Laparoscopy as a Facilitator in the Early Diagnosis of a Mullerian Aplasia During Ordinary Surgery.

Laparoscopy was introduced more than 100 years ago. However, in some fields its use still meets resistance. Technology such as laparoscopy may help to identify rare and complex disorders, even in very ordinary procedures, such as inguinal hernia repair. This report highlighted the importance of early diagnosis of a complex condition using commonly available technology. To the best of our knowledge, there has not been a similar reported case in such a young patient during laparoscopic inguinal hernia repair.

New SHH and Known SIX3 Variants in a Series of Latin American Patients with Holoprosencephaly.

Holoprosencephaly (HPE) is the failure of the embryonic forebrain to develop into 2 hemispheres promoting midline cerebral and facial defects. The wide phenotypic variability and causal heterogeneity make genetic counseling difficult. Heterozygous variants with incomplete penetrance and variable expressivity in the SHH, SIX3, ZIC2, and TGIF1 genes explain ∼25% of the known causes of nonchromosomal HPE. We studied these 4 genes and clinically described 27 Latin American families presenting with nonchromosomal HPE. Three new SHH variants and a third known SIX3 likely pathogenic variant found by Sanger sequencing explained 15% of our cases. Genotype-phenotype correlation in these 4 families and published families with identical or similar driver gene, mutated domain, conservation of residue in other species, and the type of variant explain the pathogenicity but not the phenotypic variability. Nine patients, including 2 with SHH pathogenic variants, presented benign variants of the SHH, SIX3, ZIC2, and TGIF1 genes with potential alteration of splicing, a causal proposition in need of further studies. Finding more families with the same SIX3 variant may allow further identification of genetic or environmental modifiers explaining its variable phenotypic expression.

Spontaneous Pubertal Onset in a Male Patient With Mixed Gonadal Dysgenesis With Mosaicism 45,X/ 46, X, mar (Y)/ 47,X,mar(Y),+mar(Y) - Pediatric Case Report.

This report describes an adolescent with Mixed Gonadal Dysgenesis and unexpected mosaicism [karyotype 46,X,mar(Y)/ 47,X, mar(Y),+mar(Y)].). Diagnosis with 1 month of age due to atypical genitalia. He presented a right streak gonad, which was removed due to the risk for germ cell tumor, and a left testis with epididymis barely connected and without vas deferens. Left testis maintenance was sufficient for him to undergo spontaneous puberty. The patient was non-responsive to growth hormone. Webbed neck was the only dysmorphic feature. To the best of our knowledge, there were no similar cases reported with spontaneous pubertal progress reported in the literature.

List of priority congenital anomalies for surveillance under the Brazilian Live Birth Information System. / Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil.

OBJECTIVE: To define the list of priority congenital anomalies for improving their recording on the Brazilian Live Birth Information System (Sinasc). METHODS: Based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), international protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Medical Genetics and Genomics Society. RESULTS: The list comprised eight groups of congenital anomalies distributed according to the type of related anomaly, as well as the affected part of the body and its corresponding code in ICD-10 Chapter XVII. CONCLUSION: The list of priority congenital anomalies for notification provides a basis for improving case recording on Sinasc.

List of priority congenital anomalies for surveillance under the Brazilian Information System on Live Births / Lista de anomalías congénitas prioritarias para la vigilancia bajo el Sistema de Información sobre Nacimientos Vivos en Brasil / Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil

Objective: To define the list of priority congenital anomalies for improving the registration in the Brazilian Live Birth Information System (Sinasc). Methods: Based on International Classification of Diseases, Tenth Revision (ICD-10), internation protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Society of Medical Genetics and Genomics. Results: The list comprised eight groups of congenital anomalies distributed according to the type of anomaly related, as well as the affect body part, all of which were related to some code of chapter XVII of ICD-10. Conclusion: The list of priority congenital anomalies for notification provides subsidies for improving registration at Sinasc.

