Genomic rearrangements, particularly deletions and duplications, are known to cause many genetic disorders. The chromosome 7q11.23 region in humans is prone to recurrent chromosomal rearrangement, due to the presence of low copy repeats that promote non-allelic homologous recombination. The most well characterized rearrangement of 7q11.23 is a hemizygous 1.5 million base pair (Mb) deletion spanning more than 25 genes. This deletion causes Williams-Beuren Syndrome (WBS; OMIM 194050), a multisystem developmental disorder with distinctive physical and behavioural features. Other rearrangements of the region lead to phenotypes distinct from that of WBS. Here we describe the first individual identified with duplication of the same 1.5 Mb region, resulting in severe impairment of expressive language, in striking contrast to people with WBS who have relatively well preserved language skills. We also describe the identification of a new gene for a severe form of childhood epilepsy through the analysis of individuals with deletions on chromosome 7 that extend beyond the boundaries typical for WBS. This gene, MAGI2, is part of the large protein scaffold at the post-synaptic membrane and provides a new avenue of research into both the molecular basis of infantile spasms and the development of effective therapies. Individuals with smaller than typical deletions of 7q11.23 have delineated a minimal critical region for WBS and have implicated two members of the TFII-I transcription factor family. To better understand the contribution of these genes to WBS, I have generated animal models with these genes deleted singly and in combination. Disruption of the first gene, Gtf2ird1, resulted in phenotypes reminiscent of WBS including alterations in social behaviour, natural fear response and anxiety. An alteration in serotonin function was identified in the frontal cortex and may be linked to these behavioural phenotypes. Together with a model for the second gene, Gtf2i, and the double deletion model that was generated using Cre-loxP technology, these resources will permit the study of the individual and additive effects of hemizygosity for Gtf2i and Gtf2ird1 and will greatly expand our understanding of the role the TFII-I gene family in WBS.

Submitted by admin tede (tede@pucgoias.edu.br) on 2016-09-13T13:52:57Z No. of bitstreams: 1 MARINA MACHADO SANTOS.pdf: 3084828 bytes, checksum: 7da6c5d67d268a88f71826629557e0c5 (MD5) / Made available in DSpace on 2016-09-13T13:52:58Z (GMT). No. of bitstreams: 1 MARINA MACHADO SANTOS.pdf: 3084828 bytes, checksum: 7da6c5d67d268a88f71826629557e0c5 (MD5) Previous issue date: 2016-05-16 / Chromosomal abnormalities cause specific and complex phenotypes due to imbalance in the normal dosage of genes located in a specific chromosomal segment. They account for 60% or even more of all the identifiable genetic syndromes. Williams-Beuren syndrome (WBS) is related to a group of multiple defects and intellectual disabilities, described independently by Williams et al. (1961) and Beuren et al. (1962). The WBS is a genetic disease characterized by a microdeletion of the 7q11.23 region, which delay the physical and intellectual development and it is associated with congenital cardiac abnormalities, facial dimorphism, mental retardation and occasionally infantile hypercalcemia.The existing phenotypic variation in this syndrome hinders clinical diagnosis.Through the development of new cytomolecular technologies and the increased number of studies regarding the clinical features of this syndrome, seeks a better understanding of the genotype-phenotype correlation in WBS. The present study reports some of these techniques used for the diagnosis of WBS, such as Karyotype, MLPA, PCR, with emphasis on FISH and CMA. Additionally, we described four patients who were referred to LaGene/SES and NPR/PUC by the public health service. Three of them had clinical suggestion of WBS and the fourth patient of ID. The confirmation was unsuccessful regarding the diagnostic through techniques of conventional cytogenetics for all of the patinets. FISH technique was useful in the diagnostic investigation of a patient while CMA was used to study the other 3 cases. Chromosomal microarray analysis detected long stretches of homozygosity of uncertain clinical significance at the Xq11.1q13.1 region and a microduplication at the 7q11.23 