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1
Haquet, Emmanuelle. "Recombinaison entre chromosomes non-disjoints dans la Trisomie 21 et correlations génotypes/phénotypes dans le syndrome de Down." Montpellier 2, 2006. http://www.theses.fr/2006MON20070.
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Le syndrome de Down (SD), dont l'origine génétique est majoritairement une trisomie 21, se caractérise par un grand nombre de traits phénotypiques dont la plupart présente une variabilité élevée de sévérité. Une partie de cette variabilité pourrait être due à certaines combinaisons tri-alléliques de polymorphismes nucléotidiques (SNP). Par ailleurs, un événement unique de recombinaison dans la région télomérique des chromosomes 21 homologues augmenterait de 5 fois le risque de non-disjonction. Néanmoins, la distribution fine de ces événements n'est pas connue. Nous avons entrepris d'aborder ces deux types de questions en typant une centaine de SNP du chromosome 21 sur lame de verre chez des patients SD. Nous avons mis au point le typage de deux groupes de cinquante SNP permettant chacun de répondre à l'une des questions énoncées ci-dessus. Le premier groupe couvre 2 mégabases de la région critique du syndrome de Down (21q22. 13-q22. 2). Nous avons génotypé ces SNP chez 81 patients et étudié les répartitions des génotypes entre patients avec et sans un trait phénotypique donné (dont le retard mental et les cardiopathies). Nous avons observé une association significative après correction de Bonferroni (p<0,001) et une association plus faible (p<0,05) entre deux variants intragéniques du gène KCNJ6 et la présence de cardiopathies congénitales de type anomalie de cloisonnement chez les patients SD. Le rôle potentiel de variants du gène KCNJ6 dans l'apparition d'une cardiopathie constitue une nouvelle piste de travail pour la compréhension de ce phénotype. Le second groupe de SNP étudié couvre les 7,9 Mb télomérique du chromosome 21. Nous n'avons pas observé de différence statistique entre les distributions des recombinaisons associées à une non-disjonction et les contrôles. Néanmoins, la présence d'une recombinaison unique dans une région d'environ 2 Mb, située à 2 Mb du télomère du chromosome 21, semble particulièrement décisive pour l'apparition d'une non-disjonctionDown syndrome (DS), which is mainly caused by trisomy 21, is characterized by many abnormalities affecting most organ systems. The majority of DS features are highly variable between patients in term of presence and severity. Nucleotidic variations (SNPs) within or around some triplicated genes could be partly responsible for this variability. On another hand, fine scale analysis of recombination in the sub-telomeric region should make it more precise the relationship previously reported between altered recombination and meiotic non-disjunction. We addressed these two questions by typing a hundred of SNPs along chromosome 21 in families with a trisomic child. Two set of 50 SNPs have been designed, one for each project. The first 50 SNPs set covers 2 megabases of the Down Syndrome Critical Region (21q22. 13-q22. 2). We have genotyped 81 patients and studied, for each SNP, the proportion of genotypes between patients with and without a DS trait (including mental retardation and cardiac malformation). We have observed two associations, one strong (p<0,001) and one weaker (p<0,05), between two intragenic SNPs and the presence of a septal cardiac defect. The concerned gene is KCNJ6 a potassium channel which potential implication in DS cardiopathy is a new way of investigations for understanding the variability of this DS trait. The second 50 SNPs set covers the 7. 9 sub-telomeric mégabases of chromosome 21. We could not observe significant differences between recombination distributions in context of normal and non-disjoined chromosomes. Nevertheless, the presence of a unique recombination event in a 2 Mb region, located at 2 Mb from the telomere, seems to be critical for the generation of non-disjoined chromosome 21
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Noll, Christophe. "Recherche de mécanismes thérapeutiques dans un modèle murin d'hyperhomocystéinémie : approche alimentaire et génétique." Paris 7, 2010. http://www.theses.fr/2010PA077191.
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L'hyperhomocystéinémie, intermédiaire ou modérée, est une pathologie le plus souvent liée à un déficit en vitamines et/ou à une mauvaise hygiène de vie. L'hyperhomocystéinémie est maintenant bien reconnue comme étant un facteur de risque de développement d'athérosclérose ou d'accidents cérébrovasculaires. C'est pourquoi, développer une démarche thérapeutique visant à normaliser ou réduire l'homocystéinémie est un enjeu de santé publique. Dans une première partie, nous nous sommes intéressé à une supplémentation chronique en polyphénols chez des souris hyperhomocystéinémiques. Les polyphénols sont une classe de molécules naturelles connues pour leurs propriétés antioxydantes et leurs vertus bénéfiques sur la physiologie vasculaire. Une supplémentation chronique d'un extrait polyphénolique,de vin a permis de restaurer le métabolisme hépatique de l'homocystéine, ainsi que l'activité de différentes enzymes du métabolisme des xénobiotiques. De plus, elle a permis de prévenir l'apparition d'une fibrose hépatique et de diminuer l'expression de gènes impliqués dans la dysfonction endothéliale au niveau de l'aorte des souris hyperhomocystéinémiques. Dans une deuxième partie, nous nous sommes intéressé au métabolisme de l'homocystéine dans différents modèles murins de trisomie 21. Les personnes atteintes de trisomie 21 présentent naturellement un taux d'homocystéine plus bas que la population générale, et semblent protégés contre le développement de l'athérosclérose. Nos résultats montrent l'implication de la surexpression de Dyrkia, une sérine/thréonine kinase présente sur le chromosome 21 humain, sur le métabolisme hépatique de l'homocystéine, passant par une augmentation de l'activité de la S- adénosylhomocystéine hydrolase (SAHH), enzyme permettant la condensation de l'homocystéine et de l'adénosine. Nos résultats montrent que la surexpression de Dyrkia induit une augmentation de la transcription et de l'activité hépatique de la NAD(P)H quinone oxydoréductase, une enzyme dont le produit de la réaction, le NAD+, sert de cofacteur enzymatique à la SAHH. En conclusion, nos résultats montrent que par une approche nutritionnelle, il est possible de faire diminuer le taux d'homocystéine plasmatique et de prévenir l'apparition de certains phénotypes associés à l'hyperhomocystéinémie. De plus, une approche génétique permet de moduler le métabolisme hépatique de l'homocystéine et est une première voie dans l'élaboration de nouvelles stratégies thérapeutiquesHyperhomocysteinemia, mild and moderate, is a pathology linked to vitamin deficiency and/or unhealthy lifestyle. Hyperhomocysteinemia is now well recognized as a risk factor for developping cerebrovascular disease or atherosclerosis. Thus, developping new therapeutic approaches in order to decrease plasma homocysteine level is a public health issue. The first part of this work has consisted in studying a chronic supplémentation of polyphénols on hyperhomocysteinemic mice. Polyphenols are a class of natural organic compounds recognized for their antioxidant properties and their bénéficiai effects on vascular physiology. A chronic supplémentation of a red wine polyphenolic extract restores hepatic homocysteine metabolism, and activity of several xenobiotic-metabolizing enzymes. Furthermore, this supplémentation prevents thé development of hepatic fibrosis and induces a decrease expression of gènes involved in endothelial dysfunction in aorta of hyperhomocysteinemic mice. The second part of this work has consisted in studying the hepatic homocysteine metabolism in several murine models of trisomy 21. People with trisomy 21 have a lower plasma homocysteine level and seem to be protected against cardiovascular disease. Our results show the implication of Dyrkia, a serine/thréonine kinase found on the human chromosome 21, onto the hepatic homocysteine metabolism through an increase in hepatic S-adenosylhomocysteine hydrolase (SAHH) activity, an enzyme which condenses homocysteine and adenosine. Dyrkla induces an increase in NAD(P)H:quinone oxidoreductase hepatic gene expression and activity, an enzyme which the product of the reaction is NAD+, an enzymatic co-factor of SAHH. In conclusion, our results show that by a nutritional approach, we could decrease plasma homocysteine level and prevent some phenotypes associated with hyperhomocysteinemia. Furthermore, a genetic approach could modulate hepatic homocysteine metabolism and would be a first step in developing new therapeutic strategies
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Nshimyumukiza, Léon. "Cell-free DNA-based noninvasive prenatal screening for Down syndrome in the Quebec healthcare system : health economic aspects." Doctoral thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27889.