Objetivo: Definir a lista de anomalias congênitas prioritárias para o aprimoramento do registro no Sistema de Informações sobre Nascidos Vivos (Sinasc). Métodos: A partir da Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10), protocolos internacionais e reuniões com especialistas, a lista de anomalias prioritárias foi construída considerando-se dois critérios principais: ser diagnosticável ao nascimento; e possuir intervenção disponível em diferentes níveis. A lista foi submetida a apreciação da Sociedade Brasileira de Genética Médica e Genômica. Resultados: Compuseram a lista oito grupos de anomalias distribuídos de acordo com o tipo de anomalia relacionada, bem como a parte do corpo afetada e sua correspondência ao código do capítulo XVII da CID-10. Conclusão: A lista de anomalias congênitas prioritárias para notificação fornece subsídios para o aprimoramento do registro no Sinasc.

Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil / Lista de anomalías congénitas prioritarias para la vigilancia bajo el Sistema de Información sobre Nacidos Vivos en Brasil / List of priority congenital anomalies for surveillance under the Brazilian Live Birth Information System

Objetivo: Definir a lista de anomalias congênitas prioritárias para o aprimoramento do registro no Sistema de Informações sobre Nascidos Vivos (Sinasc). Métodos: A partir da Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10), protocolos internacionais e reuniões com especialistas, a lista de anomalias prioritárias foi construída considerando-se dois critérios principais: ser diagnosticável ao nascimento; e possuir intervenção disponível em diferentes níveis. A lista foi submetida a apreciação da Sociedade Brasileira de Genética Médica e Genômica. Resultados: Compuseram a lista oito grupos de anomalias congênitas distribuídos de acordo com o tipo de anomalia relacionada, bem como a parte do corpo afetada e sua correspondência ao código do capítulo XVII da CID-10. Conclusão: A lista de anomalias congênitas prioritárias para notificação fornece subsídios para o aprimoramento do registro no Sinasc.

Objetivo: Definir la lista de anomalías congénitas prioritarias para perfeccionar el registro en el Sistema de Información de Nacidos Vivos (Sinasc). Métodos: Con base en la Clasificación Internacional de Enfermedades, Décima Revisión (CIE-10), protocolos internacionales y reuniones con especialistas, la lista de anomalías prioritarias se construyó considerando dos criterios principales: ser diagnosticables al nacer y tener intervención disponible en diferentes niveles. La lista fue sometida a la consideración de la Sociedad Brasileña de Genética y Genómica Médica. Resultados: La lista comprendía ocho grupos de anomalías congénitas distribuidos según el tipo de anomalía relacionada, así como la parte del cuerpo afectada, todos ellos relacionados con algún código del capítulo XVII de la CIE-10. Conclusión: La lista de anomalías congénitas prioritarias para notificación proporciona subsidios para mejorar el registro en Sinasc.

Objective: To define the list of priority congenital anomalies for improving their recording on the Brazilian Live Birth Information System (Sinasc). Methods: Based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), international protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Medical Genetics and Genomics Society. Results: The list comprised eight groups of congenital anomalies distributed according to the type of related anomaly, as well as the affected part of the body and its corresponding code in ICD-10 Chapter XVII. Conclusion: The list of priority congenital anomalies for notification provides a basis for improving case recording on Sinasc.

Cytogenomic Integrative Network Analysis of the Critical Region Associated with Wolf-Hirschhorn Syndrome.

Deletions in the 4p16.3 region are associated with Wolf-Hirschhorn syndrome (WHS), a contiguous gene deletion syndrome involving variable size deletions. In this study, we perform a cytogenomic integrative analysis combining classical cytogenetic methods, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and systems biology strategies, to establish the cytogenomic profile involving the 4p16.3 critical region and suggest WHS-related intracellular cell signaling cascades. The cytogenetic and clinical patient profiles were evaluated. We characterized 12 terminal deletions, one interstitial deletion, two ring chromosomes, and one classical translocation 4;8. CMA allowed delineation of the deletions, which ranged from 3.7 to 25.6 Mb with breakpoints from 4p16.3 to 4p15.33. Furthermore, the smallest region of overlapping (SRO) encompassed seven genes in a terminal region of 330 kb in the 4p16.3 region, suggesting a region of susceptibility to convulsions and microcephaly. Therefore, molecular interaction networks and topological analysis were performed to understand these WHS-related symptoms. Our results suggest that specific cell signaling pathways including dopamine receptor, NAD+ nucleosidase activity, and fibroblast growth factor-activated receptor activity are associated with the diverse pathological WHS phenotypes and their symptoms. Additionally, we identified 29 hub-bottlenecks (H-B) nodes with a major role in WHS.

