How are people with orofacial clefts attended in northwest region of São Paulo state, Brazil?

Characterization of specific birth defects is essential for conducting scientific investigations, care and therapeutic strategies. This article describes demographic, clinical and genetic aspects, risk factors and access to treatment of Brazilian patients with orofacial clefts registered in a specialized collaborative center of the Brazilian Database on Craniofacial Anomalies (BDCA). We interviewed 70 individuals with typical orofacial clefts using a standard instrument from the database and subjected them to genetic testing. The patients were grouped as syndromic and non-syndromic. The majority of individuals were of lower middle class, native ancestry and syndromic. There was a significant difference in the type of clefts regarding gender. There was no significant difference between bilateral and unilateral, between the side affected, right and left, or familial recurrence related to type of oral cleft. The risk factor familial recurrence was significantly higher among non-syndromic cases. Etiological factors were identified or suggested in 62.5% of the syndromic cases. There was a delay in diagnosis and in access to treatment in most cases. We concluded that gender, native ancestry and low family income represent risk factors. Furthermore, the distribution by cleft types and gender is similar to previous studies. The results can guide scientific investigations and care policies.

Birth defects in Brazil: Outcomes of a population-based study.

Birth defects (BDs) are functional and structural alterations in embryonic or fetal development. With an incidence of approximately 3-5%, BDs are a leading cause of infant mortality and lifelong disability. A population-based prospective case-control study was conducted for one year with 5204 infants, between March 1st, 2011 and February 29th, 2012 in the city of São José do Rio Preto, State of São Paulo, Brazil. The incidence of BDs was 3.2% [95% confidence interval (95%CI): 2.8-3.8%]. The most common congenital anomalies were heart diseases in isolation (11.2%; 95%CI: 7.3-16.9%) followed by Down syndrome (9.5%; 95%CI: 5.9-14.8%), neural tube defects (8.9%; 95%CI: 5.4-14.1), urinary tract anomalies (7.7%; 95%CI: 4.4-12.7%), and polydactyly (7.0%; 95%CI: 4.0-12.0%). The majority of mothers with Down syndrome babies had advanced age. Family members with the same BD, maternal alcohol consumption, gestational diabetes, and previous miscarriages were the most frequent risk factors. The results were similar to published data from other countries except for the incidence of Down syndrome, which was twice as high as reported by other authors and is probably due to the high sociocultural level of the region where the current study was performed, leading to pregnancies at older maternal age.

Syndromic Oral Clefts: Challenges of Genetic Assessment in Brazil and Suggestions to Improve Health Policies.

Addressing the unmet health needs of persons living with congenital anomalies in low- and middle-income countries (LMIC) is a major challenge. Registries and databases are exemplary tools capable to link research data with health programs. Since 2009, Brazil's Craniofacial Project, a multicenter and voluntary research initiative, collects socioeconomic, medical, and genetic information on individuals with craniofacial anomalies through the Brazilian Database on Craniofacial Anomalies (BDCA). This article discusses challenges to the provision of genetic assessment and counselling for individuals with syndromic oral clefts (SOC) through public health services in LMIC, such as Brazil. Subjects were selected using methods of the BDCA as described elsewhere. Among 800 records, 66 assigned as SOC with no etiologic diagnosis were preselected for genomic imbalance screening. Only 28 have timely completed basic protocol using public health services, and 22 were able to perform chromosomal microarray analysis. Pathogenic genomic imbalances were identified in 4 (18.18%) and a copy number variation of uncertain clinical significance was detected in one. Results exemplify barriers faced by the majority of the population of Brazil to reach whole genetic assessment either through public genetic services or in research settings. In this unfavorable scenario, BDCA has allowed the recognition of individuals with similar needs, optimizing the scarce genetic laboratory facilities in Brazil. Ultimately, BDCA has facilitated the translation of research into care. This experience may be successfully extended to other congenital anomalies and to LMIC with similar characteristics. A set of suggestions focusing on oral clefts is provided.