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Introduction: Au Québec, environ 110 000 femmes enceintes sont éligibles au dépistage prénatal volontaire de la trisomie 21(T21). Différentes stratégies de dépistage sélectionnent environ 4% des femmes à haut risque pour le test invasif (amniocentèse) en vue d'un diagnostic définitif. Les nouveaux tests génomiques prénataux non invasifs (TGPNI) utilisant l'ADN fœtal circulant dans le sang maternel pourraient réduire ces procédures invasives. Leur introduction dans les programmes nationaux de dépistage requiert cependant que des données sur leur coût-efficacité et leur impact budgétaire soient produites. Objectifs : L’objectif principal de cette thèse était d'évaluer les aspects économiques attendus de l'introduction du TGNI dans le programme québécois de dépistage de la trisomie 21. La première étude a consisté en une revue systématique de la littérature des évaluations économiques sur les TGPNI. La deuxième étude a porté sur l'évaluation économique de 7 stratégies de dépistages incluant le TGPNI comparées ainsi que des 6 stratégies de dépistage traditionnelles recommandées par la Société canadienne d’obstétrique et de gynécologie(SOGC). La troisième étude a porté sur l'évaluation de l'impact budgétaire attendu de l’implantation du dépistage par TGPNI dans le programme québécois de dépistage de la trisomie 21. Méthodologie: Une revue systématique de la littérature a été réalisée pour la première étude. Pour la deuxième étude, ainsi que la troisième, des modèles de décision semi-markoviens ont été élaborés pour simuler l’évaluation économique et l'impact budgétaire du dépistage par TGPNI pour une cohorte virtuelle de femmes enceintes similaire à celle des femmes enceintes du Québec en termes d'âge et de nombre de grossesses par âge. La perspective du système de santé québécois a été considérée. Pour l’évaluation économique, 13 stratégies de dépistage ont été comparées : 6 traditionnelles recommandées par la Société canadienne d’obstétrique et de gynécologie, 6 incluant le TGPNI comme test de dépistage de deuxième intention et 1 considérant le TGPNI en première intention. Quant à l’analyse d’impact budgétaire, elle a porté sur l’option considérée comme la plus coût-efficace par la deuxième étude, c’est-à-dire le TGPNI en deuxième intention offert aux femmes à haut risque (Sérum intégré +TGPNI). Cette option a été comparée à la stratégie actuellement offerte par le programme de dépistage au Québec (Sérum intégré). La principale issue pour l'analyse coût-efficacité était le coût additionnel par trisomie 21 additionnelle détectée. Celle de l'analyse d'impact budgétaire était la différence de coûts entre la stratégie incluant le TGPNI et la stratégie de dépistage actuelle. Résultats: La première étude qui a inclus 16 études a révélé que par rapport aux stratégies de dépistage actuelles, la stratégie offrant le TGPNI à toutes les femmes n'était pas coût-efficace. C'est l'option du TGPNI offert aux femmes enceintes à risque élevé qui s'avère l'option la plus coût-efficace dans la majorité des études incluses. La deuxième étude a montré que, sur un total de 13 stratégies comparées, la stratégie « Dépistage par sérum intégré suivie par le TGPNI » est celle qui coûte le moins cher et la stratégie « TGPNI universel » est celle qui coûte le plus bien qu'étant la plus efficace. Ainsi, la stratégie « Dépistage par sérum intégré suivie par le TGPNI » est considérée comme plus la coût-efficace. D'autres stratégies, bien que relativement plus efficace pour détecter le nombre de cas T21, entraînent une augmentation des coûts marginaux par cas additionnel détecté allant de 61 623 $ à 1 553 615 $. Les résultats étaient sensibles au coût du TGPNI et aux seuils considérés pour déterminer les femmes enceintes à risque élevé. La troisième étude a montré que le TGPNI offert aux femmes à haut risque identifiées par le programme de dépistage actuel serait abordable pour le système de santé québécois. Comparativement au programme de dépistage actuel, son implantation se ferait à coût neutre considérant une modeste économie annuelle de 80 432 $ (IC à 95%: 79 874 $ - 81 462 $). Les résultats étaient sensibles aux coûts du TGPNI et au taux d'acceptation des tests diagnostiques invasifs. Conclusion: Le TGPNI comme test de seconde intension, c'est-à-dire offert aux femmes à haut risque selon les critères du programme de dépistage actuel, est coût-efficace et abordable pour le système de santé québécois. Avant d'envisager son introduction, les décideurs devraient cependant considérer d'autres aspects, notamment les aspects éthiques.Introduction: In the Province of Quebec, about 110,000 pregnant women are eligible to voluntary prenatal screening for trisomy 21(T21). Conventional screening strategies select about 4% of women for invasive fetal chromosome testing. Noninvasive prenatal testing using maternal blood cell-free DNA (NIPT) is a new highly accurate screening strategy that could reduce these invasive procedures but evidence about its health economic aspects (cost-effectiveness and affordability) is still lacking. Objectives: The objective of this thesis is to evaluate the expected health economic aspects of introducing NIPT into the Quebec trisomy 21 screening program. The first study systematically reviewed the literature of full economic evaluation studies on NIPT. The second study evaluated the expected cost-effectiveness of screening strategies incorporating NIPT, as well as conventional screening strategies. The third study evaluated the expected budget impact of implementing NIPT into the Quebec trisomy 21 screening program. Methodology: A systematic review of literature was performed for the first study. For the second and third studies, semi-Markov decision-analytic models were built to simulate the cost-effectiveness and the budget impact of NIPT for a virtual cohort of pregnant women similar to that of Quebec in terms of age and pregnancy rate by age. The main outcome for the cost-effectiveness analysis was the incremental cost per additional trisomy 21 detected. The main outcome for the budget impact analysis was the difference in the overall costs between the two alternatives: the current screening strategy vs. the most cost-effective strategy incorporating NIPT). Results: The first study included 16 studies. Results show that compared to current screening practice a universal NIPT screening program is not cost-effective. A program that offers NIPT to high risk pregnant women was found to be the most cost-effective option in the majority of studies included. The second study showed that NIPT as a second-tier test for high-risk women is cost-effective compared to screening algorithms not including NIPT. Out of 13 strategies compared, the integrated serum screening strategy followed by NIPT was the most cost-effective strategy. Other strategies can improve the number of T21 cases identified, but with increasing incremental costs per case (from $ 61,623 to $1,553,615). Results were sensitive to NIPT cost and cut-offs considered to determine high risk pregnant women. The third study found that NIPT as a second-tier test offered to high-risk women identified by the current screening program is affordable for the Quebec health care system. Compared to the current screening program, this strategy could be implemented at a neutral cost considering a modest yearly saving of $80,432 (95% CI: $79,874-$81,462). Results were sensitive to the NIPT costs and the uptake-rate of invasive diagnostic tests. Conclusion: NIPT as a second-tier test offered to high-risk women identified by the current screening program is cost-effective and affordable for the Quebec health care system. Decision makers should consider its introduction after considerations of others aspects such as ethical issues.
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Leiva, Portocarrero Maria Esther. "Identification des croyances saillantes des femmes enceintes sur l'utilisation d'un outil d'aide à la décision dans le contexte du dépistage prénatal de la trisomie 21 pour l'élaboration et validation d'un questionnaire." Master's thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27801.
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Cette étude exploratoire séquentielle mixte avait pour objectif principal de développer un questionnaire qui permettra d’estimer l’influence des facteurs psychosociaux sur l’intention des femmes enceintes d'utiliser un outil d'aide à la décision (OAD) dans le contexte du dépistage prénatal de la T21. Premièrement, 46 femmes enceintes ont complété des entrevues semi structurées instruites par le Cadre des Domaines Théoriques. Cinquante-quatre croyances saillantes parmi les neuf des 12 domaines théoriques furent identifiées, dont les trois plus fréquentes furent : « La personne la plus importante pour moi qui m’encouragerait à utiliser un OAD serait mon conjoint »; « Le document devrait être présenté et expliqué par le professionnel de la santé »; et « Ne pas connaître un OAD en influence l’utilisation ». Ces résultats ont servi à l’élaboration d’un questionnaire auto administré dont la consistance interne et la stabilité dans le temps furent jugées adéquates à l’aide d’un test ré test avec un second groupe de 41 femmes enceintes. Ce questionnaire permettra de mener une enquête populationnelle dans le but d’élaborer un programme d’implantation de l’OAD.The goal of this exploratory mixed-methods sequential study was to develop a questionnaire to estimate the influence of psychosocial factors on pregnant women’s intention to use a decision aid (DA) in the context of prenatal screening for Down syndrome (T21). First, 46 pregnant women completed semi-structured interviews that were guided by the Theoretical Domains Framework. Fifty-four salient beliefs were identified matching the nine relevant theoretical domains (out of 12). The three most frequent beliefs were “The most important person who would encourage me to use the DA would be my partner”; “The document should be presented and explained by a healthcare professional”, and “Not knowing about DAs influences its use.” These results informed the development of a self-administered questionnaire whose internal consistency and stability over time were assessed as adequate using a test-retest with a second group of 41 pregnant women. This questionnaire will be used to conduct a population based survey for developing a program to implement the DA.
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Agbadje, Titilayo. "Développement d'un plan d'intervention afin de promouvoir l'utilisation d'un outil d'aide à la décision par les femmes enceintes dans le contexte du dépistage prénatal de la trisomie 21." Master's thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/30192.
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La décision de faire ou non le test de dépistage de la trisomie 21 (T21) est une décision difficile pour les femmes enceintes. Mon projet visait à développer un plan d’intervention à l’endroit des femmes enceintes afin de promouvoir l’utilisation d’un outil d’aide à la décision (OAD) pour la décision de se soumettre ou non au dépistage prénatal de la T21. Utilisant la roue du changement de comportement, nous avons mené trois groupes de discussion avec 15 femmes et retenu 10 techniques de changement de comportement (TCC) qui pourraient favoriser l’utilisation de l’OAD par les femmes enceintes : définition des objectifs (comportement et résultats), résolution de problème, plan d’action, soutien social (général et pratique), ajout d’objets à l’environnement, indice/repère, source crédible et modelling. Les TCC retenues ont été utilisées pour proposer un plan d’intervention, en tenant compte de la trajectoire de soins des femmes enceintes dans les services prénataux.Deciding whether or not to take the Down syndrome screening is a difficult decision for pregnant women. We aimed to develop an intervention plan for pregnant women to promote their use of a patient decision aid when they are making the decision about Down syndrome prenatal screening. We conducted three focus groups with 15 pregnant women to evaluate behaviour change techniques, as described in the Behaviour Change Wheel that would be appropriate for developing the intervention plan to promote the use of the decision aid by pregnant women. The ten techniques retained were: goal setting (behaviour and result), problem solving, action plan, social support (general and practical), adding objects to the environment, prompts/cues, credible sources and demonstration of the behaviour. We then developed an intervention plan using these behaviour change techniques and the clinical pathway of pregnant women in prenatal services.
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Graison, Aït Yahya Emilie. "Etude des processus de dérégulations géniques apparaissant dans la trisomie 21." Paris 7, 2008. http://www.theses.fr/2008PA077025.
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La Trisomie 21 est la maladie d'origine génétique la plus fréquente et est caractérisée par un tableau clinique complexe et très variable. Afin de déterminer l'implication des gènes tripliqués dans la pathogénèse des phénotypes de la maladie, nous avons analysé les variations d'expression des gènes du chromosome 21 sous l'effet de la Trisomie dans des lignées lymphoblastoïdes dérivées de patients trisomiques et d'individus contrôles. Pour cela, nous avons créé une puce à ADN spécifiquement dédiée à l'ensemble du contenu du chromosome 21 contenant 359 gènes, prédictions et transcrits antisens. Nous avons pu établir une classification des gènes et prédictions du chromosome 21 en fonction de leurs variations d'expression sous l'effet de la Trisomie 21 dans notre modèle cellulaire. Les gènes surexprimés sont susceptibles d'être impliqués dans la pathogénèse de la Trisomie 21 contrairement aux gènes compensés, majoritaires. Et les gènes variables pourraient intervenir dans la variabilité phénotypique entre patients trisomiques. Dans 40% à 60% des cas, les patients trisomiques présentent des malformations cardiaques. Afin d'aller plus loin dans l'identification des gènes impliqués dans la pathogénèse de ce phénotype dans la Trisomie, nous avons comparé le transcriptome de lignées lymphoblastoïdes dérivées de patients trisomiques avec malformation cardiaque à celui de lignées de patients trisomiques sans aucune malformation cardiaque grâce à l'utilisation de puces pan génomiques représentant plus de 48000 transcrits humains. L'analyse des données révèle que 82 transcrits apparaissent différentiellement exprimés entre patients trisomiques avec et sans malformation cardiaqueDown syndrome is the most common genetic disease and is characterized by numerous and highly variable clinical features. In order to determine the involvement of triplicated genes in the pathogenesis of the Down syndrome phenotypes, we analyzed chromosome 21 gene expression variations under the effect of the disease in lymphoblastoid cell lines from trisomic patients and control individuals. For this purpose, we designed an oligonucleotide microarray dedicated to the whole content of chromosome 21 containing 359 genes, predictions and antisense transcripts. We established a classification of chromosome 21 genes and predictions according to their expression variations in Down syndrome in our cellular model. Overexpressed genes are likely to be involved in Down syndrome phenotypes whereas the majority of genes which are compensated are not. Highly variable genes could rather be involved in the phenotypic variability between patients. In 40% to 60% of cases, trisomic patients show congenital heart defects. To go further in the identification of genes implicated in the pathogenesis of heart defect in Down syndrome, we compared the transcriptome of lymphoblastoid cell lines from patients with cardiac abnormalities to those of cell lines from patients without any heart defect using pangenomic microarrays representing more than 48000 human transcripts. Data analysis reveals that 82 transcripts are differentially expressed between patients with and without cardiac malformations
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Delanoë, Agathe. "Influence des facteurs sociocognitifs et de la littératie en santé sur l'intention des femmes enceintes d'utiliser un outil d'aide à la décision dans le contexte du dépistage prénatal de la trisomie 21." Master's thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27642.