Controversies on Timing of Sex Assignment and Surgery in Individuals With Disorders of Sex Development: A Perspective.

Appropriate management of disorders of sex development (DSD) has been a matter of discussion since the first guidelines were published in the 1950s. In the last decade, with the advent of the 2006 consensus, the classical methods, especially regarding timing of surgery and sex of rearing, are being questioned. In our culture, parents of DSD newborns usually want their children to undergo genital surgery as soon as possible after sexual assignment, as surgery helps them to confirm the assigned sex. Developmental psychology theories back this hypothesis. They state that anatomic differences between sexes initiate the very important process of identification with the parent of the same sex. Sex-related endocrinological issues also demand early care. For example, using dihydrotestosterone cream to increase penile length or growth hormone treatment to improve final height require intervention at young ages to obtain better results. Although the timing of surgery remains controversial, recent evidence suggests that male reconstruction should be performed between 6 and 18 months of age. Feminizing surgery is still somewhat controversial. Most guidelines agree that severe virilization requires surgical intervention, while no consensus exists regarding mild cases. Our perspective is that precocious binary sex assignment and early surgery is a better management method. There is no strong evidence for delays and the consequences can be catastrophic in adulthood.

Molecular cytogenetic evaluation of chromosomal microdeletions: the experience of a public hospital in Southern Brazil

Introduction: During the past few decades, the number of diseases identified to be caused by chromosomal microdeletions has increased quickly, bringing a new and crucial role for cytogenetics on the diagnosis of these conditions. The purpose of this study was to identify and characterize chromosomal microdeletions associated with malformation syndromes and intellectual disability. Methods: We retrospectively evaluated a consecutive series of samples from a cohort of 598 subjects with clinical symptoms of a microdeletion syndrome, including the deletion of chromosomes 4p16.3, 5p15.2, 5q35, 7q11.23, 8q24.12, 15q11.2, 16p13.3, 17p13.3, 17p11.2,2, and 22q11.2, as investigated by fluorescence in situ hybridization (FISH). Array-based comparative genomic hybridization (array-CGH) was performed on 25 samples with microdeletions. Results: A total of 598 samples were evaluated from patients whose clinical phenotypes were most indicative of 22q11.2 deletion syndrome (29.10%), Prader-Willi syndrome (23.41%), Angelman syndrome (16.89%), and Williams-Beuren syndrome (14.72%). In 142 of the samples (23.75%), a chromosomal imbalance associated with phenotypic abnormalities was found. The deletion of 7q11.23 was the most frequent (8.03%), followed by del22q11.2 (5.68%) and del15q11.2 (5%). Conclusion: Our study reinforces the idea that the effort to improve the capacity to perform molecular cytogenetic investigations associated with a qualified clinical evaluation is crucial for the detection and precise characterization of submicroscopic chromosome deletions, bringing benefits to patients, relatives, and genetic counselors. It also contributes to the continuing education of cytogeneticists and to the knowledge of chromosomal rearrangements associated with genomic disorders.