Genomic imbalances in syndromic congenital heart disease / Desequilíbrios genômicos na cardiopatia congênita sindrômica

Abstract Objective: To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). Methods: 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). Results: Clinically significant copy number variations (CNVs ≥300 kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993 kb duplication in 15q21.1 and 706 kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. Conclusion: These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.

Resumo Objetivo: Identificar desequilíbrios genômicos patogênicos em pacientes que apresentam cardiopatias congênitas (CC) e anomalias extracardíacas e exclusão da síndrome de deleção 22q11.2 (SD22q11.2). Métodos: Foram avaliados por microarray cromossômico (CMA) 78 pacientes negativos para a deleção 22q11.2, previamente testados por hibridação in situ com fluorescência (FISH) e/ou amplificação de múltiplas sondas dependentes de ligação (MLPA). Resultados: Foram identificadas variações do número de cópias de DNA (CNVs) clinicamente significativas (≥ 300 kb) em 10% (8/78) dos casos, além de CNVs potencialmente relevantes em dois casos (duplicação de 993 kb em 15q21.1 e duplicação de 706 kb em 2p22.3). Genes envolvidos como IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1 e LTPB1 são conhecidos por atuar no desenvolvimento cardíaco e podem ser genes candidatos a CC. Conclusão: Esses dados mostram que pacientes que apresentam CC, com anomalias extracardíacas e exclusão da SD22q11.2, devem ser investigados por CMA. Ainda, este estudo enfatiza a possível função das CNVs nas CC.

Genomic imbalances in syndromic congenital heart disease.

OBJECTIVE: To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). METHODS: 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). RESULTS: Clinically significant copy number variations (CNVs ≥300kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993kb duplication in 15q21.1 and 706kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. CONCLUSION: These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.

A multicentric association study between 39 genes and nonsyndromic cleft lip and palate in a Brazilian population.

PURPOSE: The aim of this study was to use the TaqMan OpenArray system to evaluate associations between 39 genes and the etiology of nonsyndromic cleft lip and palate (NSCLP) in a Brazilian population. MATERIAL AND METHODS: This case-control association study was designed with 80.11% statistical power according to logistic regression (GPOWER software). The case group had 182 patients with NSCLP enrolled in the Brazilian Database on Orofacial Clefts. The controls included 355 healthy individuals with no history of oral clefting in the past three generations. All samples were genotyped for 253 tag single nucleotide polymorphisms (tagSNPs) in 39 genes, including two that had recently been associated with this process. The association analysis was performed using logistic regression and stepwise regression. The results were corrected for multiple testing [Bonferroni correction and False Discovery Rate (FDR)]. RESULTS: Twenty-four SNPs in 16 genes were significantly associated with the etiology of NSCLP, including MSX1, SPRY1, MSX2, PRSS35, TFAP2A, SHH, VAX1, TBX10, WNT11, PAX9, BMP4, JAG2, AXIN2, DVL2, KIF7, and TCBE3. Stepwise regression analysis revealed that 11 genes contributed to 15.5% of the etiology of NSCLP in the sample. CONCLUSION: This is the first study to associate KIF7 and TCEB3 with the etiology of NSCLP. New technological approaches using the same design should help to identify further etiological susceptibility variants.

Effects of a genetic counseling model on mothers of children with down syndrome: a Brazilian pilot study.

Down syndrome occurs in approximately 1:600 live births. Genetic counseling is indicated for these families and may be beneficial for adaptation to the challenges that accompany by this diagnosis. Although the basic counseling goals are similar, there are many models of genetic counseling practiced around the world. The aim of this article is to report the results of a pilot study that evaluated the level of satisfaction with a model of service delivery of genetic counseling practiced in Brazil, the knowledge assimilated about Down syndrome and whether this process resulted in a feeling of well-being and psychological support. Thirty mothers of under 6-month-old children with Down syndrome were interviewed after having two sessions of genetic counseling in a public healthcare service within a period of 30 days. A semi-structured questionnaire was developed by the researchers to collect identification, socioeconomic and demographic data and to assess the client's satisfaction with the model of genetic counseling. Data were collected using both open and closed questions. The reported level of satisfaction was high. The knowledge assimilated about Down syndrome after only two sessions was considered technically vague by raters in 44 % of cases. Most mothers (96.7 %) reported that genetic counseling was beneficial and provided psychological support. The model was considered satisfactory, but further research is needed to identify ways to improve knowledge retention by this population. These results highlight the utility of referring families for genetic counseling when there is a suspicion of a diagnosis of Down syndrome.