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Les femmes enceintes font face au choix difficile de passer ou non un test de dépistage prénatal pour la trisomie 21 (T21). Ce choix est difficile car il implique la considération de risques, une perte ou des regrets possibles, ainsi que la mise au défi de valeurs personnelles. Le recours à un outil d’aide à la décision (OAD) pourrait faciliter une décision fondée sur les données probantes et les valeurs et préférences des femmes enceintes. Cependant, malgré leurs effets bénéfiques démontrés, les OAD ne sont pas systématiquement utilisés dans le suivi prénatal. L’objectif de ce mémoire a donc été d’identifier les variables psychosociales et de littératie en santé influençant l'intention des femmes enceintes d'utiliser un OAD dans le contexte du dépistage prénatal de la T21. Dans cette étude quantitative transversale descriptive, nous avons mené une enquête auprès de 350 femmes enceintes dans la province de Québec (Canada) au moyen d’un panel en ligne. Un questionnaire auto-administré fondé sur une version étendue de la Théorie du comportement planifié a permis d’évaluer sept construits psychosociaux (intention, attitude, regret anticipé, norme subjective, norme descriptive, norme morale et perception de contrôle), quatre variables de littératie, et de recueillir des données sociodémographiques. Nous avons effectué des analyses descriptives, bivariées et multivariées. Par ordre d’importance, l’attitude (rapport de côte [RC] 9.16; intervalle de confiance [IC] 95% 4.02-20.85), la norme morale (RC 7.97; IC 95% 4.49-14.14), la norme descriptive (RC 2.83; IC 95% 1.63-4.92) et le regret anticipé (RC 2.43; IC 95%1.71-3.46) ont été identifiés comme les facteurs déterminant l’intention des femmes enceintes d’utiliser un OAD. La littératie en santé n’a montré aucun effet significatif sur l’intention des femmes enceintes (P : 0.43-0.92). Ces résultats permettront l’élaboration d’une intervention efficace afin d’implanter un OAD dans le contexte du dépistage prénatal de la T21.Pregnant women face a choice about whether or not to have a prenatal test for Trisomy 21 (T21) or Down syndrome. This choice is difficult as it involves risk, possible loss or regret, and challenges to personal values. Using decision aids (DA) could help pregnant women make evidence-based decisions aligned with their values and preferences. However, in spite of their advantages, DA are not used systematically in prenatal care. The goal of this study was therefore to identify the psychosocial and health literacy variables that influence pregnant women’s intentions to use a DA for deciding about prenatal T21 testing. For this quantitative cross-sectional descriptive study, we surveyed 350 pregnant women in the province of Quebec (Canada) using a web panel. The women completed a self-administered questionnaire based on an expanded version of the Theory of Planned Behaviour evaluating seven psychosocial constructs (intention, attitude, anticipated regret, subjective norm, descriptive norm, moral norm and perceived control) and four health literacy variables. The survey also collected sociodemographic data. We performed descriptive, bivariate and multivariate analyses. In order of importance, factors identified as determining pregnant women’s intention to use a DA were: attitude (odds ratio/OR 9.16; 95% confidence interval/CI 4.02–20.85), moral norm (OR 7.97, 95% CI 4.49–14.14), descriptive norm (OR 2.83; 95% CI 1.63–4.92) and anticipated regret (OR 2.43; 95%CI 1.71–3.46). Health literacy showed no significant effect (P values range: 0.43-0.92) on pregnant women’s intention to use a DA. These conclusions could inform the design of an intervention that takes these determining factors into account.
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Marechal, Damien. "Implication de la région Abcg1-U2af1 dans le syndrome de Down : effets de doses de la région et rôle du gène Cbs dans les défauts de mémorisation." Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00856595.
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Le syndrome de Down (SD), ou Trisomie 21, est l'aneuploïdie la plus fréquente chez l'humain. Le désordre génomique est tel qu'aucun traitement unique ne peut pallier à tous les symptômes (retard mental, troubles moteurs...). C'est pourquoi l'utilisation de modèles murins permet d'étudier l'impact de régions partielles du Hsa21 dans l'apparition des déficits. Mon projet de thèse s'est orienté sur un locus télomérique encadré par les gènes Abcg1 et U2af1. Mes recherches se sont focalisées sur deux modèles, Ts1Yah et Ms2Yah, dédiés à cette région. L'étude de ces lignées, combinées à d'autres modèles transgéniques, a montré la contribution de l'intervalle génique dans l'optimisation de l'apprentissage locomoteur. Dans un deuxième temps, le gène Cbs, candidat à la perte de fonction de mémoire, a permis de mettre en évidence un sauvetage fonctionnel dans une expérience à effets de doses. Cette découverte ouvre la voie à de nouvelles perspectives thérapeutiques.
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Nguyen, Thu-Lan. "Correction des déficits cognitifs chez des modèles murins de trisomie 21 par un inhibiteur de la kinase DYRK1A : étude pharmacologique et mécanistique." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ124/document.
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La trisomie 21 (T21) résulte de la présence d’une extra-copie du chromosome 21 (Chr21). Parmi les gènes candidats impliqués dans les déficits cognitifs liés à la T21, DYRK1A est un des plus pertinents. Des études ont montré une corrélation entre l’augmentation de son activité kinase avec les déficits mnésiques observés dans les modèles murins de T21. Afin de comprendre les mécanismes sous-jacents aux altérations cognitives causées par son surdosage, nous avons utilisé des modèles murins sur-exprimant DYRK1A seule ou en plus d’autres gènes orthologues au Chr21, ainsi que des inhibiteurs spécifiques de DYRK1A (Leucettines) synthétisés par ManRos Therapeutics. Ici sont présentées les conséquences d’un traitement chronique avec ces Leucettines sur la cognition de ces animaux. Des analyses du phosphoprotéome de ces souris traitées ou non avec une des Leucettines, la L41, a mis en lumière des cibles et mécanismes biologiques impliqués dans les perturbations mnésiques de ces animaux. Enfin, ce projet a surtout permis de mettre en évidence un nouvel inhibiteur plus sélectif pour DYRK1A comme candidat-médicament pour l’amélioration des fonctions cognitives des porteurs de la T21Down Syndrome (DS), is due to the presence of an extra copy of chromosome 21 (Ch21). Among the candidates implicated in DS intellectual disabilities, DYRK1A is one of the most relevant. Several studies have shown a correlation between an increase of its kinase activity and the intellectual defects observed in DS models. In order to understand the mechanisms underlying the impact of DYRK1A overdosage on cognitive alterations, we used several trisomic mouse models expressing DYRK1A alone or with additional Hsa21 orthologous genes and specific DYRK1A inhibitors (Leucettines) from ManRos Therapeutics. We will present here the consequence of the Leucettines treatment following repetitive administration to several DS mouse models on the behavior and cognition. Further analysis of the phosphoproteome of DS mouse models treated or not with one of the Leucettine, the L41, unravels a few targets and pathways which are involved in the cognitive alterations observed in these trisomic mice. These results support the potential of more selective DYRK1A inhibitor as a therapeutic approach to improve cognitive functions in DS patients
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Mouton-Liger, François. "Fonction, régulation de PCP4 et trisomie 21 : analyse de modèles murins de surexpression." Paris 7, 2008. http://www.theses.fr/2008PA077062.
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La Trisomie 21 est la plus fréquente anomalie chromosomique et se caractérise par un tableau clinique complexe avec notamment un retard mental constant. Les déficiences cognitives dont l'origine demeure mal connue, pourraient être la conséquence d'altérations du développement précoce du système nerveux. PCP4/PEP-19 (Purkinje Cell Protein 4) est une protéine, dont le gène est localisé sur le chromosome 21, impliquée dans la transduction du signal calcique et modulant l'activation des cibles du complexe Ca2+-Calmoduline, dont la CaMKII. PCP4 possède une expression précoce dans le neuroectoderme, suggérant un rôle dans le développement des différentes structures du système nerveux. Pour confirmer cette hypothèse, un modèle de surexpression de PCP4 a été construit par transgénèse : les souris TgPCP4. Notre étude à plusieurs stades de développement, au niveau du transcrit et de la protéine, montre chez les TgPCP4 la présence de PCP4 dans des régions du système nerveux, où il est normalement observé plus tard au cours de l'embryogenèse. L'analyse par des marqueurs de différenciation neuronale montre que la surexpression de PCP4 induit une maturation neuronale précoce au niveau des ganglions nerveux et du rhombencéphale. Dans ces régions, nous avons mis en évidence une modulation de l'activité de la CaMKIIô, suggérant son implication dans ce mécanisme. Des résultats similaires ont été obtenus sur les souris TslCje, trisomiques pour une région du chromosome 16 murin orthologues du 21 humain pour 85 gènes (dont pcp4\ indiquant que les conséquences de cette surexpression peuvent être maintenues dans le contexte multigénique de la Trisomie 21Pcp4/pepl9 is a modulator of Ca2+-CaM, a key molecule for calcium signaling, expressed in postmitotic neuroectoderm cells during mouse embryogenesis. PCP4 gene is located on human chromosome 21, and present in three copies in Down syndrome (DS). To evaluate the consequences of 3 copies of this gene on the development of these cells in the nervous System, we constructed a transgenic (TgPCP4) mouse model, with one copy of human PCP4, and investigated the effects in this model. We showed that pcp4 overexpression is present at transcript and protein levels, and overexpression induced precocious neuronal differentiation, as shown by the distribution and levels of early neuronal markers. We also demonstrated that pcp4 overexpression was associated with an increase in CaMKIIdelta activation, TgPCP4 and TslCje, a mouse model of DS, developed similar modifications, demonstrating that these mechanisms may account for abnormal neuronal development in DS
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Nehring, Wendy M., and Cecily L. Betz. "Down Syndrome." Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etsu-works/6712.
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Book Summary: Nurses play a key role in high-quality health care for people with intellectual and developmental disabilities (IDD)--and now this up-to-date textbook fully prepares them to provide patients with the best possible services across the lifespan. The most comprehensive text available for nurses who specialize in IDD, this essential book clarifies evidence-based practices and gives readers an integrated, interdisciplinary approach to care that meets each person's individual needs.
Cecily Betz and Wendy Nehring--authors of the respected text Promoting Health Care Transitions for Adolescents with Special Health Care Needs and Disabilities--gather the latest research and wisdom of 18 diverse authorities in the medical field. Together, they give pre- and in-service nurses the foundation of knowledge they need to help ensure equal access to health care for people with IDD choose from today's models and philosophies of carepromote their patients' psychosocial developmentprovide effective physical careconduct health assessments and develop individualized plans of caremaintain successful interdisciplinary collaboration with other professionals address the issues associated with specific disabilities, including autism, Down syndrome, cerebral palsy, fragile X, sensory impairment, and medical and behavioral health problems support developmental transitions across the lifespan expand their knowledge of genetics and apply it to nursing practice skillfully manage ethical and legal issuesunderstand the service agencies used by individuals with IDD Enhanced with clinical practice guidelines to support effective work with individuals who have IDD, this textbook lights every nurse's path to person-centered, evidence-based care that improves their patients' lives.