Fatores associados à mortalidade em recém-nascidos com gastrosquise / Associated factors for perinatal mortality in gastroschisis

OBJETIVO: Analisar a taxa de mortalidade perinatal dos casos de gastrosquise e os possíveis fatores associados. MÉTODOS: Foi realizado estudo de coorte retrospectivo entre 1992 e 2012. Foram incluídos todos os casos de gastrosquise nascidos no Hospital de Clínicas de Porto Alegre (HCPA) naquele período. O diagnóstico de gastrosquise foi obtido por meio do exame ultrassonográfico morfológico ou pelo exame clínico ao nascimento nos casos desconhecidos no pré-natal. As variáveis de nascimento (peso ao nascer, idade gestacional e escore de Apgar, modo de parto, tipo de gastrosquise e anomalias associadas) e cirúrgicas (tipo de fechamento cirúrgico, reintervenção e sepse) foram comparadas entre os casos sobreviventes e os óbitos. Os resultados desta comparação foram analisados de acordo com o tipo de variável por meio de testes paramétricos e não paramétricos (Mann-Whitney ou teste t de Student, χ² ou teste exato de Fisher) sendo considerado o nível de significância de 5% (p=0,05). RESULTADOS: Foram incluídos 64 recém-nascidos com gastrosquise, 59 deles (92,2%) diagnosticados durante o pré-natal. Vinte e seis casos (40,6%) tinham somente intestino exposto, classificados como gastrosquise simples, 22 tinham intestino e estômago (34,4%) e 16 tinham intestino e outros órgãos (25%), totalizando 38 casos de gastrosquise complexa. O reparo cirúrgico primário foi realizado em 44 casos (68,8%). A mortalidade foi de 23,4% (15 mortes). Os casos de óbito tinham peso ao nascer (p=0,001), escore de Apgar (p=0,03) e idade gestacional (p=0,03) significativamente menores que os sobreviventes. Não houve diferença no modo de parto (p=0,8) e, com relação ao conteúdo eviscerado, não houve diferença entre os casos de gastrosquise simples e complexa (p=0,06). A mortalidade foi significativamente mais elevada entre os casos que necessitaram de reintervenção (p=0,001) e com sepse (p=0,008). CONCLUSÃO: A mortalidade perinatal da gastrosquise parece depender principalmente da prematuridade, baixo peso e complicações cirúrgicas.

PURPOSE: To analyze the perinatal mortality rate in cases of gastroschisis and possible associated factors. METHODS: A retrospective cohort study was conducted between 1992 and 2012. All cases of gastroschisis born in Hospital de Clínicas de Porto Alegre (HCPA) during that period were included. The diagnosis of gastroschisis was obtained by morphological ultrasound examination or clinical examination at birth in prenatally unknown cases. The variables of birth (birthweight, gestational age and Apgar score, mode of delivery, type of gastroschisis and associated anomalies) and the surgical ones (type of surgical closure, reintervention and sepsis) were compared between surviving cases and deaths. The results of this comparison were analyzed according to the type of variable using parametric and non-parametric tests (Mann-Whitney or Student's t-test, χ² or Fisher's exact test), with the level of significance set at 5% (p=0.05). RESULTS: Sixty-four newborns with gastroschisis were included, 59 of them (92.2%) diagnosed during the prenatal period. Twenty-six patients (40.6%) had only exposed intestines, classified as simple gastroschisis, 22 had exposure of the intestines and stomach (34.4%) and 16 had exposure of the intestine and other organs (25%), for a total of 38 cases of complex gastroschisis. Primary surgical repair was performed in 44 cases (68.8%). The mortality rate was 23.4% (15 deaths). Babies who died had significantly lower birth weight (p=0.001), gestational age (p=0.03) and Apgar score (p=0.03) than survivors. There was no difference in mode of delivery (p=0.8) and, with respect to gut contents, there was no difference between the cases of simple and complex gastroschisis (p=0.06). Mortality was significantly higher in patients with sepsis (p=0.008) and reintervention (p=0.001). CONCLUSION: in the present study, perinatal mortality due to gastroschisis seemed to depend mainly on prematurity, low birth weight, and surgical complications.

[Associated factors for perinatal mortality in gastroschisis]. / Fatores associados à mortalidade em recém-nascidos com gastrosquise.

