49,XXXXY: investigação da idade no diagnóstico, apresentação clínica e tratamento: uma revisão narrativa da literatura / 49,XXXXY: age investigation in diagnosis, clinical and treatment: a narrative review review of the literature

O cariótipo 49,XXXXY, uma variante rara da Síndrome de Klinefelter, acomete 1:85.000­100.000 nascidos vivos do sexo masculino e surge a partir de uma dupla não disjunção durante as duas rodadas da meiose (I e II) materna. No entanto, as pesquisas envolvendo indivíduos com essa constituição cromossômica são limitadas. Deste modo, este estudo tem como objetivo geral caracterizar a idade no diagnóstico, a apresentação clínica e o tratamento de indivíduos 49,XXXXY. Foi realizada uma revisão da literatura na base de dados PubMed utilizando os descritores 49,XXXXY and diagnosis e 49,XXXXY. Os critérios de inclusão foram: artigos originais e relato de caso, idioma inglês, versão completa disponível online gratuitamente e que contenham as informações que respondam integralmente ao objetivo geral. Os resultados dos 20 estudos incluídos nessa revisão mostraram que a identificação de indivíduos com cariótipo 49,XXXXY ocorre geralmente após o nascimento, sendo que o diagnóstico no pré-natal é extremamente raro. A presença de diversas anomalias congênitas pode contribuir significativamente para o diagnóstico precoce, ao contrário de pacientes com cariótipo 47,XXY, que geralmente são assintomáticos até a puberdade. Nossos achados podem contribuir para despertar a atenção dos profissionais de saúde no reconhecimento desse distúrbio genético, visto que o diagnóstico precoce dessa síndrome permite o tratamento adequado mais rapidamente, a fim de se obter menor impacto no desenvolvimento global desse indivíduo, com consequente melhora na sua qualidade de vida.

Haplotype analysis of VEGF gene polymorphisms in polycystic ovary syndrome.

This study evaluated the association of polymorphisms of VEGF (endothelial vascular growth factor) gene + 936C/T (rs3025039), 1154 G/A (rs 1570360) and -2578 C/A (rs 699947) in patients with polycystic ovary syndrome (PCOS) and to perform the haplotypes formed by the alleles in the Brazilian population. A total of 110 women without PCOS and 112 women with PCOS were included in the study. Genotyping analyses were performed using the PCR-RFLP assays (rs 3025039 and rs 699947) and by allelic discrimination using the real-time PCR technique (rs 1570360). In the univariate analysis, we observed a significant difference between the groups for the polymorphism rs 1570360 and this polymorphism presented statistical differences between the groups for the recessive model (p = .04). The frequency of the T-G-C haplotype showed a statistically significant difference between women with PCOS and controls (p = .05). The -2578 A/C polymorphism was more frequent in the control group, which may be associated with a protective characteristic for the PCOS manifestation. In the sample analysis, polymorphism rs 1570360 is associated with PCOS and the T-G-C haplotype could be associated with protective factors.

Mortality by sickle cell disease in Brazil.

This work aimed to characterize mortality by sickle cell disease in Brazil. The MEDLINE electronic database was searched using the terms 'mortality' and 'sickle cell disease' and 'Brazil' for articles published in the last five years aiming to provide a current analysis of the subject in question. Eight studies on mortality by sickle cell disease were carried out in the Brazilian states of Maranhão, Bahia, Minas Gerais, Rio de Janeiro and Mato Grosso do Sul. The majority of the deaths occurred in patients with sickle cell anemia, which is the most common genotype and causes the most severe clinical manifestation of the disease. In summary, there are few published studies on mortality related to sickle cell disease in Brazil, and most are from the state of Minas Gerais. This study emphasizes the importance of developing more studies on sickle cell disease mortality, so that it may be possible to profile gene carriers and give health professionals more data to strategize the delivery of more effective assistance to these individuals. Despite the early diagnosis of sickle cell disease by the Neonatal Screening Program and the use of preventive and therapeutic measures (penicillin, immunization and hydroxyurea), mortality by sickle cell disease on the world stage is still significant.