Implementing the brazilian database on orofacial clefts.

Background. High-quality clinical and genetic descriptions are crucial to improve knowledge of orofacial clefts and support specific healthcare polices. The objective of this study is to discuss the potential and perspectives of the Brazilian Database on Orofacial Clefts. Methods. From 2008 to 2010, clinical and familial information on 370 subjects was collected by geneticists in eight different services. Data was centrally processed using an international system for case classification and coding. Results. Cleft lip with cleft palate amounted to 198 (53.5%), cleft palate to 99 (26.8%), and cleft lip to 73 (19.7%) cases. Parental consanguinity was present in 5.7% and familial history of cleft was present in 26.3% subjects. Rate of associated major plus minor defects was 48% and syndromic cases amounted to 25% of the samples. Conclusions. Overall results corroborate the literature. Adopted tools are user friendly and could be incorporated into routine patient care. The BDOC exemplifies a network for clinical and genetic research. The data may be useful to develop and improve personalized treatment, family planning, and healthcare policies. This experience should be of interest for geneticists, laboratory-based researchers, and clinicians entrusted with OC worldwide.

Birth defects: Risk factors and consequences.

Birth defects (BDs) or congenital anomalies include all structural and functional alterations in embryonic or fetal development resulting from genetic, environmental or unknown causes, which result in physical and/or mental impairment. BDs occur in about 3% of newborn babies and in most cases of pregnancy loss. BDs are a very complex and heterogeneous group of single or multiple changes that, in most cases, are of unknown etiology. Among the risk factors are advanced maternal and paternal ages, parental consanguinity, teratogenic agents such as infectious agents and drugs, and poor nutrition, in particular folic acid deficiency. One of the consequences of these defects is the high death rate within the first year of life. Information on BDs is becoming increasingly more important throughout the world so that preventive measures can be taken. Knowledge of BDs enables the development of therapeutic and preventive strategies besides adequate genetic counseling.

Preliminary Analysis of the Nonsynonymous Polymorphism rs17563 in BMP4 Gene in Brazilian Population Suggests Protection for Nonsyndromic Cleft Lip and Palate.

Cleft lip with or without palate (CL±P) is common congenital anomalies in humans. Experimental evidence has demonstrated that bone morphogenetic protein 4 gene (Bmp4) is involved in the etiology of CL±P in animal models. The nonsynonymous polymorphism rs17563 T>C (p.V152A) in the BMP4 gene has been associated to the risk of nonsyndromic CL±P in Chinese population and microforms from different ethnic backgrounds. The aim of this study was to investigate the role of BMP4 gene in CL±P in Brazilian sample using genetic association approach. Our sample was composed by 123 patients with nonsyndromic CL±P and 246 controls, in which absence of CL±P was confirmed in 3 generations. The rs17563 polymorphism was genotyped by PCR-RFLP technique. Logistic regression was performed to evaluate allele and genotype association. Our data showed statistical power to detect association (86.83%) in this sample. Logistic regression results showed significant association between C allele and CL±P (P = 0.00018, OR = 0.40, and 95% CI = 0.25-0.65), as well as CC genotype and CL±P (P = 0.00018, OR = 0.35, and 95% CI = 0.19-0.66). So, there is a strong association between nonsyndromic CL±P and BMP4 rs17563 polymorphism in our sample and the C allele had a protective effect against the occurrence of nonsyndromic CL±P.