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Nehring, Wendy M. "Down Syndrome." Digital Commons @ East Tennessee State University, 2009. https://dc.etsu.edu/etsu-works/6715.
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Written by nurse practitioners for nurse practitioners, this one-of-a-kind resource provides the expert guidance you need to provide comprehensive primary care to children with special needs and their families. It addresses specific conditions that require alterations in standard primary care and offers practical advice on managing the major issues common to children with chronic conditions. A consistent format makes it easy to locate essential information on each condition. Plus, valuable resources help you manage the issues and gaps in health care coverage that may hinder quality care.
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Miry, Claire. "Aspects pratiques et enjeux éthiques du dépistage prénatal non invasif de la trisomie 21 : mise au point et enquête auprès de professionnels de santé et de patientes." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5030.
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La place du Dépistage Prénatal Non Invasif (DPNI) n’est pas encore clairement définie dans le dépistage prénatal de la trisomie 21 en France. Nos objectifs étaient d’évaluer la compréhension, les connaissances, et l’attitude de professionnels de santé et de patientes concernant le DPNI.Une étude prospective multicentrique par questionnaire auprès de patientes enceintes et de professionnels de santé a été menée dans différents hôpitaux français entre février 2014 et juillet 2015.Sur les 260 questionnaires recueillis chez les professionnels, le score moyen de connaissances était 5,38±2,83(sur 10)et 92,7%(n=241) avaient une attitude favorable face au DPNI. En analyse multivariée, les facteurs associés à un bon niveau de connaissances étaient la profession de gynécologue ou de conseiller en génétique, l’âge<30 ans, le fait de travailler à l’hôpital ou en cabinet et le fait de suivre>50 grossesses par an.Sur les 380 questionnaires de patientes, le score moyen de connaissances était faible 2,20±1,88(sur 10) et 89,9%(n=328) avaient une attitude favorable face au DPNI. En analyse multivariée, les facteurs associés à un bon niveau de connaissances chez les patientes étaient l’âge maternel et le fait de consulter en secteur privé.Le niveau de connaissances des professionnels et des patientes sur le DPNI est faible. La plupart des patientes ne peuvent pas formuler de consentement éclairé. Toutefois, la plupart des professionnels et des patientes sont très en faveur de ce test. La généralisation du DPNI dans le dépistage de la trisomie 21 implique un important programme de formation des professionnels afin qu'ils délivrent une information prénatale de qualité et non directiveThe place of Non Invasive Prenatal Testing(NIPT) is not clearly established for prenatal screening for Down syndrome in France. Our objectives were to assess the understanding, knowledge of, and attitudes towards NIPT in French patients and healthcare providers.A prospective multicenter study was performed in several French hospital centers between February 2014 and July 2015. A survey was administered to pregnant patients and to healthcare professionals.A total of 260 questionnaires were completed by healthcare providers. The average knowledge score was 5,38±2,83(out of a possible 10). In multivariate analysis, the characteristics associated with satisfactory knowledge were: profession as obstetrician or genetic counsellor, age<30 years, working in hospital or in doctor’s office, more than 50 pregnancies followed per year. Among professionals, 92,7%n=241) had a favorable attitude towards NIPT.We collected 380 questionnaires from pregnant women. The average knowledge score was very low: 2,20±1,88(out of 10). In multivariate analysis, the two significant characteristics associated with satisfactory knowledge was maternal age and having prenatal care in private practice. Among patients, 89,9%(n=328) had a favorable attitude towards NIPT.The level of knowledge of NIPT of healthcare professionals and patients is low. Many patients can not provide informed consent. However most professionals and patients are in favor of the use of this test. The input of NIPT in prenatal screening for trisomy 21 requires a considerable teaching program for healthcare providers so they can give balanced pretest information and non-directive counselling
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Landry, Oriane. "Executive function in Down syndrome." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=79785.
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Persons with Down syndrome and MA matched typically developing children were tested on two measures each of hot and cool executive function (EF). Tasks were selected to be developmentally appropriate for mental ages between 3 and 6 years. Participants with Down syndrome performed at the same level as verbal mental age (VMA, M = 47.53 months) matched typically developing children on the Children's Gambling Task (Kerr & Zelazo, 2001), a delay of gratification task (Thompson, Barresi, & Moore, 1997) the Dimensional Change Card Sort (DCCS; Frye, Zelazo, & Palfai, 1995), and the Self-Ordered Pointing task (Petrides & Milner, 1982), but showed a disadvantage on the DCCS, a cool EF task, when matched on performance mental age (PMA, M = 58.34 months). These results reflect the complex cognitive profiles of persons with Down syndrome and highlight the need for more precise matching procedures.
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Myrelid, Åsa. "Down syndrome : Growth and endocrine impact." Doctoral thesis, Uppsala universitet, Pediatrik, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-106756.
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Down syndrome (DS) is associated with psychomotor retardation, short stature and endocrine dysfunction. Statural growth is a well-known indicator of health. The growth in DS differs markedly from that of other children and there is a 20 cm reduction of final height as compared to target height. We developed growth charts specific for Swedish children with DS, in order to facilitate early diagnosis of concomitant diseases that influence growth. The growth charts are available for paediatricians and child health care professionals in Sweden. The mechanism underlying the impaired growth in DS is unknown. Height is influenced by parental factors, energy intake, hormone balance and general health. In DS, genetic factors deriving from the extra chromosome 21 further affect growth. Children with DS seem to have reasonable levels of growth hormone (GH), even though GH treatment for limited periods of time improves growth velocity. Within the present project, the subjects of a previous study on early GH therapy in DS were followed up regarding late effects. We found a larger adult head circumference and better psychomotor abilities in the previously treated subjects despite a lack of effect on final height. In adult life, GH has effects on psychological well-being and metabolism. The clinical features in adults with DS might indicate impaired GH secretion. Ten young adults with DS were studied and compared with ten healthy controls. The GH secretion in the DS subjects did not differ from that in the controls. The fat body mass percentage was increased in DS, in line with the high prevalence of overweight/obesity. The finding of an increased HOMA index as well as a high relative rate of hepatic glucose production in DS indicates reduced insulin sensitivity both peripherally and in the liver. Thyroid dysfunction is common in DS. There is a 30-fold increase in congenital hypothyroidism, and acquired hypothyroidism has been reported to be present in up to 50% of adults with DS. We collected neonatal screening results and hospital records for the first ten years of life of 68 children with DS. The mean TSH concentration was increased neonatally, indicating marginal hypothyroidism early in life in DS. However, the neonatal TSH level did not predict development of manifest hypothyroidism later in life.Downs syndrom (DS) är en vanlig kromosomavvikelse. Kortvuxenhet och psykomotorisk utvecklingsstörning är kardinaltecken vid DS. Endokrina avvikelser är också frekvent förekommande. Tillväxt är en bra indikator på barns hälsa. Nyfödda barn med DS är kortare än andra nyfödda, och skillnaden i längd ökar under barndomen. Sjukdomar som påverkar tillväxten upptäcks ofta via ett förändrat tillväxtmönster. Detta kan lätt förbises vid DS eftersom tillväxten redan är avvikande. Användning av syndromspecifika tillväxtkurvor ökar möjligheterna till diagnostik av sjukdomar som stör längdtillväxten. Vi har framställt tillväxtkurvor för barn med DS, vilka finns tillgängliga inom svensk barnsjukvård och barnhälsovård. Längdtillväxt styrs av nedärvda faktorer från föräldrarna liksom av nutrition, hälsa och hormoner. Genetiska faktorer, kopplade till kromosom 21, kan påverka tillväxten vid DS, men tillväxtstörningens exakta bakgrund är inte känd. I vuxen ålder är personer med DS ungefär 20 cm kortare än förväntat med hänsyn till föräldralängder. Trots att barn med DS har relativt normala nivåer av tillväxthormon (STH eller GH) förbättras deras tillväxt vid STH-behandling. Inom avhandlingsarbetet följde vi upp ungdomar med DS, vilka behandlats med STH i tidig barndom. Vi kunde påvisa större huvudomfång samt förbättrad kognitiv och motorisk förmåga, trots avsaknad av effekt på slutlängden. Tillväxthormon har i vuxen ålder effekt både på ämnesomsättning och psykologiskt välbefinnande. Vuxna individer med DS uppvisar flera tecken förenliga med STH-brist. Vi jämförde tio unga vuxna med DS med tio friska kontrollindivider avseende förmågan att insöndra STH. STH-insöndringen hos individerna med DS skiljde sig inte från den hos kontrollerna. Vid samtidig undersökning av kroppssammansättning påvisades en ökad andel kroppsfett hos individerna med DS, resultat i linje med den frekventa förekomsten av övervikt/fetma. Individerna med DS hade en förhöjd glukosproduktion, som tillsammans med ett ökat HOMA-index talar för förekomst av minskad insulinkänslighet både på levernivå och perifert. Brist på sköldkörtelhormon är mycket vanligt vid DS och upp till hälften av vuxna med DS kan ha hypotyreos. Vi studerade 68 barn med DS avseende nivåer av tyroideastimulerande hormon (TSH) vid PKU-provtagning. Vi följde också barnens journalhandlingar från de tio första levnadsåren i syfte att undersöka om den neonatala TSH-nivån kan prediktera framtida underfunktion av sköldkörteln. Resultaten visade att barn med DS har en förhöjd nivå av TSH neonatalt, vilket indikerar en brist på sköldkörtelhormon redan i nyföddhetsperioden, men nivån förutsäger inte utveckling av manifest hypotyreos senare under barndomen.
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Baylis, Pamela J. "Reading in children with Down syndrome." Thesis, University of York, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428046.
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Marttala, J. (Jaana). "First trimester screening and Down syndrome." Doctoral thesis, Oulun yliopisto, 2011. http://urn.fi/urn:isbn:9789514294815.
