Down Syndrome Resulting from a Rare non-Robertsonian Translocation t(11;21)(p13;q22)

Introduction: Down syndrome (DS) is a common genetic disorder, occurring in approximately 1 in 700 births. It results from an extra copy (triplication) of the whole or part of the long arm of chromosome 21 caused by different cytogenetic alterations: free trisomy, Robertsonian translocations, mosaicism, duplication of the critical region and other structural rearrangements. Non-Robertsonian chromosome translocations are very rare events with few cases reported. Case Report: We identified the non-Robertsonian translocation t(11;21)(p13;q22) and two chromosomes 21 in a female child referred with a clinical diagnosis of trisomy 21.  The infant developed the transient myeloproliferative disorder at 17 months. Cytogenetic analysis was performed in lymphocytes and bone marrow metaphases according to standard procedure - G banding and fluorescence in situ hybridization.  The karyotype study of the parents revealed that her phenotypically normal mother carries the same reciprocal translocation. Conclusion: This is the second report of the translocation t(11;21)(p13;q22),  the first one resulting in DS.  This description expands knowledge about cytogenetic variability in the etiology of DS. Future studies are needed to investigate the long-term clinical effects of the trisomy 21 associated with t(11;21)(p13;q22)

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Diretriz da Sociedade Brasileira de Cardiologia sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas

This guideline aimed to update the concepts and formulate the standards of conduct and scientific evidence that support them, regarding the diagnosis and treatment of the Cardiomyopathy of Chagas disease, with special emphasis on the rationality base that supported it.  Chagas disease in the 21st century maintains an epidemiological pattern of endemicity in 21 Latin American countries. Researchers and managers from endemic and non-endemic countries point to the need to adopt comprehensive public health policies to effectively control the interhuman transmission of T. cruzi infection, and to obtain an optimized level of care for already infected individuals, focusing on diagnostic and therapeutic opportunistic opportunities.   Pathogenic and pathophysiological mechanisms of the Cardiomyopathy of Chagas disease were revisited after in-depth updating and the notion that necrosis and fibrosis are stimulated by tissue parasitic persistence and adverse immune reaction, as fundamental mechanisms, assisted by autonomic and microvascular disorders, was well established. Some of them have recently formed potential targets of therapies.  The natural history of the acute and chronic phases was reviewed, with enhancement for oral transmission, indeterminate form and chronic syndromes. Recent meta-analyses of observational studies have estimated the risk of evolution from acute and indeterminate forms and mortality after chronic cardiomyopathy. Therapeutic approaches applicable to individuals with Indeterminate form of Chagas disease were specifically addressed. All methods to detect structural and/or functional alterations with various cardiac imaging techniques were also reviewed, with recommendations for use in various clinical scenarios. Mortality risk stratification based on the Rassi score, with recent studies of its application, was complemented by methods that detect myocardial fibrosis.  The current methodology for etiological diagnosis and the consequent implications of trypanonomic treatment deserved a comprehensive and in-depth approach. Also the treatment of patients at risk or with heart failure, arrhythmias and thromboembolic events, based on pharmacological and complementary resources, received special attention. Additional chapters supported the conducts applicable to several special contexts, including t. cruzi/HIV co-infection, risk during surgeries, in pregnant women, in the reactivation of infection after heart transplantation, and others.     Finally, two chapters of great social significance, addressing the structuring of specialized services to care for individuals with the Cardiomyopathy of Chagas disease, and reviewing the concepts of severe heart disease and its medical-labor implications completed this guideline.Esta diretriz teve como objetivo principal atualizar os conceitos e formular as normas de conduta e evidências científicas que as suportam, quanto ao diagnóstico e tratamento da CDC, com especial ênfase na base de racionalidade que a embasou. A DC no século XXI mantém padrão epidemiológico de endemicidade em 21 países da América Latina. Investigadores e gestores de países endêmicos e não endêmicos indigitam a necessidade de se adotarem políticas abrangentes, de saúde pública, para controle eficaz da transmissão inter-humanos da infecção pelo T. cruzi, e obter-se nível otimizado de atendimento aos indivíduos já infectados, com foco em oportunização diagnóstica e terapêutica. Mecanismos patogênicos e fisiopatológicos da CDC foram revisitados após atualização aprofundada e ficou bem consolidada a noção de que necrose e fibrose sejam estimuladas pela persistência parasitária tissular e reação imune adversa, como mecanismos fundamentais, coadjuvados por distúrbios autonômicos e microvasculares. Alguns deles recentemente constituíram alvos potenciais de terapêuticas. A história natural das fases aguda e crônica foi revista, com realce para a transmissão oral, a forma indeterminada e as síndromes crônicas. Metanálises recentes de estudos observacionais estimaram o risco de evolução a partir das formas aguda e indeterminada e de mortalidade após instalação da cardiomiopatia crônica. Condutas terapêuticas aplicáveis aos indivíduos com a FIDC foram abordadas especificamente. Todos os métodos para detectar alterações estruturais e/ou funcionais com variadas técnicas de imageamento cardíaco também foram revisados, com recomendações de uso nos vários cenários clínicos. Estratificação de risco de mortalidade fundamentada no escore de Rassi, com estudos recentes de sua aplicação, foi complementada por métodos que detectam fibrose miocárdica. A metodologia atual para diagnóstico etiológico e as consequentes implicações do tratamento tripanossomicida mereceram enfoque abrangente e aprofundado. Também o tratamento de pacientes em risco ou com insuficiência cardíaca, arritmias e eventos tromboembólicos, baseado em recursos farmacológicos e complementares, recebeu especial atenção. Capítulos suplementares subsidiaram as condutas aplicáveis a diversos contextos especiais, entre eles o da co-infecção por T. cruzi/HIV, risco durante cirurgias, em grávidas, na reativação da infecção após transplante cardíacos, e outros.    Por fim, dois capítulos de grande significado social, abordando a estruturação de serviços especializados para atendimento aos indivíduos com a CDC, e revisando os conceitos de cardiopatia grave e suas implicações médico-trabalhistas completaram esta diretriz.&nbsp