region, the latter is defined as a critical region of WBS. The study of genotype-phenotype correlation in WBS has been established for some genes detected by CMA. But other genes did not show a strong relation to the syndrome, thus requiring further investigation. / As anomalias cromossômicas causam fenótipos específicos e complexos resultantes de desequilíbrios na dose normal de genes localizados em um segmento cromossômico específico, sendo responsáveis por 60 % ou mais das síndromes genéticas identificáveis. A Síndrome de Williams-Beuren (SWB) caracteriza-se por anomalias múltiplas e deficiência intelectual, descrita independentemente por Williams et al. (1961) e por Beuren et al. (1962). A SWB consiste em uma doença genética causada pela microdeleção em 7q11.23, que ocasiona o atraso no desenvolvimento físico e intelectual associado com alterações cardíacas congênitas, dimorfismos faciais, retardo mental e ocasionalmente hipercalcemia infantil. A variação fenotípica existente nesta síndrome dificulta o seu diagnóstico clínico. Com o desenvolvimento de novas tecnologias citomoleculares e o aumento de estudos voltados para o conhecimento das características clínicas desta síndrome, busca-se explicar melhor a correlação genótipo-fenótipo na SWB. O presente estudo relata algumas técnicas utilizadas para o diagnóstico da SWB, como Cariótipo, MLPA e PCR, dando ênfase em FISH e CMA. Adicionalmente, são descritos quatro pacientes encaminhados ao LaGene/SES e NPR/PUC pelo serviço público de saúde, onde três destes pacientes apresentavam hipótese diagnóstica para a SWB e um paciente para a DI. Para os quatro pacientes não houve êxito no diagnóstico pela citogenética convencional. A técnica de FISH foi útil na elucidação diagnóstica para um paciente, enquanto que a CMA foi utilizada no estudo dos outros 3 casos. A análise cromossômica por microarranjo detectou longos trechos contínuos de homozigose de significado clínico incerto em Xq11.1q13.1 e um caso de microduplicação na região 7q11.23, que é definida como região crítica da SWB. O estudo da correlação genótipo-fenótipo na Síndrome de Williams-Beuren foi estabelecido para alguns dos genes detectados pelo CMA. Entretanto outros genes detectados não tiveram sua relação estabelecida, necessitando assim de estudos posteriores.

The complicated problem of efficient stimulation of elastic fiber production in already developed human tissues has not yet been solved. The present study introduces sodium ascorbate (SA) as a stimulator of elastogenesis in cultures of different cell types including fibroblasts isolated from patients with elastopathy genetic diseases. We then elucidated mechanisms of elastogenic action of SA. SA exercises its net elastogenic effect only after being actively transported into the cell interior through two separate mechanisms. These are the “fast effect,” which reflects the greater stability of intracellular tropoelastin, and the “late effect,” which reflects the true enhancement of the elastin gene expression occurring after SA-induced activation of c-src tyrosine kinase and the consecutive phosphorylation of IGF-1 receptor, which triggers the downstream signals leading to activation of the elastin gene expression. In conclusion, for the first time we have established that SA is a potent stimulator of elastic fiber production.

The complicated problem of efficient stimulation of elastic fiber production in already developed human tissues has not yet been solved. The present study introduces sodium ascorbate (SA) as a stimulator of elastogenesis in cultures of different cell types including fibroblasts isolated from patients with elastopathy genetic diseases. We then elucidated mechanisms of elastogenic action of SA. SA exercises its net elastogenic effect only after being actively transported into the cell interior through two separate mechanisms. These are the “fast effect,” which reflects the greater stability of intracellular tropoelastin, and the “late effect,” which reflects the true enhancement of the elastin gene expression occurring after SA-induced activation of c-src tyrosine kinase and the consecutive phosphorylation of IGF-1 receptor, which triggers the downstream signals leading to activation of the elastin gene expression. In conclusion, for the first time we have established that SA is a potent stimulator of elastic fiber production.