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Abstract The purpose of this study was to evaluate extended first trimester screening for severe chromosomal disorders and adverse pregnancy outcomes in singleton pregnancies among the general population in Finland. Maternal serum biochemical markers, pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG), and fetal nuchal translucency (NT) thickness were measured during the gestational weeks 8+0–13+6. A computerized risk figure program was used to calculate an individual risk figure for chromosomal disorders. It was investigated whether the screening parameter, PAPP-A, is associated with adverse pregnancy outcomes. The prevalence of Down syndrome (DS) cases in Finland during the years 2002–2006 was 1:364 (N=795). The proportion of women aged 35 years or older increased from 5–10% in the years 1980–1990 to 19.1% during the study period. Most DS cases (61.1%) presented in that age group. The first trimester combined screening for Down syndrome yielded a detection rate (DR) of 81.9% for a 4.3% false positive rate (FPR). The performance was evaluated among 76949 voluntary women during the study period of 01.05.2002–31.12.2008. There were 188 cases of DS. The screening worked better among the older women. The number of invasive procedures needed to detect one case of DS was higher among the younger women. Adding specific algorithms for screening of other chromosomal abnormalities yielded DR of 74.0% for trisomy 18 (T18) and 54.5% for trisomy 13 (T13) with an additional increase of 0.3% FPR. For chromosomal abnormalities other than T18 and T13, the specific algorithms did not improve the screening performance. Low first trimester maternal serum levels of PAPP-A (≤0.30 MoM) were significantly associated with small for gestational age (SGA) newborns and stillbirths (SBs). The combined screening method for DS works well in practice and has been standardized in Finland. In screening for trisomies 18 and 13 a specific algorithm is reasonable. Low first trimester levels of PAPP-A could be used as an independent marker for pregnancies at high risk for SGA babies and SBsTiivistelmä Tutkimuksen tarkoituksena oli arvioida laajennetun ensimmäisen raskauskolmanneksen kromosomipoikkeavuuksien seulonnan toimivuutta yksisikiöisissä raskauksissa suomalaisessa normaaliväestössä. Äidin seerumin biokemialliset merkkiaineet, raskauteen liittyvä valkuaisaine A (PAPP-A) ja raskaushormoni (fβ-hCG) sekä sikiön niskaturvotus mitattiin raskausviikoilla 8+0–13+6. Yksilöllinen riskiluku kromosomipoikkeavuuksille laskettiin käyttäen tietokoneen riskinlaskentaohjelmaa. Seulonnan merkkiaineen, PAPP-A:n, matalien pitoisuuksien yhteyttä epäsuotuisiin raskauden lopputuloksiin tutkittiin. Downin oireyhtymän esiintyvyys Suomessa oli 1:364 (N=795) vuosina 2002–2006. 35-vuotiaiden tai sitä vanhempien naisten osuus oli tutkimusaikana 19.1 %, mikä on huomattavasti suurempi kuin vuosien 1980–1990: 5–10 %. Näiden naisten sikiöiden joukosta löytyi suurin osa Down oireyhtymistä (61.1 %). Ensimmäisen raskauskolmanneksen yhdistelmäseulonnan toimivuutta tutkittiin aikana 01.05.2002–31.12.2008. Tutkimukseen osallistui 76 949 vapaaehtoista naista. Joukossa oli 188 Downin oireyhtymätapausta. Seulonnan herkkyys Downin oireyhtymälle oli 81.9 % ja tarkkuus 4.3 %. Seulonta toimi parhaiten vanhempien naisten joukossa. Niiden kajoavien toimenpiteiden määrä, jotka tarvittiin yhden Down-sikiön löytämiseksi, oli suurempi nuorten naisten joukossa. Tutkimuksessa Downin oireyhtymän algoritmiin lisättiin spesifiset algoritmit trisomioille 18 ja 13, jolloin saavutettiin 74.0 %:n herkkyys trisomialle 18 ja 54.5 %:n herkkyys trisomialle 13. Väärien positiivisten seulontatulosten määrä kasvoi 0.3 %:n verran. Seulonnan toimivuus muiden kromosomipoikkeavuuksien joukossa ei parantunut spesifisten algoritmien avulla. Lisäksi matalan PAPP-A-pitoisuuden yhteys pienipainoisuuten ja kuolleena syntyneisyyteen oli tilastollisesti merkittävä. Tutkimus osoitti, että esimmäisen raskauskolmanneksen yhdistelmäseulonta toimii hyvin käytännössä. Trisomioiden 18 ja 13 seulonnassa spesifisten algoritmien käyttö on järkevää. Matalaa ensimmäisen raskauskolmanneksen PAPP-A-arvoa voitaisiin käyttää itsenäisenä riskimerkkiaineena raskauksille, joissa pienipainoisuuden ja kuolleena syntymisen riski on kohonnut
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Niemimaa, M. (Marko). "First trimester screening for Down syndrome." Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:9514270290.
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Abstract
The aim of the present study was to evaluate the efficacy of the first trimester screening for Down syndrome (DS) in an unselected low-risk Finnish population. The study involved 4,617 women who attended screening between the 8th and 14th weeks of pregnancy in 1998-2000. They gave a blood sample for the measurement of pregnancy associated plasma protein A (PAPP-A) and free beta human chorionic gonadotrophin (β-hCG). Of these women, 3,178 also had an ultrasound examination for the measurement of fetal nuchal translucency (NT). The risk figure for every screened woman was calculated using a computerized risk figure program. The risk 1 in 250 was used as a cut-off. The subgroup of screen positives comprised 5.8% of the study group.
There were 16 DS cases. The combined method (maternal age, NT and the biochemical markers) detected 77% of the affected pregnancies. NT combined with maternal age gave a detection rate of 69%. Serum markers without NT combined with maternal age found 75% of the Down's.
In 49 consecutive singleton in-vitro-fertilization pregnancies, the β-hCG value was more often elevated compared to spontaneous pregnancies, increasing the false positive rate. In 67 twin pregnancies, the serum marker levels were approximately double those in singletons. Smoking reduced PAPP-A by 20% making the smokers more likely to get a positive screening result.
To determine the impact of the screening on the live born incidence of DS, two historical populations were compared. The first group was screened by second trimester serum samples (β-hCG and AFP) and the second group by first trimester ultrasound examination. When detection rates were at the same level, the second trimester screening reduced the number of live born Down's children more effectively.
In conclusion, the first trimester combined method (maternal age, NT, β-hCG and PAPP-A) for Down syndrome screening is efficient in an unselected low risk population. The biochemical screening is not recommended in IVF-pregnancies.
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Gee, Courtney. "Down Syndrome and Self-esteem: the Media's Portrayal of Self-esteem in Characters Who Have Down Syndrome." Thesis, University of North Texas, 2012. https://digital.library.unt.edu/ark:/67531/metadc177198/.
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Representations of people with a developmental disability are virtually not covered in the media. Although there is little coverage of people with developmental disabilities in the media, there are a few entertainment television characters who have Down syndrome and are represented in the media. This study will take a look at the history of how people with disabilities were represented in the media and examine how two television characters with Down syndrome were portrayed on the shows by examining their self-esteem. This study seeks to focus on portrayal of people with Down Syndrome because the physical features that people with Down Syndrome possess are easy to identify. Specifically, the study examines the portrayal of self-esteem in two television characters, Corky Thatcher (Life Goes On) and Becky Faye Jackson (Glee). The researcher will also examine how the portrayal of self-esteem in the two characters is similar or different in people who have Down Syndrome. In the study the researcher found that the representation of the character Corky was different from the character Becky. But both characters tackled issues that affected the Down Syndrome community and it affected their self-esteem. Corky and Becky were different from the interviewees in the way they realized their competencies. Although the interviewees who have Down Syndrome and the television characters used self-evaluation differently to evaluate one's own self-esteem, they all seem to exhibit a positive level of self-esteem.
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Kent, Annie. ""I am not Down syndrome" : a narrative exploration of life and identity in school-leavers with Down syndrome." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8521/.
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Historically, there has been an effort to improve the inclusion of those with ‘disabilities’ including Down syndrome (DS). Societal perceptions of DS have been largely negative and may influence how individuals view their lives. Although there has been literature which has explored other people’s perspectives, there has been less which has asked those with DS to share their stories. The aim of the study was to explore the lived experiences and identity of four school-leavers with DS. A narrative approach was employed to elicit stories whilst participants were being recorded on film. A restorying procedure, a narrative tone and thematic analyses were then used to interpret the narratives. The findings revealed diversity in the way the participants spoke about their lives. All participants experienced factors which would have had a positive contribution on their identity development. However, some experienced other factors which may put them at-risk of foreclosing on their identity development. The implication of identity development for generating pragmatic or ambitious aspirations is discussed. I recommend that future research explores what is currently happening in educational settings to promote identity formation in those with DS and how this might be refined to harness positive outcomes for this group.
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Ashworth, Anna Fiona. "Sleep and cognition in children with Down Syndrome and William's Syndrome." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/10020765/.
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This thesis provides a novel contribution to cognitive and developmental psychology by investigating the relationship between sleep, behaviour and cognition in 41 healthy typically developing (TD) children, 22 children with Down syndrome (OS) and 22 with Williams syndrome (WS). In addition, developmental changes in sleep and cognition, and the importance of sleep for consolidation of new memories were assessed in these groups. Finally, the influence of children's sleep and behaviour on their mothers' sleep and wellbeing were examined. The research used a battery of standardised and novel cognitive tasks, objective measures of sleep, and questionnaires. Sleep problems were syndrome-specific, with poor sleep quality and oxyhaemoglobin desaturation occurring more frequently in OS, suggestive of breathing difficulties during sleep, and long sleep latencies in the WS group. TD children performed well on cognitive tasks of short term memory, working memory and sustained attention compared to children with OS and WS, and their performance generally improved with increasing age, which tended not to be the case for the clinical groups. In the TD group, improved sleep quality and higher, less variable oxyhaemoglobin saturation related to better performance on cognitive tasks and fewer behavioural problems. Few associations between sleep, cognition and behaviour were found in the OS and WS groups. TD children and children with WS showed evidence of sleep-dependent memory consolidation for explicitly learnt material on two tasks. Mothers of children with OS had the poorest sleep and most daytime sleepiness, though not related to children's sleep or daytime behaviour. The findings indicate that sleep problems should be assessed and managed in clinical groups. Educational strategies should be implemented to reinforce sleep-related learning gains. Future research could examine whether sleep-dependent learning occurs in relation to specific aspects of sleep architecture in children with OS and WS, as it does in adults and TD children.
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Landry, Thérèse. "Trisomie 21 : étude de consanguinité et d'apparentement au Saguenay Lac St-Jean /." Thèse, Chicoutimi : Ste-Foy : Université du Québec à Chicoutimi ;. Université Laval, 1997. http://theses.uqac.ca.
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Hess, Brittany A. "Vocabulary Size in Children with Down Syndrome:." Digital Archive @ GSU, 2012. http://digitalarchive.gsu.edu/psych_theses/93.
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Children with Down Syndrome (DS) experience cognitive delays with language being one of the most impaired domains. Exploring the effects of congenital heart defects (CHD), hospitalization, hearing impairment, and parental concern can provide a more precise view of factors affecting language development. Participants were 49 children with DS, 22 to 54 months of age. Expressive and receptive vocabulary size was obtained using a word count with the MacArthur Communication Development Inventory (MCDI). Medical information was obtained from the child’s medical file. Results showed expressive vocabulary was marginally significantly different between children with DS and no CHD, a CHD that did not require surgery, and a CHD that did require surgery, such that children with a CHD requiring surgery had the smallest vocabulary. Children had significantly more health problems when they had a CHD that required surgery. Expressive and receptive vocabularies were significantly smaller for children with hearing impairment.
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Hitzig, Sander L. "Visual filtering in persons with Down syndrome." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33903.