Exame intraoperatório por congelação na avaliação do linfonodo sentinela axilar no câncer de mama / Intraoperative frozen section assessment in the evaluation of axillary sentinel lymph node in breast cancer

INTRODUÇÃO: O exame intraoperatório por congelação tornou-se um procedimento de rotina na avaliação do linfonodo sentinela axilar no câncer de mama. OBJETIVOS: Avaliar a acurácia e a sensibilidade do FS na detecção de metástases em linfonodo sentinela axilar e investigar o valor preditivo para metástases de variáveis, como idade dos pacientes, estadiamento, tipo histológico, grau e expressão do receptor de estrogênio do tumor. MATERIAL E MÉTODOS: Foram analisados, retrospectivamente, os resultados de 177 procedimentos de congelação. A idade dos pacientes e as características dos tumores foram organizadas em um banco de dados e a relação com a presença de metástases foi analisada. RESULTADOS: Foram detectadas metástases em 22 (12%) casos. Todas as macrometastases e uma micrometastases foram detectadas pelo método de congelação. Micrometastases adicionais foram identificadas nas análises pós-operatórias, cinco por coloração com hematoxilina e eosina (H) e três por imuno-histoquímica. O método de congelação mostrou acurácia geral de 95%, sensibilidade de 64% e especificidade de 100%. Nenhuma associação significativa foi observada entre a presença de metástases e as variáveis analisadas. CONCLUSÃO: Nossos resultados mostram que o exame por congelação possui acurácia e sensibilidade elevadas para a detecção de macrometastases; no entanto, é pouco eficiente na identificação de micrometastases. O uso de imuno-histoquímica melhora a detecção de metástases na análise pós-operatória. A idade do paciente e as características do tumor, como estadiamento, tipo histológico, grau e a expressão do receptor de estrogênio têm de valor preditivo baixo para metástases nodais em câncer de mama.

INTRODUCTION: Intraoperative frozen section analysis has become a routine procedure to evaluate the status of axillary sentinel lymph nodes in breast cancer. OBJECTIVES: To evaluate the accuracy and sensitivity of FS in the detection of metastases in axillary sentinel lymph nodes and to investigate the predictive value of variables such as patients' age, tumor staging, histology, grade, and estrogen receptor expression. MATERIAL AND METHODS: We analyzed retrospectively the results of 177 FS procedures. The patients' age and tumor characteristics were organized in a database and the association with the presence of metastases was analyzed. RESULTS: Metastases were detected in 22 cases (12%). All macrometastases and one micrometastasis were detected by FS. Additional micrometastases were detected in post-operative analysis, from which five were determined by hematoxylin and eosin staining (H) and three by immunohistochemistry (IHC). FS diagnosis data proved to have an overall accuracy of 95%, sensitivity of 64%, and specificity of 100%. None of the analyzed variables showed significant association with lymph node metastases. CONCLUSION: Our results show that intraoperative FS is a highly accurate and sensitive method to detect macrometastases. However, it is inaccurate in the detection of micrometastases. The use of IHC improves the detection of micrometastases in postoperative analyses. The patient's age and tumor characteristics such as staging, histology, grade and estrogen receptor expression have low predictive value for lymph node metastasis in breast cancer.

Insertional translocation of 15q25-q26 into 11p13 and duplication at 8p23.1 characterized by high resolution arrays in a boy with congenital malformations and aniridia.

We report on a boy presenting submucous cleft palate, hydronephrosis, ventriculoseptal defect, aniridia, and developmental delay. Additional material on 11p13 was cytogenetically visible and array analyses identified a duplicated segment on 15q25-26 chromosome region; further, array analyses revealed a small deletion (49 kb) at 11p13 region involving the ELP4 gene and a duplication at 8p23.1. Results were confirmed with both molecular and molecular cytogenetics techniques. Possibilities for etiological basis of clinical phenotype are discussed.

Birth defects in newborns and stillborns: an example of the Brazilian reality.

BACKGROUND: This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects. METHODS: For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases. RESULT: The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death. CONCLUSIONS: The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments.

Dominant inheritance and intra-familial variations in the association of Sturge-Weber and Klippel-Trenaunay-Weber syndromes.

This case report shows a genealogical study where a woman has limb hypertrophy and her son has an association of Sturge-Weber syndrome with Klippel-Trenaunay-Weber syndrome. The Sturge-Weber and Klippel-Trenaunay-Weber syndromes appear to be different manifestations of the same affliction. Familial aggregation exists and transmission may be almost imperceptible between generations. Identification of minor manifestations may prove to be a valuable contribution to genetic counseling of families and the prevention of new cases.