There is evidence from family studies for the importance of genetic factors in the development of autism spectrum disorders (ASDs) but the identification of major genes has not been achieved to date. There are several reports of deletions and duplications in individuals with ASDs, some of which are not unique to an individual. In most cases, the frequencies and relevance of these abnormalities are unknown, as they have been identified serendipitously in one or a few individuals. My overall hypothesis was that such rearrangements would facilitate the identification of “culprit” genes associated with ASDs by identifying a small chromosomal region for candidate gene testing. I molecularly characterized two overlapping 2p15-2p16.1 deletions detected in unrelated individuals with confirmed autistic disorder (Subject 1) or autistic features (Subject 2), a 1.4Mb deletion on chromosome Xp22 (Subject 1) and a duplication of chromosome 7q11.23, reciprocal to the Williams-Beuren Syndrome (WBS) deletion, in one individual with an ASD (Subject 3). Using real-time semi-quantitative PCR, I screened a total of 798 individuals with an ASD and 186 healthy controls for the presence of similar abnormalities. No additional cases were identified in either group. Subsequently, I selected 6 genes [Orthodenticle homolog 1 (OTX1), Variable charge, X-linked (VCX), Neuroligin 4, X-linked (NLGN4X), Syntaxin 1A (STX1A), Cytoplasmic linker 2 (CYLN2) and General transcription factor IIi (GTF2i)], based on their function and localization within or in the vicinity of the rearrangements and tested them for association with ASDs. Although there was no evidence for association for any marker or haplotype in most of the genes tested, this was not so for GTF2i. Haplotype transmission disequilibrium testing revealed an increased transmission, from healthy parents to their affected offspring, of the common alleles of one marker and one haplotype in GTF2i (P = 0.0010 and 0.0005, respectively). This gene encodes a brain-expressed transcription factor previously implicated in the mental retardation associated with WBS. Based on these findings, I propose that, although the genomic rearrangements reported herein are not a common cause of ASDs, the GTF2i gene within the WBS critical region is important in the aetiology of autism. / Thesis (Ph.D, Physiology) -- Queen's University, 2009-11-20 00:35:11.727

A síndrome de Williams Beuren (SWB), doença congênita causada pela microdeleção do cromossomo 7, incluindo o gene da elastina, pode conferir às pessoas afetadas, facies típico, retardo mental, cardiopatia congênita, hipertensão, alterações gástricas, distúrbios de desenvolvimento de dentes, dentre outras alterações. O objetivo desse estudo foi conhecer as alterações faciais e bucais, a condição de saúde bucal, características oclusais e aspectos da ATM, bem como as alterações sistêmicas e condições médicas que afetam o manejo odontológico em uma amostra significativa de indivíduos brasileiros com a SWB. Para tanto, examinamos 25 indivíduos com SWB, com média de idade de 13 anos (4 a 26 anos). Os resultados mostraram que todos os participantes exibiam algum grau de retardo mental. A hiperacusia foi encontrada em 88% (22/25), cardiopatia congênita, em 76% (19/25); especialmente estenose aórtica supravalvar), hiperatividade em 68% (17/25) e hipertensão arterial em 40% (10/25) dos participantes. Distúrbios de desenvolvimento de dente foram encontrados em todos os participantes sendo que o mais frequente foi a retenção prolongada de dentes decíduos (64% - 16/25), seguido do diastemas generalizados (60% - 15/25), anodontia parcial (42% - 9/21), hipoplasia de esmalte (28% - 7/25), incisivos em forma de chave de fenda (24% - 6/25), microdontia (8% - 2/25). Em iguais porcentagens (4% - 1/25), foram encontrados casos de geminação, taurodontismo e dente conóide. Quanto à presença de alterações oclusais, todos os pacientes examinados apresentaram maloclusão. A maioria exibiu maloclusão classe III dentária de