ACE I/D Polymorphism in Brazilian Women with Endometriosis / Polimorfismo ACE I/D em Mulheres Brasileiras com Endometriose

Endometriosis is a chronic gynecological disease that displays some features similar to malignancy, such as local invasion, aggressive spread to distant organs and angiogenesis. Polymorphisms of the ACE gene have been linked with some vascular disease. To determine the frequency of the ACE I/D polymorphism in Brazilian patients with endometriosis compared to controls. This case-control study included a total of 134 women (49 endometriosis patients and 85 controls) who had undergone a laparoscopy or laparotomy. Molecular analysis was performed by polymerase chain reaction (PCR). For the statistical analysis, the chi-square and multiple logistic regression tests were used. The I/D ACE genotype frequencies in cases and controls were, respectively: II 16.3% and 16.5%; ID 24.5% and 20%; DD 59.2% and 63.5%. There was no statistically significant difference between cases and controls, either in the genotype frequencies (χ2 = 0.385; p = 0.825) or in the allele frequencies (χ2 = 0.098; p = 0.75) of the ACE I/D polymorphism. However, the genotype distribution was not consistent with the Hardy-Weinberg equilibrium, either in patients (χ2 = 7.84; p = 0.005) or in controls (χ2 = 20.09; p <0.0001). Multiple logistic regression analysis has not shown any differences amongst groups for the polymorphism studied [(OR 1.51; CI 95% 0.52- 4.41); p=0.4523]. Despite of the small sample size, the present study suggests that I/D ACE polymorphism is not related with endometriosis in brazilian patients.(AU)

A endometriose é uma doença ginecológica crônica que apresenta algumas características semelhantes à malignidade, tais como invasão local, disseminação para órgãos distantes e angiogênese. Polimorfismos no gene ACE têm sido relacionados com algumas doenças vasculares. Determinar a frequência do polimorfismo ACE I/D em pacientes brasileiros com endometriose em comparação aos controles. Estudo caso-controle que incluiu um total de 134 mulheres (49 pacientes com endometriose e 85 controles) que se submeteram a uma laparoscopia ou laparotomia. A análise molecular foi realizada por Reação em Cadeia da Polimerase (PCR). A análise estatística utilizou os testes de qui-quadrado e regressão logística. As frequências genotípicas ACE I/D em casos e controles foram, respectivamente: II 16,3% e 16,5%; ID 24,5% e 20%; DD 59,2% e 63,5%. Não houve diferença estatisticamente significativa entre os casos e controles, tanto nas frequências genotípicas (χ2 = 0,385; p = 0,825) ou nas frequências alélicas (χ2 = 0,098; p = 0,75) do polimorfismo ACE I/D. Entretanto, a distribuição genotípica não foi consistente com o equilíbrio de Hardy-Weinberg, tanto nos pacientes (χ2 = 7,84; p = 0,005) ou nos controles (χ2 = 20,09; p <0,0001). A análise de regressão logística não mostrou qualquer diferença entre os grupos para o polimorfismo estudado [(OR 1,51; CI 95% 0,52-4,41); p=0,4523]. Apesar do pequeno número de amostras, o presente estudo mostra que em pacientes brasileiras o polimorfismo ACE I/D não está relacionado com endometriose.(AU)

[Turner syndrome and genetic polymorphism: a systematic review]. / Síndrome de Turner e polimorfismo genético: uma revisão sistemática.

OBJECTIVE: To present the main results of the literature on genetic polymorphisms in Turner Syndrome and their association with the clinical signs and the etiology of this chromosomal disorder. DATA SOURCE: The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review. DATA SYNTHESIS: The polymorphisms investigated in patients with Turner Syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner Syndrome. The role of single nucleotide polymorphisms (SNPs) in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed. CONCLUSIONS: Genetic polymorphisms appear to be associated with Turner Syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner Syndrome.

Qualidade de vida em pacientes com endometriose: um estudo de revisão / Quality of life in patients with endometriosis: a review study / Calidad de vida de pacientes con endometriosis: un estudio de revisión