Adesão ao tratamento após aconselhamento genético na Síndrome de Down / Adhesión a la estimulación después del asesoramiento genético en Síndrome de Down / Adherence to treatment post genetic counseling in Down Syndrome

A estimulação precoce traz benefícios significativos aos indivíduos com síndrome de Down (SD), a seus familiares e à sociedade. Este estudo avaliou o efeito do aconselhamento genético (AG) sobre o comportamento de adesão de pais ao tratamento de estimulação, os fatores que influenciaram o acesso ao AG e ao tratamento e a satisfação com o AG. Participaram do estudo 12 casais de pais, entrevistados mediante roteiros semiestruturados, em três etapas: pré-AG, pós-AG e follow-up. Apesar da dificuldade de acesso ao AG e aos tratamentos, a maioria ficou satisfeita com o AG recebido. Este processo influenciou significantemente o comportamento de adesão ao tratamento, pois, provavelmente, as orientações recebidas foram responsáveis pela mudança do comportamento. Regras bem-definidas promovem modificações comportamentais e são úteis na SD. Operam como estímulo discriminativo para o comportamento de adesão dos pais ao tratamento de seus filhos.(AU)

Early stimulation provides significant benefits for Down syndrome individuals, their families and society. This study evaluated the effect of genetic counseling on the adherence behavior of parents to stimulation therapy, the factors that influence access to genetic counseling and to treatment and the satisfaction supplied by counseling. The parents of 12 individuals participated in this study using routine semi-structured interviews at three stages: before counseling, after counseling and follow-up. In spite of the difficulties to access genetic counseling and treatment, most parents were satisfied with the service. This process significantly influenced the adherence to treatment as, probably, the guidance was responsible for changes in behavior. Well-defined rules, useful in Down syndrome, promoted behavioral changes. Rules function as a discriminative stimulus for parents to adherence to the treatment of their children.(AU)

La estimulación precoz trae beneficios significativos para los individuos con síndrome de Down (SD), familiares y sociedad. Este estudio evaluó el efecto del asesoramiento genético (AG) sobre el comportamiento de adhesión de los padres al tratamiento de estimulación, los factores que influenciaron el acceso al AG, al tratamiento y la satisfacción con el AG. Participaron del estudio 12 parejas de padres, entrevistados con el uso de cuestionario semi-estructurados, en tres etapas: pre-AG, pos-AG y follow-up A pesar de la dificultad de acceso al AG y a los tratamientos, la mayoría se quedó satisfecho con el AG recibido. Este proceso influyó significativamente en el comportamiento de adhesión al tratamiento pues, probablemente, las orientaciones recibidas fueron responsables por el cambio de comportamiento. Reglas bien definidas promueven modificaciones de comportamiento y son útiles en el SD. Operan como estímulo discriminatorio para el comportamiento de adhesión de los padres al tratamiento de sus hijos.(AU)

Adesão ao tratamento após aconselhamento genético na Síndrome de Down / Adhesión a la estimulación después del asesoramiento genético en Síndrome de Down / Adherence to treatment post genetic counseling in Down Syndrome

A estimulação precoce traz benefícios significativos aos indivíduos com síndrome de Down (SD), a seus familiares e à sociedade. Este estudo avaliou o efeito do aconselhamento genético (AG) sobre o comportamento de adesão de pais ao tratamento de estimulação, os fatores que influenciaram o acesso ao AG e ao tratamento e a satisfação com o AG. Participaram do estudo 12 casais de pais, entrevistados mediante roteiros semiestruturados, em três etapas: pré-AG, pós-AG e follow-up. Apesar da dificuldade de acesso ao AG e aos tratamentos, a maioria ficou satisfeita com o AG recebido. Este processo influenciou significantemente o comportamento de adesão ao tratamento, pois, provavelmente, as orientações recebidas foram responsáveis pela mudança do comportamento. Regras bem-definidas promovem modificações comportamentais e são úteis na SD. Operam como estímulo discriminativo para o comportamento de adesão dos pais ao tratamento de seus filhos.