Angle (11/19,57 %) e mordida cruzada (11/25, 44%). Setenta e dois por cento dos pacientes exibiam algum hábito parafuncional. A experiência presente e passada de cárie, entre os 25 pacientes examinados, foi classificada como muito baixa, de acordo com o índice CPO-D e ceo-d, e 76% apresentaram gengivite. Os pacientes exibiram alteração da amplitude dos movimentos excursivos de mandíbula (abertura máxima - 12/22, 54%; lateralidade - 6/9, 66%; e protrusão - 7/9; 77%), bem como alterações nas ATMs, como dor à palpação (3/22, 13%) e ruídos articulares (4/25, 16%). Concluímos que distúrbios de desenvolvimento de dentes e maloclusão são frequentes em pessoas brasileiras afetadas pela SWB, e que a maioria delas apresenta alterações sistêmicas e comportamentais que podem interferir no manejo clínico odontológico. / The Williams Beuren syndrome (WBS), congenital disease caused by micro deletion of chromosome 7, including the elastin gene, is characterized by typical facies, mental retardation, congenital heart disease, hypertension, gastric alterations, teeth development disorders, among other changes. The aim of this study was to know facial and oral abnormalities, the oral health condition, occlusal features and aspects of temporomandibular joint, as well as systemic and medical conditions that affect the dental management on a significant sample of Brazilian individuals with WBS. For this, we examined 25 patients with SWB, with a mean age of 13 years (4-26 years). The results showed that all participants had some degree of mental retardation. The hyperacusis was found in 88% (22/25), congenital heart disease in 76% (19/25; especially supravalvular aortic stenosis), hyperactivity in 68% (17/25) and hypertension in 40% (10/25) of participants. Tooth development disorders were found in all participants with the most frequent was prolonged retention of the deciduous teeth (64% - 16/25), followed by generalized diastema (60% - 15/25), hypodontia (42% - 9/21), enamel hypoplasia (28% - 7/25), incisor-shaped screwdriver (24%- 6/25), microdontia (8% - 2/25). In equal percentages (4% - 1/25) were found cases of gemination, taurodontism and conoid tooth. For the presence of occlusal changes, all the patients examined presented malocclusion. Most showed malocclusion class III dental malocclusion (11/19, 57%) and crossbite (11/25, 44%). Seventy-two percent of patients had some parafunctional habit. Present and past caries experience among the 25 patients examined was classified as very low, according to the DMFT, and 76% had gingivitis. The patients exhibited change in amplitude of excursive movements of the jaw (maximun mouth opening - 12/22, 54%; laterality - 6/9, 66%; e protrusion - 7/9; 77%), as well as changes in ATMs, such as pain on palpation (3/22,13%) and joint sounds (4/25, 16%). We conclude that teeth and malocclusion development disorders are common in Brazilian people affected by WBS, and most of them have systemic and behavioral changes that can interfere with dental clinical management.

Le syndrome de Williams-Beuren (SWB} est une maladie génétique rare causée par une microdélétion de la région 7q11.23. A la suite de l'observation clinique d'une jeune fille atteinte du SWB ayant développé un lymphome de Burkitt à l'âge de 7 ans, nous nous sommes intéressé au lien génétique entre SWB et cancer. L'étude d'une série de cas de cancers survenus chez des enfants atteints de SWB a montré que les lymphomes non-hodgkiniens de type B étaient surreprésentés dans cette population puisque 73% des cancers chez les enfants atteints du SWB étaient des LNH-B. La région critique du SWB a été explorée par CGH-array et séquencage haut-débit dans les échantillons sains et tumoraux de 2 patients atteints de SWB. Aucune perte d'hétérozygotie de la région 7q11.23 n'a été trouvé. En outre, une délétion somatique de la région 7q11.23 a été identifiée dans un lymphome de Burkitt sporadique (Guenat D et al., J Hematol Oncol, 2014). Nous avons ensuite exploré les mécanismes de réponses