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A forced-choice reaction time (RT) task was used to examine the efficiency of visual filtering (the inhibition of processing of irrelevant stimuli) and the concomitant ability to narrow the focus of the attentional lens in persons with Down syndrome (n = 10) and children of average intelligence (n = 13) matched for mental age (MA) (average MA = approximately 5.7 years). Conditions varied with regard to the presence or absence of distractors and their proximity to a target stimulus, and the presence or absence of a visual window within which the target stimulus was presented. Although the study yielded no significant results due to a lack of power, the mean correct reaction times (RTs) indicate that both the adults with Down syndrome and the typically developing children were less efficient at filtering close distractors as compared to far distractors or no distractors. As well, the results suggest that the presence of the visual window failed to facilitate performance in both groups. Further investigation is warranted to determine the status of visual filtering in persons with Down syndrome relative to their level of functioning at an MA level of approximately 5 years, a period that is critical in the development of attentional processes.
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Barr, Agholme Monica. "Periodontal disease in adolescents with Down syndrome /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3391X/.
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Lomartire, Laura <1982>. "Down Syndrome: Neuropsychological phenotype and mitochondrial DNA." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4552/.
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Introduction. Down Syndrome (DS) is the most known autosomal trisomy, due to the presence in three copies of chromosome 21. Many studies were designed to identify phenotypic and clinical consequences related to the triple gene dosage. However, the general conclusion is a senescent phenotype; in particular, the most features of physiological aging, such as skin and hair changes, vision and hearing impairments, thyroid dysfunction, Alzheimer-like dementia, congenital heart defects, gastrointestinal malformations, immune system changes, appear in DS earlier than in normal age-matched subjects. The only established risk factor for the DS is advanced maternal age, responsible for changes in the meiosis of oocytes, in particular the meiotic nondisjunction of chromosome 21. In this process mitochondria play an important role since mitochondrial dysfunction, due to a variety of extrinsic and intrinsic influences, can profoundly influence the level of ATP generation in oocytes, required for a correct chromosomal segregation. Aim. The aim of this study is to investigate an integrated set of molecular genetic parameters (sequencing of complete mtDNA, heteroplasmy of the mtDNA control region, genotypes of APOE gene) in order to identify a possible association with the early neurocognitive decline observed in DS. Results. MtDNA point mutations do not accumulate with age in our study sample and do not correlate with early neurocognitive decline of DS subjects. It seems that D-loop heteroplasmy is largely not inherited and tends to accumulate somatically. Furthermore, in our study sample no association of cognitive impairment and ApoE genotype is found. Conclusions. Overall, our data cast some doubts on the involvement of these mutations in the decline of cognitive functions observed in DS.
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Abdollahi, Sodabeh. "The socialisation of children with down syndrome." Thesis, University of Sussex, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426207.
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Czerminski, Jan T. "Modeling Down Syndrome Neurodevelopment with Dosage Compensation." eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1037.
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Due to their underlying genetic complexity, chromosomal disorders such as Down syndrome (DS), which is caused by trisomy 21, have long been understudied and continue to lack effective treatments. With over 200 genes on the extra chromosome, even the specific cell pathologies and pathways impacted in DS are not known, and it has not been considered a viable target for the burgeoning field of gene therapy. Recently, our lab demonstrated that the natural mechanism of dosage compensation can be harnessed to silence the trisomic chromosome in pluripotent cells. Using an inducible XIST transgene allows us to study the effects of trisomy in a tightly controlled system by comparing the same cells with either two or three active copies of chromosome 21. In addition, it raises the prospect that insertion of a single gene into a trisomic chromosome could potentially be developed in the future for “chromosome therapy”.
This thesis aims to utilize this inducible system for dosage compensation to study the neurodevelopmental effects of trisomy 21 in vitro, and to answer basic epigenetic questions critical to the viability of chromosome silencing as a therapeutic approach. Foremost, for XIST to have any prospect as a therapeutic, and to strengthen its experimental utility, it must be able to initiate chromosome silencing beyond its natural context of pluripotency. Here I demonstrate that, contrary to the current literature, XIST is capable of initiating chromosome silencing in differentiated cells and producing fully dosage compensated DS neurons. Additionally, I show that silencing of the trisomic chromosome in neural stem cells enhances their terminal differentiation to neurons, and transcriptome analysis provides evidence of a specific pathway involved. Separate experiments utilize novel three-dimensional organoid technology and transcriptome analysis to model DS neurodevelopment in relation to isogenic euploid cells. Overall, this work demonstrates that dosage compensation provides a powerful experimental tool to examine early DS neurodevelopment, and establishes that XIST function does not require pluripotency, thereby overcoming a perceived obstacle to the potential of XIST as a therapeutic strategy for trisomy.
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Keller-Bell, Yolanda D. "Linguistic processing in chidren with Down Syndrome /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488203552778717.
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Fontanesi, Elisa <1984>. "Epigenetic signature in persons with Down Syndrome." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6821/.
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Persons affected by Down Syndrome show a heterogeneous phenotype that includes developmental defects and cognitive and haematological disorders. Premature accelerated aging and the consequent development of age associated diseases like Alzheimer Disease (AD) seem to be the cause of higher mortality late in life of DS persons.
Down Syndrome is caused by the complete or partial trisomy of chromosome 21, but it is not clear if the molecular alterations of the disease are triggered by the specific functions of a limited number of genes on chromosome 21 or by the disruption of genetic homeostasis due the presence of a trisomic chromosome. As epigenomic studies can help to shed light on this issue, here we used the Infinium HumanMethilation450 BeadChip to analyse blood DNA methylation patterns of 29 persons affected by Down syndrome (DSP), using their healthy siblings (DSS) and mothers (DSM) as controls. In this way we obtained a family-based model that allowed us to monitor possible confounding effects on DNA methylation patterns deriving from genetic and environmental factors.
We showed that defects in DNA methylation map in genes involved in developmental, neurological and haematological pathways. These genes are enriched on chromosome 21 but localize also in the rest of the genome, suggesting that the trisomy of specific genes on chromosome 21 induces a cascade of events that engages many genes on other chromosomes and results in a global alteration of genomic function. We also analysed the methylation status of three target regions localized at the promoter (Ribo) and at the 5’ sequences of 18S and 28S regions of the rDNA, identifying differently methylated CpG sites.
In conclusion, we identified an epigenetic signature of Down Syndrome in blood cells that sustains a link between developmental defects and disease phenotype, including segmental premature aging.
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Turcot, Valérie. "Génétique et épigénétique du syndrome métabolique." Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/29169/29169.pdf.
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Koenig, Katherine A. "PERFORMANCE ON ELEMENTARY COGNITIVE TASKS IN DOWN SYNDROME AND FRAGILE X SYNDROME." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1187138851.
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Leung, Kwong-ki. "Hearing loss in school children with down syndrome." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B3798679X.
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Breslin, Jennifer H. "Sleep Disturbance, Cognition, and Behavior in Down Syndrome." Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/201494.
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Children and adolescents with Down Syndrome (DS) have a high incidence of sleep problems, including Obstructive Sleep Apnea Syndrome (OSAS). They are also likely to have deficits in neuropsychological tasks tapping prefrontal function and hippocampal function. There has recent revival of literature suggesting an active role for sleep in memory consolidation and problem-solving in both children and adults. Furthermore, given the cognitive and behavioral sequellae of OSAS in typically developing children it is logical to test if the hypoxemia and increased sleep fragmentation, the two major pathophysiological mechanisms of OSAS, seen in children with DS and OSAS may exacerbate learning or behavior disorders.Forty children with DS aged 7-18 were administered the Arizona Cognitive Test Battery (ACTB) for DS (Edgin et al., 2010), and in-home ambulatory polysomnography. Their parents were asked to complete several questionnaires assessing their child's sleep and behavior. Seventy-seven percent (n = 40) of our sample met criteria for pediatric sleep apnea (AHI>1.5), and the mean apnea hypoppnea index (AHI) was 8.4 events per hour. Our sample had a mean arousal index of 10.3, a respiratory arousal index of 3.2, and a SaO2 nadir of 86.9%. Over 70% of our sample had a SaO2 nadir below 90%. We examined the relationship between OSAS severity and cognitive and behavioral outcomes. We found that children with DS with a lower apnea hypopnea index (AHI) attained a greater number of stages on the CANTAB PAL task compared to chronologically age-matched children with higher AHI, and the variance in performance was partially explained by sleep fragmentation (i.e., the arousal index) and experimenter-rated "attention" but not hypoxemia. In addition, we also found that the low apnea group showed a trend toward outperforming the high apnea group on the KBIT-II Verbal IQ scale and DAS-2 Pattern Construction subtest.These findings have important clinical implications. First, these results suggest that early screening for OSAS in DS is important, as OSAS severity seems to explain some of the variance in cognitive functioning. Second, these findings suggest that an early intervention for OSAS might be warranted.
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Leung, Kwong-ki, and 梁廣基. "Hearing loss in school children with down syndrome." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B3798679X.
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Hamburg, Sarah. "Resting-state EEG in adults with Down syndrome." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10048443/.
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Individuals with Down syndrome (DS) show a high degree of inter-subject variability in cognitive ability. Elucidating factors associated with variability in cognitive function can inform us about intellectual disability severity and potentially provide biomarkers of ability for clinical trials targeting cognition in individuals with DS (including trials aimed at preventing cognitive decline). Resting-state electroencephalography (EEG) can be used to obtain information about neural factors that may be underlying variability in cognitive function. This thesis uses eyes-open (EO; n=48) and eyes-closed (EC; n=36) resting-state EEG paradigms in adults with DS free from detectable signs of cognitive decline or dementia to identify EEG measures associated with general cognitive ability, and to investigate age-related changes in EEG activity in this population. Oscillations of interest were then modelled using dynamic causal modelling (DCM) to identify potential neurophysiological mechanisms underlying individual differences in general cognitive ability. Initial analysis suggested that individuals with DS have an overall slower EC EEG spectrum (and particularly strong differences in alpha activity) compared to typically-developing age-matched control subjects (open source control dataset used). Within individuals with DS, increasing age was associated with EEG changes in both paradigms. When controlling for age, higher general cognitive ability was associated with higher delta power (EO only), higher theta power (EC only), and higher alpha peak amplitude (EC only). Modelling the theta-alpha network identified “intrinsic self-inhibition” as the most important neurophysiological parameter underlying the relationship between theta-alpha activity and general cognitive ability in this sample. Further analysis revealed a strong inverse relationship between occipital intrinsic self-inhibition and general cognitive ability. Findings of this thesis enhance our understanding of neural factors associated with individual differences in general cognitive ability in adults with DS, provide a potential biomarker of ability for clinical trials, and indicate potential targets for cognitive enhancement in this population. The finding that increased inhibition may be associated with cognitive impairment in this population is in keeping with animal model literature and warrants further investigation.
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Ruparelia, A. H. "Axonal transport in mouse models of Down syndrome." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1395925/.