Early stimulation provides significant benefits for Down syndrome individuals, their families and society. This study evaluated the effect of genetic counseling on the adherence behavior of parents to stimulation therapy, the factors that influence access to genetic counseling and to treatment and the satisfaction supplied by counseling. The parents of 12 individuals participated in this study using routine semi-structured interviews at three stages: before counseling, after counseling and follow-up. In spite of the difficulties to access genetic counseling and treatment, most parents were satisfied with the service. This process significantly influenced the adherence to treatment as, probably, the guidance was responsible for changes in behavior. Well-defined rules, useful in Down syndrome, promoted behavioral changes. Rules function as a discriminative stimulus for parents to adherence to the treatment of their children.

La estimulación precoz trae beneficios significativos para los individuos con síndrome de Down (SD), familiares y sociedad. Este estudio evaluó el efecto del asesoramiento genético (AG) sobre el comportamiento de adhesión de los padres al tratamiento de estimulación, los factores que influenciaron el acceso al AG, al tratamiento y la satisfacción con el AG. Participaron del estudio 12 parejas de padres, entrevistados con el uso de cuestionario semi-estructurados, en tres etapas: pre-AG, pos-AG y follow-up A pesar de la dificultad de acceso al AG y a los tratamientos, la mayoría se quedó satisfecho con el AG recibido. Este proceso influyó significativamente en el comportamiento de adhesión al tratamiento pues, probablemente, las orientaciones recibidas fueron responsables por el cambio de comportamiento. Reglas bien definidas promueven modificaciones de comportamiento y son útiles en el SD. Operan como estímulo discriminatorio para el comportamiento de adhesión de los padres al tratamiento de sus hijos.

Fluorescence in situ hybridization (FISH) screening for the 22 q11. 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 percent). 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.

Atualização em autismo: aspectos genético-clínicos / Actualización en autismo: aspectos genetico y clinicos / Autism update: genetic and clinic aspects

O autismo é uma doença heterogênea e complexa sem etiologia definida, mas com fatores genéticos certamente participantes. Osmecanismos genéticos envolvidos e sua interação com o ambiente também não estão esclarecidos. Entretanto, diversos genes têm sidosugeridos como responsáveis pelo aparecimento da doença, a maioria deles relacionados à morfogênese e funcionamento do sistemanervoso central. Este artigo apresenta uma atualização sobre os aspectos da susceptiblidade genética e a clínica das Doenças doEspectro Autista. Embora a literatura sobre o tema seja ampla, os resultados sobre susceptibilidade são ainda escassos e contraditórios,com muitos aspectos etiopatológicos a serem esclarecidos. É necessário modificar o foco de atenção à saúde da família e ampliar oatendimento às doenças genéticas, bem como os enfermeiros desenvolverem pesquisas científicas nessa área e acompanharem odesenvolvimento científico, visando melhorar o bem-estar da pessoa acometida por autismo e seus familiares.

Autism is a complex and heterogeneous disease without defined etiology, but with participant genetic factors. The genetic mechanisminvolved and their interactions with the environment are not clear. Meanwhile, several genes have been suggested as responsible for thedisease, most of them related to morphogenesis and functioning of the central nervous system. This article presents an update onaspects of genetics susceptibility and the clinic of Diseases of the Autism Spectrum. Although the literature on the topic is broad, resultsof susceptibility are still scarce and contradictory, with many etiopatological aspects to be clarified. It is necessary to modify the focustowards to health family and spread the understanding of genetic diseases as well as the nurses do develop scientific researches in thisfield and follow closely the scientifical development aiming to improve the wellfare of an autistic patient and its family.