aux dommages à l'ADN dans des lignées de fibroblastes primaires dérivées de patients atteints du SWB ainsi que dans des lignées 293T traitées avec des siRNA ciblant RFC2, BAZ1B et GTF2/, 3 gènes localisés en 7q11.23 et codant des protéines de réparation de l'ADN. Les cellules dérivées de patients SWB ont montré un défaut de signalisation dans les voies ATM/ATR-dépendantes en réponse aux dommages à l'ADN (Guenat D et al., DNA repair, article soumis). L'haploinsuffisance de la région 7q11.23 associée au SWB pourrait donc jouer un rôle dans la lymphomagenèse B par l'altération de voies de réponse aux dommages à l'ADN ATM/ATR-dépendantes. Cependant, ces résultats mériteraient d'être confirmés dans des modèles murins reproduisant le génotype complet du SWB. Enfin, des données épidémiologiques exhaustives sur l'incidence des pathologies tumorales chez les individus atteints du SWB sont indispensables pour affirmer qu'une prédisposition au cancer existe chez ces patients / Williams-Beuren syndrome (WBS) is a genetic disorder caused by a microdeletion at 7q11.23. The case of a young girl with WBS who developed a Burkitt lymphoma at the age of 7 leads us to explore the genetic link between WBS and cancer. The study of a series of cancers occurred in WBS patients during childhood have shown that B-cell non hodgkin lymphoma are over-represented in this population since 73% cancer cases in WBS were B-NHL. The critical region of WBS was explored by array-CGH and high-throughput sequencing in normal and tumor samples from WBS patients. No loss of heterozygosity at 7q11.23 was found. ln addition, a somatic deletion at 7q11.23 was observed in a sporadic case of Burkitt lymphoma (Guenat D et al., J Hematol Oncol, 2014). DNA damage response mechanisms were then explored in primary fibroblast cell lines derived from WBS patients as well as in 293T cell line treated with siRNA targeting RFC2, GTF2/ and BAZ1 B, 3 genes mapping at 7q11.23 that encode proteins involved in DNA damage response. WBS patients cell lines have shown a defect in ATM/ ATR-dependent DNA damage response pathways (Guenat D et al., DNA Repair, article submitted). Haploinsufficiency of the 7q11.23 region associated with WBS might play a role in B-cell lymphomagenesis through the alteration of ATM/ATR-dependent DNA damage response pathways. However, these results deserve to be confirmed in mouse models that reproduce the complete genotype of human WBS. Finally, strong epidemiological data would be required to confirm the predisposition to cancer in WBS patients.

A síndrome de Williams Beuren (SWB), doença congênita causada pela microdeleção do cromossomo 7, incluindo o gene da elastina, pode conferir às pessoas afetadas, facies típico, retardo mental, cardiopatia congênita, hipertensão, alterações gástricas, distúrbios de desenvolvimento de dentes, dentre outras alterações. O objetivo desse estudo foi conhecer as alterações faciais e bucais, a condição de saúde bucal, características oclusais e aspectos da ATM, bem como as alterações sistêmicas e condições médicas que afetam o manejo odontológico em uma amostra significativa de indivíduos brasileiros com a SWB. Para tanto, examinamos 25 indivíduos com SWB, com média de idade de 13 anos (4 a 26 anos). Os resultados mostraram que todos os participantes exibiam algum grau de retardo mental. A hiperacusia foi encontrada em 88% (22/25), cardiopatia congênita, em 76% (19/25); especialmente estenose aórtica supravalvar), hiperatividade em 68% (17/25) e hipertensão arterial em 40% (10/25) dos participantes. Distúrbios de desenvolvimento de dente foram encontrados em todos os participantes sendo que o mais frequente foi a retenção prolongada de dentes decíduos (64% - 16/25), seguido do diastemas generalizados (60% - 15/25), anodontia parcial (42% - 9/21), hipoplasia de esmalte (28% - 7/25), incisivos em forma de chave de fenda (24% - 6/25), microdontia (8% - 2/25). Em iguais porcentagens (4% - 1/25), foram encontrados casos de geminação, taurodontismo e dente