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Down syndrome (DS) is a complex condition resulting in the most common genetic form of intellectual disability. Trisomy of chromosome 21 in humans (Hsa21) causes DS, likely due to overexpression of some of the 500 genes on this chromosome. People with DS are more susceptible to early-onset Alzheimer Disease (AD), and the histopathological and endocytic perturbations that characterise AD are present at an earlier age in people with DS than the general population with AD. They also display aberrant dendritic spine morphology, which is associated with learning and memory deficits. The Ts65Dn mouse model of DS carries 122 genes on its translocated chromosome and recapitulates these DS-associated phenotypes. Neurodegeneration in these mice may be caused by impaired retrograde axonal transport of essential neurotrophic factors. The triplication of the Hsa21-encoded amyloid precursor protein (APP) gene is proposed to cause enlarged early endosomes and a perturbed endocytic pathway that subsequently leads to axonal transport deficits. However the genetic contribution of other Hsa21 genes to axonal transport deficits remains unknown. The research in this thesis aimed to recapitulate the axonal transport, endocytic and dendritic phenotypes in Ts65Dn mice, and to elucidate the contribution of Hsa21 genes, to the pathogenesis of these deleterious phenotypes. Live-cell imaging of quantum dot-labelled brain-derived neurotrophic factor (BDNF) in Ts65Dn hippocampal neurons revealed impaired BDNF axonal transport. Neurons from these mice also displayed a greater number of enlarged early endosomes and reduced dendritic surface area and volume. The Ts1Rhr mouse model encodes 31 duplicated genes that are orthologous to the human DS critical region (DSCR), and has disomic APP expression levels. Ts1Rhr hippocampal neurons also revealed impaired BDNF axonal transport, however endosomal and dendritic morphology was spared. This suggests that in addition to APP, one or more genes orthologous to the human DSCR may be necessary for axonal transport deficits but not for the enlarged early endosome phenotype or dendritic abnormalities. Other putative mechanisms, such as perturbed cytoskeleton and motor protein function, may additionally exacerbate impaired axonal transport of neurotrophins.
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Passarini, John Richard. "Motor skill development of children with Down syndrome." Thesis, Boston University, 2001. https://hdl.handle.net/2144/33533.
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Thesis (Ed.D.)--Boston UniversityThis study was conducted for the purpose of determining the effectiveness of a home-based motor activity program on children with Down syndrome 6 to 10 years of age. Twenty-six children with Down syndrome and their respective families participated in this twelve-week study. The Circles Of Learning instructional program was created, and fieldtested. The Test of Gross Motor Development (TGMD) provided base-line data for measures of progress in fundamental motor skills. Parents were instructed in how to teach locomotor skills and object control skills as measured by the TGMD. The methods required seven distinct activities: the creation of an instructional manual; recruitment and instruction of project assistants; identification and recruitment of the subjects and their families; pretest and posttest assessment of subjects; instructional training of parents; and the twelve week intervention. The comparison (C) group received the Handwriting Without Tears program during the 12 week intervention period. When compared with the (C) group, all subjects in the experimental (E) group showed statistically significant improvement in the acquisition of fundamental motor skills as measured by the TGMD. Four (E) group subjects improved to the "average" range for typically developing children. Ten of the 11 (E) group subjects continued to improved their demonstrated fundamental motor skill performance two weeks after the intervention, while one subject maintained his gains. Weekly parent comments during the intervention gave testimony to the effectiveness of the intervention supporting primary and secondary gains for the subjects. Parents reported that interactions between family members and the subjects increased and fundamental motor skills improved during spontaneous unstructured play and during organized activities at home and at school. This study challenges the previous research suggesting children with Down syndrome need specialized motor development programs. Furthermore, this study demonstrates that the acquisition of fundamental motor skills for children with Down syndrome can be accelerated.
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Sutter, Kimberlee Ann, and Kimberlee Ann Sutter. "Siblings of Children with Down Syndrome: Voices Hear." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/622942.
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The purpose of this study was to explore the meanings of the relationship of school-age siblings of brothers or sisters with Down syndrome in order to gain a greater understanding of the lived experience from the view point of the school-age sibling. Sibling spend more time together than any other family subsystem and siblings actively shape one another’s lives and prepare each other for future experiences. With children with Down syndrome living into their 60’s, the question regarding the sibling relationship is becoming an important focus due to the possible demands on the sibling to care for the individual with Down syndrome. Therefore, it is important to understand the sibling relationship at an early stage of their lives and what the lived experience is for the sibling. The framework for this study was developed from the author’s worldview of reciprocal interaction and epistemology of constructionism. The influences of the environment and other individuals on the sibling supported the use of the theoretical framework of Bronfenbrenner’s Bioecological System Theory. The notion that children are continually evolving holistic individuals who are developing through task achievements and, with the influences of family members, supported the use of Erikson’s psychosocial developmental theory. These two theories were combined to frame this study. Interpretive phenomenology was used as the method of research in this study. The sample consisted of seven school-age siblings, between the ages of eight to eleven years of age, of children with Down syndrome. Data analysis involved the use of the hermeneutic circle. From the analysis emerged seven themes: always together, tolerance, intense love, responsibility for my brother or sister, things will change when child with Down syndrome gets better, no difference from other families, and impact on other relationships. Two themes provided new information about the meaning of the lived experience of being a sibling, always together and things will change when child with Down syndrome gets better. The knowledge gained from this study will allow us to begin to hear sibling’s voices so that we can see what we need to do in the future to help with support and future research.
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Roy, Anindita. "The fetal pathogenesis of Down syndrome-associated leukaemias." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/12670.
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Children with Down syndrome (DS; trisomy 21) have markedly increased susceptibility to acute megakaryoblastic leukaemia (AMKL) and acute lymphoblastic leukaemia (ALL) which, at least for AMKL, have their origin in fetal life. My project aims to identify and characterise abnormalities in haematopoiesis in human fetal DS in order to understand how T21 leads to the increase in leukaemia susceptibility in DS. Since both AMKL and ALL are increased in DS, I first investigated the hypothesis that T21 perturbs the earliest multipotent progenitor (MPP) and/or haematopoietic stem cell (HSC) compartment and found that the HSC compartment is always expanded in DS FL compared to normal FL and that this had markedly increased CD7 expression. The DS FL HSC/ MPP compartment was also functionally abnormal with increased clonogenicity and megakaryocyte-erythroid potential and a distinct gene expression signature. Since no mutations in GATA1 or JAK2 were detected, my data support a direct role for T21 in the abnormalities of HSC number and function. To investigate whether differences in the FL microenvironment contribute to the abnormal HSC/myeloid progenitor compartment in DS FL, I analysed HSC/progenitors in fetal BM in DS by flow cytometry and in vitro assays. Although both MEP and myeloid progenitor/HSC clonogenicity and self-renewal were increased, this was less marked than in DS FL, indicating the effects of T21 are not limited to FL haematopoiesis but also supporting a role for the HSC/progenitor microenvironment. To investigate the role of T21 in initiation of ALL, I tested the hypothesis that T21 perturbs lymphopoiesis by characterising the lymphoid progenitor population in FL and fetal BM. I found a marked reduction in B progenitors, particularly at the committed B progenitor (CBP) level in DS FL and fetal BM which was confirmed by in vitro lymphoid cultures and gene expression patterns. These studies have characterised normal human fetal haematopoiesis for the first time and show that HSC, MPP and LMPP populations with full lymphoid differentiation are present in FL indicating that FL, and not just BM, is an active site of lymphopoiesis during fetal life which has implications for the origin of infant ALL. I have also demonstrated that T21 perturbs haematopoiesis at the HSC level, leading both to myeloid progenitor expansion and a block to B-cell differentiation. These findings increase our understanding of the role of T21 in initiating and maintaining leukaemia-initiating cells and suggest a tractable model for investigating the effects of aneuploidy on cell growth and differentiation.
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Kirchner, Rebecca. "Symptoms of Autism Spectrum Disorder in Individuals with Down Syndrome or Williams Syndrome." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1497867112162048.
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Rahman, Amira. "Numerical abilities in children with Fragile X syndrome, Down syndrome and typically developing children : a cross syndrome perspective." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=83143.
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In the present study, performance on a range of mathematical reasoning and number processing tasks was assessed across two syndrome groups for which numerical ability is under-researched: Fragile X syndrome and Down syndrome. Given the paucity of current research, it was unknown whether all aspects of arithmetic and number processing would be globally affected across groups or whether there would be syndrome specific proficiencies and deficiencies. Statistical analysis revealed that males with fragile X syndrome performed significantly worse on all tasks even when performance was compared to typically developing children of a similar developmental level. However, when performance was compared to children with Down syndrome differing profiles emerged, with greater weaknesses by the fragile X syndrome males on specific tasks requiring mental arithmetic and basic numeracy skills. The importance of using syndrome specific information in the assessment of math disabilities and the design of early educational interventions are discussed.
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Dessay, Sabine. "Le syndrome FG : recherche des gènes impliqués." Tours, 2001. http://www.theses.fr/2001TOUR3306.
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Le syndrome FG est une génopathie rare liée au chromosome X, qui se caractérise par l'association d'un retard mental, d'une dysmorphie faciale (front haut et large, télécanthus, épi frontal), d'une hypotonie congénitale, d'une constipation et d'anomalies anales. Cependant il existe une hétérogénéité phénotypique importante. Une première analyse de liaison effectuée sur 10 familles avait permis de localiser un premier gène impliqué dans la région Xq12-q21. 31 et de démontrer une hétérogénéité génétique. Cette hétérogénéité fut confirmée par l'étude d'une inversion paracentrique du chromosome X co-ségrégeant avec un syndrome FG dans une famille. Une analyse par hybridation in situ a permis de localiser les points de cassure entre les marqueurs DXS1194 et AR en Xq11, et entre les gènes GCP et G6PD en Xq28. Dans un premier temps, l'analyse de 13 nouvelles familles, comparée aux premiers résultats, nous a permis de confirmer l'hétérogénéité génétique avec la description d'au moins 4 loci FG différents impliqués sur le chromosome X : FGS1 (Xq13. 2-q21. 1), FGS2 (Xq11 ou Xq28), FGS3 (Xp22. 3) et un quatrième en Xq22. De plus nous avons exclu quatre gènes candidats par séquençage de la séquence codante chez des patients FG : le gène IGBP1 en Xq21, et les gènes PRKX, VCXA et ARHGAP6 en Xp22. 3. Dans un second temps, l'étude moléculaire de l'inversion nous a permis d'identifier qu'une microduplication est associée en Xq28 à l'inversion. Cette duplication inclut une partie du gène TKR et la totalité des gènes EMD et FLN-A. L'expression en double dose des gènes FLN-A et EMD , chez nos patients porteurs de l'inversion, nous amène à discuter de leur implication dans la physiopathologie de ce syndrome. Notre étude confirme que le syndrome FG est une entité clinique complexe et génétiquement hétérogène.
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Hill, Elizabeth Anne. "Prevalence and treatment of obstructive sleep apnoea/hypopnoea syndrome in adults with Down syndrome." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22917.