El autismo es una enfermedad heterogénea compleja sin etiología definida, pero con factores genéticos participantes. Los mecanismosde la genética y su interacción con el medio ambiente también son poco claros. Mientras tanto, varios genes que se han sugerido comoresponsables de la aparición de la enfermedad, la mayoría de ellos relacionados con la morfogénesis y funcionamiento del sistemanervioso central. Este documento representa una actualización de los aspectos de la susceptibilidad genética y las clínicas del Autismo.Aunque la bibliografía sobre el tema es amplia, los resultados de susceptibilidad son todavía escasos y contradictorios, con muchasaspectos etiopatologicos por aclarar. Es necesario modificar el enfoque hacia la salud de la familia y la difusión de la comprensión de lasenfermedades genéticas, así como el personal de enfermería desarrollar investigaciones científicas en este campo y seguir de cerca eldesarrollo científico con el fin de mejorar el bien estar del paciente autista y su familia.

Avaliação morfológica e imuno - histoquímica de linfomas gástricos primários / Morphologic and immunohistochemical evaluation of primary gastric lymphomas

INTRODUÇÃO: Os linfomas gástricos primários representam cerca de 50 por cento dos linfomas não-Hodgkin extranodais e de 2 por cento a 8 por cento das neoplasias malignas do estômago. A maioria é formada pela proliferação de linfócitos B, que ocorre a partir do tecido linfóide associado à mucosa. Esse tecido, inexistente no estômago em condições normais, surge como conseqüência de gastrite crônica, na maioria das vezes associada à bactéria Helicobacter pylori. A inflamação crônica provocada pela infecção bacteriana parece sensibilizar linfócitos T, levando a estímulo constante de linfócitos B, que passam a proliferar inicialmente em padrão reacional. Posteriormente surgem alterações genômicas nessas células, que provocam ganho proliferativo, seleção clonal e transformação neoplásica, dando origem a linfoma de baixo grau. Alterações genéticas adicionais, como mutações em p53, podem induzir transformação para alto grau. MATERIAL E MÉTODOS: Foram estudados 32 casos de linfomas gástricos: 15 de baixo e 17 de alto grau. Foram investigados sexo e idade dos pacientes, características morfológicas das lesões,índice de proliferação celular e colonização pelo Helicobacter pylori. Verificou-se a expressão de CD20, Ki-67, p53, BCL-2 e BCL-6 por imuno-histoquímica. RESULTADOS: Os linfomas gástricos ocorreram mais freqüentemente em homens, e a faixa etária mais elevada foi observada no grupo de baixo grau. Lesões linfoepiteliais foram observadas em 93 por cento dos linfomas desse grupo. O índice de proliferação celular e a expressão do p53 foram mais elevados no grupo de alto grau. A expressão do BCL-2 foi mais elevada nos linfomas de baixo grau. Não houve diferença significante quanto à expressão do BCL-6 nos dois grupos. CONCLUSÃO: Os resultados sugerem a participação dos genes p53 e BCL-2 na patogênese e na evolução dos linfomas gástricos.

CFTR molecular analysis reveals infrequent allele frequencies in nine cystic fibrosis patients from São Paulo State, Brazil.

Although cystic fibrosis (CF) is the most common autosomal recessive disorder in whites, it is thought to be relatively rare or, alternatively, underdiagnosed in Latin America. In Brazil, different groups have shown a DF508 mutation frequency ranging from 30.7% to 50.8%. Such variation may be explained by the ethnic differences observed in this country, which is genetically very heterogeneous. We describe the molecular analysis for 32 mutations of the CFTR gene in nine unrelated patients with cystic fibrosis from São Paulo State, Brazil. The main observation of this study was the absence of 30 out of the 32 mutations in 12 alleles among these patients. Except for mutations DF508 and N1303K, no other mutation could be detected in any of the studied patients. In one of two alleles, a DF508 mutation was detected in four patients (22% of the total sample) and an N1303K mutation was detected in two patients (11% of the total sample). One patient was a compound heterozygote for DF508/N1303K. Although the sample studied here was small, it may be possible that our patients have infrequent alleles once these can occur at higher frequencies in selected populations and also show relevant regional differences. Additional investigations in a larger sample are currently in progress in our laboratory to confirm our results, and further studies are still needed to determine the frequencies of CF gene mutations in different regions and ethnic groups in the Brazilian population.