conóide. Quanto à presença de alterações oclusais, todos os pacientes examinados apresentaram maloclusão. A maioria exibiu maloclusão classe III dentária de Angle (11/19,57 %) e mordida cruzada (11/25, 44%). Setenta e dois por cento dos pacientes exibiam algum hábito parafuncional. A experiência presente e passada de cárie, entre os 25 pacientes examinados, foi classificada como muito baixa, de acordo com o índice CPO-D e ceo-d, e 76% apresentaram gengivite. Os pacientes exibiram alteração da amplitude dos movimentos excursivos de mandíbula (abertura máxima - 12/22, 54%; lateralidade - 6/9, 66%; e protrusão - 7/9; 77%), bem como alterações nas ATMs, como dor à palpação (3/22, 13%) e ruídos articulares (4/25, 16%). Concluímos que distúrbios de desenvolvimento de dentes e maloclusão são frequentes em pessoas brasileiras afetadas pela SWB, e que a maioria delas apresenta alterações sistêmicas e comportamentais que podem interferir no manejo clínico odontológico. / The Williams Beuren syndrome (WBS), congenital disease caused by micro deletion of chromosome 7, including the elastin gene, is characterized by typical facies, mental retardation, congenital heart disease, hypertension, gastric alterations, teeth development disorders, among other changes. The aim of this study was to know facial and oral abnormalities, the oral health condition, occlusal features and aspects of temporomandibular joint, as well as systemic and medical conditions that affect the dental management on a significant sample of Brazilian individuals with WBS. For this, we examined 25 patients with SWB, with a mean age of 13 years (4-26 years). The results showed that all participants had some degree of mental retardation. The hyperacusis was found in 88% (22/25), congenital heart disease in 76% (19/25; especially supravalvular aortic stenosis), hyperactivity in 68% (17/25) and hypertension in 40% (10/25) of participants. Tooth development disorders were found in all participants with the most frequent was prolonged retention of the deciduous teeth (64% - 16/25), followed by generalized diastema (60% - 15/25), hypodontia (42% - 9/21), enamel hypoplasia (28% - 7/25), incisor-shaped screwdriver (24%- 6/25), microdontia (8% - 2/25). In equal percentages (4% - 1/25) were found cases of gemination, taurodontism and conoid tooth. For the presence of occlusal changes, all the patients examined presented malocclusion. Most showed malocclusion class III dental malocclusion (11/19, 57%) and crossbite (11/25, 44%). Seventy-two percent of patients had some parafunctional habit. Present and past caries experience among the 25 patients examined was classified as very low, according to the DMFT, and 76% had gingivitis. The patients exhibited change in amplitude of excursive movements of the jaw (maximun mouth opening - 12/22, 54%; laterality - 6/9, 66%; e protrusion - 7/9; 77%), as well as changes in ATMs, such as pain on palpation (3/22,13%) and joint sounds (4/25, 16%). We conclude that teeth and malocclusion development disorders are common in Brazilian people affected by WBS, and most of them have systemic and behavioral changes that can interfere with dental clinical management.

Made available in DSpace on 2016-03-15T19:40:48Z (GMT). No. of bitstreams: 1 Yara Garzuzi.pdf: 551486 bytes, checksum: 44776cb6bcf0c1a4ffc2f15d4da4b0ab (MD5) Previous issue date: 2009-09-03 / Fundo Mackenzie de Pesquisa / There are few studies in Brazil that comprise the theme of behavioral phenotypes in people with genetic syndromes. The knowledge of behavioral patterns associated with such syndromes contributes to the planning of standardized therapeutic assessment, intervention and handling strategies, and for an improvement in assistance practices. This study presents three genetic syndromes, which have as their common behavioral phenotype the presence of mental retardation that is associated with neurobiological, clinical, behavioral, social and psychiatric patterns specific to each of them. To describe and compare