Frequency of the BCR/ABL rearrangements and associated alterations detected by FISH during monitoring of patients taking imatinib mesylate in isolation

A introdução do mesilato de imatinibe como tratamento da leucemia mielóide crônica tem salvado muitos pacientes, mas o sucesso da terapia tem sido prejudicado pela resistência e possível não destruição do clone maligno. Este artigo descreve a resposta citogenética e padrões citogenéticos anormais envolvendo os genes ABL e BCR detectados por FISH em pacientes em uso exclusivo de imatinibe. Os resultados mostraram que outras alterações envolvendo os genes BCR e ABL não parecem estar relacionadas à resistência à droga, elas ocorrem em baixas freqüências e podem não estar associadas à resposta citogenética ou ao tempo de tratamento. Contudo, a resposta ao imatinibe parece ser individual e imprevisível, independente do tempo e do início do tratamento após o diagnóstico.The introduction of imatinib mesylate as treatment of chronic myelogenous leukemia has saved many patients, but the success of therapy is hampered by resistance and possible non-destruction of the malignant clone. This article describes the cytogenetic responses and abnormal cytogenetic patterns involving the ABL and BCR genes detected by FISH in patients who use exclusively imatinib. The results showed that other alterations involving the BCR and ABL genes do not seem to be related to resistance to the drug as they occur in low frequencies and can not be associated to the cytogenetic response or to the time of treatment. Moreover, the response to imatinib seems to be individual and unpredictable, independent of the time of treatment and of its initiation after diagnosis

Atypical chromosome abnormalities in acute myeloid leukemia type M4

This study reports an adult AML-M4 patient with atypical chromosomal aberrations present in all dividing bone marrow cell at diagnosis: t(1;8)(p32.1;q24.2), der(9)t(9;10)(q22;?), and ins(19;9)(p13.3;q22q34) that may have originated transcripts with leukemogenic potential.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Fluorescence in situ hybridization (FISH) screening for the 22q11.2 deletion in patients with clinical features of velocardiofacial syndrome but without cardiac anomalies

The velocardiofacial syndrome (VCFS), a condition associated with 22q11.2 deletions, is characterized by a typical facies, palatal anomalies, learning disabilities, behavioral disturbances and cardiac defects. We investigated the frequency of these chromosomal deletions in 16 individuals with VCFS features who presented no cardiac anomalies, one of the main characteristics of VCFS. Fluorescent in situ hybridization (FISH) with the N25 (D22S75; 22q11.2) probe revealed deletions in ten individuals (62%). Therefore, even in the absence of cardiac anomalies testing for the 22q11.2 microdeletions in individuals showing other clinical features of this syndrome is recommended