpG sites in the AgeCoDe cohort, we found that 9 showed significant methylation differences related to AD dementia, including one in the ADAM10 gene. This gene has previously been shown to play a role in the prevention of amyloid plaque formation in the brain.Conclusion: The differentially methylated regions may help understand the interaction between methylation alterations and cognitive function. In addition, ADAM10 might be a valuable blood-based biomarker for at least the early detection of AD.</p
Interstitial deletion of the short arm of chromosome 1: Attempt to establish a clinical phenotype (46,XX,del (1)(p22p32))
No full textA Low-Grade Follicular Thyroid Carcinoma in a Woman with down Syndrome
No full textAims Analysis of a thyroid neoplasm in a person with Down syndrome. Method Report of a case and review of the literature. Results A 34-year-old woman with Down syndrome developed a right thyroid low-grade follicular carcinoma. She is alive 20 years after the discovery of the initial tumor. A review of the literature including epidemiological studies revealed only one unspecified cancer, one papillary carcinoma and one lymphoma. Persons with Down syndrome present an excess of goiter and thyroiditis and often are overweight and have low serum selenium, all these conditions being risk factors for thyroid carcinomas. Conclusion Thyroid malignant neoplasms are very rare in persons with Down syndrome. We suspect that some constitutional, hormonal and genetic factors could protect these subjects against thyroid carcinoma. </jats:sec
The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome.
No full textInternational audienceTrisomy 21 or Down syndrome is a chromosomal disorder resulting from the presence of all or part of an extra Chromosome 21. It is a common birth defect, the most frequent and most recognizable form of mental retardation, appearing in about 1 of every 700 newborns. Although the syndrome had been described thousands of years before, it was named after John Langdon Down who reported its clinical description in 1866. The suspected association of Down syndrome with a chromosomal abnormality was confirmed by Lejeune et al. in 1959. Fifty years after the discovery of the origin of Down syndrome, the term "mongolism" is still inappropriately used; persons with Down syndrome are still institutionalized. Health problems associated with that syndrome often receive no or little medical care, and many patients still die prematurely in infancy or early adulthood. Nevertheless, working against this negative reality, community-based associations have lobbied for medical care and research to support persons with Down syndrome. Different Trisomy 21 research groups have already identified candidate genes that are potentially involved in the formation of specific Down syndrome features. These advances in turn may help to develop targeted medical treatments for persons with Trisomy 21. A review on those achievements is discussed
Prevalence and Description of Hidradenitis Suppurativa in Down Syndrome: A Cross-sectional Study of 783 Subjects
No full textSafety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome: a randomized phase Ib clinical trial (PERSEUS study)
No full text© 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Purpose: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance.
Methods: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation.
Results: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in theEGCGgroup and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work.
Conclusion: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population.Peer ReviewedArticle signat per 26 autors/es: Cécile Cieuta-Walti, Aida Cuenca-Royo, Klaus Langohr, Claire Rakic, Ma Ángeles López-Vílchez, Julián Lirio, Domingo González-Lamuño Leguina, Teresa Bermejo González, Jordi García García, Maria Rimblas Roure, Ana Aldea-Perona, Laura Forcano, Maria Gomis-Gonzalez, Sebastià Videla Cés, Florence Lacaille, Aimé Ravel, Clotilde Mircher, Hervé Walti, Nathalie Janel, Julien Dairou, Marilyne Lévy, Sophie Durand, Mara Dierssen, Silvia Sacco, Rafael de la Torre Fornell, PERSEUS Study GroupPostprint (author's final draft
Effect of leucovorin (folinic acid) on the developmental quotient of children with Down's syndrome (trisomy 21) and influence of thyroid status.
No full textInternational audienceBACKGROUND: Seven genes involved in folate metabolism are located on chromosome 21. Previous studies have shown that folate deficiency may contribute to mental retardation in Down's syndrome (DS). METHODOLOGY: We investigated the effect of oral folate supplementation (daily dose of 1.0+/-0.3 mg/kg) on cognitive functions in DS children, aged from 3 to 30 months. They received 1 mg/kg leucovorin or placebo daily, for 12 months, in a single-centre, randomised, double-blind study. Folinic acid (leucovorin, LV) was preferred to folic acid as its bioavailability is higher. The developmental age (DA) of the patients was assessed on the Brunet-Lezine scale, from baseline to the end of treatment. RESULTS: The intent-to-treat analysis (113 patients) did not show a positive effect of leucovorin treatment. However, it identified important factors influencing treatment effect, such as age, sex, and concomitant treatments, including thyroid treatment in particular. A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period. This analysis of 87 patients (43 LV-treated vs. 44 patients on placebo) revealed a positive effect of leucovorin on developmental age (DA). DA was 53.1% the normal value with leucovorin and only 44.1% with placebo (p<0.05). This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment (59.5% vs. 41.8%, p<0.05). No adverse event related to leucovorin was observed. CONCLUSION: These results suggest that leucovorin improves the psychomotor development of children with Down's syndrome, at least in some subgroups of the DS population, particularly those on thyroxin treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00294593
No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down's syndrome among French mothers
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