the major behavior patterns of children and adolescents with Prader-Willi Syndrome (PWS), Williams-Beuren Syndrome (WBS) and Down Syndrome (DS). The sample consisted of 68 children and adolescents with diagnosis for the syndromes. From these subjects, 11 presented cytogenetic-molecular diagnosis for PWS, 10 presented clinical and/or cytogeneticmolecular diagnosis for WBS, and 47 presented clinical and/or cytogenetic-molecular diagnosis for DS. The Child Behavior Checklist for ages 1½ 5 (CBCL/1½ 5) and the Child Behavior Checklist for ages 6-18 (CBCL/6 18) were used for data collection. The major results of the comparison between groups showed that, with respect to behavior changes, the PWS group scored higher, followed by the WBS group and the DS group, respectively. The following main patterns were found: in PWS, Externalizing Problems, Social Problems, Thought Problems and Aggressive Behavior; in WBS, Social and Attention Problems; and in DS, Total Problems. Statistically significant differences were also observed between some of this response patterns when groups paired by sex and age were compared (PWS-DS and WBS-DS).The changes found mainly in groups with PWS and WBS interfere considerably with the social adjustment of these children and adolescents. If these changes are not treated, they may result in the development of risk factors for several psychiatric comorbidities tending to chronicity. Therefore, it is necessary to implement public health services for the care of behavioral changes and to help families to deal with these groups of children and adolescents. / No Brasil, são poucos os estudos que abrangem a temática dos fenótipos comportamentais em pessoas com síndromes genéticas. O conhecimento de padrões comportamentais associados a tais síndromes contribui para o planejamento de estratégias de avaliação, intervenção e manejo terapêutico padronizados, e para uma melhoria das práticas assistenciais. Este estudo apresenta três síndromes genéticas cujo fenótipo comportamental comum é a presença da deficiência mental que se associa a padrões neurobiológicos, clínicos, comportamentais, sociais e psiquiátricos específicos a cada uma delas. Descrever e comparar os principais padrões de comportamento de crianças e adolescentes com Síndrome de Prader-Willi (SPW), Síndrome de Williams-Beuren (SWB) e Síndrome de Down (SD). A amostra foi composta por 68 crianças e adolescentes com diagnóstico para as síndromes. Desses participantes, 11 apresentavam diagnóstico citogenético-molecular para a SPW, 10 apresentavam diagnóstico clínico e/ou citogenético-molecular para a SWB, e 47 apresentavam diagnóstico clínico e/ou citogenético-molecular para a SD. Para a coleta de dados, utilizaram-se o Inventário dos Comportamentos de Crianças de 1½ a 5 anos (CBCL/1½ 5) e o Inventário dos Comportamentos de Crianças e Adolescentes de 6 a 18 anos (CBCL/6 18). Os principais resultados da comparação entre os grupos mostraram que, em relação a alterações de comportamento, o grupo com SPW obteve as maiores pontuações, seguido pelo grupo com SWB e pelo grupo com SD, respectivamente. Os principais padrões encontrados foram: Na SPW, problemas externalizantes, problemas sociais, problemas de pensamento e comportamento agressivo; na SWB, problemas sociais e de atenção; e, na SD, problemas totais. Observaram-se, ainda, diferenças estatisticamente significativas entre alguns desses padrões de resposta quando se compararam os grupos pareados por sexo e idade (SPW-SD e SWB-SD). As alterações encontradas principalmente nos grupos com SPW e SWB interferem de maneira considerável na adaptação social dessas crianças e adolescentes. Se essas alterações não forem tratadas, poderão configurar o desenvolvimento de fatores de risco para diversas comorbidades psiquiátricas com tendência à cronicidade. Por isso, fazem-se necessários a implementação de serviços públicos de saúde para o cuidado das alterações comportamentais e o auxílio do manejo familiar desses grupos de crianças e adolescentes.