Objetivo: Avaliar a qualidade de vida (QV) em pacientes com endometriose. Métodos: Realizou-se uma revisão bibliográfica na base de dados PubMed buscando artigos publicados nos últimos 10 anos utilizando os descritores quality of life and endometriosis e os seguintes filtros: artigos com abstract disponível, em humanos do sexo feminino, idioma inglês/ português e cujos termos constavam no título/abstract. A busca resultou em 147 artigos, dos quais, de acordo com os critérios de inclusão, restaram 12 para leitura. Resultados: Todos os artigos evidenciaram que as mulheres com endometriose apresentaram uma redução na QV, e cinco estudos associaram nível socioeconômico, intensidade da dor e hábitos saudáveis como fatores que influenciam a QV. No entanto, nenhum estudo propôs estratégias para a melhora da QV. A presente revisão evidencia os benefícios da abordagem fisioterapêutica, psicológica e da prática de atividade física em elevar a QV, como uma maneira de minimizar os sintomas da endometriose, em especial, a dor e os sintomas psicológicos. A avaliação da QV em endometriose poderia ser utilizada como um indicador prognóstico da melhora clínica. Conclusão: Mulheres com endometriose apresentam significativa redução em sua qualidade de vida, influenciada pelos aspectos físicos e psicológicos, entre outros.

Objective: This study aims to assess the quality of life (QoL) in patients with endometriosis. Methods: We conducted a literature review searching for articles published in the last 10 years in the PubMed database, using the descriptors ?quality of life? and ?endometriosis? and the following filters: in human female, articles with abstract available, English/Portuguese language, and containing the terms in the title/abstract. The search retrieved 147 articles, of which 12 remained for reading, according to the inclusion criteria. Results: All the articles pointed out that women with endometriosis showed a reduction in QoL, and five studies have linked socioeconomic status, severity of pain and healthy habits as factors that influence QoL. However, neither of the studies suggests strategies for the improvement of QoL. This review shows the benefits of the physiotherapeutic and psychological approach, and physical activity practice in raising QoL as a way to minimize the symptoms of endometriosis, especially pain and psychological symptoms. The assessment of QoL in endometriosis could be used as a prognostic indicator of clinical improvement. Conclusion: Women with endometriosis exhibit a significant reduction in their QoL, influenced by physical and psychological aspects, among others.

Objetivo: Evaluar la calidad de vida (CV) de pacientes com endometriosis. Métodos: Se realizó una revisión bibliográfica em la base de datos PubMed con búsqueda de artículos publicados en los últimos 10 años utilizándose de los descriptores quality of life and endometriosis y los siguientes filtros: artículos com abstract disponible, en humanos del sexo femenino, idioma inglés/portugués y cuyos términos estaban en el título/abstract. La búsqueda resultó en 147 artículos, de los cuales, según los critérios de inclusión, restaron 12 para la lectura. Resultados: Todos los artículos evidenciaron que las mujeres con endometriosis presentaron reducción en la CV, y cinco estudios asociaron el nível socioeconómico, la intensidad del dolor y hábitos saludables como factores que influyen en la CV. Sin embargo, ningún estudio há propuesto estrategias para mejorar la CV. Esta revisión evidencia los beneficios del abordaje fisioterapéutico, psicológico y de La práctica de actividad física en mejorar la CV, como una manera de minimizar los síntomas de la endometriosis, en especial, El dolor y los síntomas psicológicos. La evaluación de la CV em endometriosis podría ser utilizada como un indicador pronóstico de la mejora clínica. Conclusión: Mujeres con endometriosis presentan reducción significativa de la calidad de vida debido, entre otros aspectos, a los físicos y psicológicos.

Genetic polymorphisms and endometriosis: contribution of genes that regulate vascular function and tissue remodeling.

Endometriosis is a benign gynecological disease characterized by the presence and growth of endometrial cells outside the uterus. Genetic, endocrine, immunological, and environmental factors have been suggested in its pathogenesis. A great number of studies have related genetic polymorphisms as a factor that contributes to the development of endometriosis. This review presents a detailed description of the contribution of genetic polymorphisms in genes that regulate vascular function and tissue remodeling in endometriosis (alpha 2-HS glycoprotein [AHSG], epidermal growth factor receptor [EGFR], vascular endothelial growth factor [VEGF], endostatin, plasminogen activator inhibitor 1 [PAI-1], angiotensin I-converting enzyme [ACE], and matrix metalloproteinases [MMPs]). Some polymorphisms of the VEGF (-460 C/T, +405 G/C, +936 C/T), PAI, MMP-1, 2, and 3 genes were widely studied, while polymorphisms of the AHSG, EGF, endostatin, and VEGF (-1154 G/A, -2578 A/C) genes were not. In this latter case, additional studies are required to confirm the findings of the few studies that have analyzed these single nucleotide polymorphisms (SNPs). Additionally, studies that found a positive or negative association of SNP with endometriosis emphasize the relevance of studies with a large number of control cases to confirm their findings. The haplotype analysis was performed only for the VEGF (-460, +405, -1154 and -2578), ACE (-240/2350) and MMP-1, 2, 3, and 9 genes, and in most of them, there was no association with endometriosis. Of the eight works that analyzed haplotypes of the VEGF gene, five did not associate them with endometriosis. Haplotypes of ACE and MMP-2 genes were not associated with endometriosis, while those of MMP-1, 3, and 9 genes were related to a high risk for the disease.