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Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is characterised by repeated cycles of upper airway obstruction during sleep, leading to diurnal symptoms. Individuals with Down syndrome (DS) are predisposed to this as the DS phenotype overlaps with OSAHS risk factors. Around 2-4% of the general adult population and 55% of children with DS have OSAHS but, to date, no large-scale study has assessed OSAHS prevalence or efficacy of treatment in DS adults. This study aimed to: 1) Systematically assess subjective and objective OSAHS prevalence; 2) Assess the effectiveness of continuous positive airway pressure (CPAP) in an adult DS population. Standard questionnaires including pictorial Epworth Sleepiness Scale (pESS) and Developmental Behaviour Checklist for Adults (DBC-A) were sent to UK adults aged ≥16yr with DS and their caregivers. All questionnaire responders were invited to undergo home polygraphy. Symptomatic adults with DS with ≥10 apnoeas/hypopnoeas per hour in bed (AH) on home polygraphy were invited to participate in a prospective randomised controlled trial (RCT) of CPAP v. lifestyle advice, with review at 1, 3, 6 and 12m. Participants in the lifestyle arm were offered CPAP at 1m. Standard measurements of sleepiness, behaviour, cognitive function and general health were undertaken. Standard statistical analyses were conducted, with significance set at p < 0.001 to control for multiple testing. Of 5270 questionnaires sent, 1105 responses were valid (21%). Responders (55% males) were overweight/obese young adults: mean BMI 29.0±6.8kg/m2; mean age 28±9 years. Women had a higher BMI (p < 0.0001), but collar size was greater in men (p < 0.0001). Mean pESS scores were broadly within the normal range (7±5/24). No significant gender differences in OSAHS symptoms were noted. Individuals with probable OSAHS had higher pESS and DBC-A scores, and significantly more symptoms of OSAHS. Subjective OSAHS prevalence was estimated at 35%. Of the 790 individuals invited, 149 underwent polygraphy, with 134 valid studies obtained: mean AH 21.8(10.9-42.7); mean oximetry desaturation index (ODI) 6.6(2.3-20.0). No significant gender differences were observed. Forty-two percent of participants met standard clinical diagnostic criteria for OSAHS. Twenty-eight eligible adults with DS (19 male) were randomised: age 28±9yr; BMI 31.5±7.9kg/m2; AH 28.6(14.8-47.9); ODI 7.3(1.8-21.9); pESS 11±6/24. Groups did not differ significantly at baseline. By 12m, 4 participants had withdrawn (all remaining participants on CPAP). The pESS (p=0.001), DBC-A Disruptive (p < 0.0001) and Kaufmann Brief Intelligence Test verbal subscale (p=0.001) scores improved significantly. This first large study of OSAHS prevalence in the adult DS population estimates a prevalence of 35-42% - around 10 times higher than in the general adult population. Sustained, significant improvements in sleepiness, cognitive function and behavioural/emotional outcomes with CPAP use over a 12m period were demonstrated during this first RCT of CPAP in adults with DS. A larger trial of CPAP in this population is warranted.
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Christodoulou, Christa. "Cypriot Greek Down syndrome : their grammar and its interfaces." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/37171.
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This dissertation investigates the linguistic performance of 16 Cypriot Greek individuals diagnosed with Down Syndrome (henceforth, CGDS), aged 19;0 to 45;11, and compares their performance to 17 Cypriot Greek Typically Developing Children (hereafter, CGTDC), aged 7;0 to 8;11. Three hypotheses were tested to determine whether the differences between the two groups, as well as the Grammar of Cypriot Greek adults with typical development (henceforth, CGTD) were: (i) syntactically, (ii) morphologically, or (iii) phonetically and phonologically conditioned.
When consulting previous research, a number of shortcomings were observed. Therefore, an innovative methodology was employed to address these issues. Contrary to previous research, which argues for an overall inflectional impairment (either syntactically or morphologically conditioned), this dissertation establishes that the vast majority of differences between the two groups are phonetically conditioned. These differences are due to the distinct physiology of the articulation apparatus in CGDS. Furthermore, a small number of phonologically conditioned differences were either due to (i) the phonological environment (syllable structure and word-position) or (ii) phonological feature underspecification. However, there is also a very small residue of differences that are morphologically conditioned. When a produced feature value does not match the target, CGDS and CGTDC exhibit the same three strategies: (i) use of an alternative feature value (as the default) to the targeted one, (ii) affix drop and (iii) full-word omission.
I propose a unified analysis, according to which the morphological differences between CGDS, CGTDC and CGTD are due to a failure of Blocking. The competition between a phonetic exponent that includes (i) all feature values resulting from the syntactic derivation, and (ii) a subset of the features, but no contrasting features, fails to be resolved in favour of the most specified form. I further propose that this may be extended to phonological features. Finally, I propose that full-word and phoneme omissions suggest a problem with vocabulary or sound insertion, which may be rooted in phonological and verbal short-term memory limitations.
In sum, I argue that the adult CGDS Grammar is not an impaired version of the adult CGTD Grammar.
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Boyd, Lee-Ann Michelle. "Selective attention and distractibility in children with Down syndrome." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61282.
Full textAbstract:
The goal of this study was to examine selective attention and distractibility within the visual modality in children with Down syndrome as compared to children of normal intelligence matched for mental age. Selective attention was defined as the children's abilities to identify and respond to a target stimulus on a forced choice reaction time task. Distractibility was considered to be the extent to which the children's performances on the task were interfered with by extraneous stimuli in the visual field. Conditions on the task varied with regard to the presence or absence and location (close and far) of distracting stimuli and the presence or absence and size (small, medium and large) of boundary cues. Participants included 10 children with Down syndrome and 10 children of normal intelligence matched for mental age. The primary finding of this study was that the performance of children with Down syndrome was more adversely affected by the presence of distractors than that of the children of normal intelligence. This finding indicates that children with Down syndrome suffer from selective attention deficits and increased distractibility. The selective attention of children with Down syndrome is characterized as distractor-controlled as a result of a defective attentional (zoom) lens that "wanders" in visual space.
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Catuara, Solarz Silvina 1986. "Neuroplasticity-targeted therapy for Down syndrome: a translational approach." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/523544.
Full textAbstract:
This Thesis aims at addressing the therapeutic potential of a neuroplasticity-targeted treatment for intellectual disability (ID) in Down syndrome (DS). The therapy consisted of the administration of the green tea catechin Epigallocatechin-3-gallate (EGCG), which is a natural modulator of Hsa21 candidate genes Dyrk1A and APP, in combination with cognitive stimulation. The assessment of the therapeutic efficacy of this intervention was performed using a translational approach, including preclinical studies with a mouse model of DS and clinical trials with humans with DS.
In this work we show for the first time that this combined therapy significantly ameliorates cognitive deficits in mice and young adults with DS, by modifying brain neuronal networks structure and function.Esta Tesis tiene como objetivo examinar el potencial terapéutico de una intervención orientada a mejorar la neuroplasticidad cerebral, propuesta para mitigar la discapacidad intelectual (DI) en el síndrome de Down (SD). La terapia consistió en la administración de la catequina del té verde, Epigalocatequina-3-galato (EGCG), que es un modulador natural de dos genes candidatos que se encuentran en Hsa21, Dyrk1A y APP, en combinación con estimulación cognitiva. La evaluación de la eficacia terapéutica de esta intervención se realizó utilizando un enfoque de la translacional, incluyendo estudios preclínicos con un modelo de ratón de SD y ensayos clínicos con adultos jóvenes con SD. Este trabajo demuestra por primera vez que esta terapia combinada atenúa significativamente los déficits cognitivos en ratones y adultos jóvenes con SD, mediante la modificación de la estructura y función de redes neuronales en el cerebro.
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Ho, Siu-lai Daphne. "Phonological deficits in Cantonese-speaking children with Down Syndrome." Click to view the E-thesis via HKUTO, 1997. http://sunzi.lib.hku.hk/hkuto/record/B36209442.
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Thesis (B.Sc)--University of Hong Kong, 1997."A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, April 30, 1997." Also available in print.
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Lloyd, Robyn School of Optometry & Visual Science UNSW. "Achromatic and chromatic VEPs in adults with down syndrome." Awarded by:University of New South Wales. School of Optometry and Visual Science, 2005. http://handle.unsw.edu.au/1959.4/23957.
Full textAbstract:
Previous studies have found that spatial processing in children and adults with Down syndrome is different in comparison to the normal population. Some previous studies have also found that there is a high prevalence of colour vision deficiencies in people with Down syndrome. The aim of the present study was to use an objective test, the transient visual evoked potential (VEP), to assess achromatic and chromatic visual processing in adults with Down syndrome. Achromatic VEPs were recorded in response to black-white stimuli presented in patternreversal mode. Chromatic VEPs were recorded in response to two types of colour pattern, presented in pattern onset-offset mode. The two colour types were intended to preferentially stimulate the two principal chromatic pathways of the visual system, the ???redgreen??? and ???blue-yellow??? colour-opponent pathways. These stimuli are here termed the ???LM??? and ???S-(L+M) stimuli, respectively, reflecting the cone types that input to the pathways they are intended to stimulate. Each subject also completed two subjective colour vision tests, the Colour Vision Test Made Easy (CVTME) and the City University Colour Vision Test (CUT). Morphology of the achromatic and chromatic VEPs was found to differ between the group with Down syndrome and an age-matched control group. The latency of the P100 component of the achromatic VEP was found to be significantly later in the group with Down syndrome compared to the control group (the N75 latency was earlier in the group with Down syndrome, but not significantly so). The group-averaged peak-to-peak amplitude of the achromatic VEP was significantly lower in the group with Down syndrome compared to the control group. The major positive component of the VEP in response to the L-M stimulus was of significantly longer latency compared to that of the control group. The major negative component and the peak-to-peak amplitude of this response were not significantly different between the groups. For the response to S-(L+M) stimuli, the latency of the major negativity was significantly earlier in the group with Down syndrome and the major positivity was later, but not significantly so. Amplitude of this response was significantly higher in adults with Down syndrome compared to the control group. Most subjects in both groups passed both the CVTME and CUT. Our findings indicate that chromatic VEPs are abnormal in Down syndrome, and this may reflect abnormal processing of chromatic stimuli in this population. Alternatively, these abnormalities may arise due to abnormal cortical morphology, which may occur with normal or abnormal processing of chromatic signals. These findings further indicate that abnormality of chromatic VEPs may be expected in Down syndrome, and is not necessarily indicative of pathology or other abnormal function that is unrelated to the syndrome.
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Newman, Mary Catherine 1949. "Implicit and explicit memory in individuals with Down syndrome." Thesis, The University of Arizona, 1992. http://hdl.handle.net/10150/278164.
Full textAbstract:
A growing body of literature focuses on comparisons between developmental disabilities of diverse etiologies including Down syndrome (DS). Earlier research emphasized the limitations of this population, and frequently subjects with DS did not compare favorably with control groups. The current investigation examined the implicit and explicit memory skills of individuals with Down syndrome, other developmental disabilities, and MA-matched nonhandicapped children while controlling for confounding variables. In contrast to many previous studies, it was determined that under controlled conditions, free recall and recognition memory of children with DS are equivalent to that of NDS and NH groups. And performance on a pursuit rotor task was also comparable between groups. However, priming of subjects with DS was inferior to controls, a deficit similar to that previously identified in patients with Alzheimer's disease. In addition, the DS group was mildly impaired in both word fluency and attention.