Made available in DSpace on 2016-03-15T19:39:35Z (GMT). No. of bitstreams: 1 Miriam Segin.pdf: 2813413 bytes, checksum: f192e7858349d5ff3ad275af7e9ccf69 (MD5) Previous issue date: 2010-08-25 / Williams-Beuren Syndrome (WBS) is a genetic affection determined by the microdelation of contiguous genes in 7q11.23. The genetic profile of WBS is characterized by the visualconstructive deficit that contrasts with the good performance in verbal tasks, which sustains the hypothesis of dissociation between these abilities. This grants the syndrome peculiar cognitive and behavioral frames. The objective of this research is to describe the pattern of competences in tasks of linguistic abilities in 22 children and adolescents with WBS, aged between 7and 18 (M=11,6; DP=3,7), students of the 1st to 6th grades of elementary and special schools. We used the following instruments: WISC-III (to evaluate intellectual abilities); Wisconsin (used in neuropsychological assessment of abstract reasoning and cognitive strategies); CBCL/6-18 (behavioral assessment); Token-Comp (TT) used to working memory assessment; Peabody Picture Vocabulary Test (PPVT) used to receptive language assessment; Phonological Awareness by Oral Production Test; Syntactic Awareness Test; Word-Reading Efficiency Test; Test of Naming Images by Choosing Words; Test of Naming Images by Writing. The results of WISC-III, Wisconsin and CBCL/6-18 demonstrate mild to moderate intellectual disability, difficulty in concentration and identification of patterns of change, emotional and relationship problems, lack of attention, behavior disorders, challenge and opposition and somatic complaints. The results of TT and PPVT show that the receptive vocabulary is below expected for the level of schooling and age, and is close to the data found in 4-year-old-children. In the abilities of phonological and syntactic awareness, results indicate great deficiencies, with performances equivalent to those of 3-year-old children at the Phonological Awareness by Oral Production Test and of 4-year-olds at the Syntactic Awareness Test. No progression was found according to the increase of school grade. The tests Word-Reading Efficiency, Naming Images by Choosing Words and Naming Images by Writing were taken by 4 participants that presented deficits in the reading ability with graphophonemic decoding. They make more orthographic and semantic mistakes and show low capacity of naming by writing. Thus, it was possible to verify that the sample presents deficits in receptive language and work memory, difficulties in phonological and syntactic processing tasks, which are important factors to the proper development of the capacity to read and write / A Síndrome de Williams-Beuren (SWB) é uma afecção genética determinada pela microdeleção de genes contíguos em 7q11.23. O perfil cognitivo da SWB é conhecido pelo prejuízo viso-construtivo que contrasta com melhor desempenho em tarefas verbais, o que sustenta a hipótese de dissociação entre essas habilidades, conferindo a esta síndrome um quadro cognitivo e comportamental peculiar. O objetivo deste estudo é descrever o padrão das competências em provas de habilidades lingüísticas de 22 crianças e adolescentes com SWB, com idades entre 7 e 18 anos (M= 11,6; DP=3,7), estudantes do 1º ao 6º ano do ensino fundamental e de Escolas Especiais. Foram utilizados os instrumentos: WISC-III (avaliação do potencial intelectual); Wisconsin (avaliação neuropsicológica de habilidades de raciocínio abstrato e estratégias cognitivas); CBCL/6 18 (perfil comportamental); Token-Comp (TT) (memória de trabalho); Teste de Vocabulário por Imagens Peabody (TVIP) (linguagem receptiva); Prova de Consciência Fonológica por produção Oral (PCFO); Prova de Consciência Sintática (PCS); Teste de Competência de Leitura de Palavras (TCLP); Teste de nomeação de figuras por escolha de palavras (TNF1 escolha) e o Teste de nomeação de figuras por escrita (TNF2 escrita). Os resultados nos testes WISC-III, Wisconsin e CBCL/6 18 apresentaram deficiência intelectual de leve à moderada, maior dificuldade em concentração e identificação de padrões de mudança, problemas afetivos e de relacionamento, desatenção, transtornos de conduta, desafio e oposição e queixas somáticas. Nos testes TT e TVIP foi possível observar que o vocabulário receptivo está abaixo do esperado para a escolaridade e para a idade, próximo ao encontrado em crianças de 4 anos. Nas habilidades de consciência fonológica e consciência sintática, os resultados mostraram grande comprometimento, com desempenho equivalente ao de crianças de 3 anos de idade na PCFO e de 4 anos na PCS, sendo que não foi identificada progressão em relação á série. Os testes TCLP, TNF1 e TNF2 foram realizados por 4 sujeitos que apresentam déficits de habilidade de leitura com decodificação grafofonemica, cometem mais erros semânticos e ortográficos e revelam baixa capacidade de nomeação por escrita. Desta maneira, foi possível identificar que, nessa amostra, há comprometimento de linguagem receptiva e de memória de trabalho, dificuldades em tarefas de processamento fonológico e sintático, os quais são fatores importantes para o bom desenvolvimento da leitura e da escrita