Polimorfismos genéticos e endometriose: a contribuição dos genes que regulam a função vascular e o remodelamento de tecidos / Genetic polymorphisms and endometriosis: contribution of genes that regulate vascular function and tissue remodeling

A endometriose é uma doença ginecológica benigna caracterizada pela presença e crescimento de células endometriais fora do útero. Fatores genéticos, endócrinos, imunológicos e ambientais têm sido sugeridos em sua patogênese. Um grande número de estudos tem relacionado polimorfismos genéticos como um fator que contribui para o desenvolvimento da endometriose. Nesta revisão, apresentamos uma descrição detalhada da contribuição de polimorfismos genéticos nos genes que regulam a função vascular e o remodelamento do tecido em endometriose (AHSG, EGFR, EGF, VEGF, endostatina, PAI-1, ACE e MMPs). Alguns polimorfismos dos genes VEGF (-460 C/T, +405 G/C, +936 C/T), PAI, MMP-1, 2 e 3 foram amplamente estudados, enquanto outros dos genes AHSG, EGF, endostatina e VEGF (-1154 G/A, -2578 A/C), não. Nesse último caso, estudos adicionais tornam-se necessários para confirmar os achados encontrados pelos poucos trabalhos que analisaram esses polimorfismos de único nucleotídeo (SNP). Além disso, os estudos que encontraram associação positiva ou negativa do SNP com endometriose enfatizam a importância de estudos com grande número de casos-controles para confirmar os achados por eles publicados. A análise por haplótipo foi realizada apenas para os genes VEGF (-460, +405, -1154 e -2578), ACE (-240/2350) e MMP-1, 2, 3 e 9, e, na maioria deles, não houve associação com endometriose. Dos oito trabalhos que analisaram haplótipos do gene VEGF, cinco deles não os associaram à endometriose. Os haplótipos dos genes ACE e MMP-2 não foram associados à endometriose, enquanto aqueles dos genes MMP-1, 3 e 9 foram relacionados a risco elevado da doença.

Endometriosis is a benign gynecological disease characterized by the presence and growth of endometrial cells outside the uterus. Genetic, endocrine, immunological, and environmental factors have been suggested in its pathogenesis. A great number of studies have related genetic polymorphisms as a factor that contributes to the development of endometriosis. This review presents a detailed description of the contribution of genetic polymorphisms in genes that regulate vascular function and tissue remodeling in endometriosis (alpha 2-HS glycoprotein [AHSG], epidermal growth factor receptor [EGFR], vascular endothelial growth factor [VEGF], endostatin, plasminogen activator inhibitor 1 [PAI-1], angiotensin I-converting enzyme [ACE], and matrix metalloproteinases [MMPs]). Some polymorphisms of the VEGF (-460 C/T, +405 G/C, +936 C/T), PAI, MMP-1, 2, and 3 genes were widely studied, while polymorphisms of the AHSG, EGF, endostatin, and VEGF (-1154 G/A, -2578 A/C) genes were not. In this latter case, additional studies are required to confirm the findings of the few studies that have analyzed these single nucleotide polymorphisms (SNPs). Additionally, studies that found a positive or negative association of SNP with endometriosis emphasize the relevance of studies with a large number of control cases to confirm their findings. The haplotype analysis was performed only for the VEGF (-460, +405, -1154 and -2578), ACE (-240/2350) and MMP-1, 2, 3, and 9 genes, and in most of them, there was no association with endometriosis. Of the eight works that analyzed haplotypes of the VEGF gene, five did not associate them with endometriosis. Haplotypes of ACE and MMP-2 genes were not associated with endometriosis, while those of MMP-1, 3, and 9 genes were related to a high risk for the disease.