PURPOSE: To analyze the perinatal mortality rate in cases of gastroschisis and possible associated factors. METHODS: A retrospective cohort study was conducted between 1992 and 2012. All cases of gastroschisis born in Hospital de Clínicas de Porto Alegre (HCPA) during that period were included. The diagnosis of gastroschisis was obtained by morphological ultrasound examination or clinical examination at birth in prenatally unknown cases. The variables of birth (birthweight, gestational age and Apgar score, mode of delivery, type of gastroschisis and associated anomalies) and the surgical ones (type of surgical closure, reintervention and sepsis) were compared between surviving cases and deaths. The results of this comparison were analyzed according to the type of variable using parametric and non-parametric tests (Mann-Whitney or Student's t-test, χ² or Fisher's exact test), with the level of significance set at 5% (p=0.05). RESULTS: Sixty-four newborns with gastroschisis were included, 59 of them (92.2%) diagnosed during the prenatal period. Twenty-six patients (40.6%) had only exposed intestines, classified as simple gastroschisis, 22 had exposure of the intestines and stomach (34.4%) and 16 had exposure of the intestine and other organs (25%), for a total of 38 cases of complex gastroschisis. Primary surgical repair was performed in 44 cases (68.8%). The mortality rate was 23.4% (15 deaths). Babies who died had significantly lower birth weight (p=0.001), gestational age (p=0.03) and Apgar score (p=0.03) than survivors. There was no difference in mode of delivery (p=0.8) and, with respect to gut contents, there was no difference between the cases of simple and complex gastroschisis (p=0.06). Mortality was significantly higher in patients with sepsis (p=0.008) and reintervention (p=0.001). CONCLUSION: in the present study, perinatal mortality due to gastroschisis seemed to depend mainly on prematurity, low birth weight, and surgical complications.

Clinical variability in KBG syndrome: report of three unrelated families.

The KBG syndrome is characterized by short stature, macrodontia, a specific combination of minor anomalies, developmental delay, and/or mental retardation. We reported on four patients from three unrelated families. The most frequent clinical findings were: atypical face, long/flat philtrum, thin upper lip, macrodontia, dental malposition, enamel hypoplasia, and cleft teeth. Skeletal anomalies such as cervical ribs and vertebral abnormalities were also noted. Hand anomalies were observed in three patients. Mental retardation and developmental delay were present in three of the four patients. There is wide clinical variability in the expression of this syndrome. The males are usually more severely affected then the females, suggesting possible X-linked inheritance in some cases.

Fatores de risco para gastrosquise: revisão de literatura / Gastroschisis risk factors: a literature review

Gastrosquise é malformação da parede abdominal que em média tem 1 a 5 cm, é paraumbilical e geralmente está localizada à direita. A exteriorização de estruturas intra-abdominais, principalmente do intestino, pode ocorrer através deste defeito. Sua etiologia não está definida. A principal hipótese é que este defeito resulte da disrupção da artéria onfalomesentérica direita no período da organogênese. Estudos caso-controle estão sendo realizados para a determinação de fatores de risco, o que poderia trazer pistas sobre a etiologia do defeito. De todos os possíveis fatores de risco estudados, somente a idade materna abaixo de 25 anos está realmente associada. Os demais fatores tiveram razões de chance estatisticamente significativos, mas os intervalos de confiança foram grandes demais para se estabelecer correlação fidedigna. Baseado nos resultados dos estudos realizados até o momento, pode-se dizer que a gastrosquise não tem herança mendeliana, e possivelmente decorra da associação de predisposição genética e de fatores ambientais desencadeantes. Somente com o esclarecimento da fisiopatologia deste defeito é que conseguiremos estudar melhor os fatores de risco associados e reconhecer a população de mulheres que necessita de maiores cuidados e acompanhamento para prevenir este defeito

Avaliação de teratógenos potenciais na população brasileira / Evaluation of potential teratogens in Brazilian population

O fato de agentes ambientais, nomeadamente fármacos, infecções maternas, e agentes químicos ou físicos poderem causar danos ao embrião ou feto em desenvolvimento é um problema reconhecido principalmente a partir do século 20. Nos países em desenvolvimento, existem características especiais que podem tornar esse problema mais agudo. Essas características incluem níveis educacionais e econômicos baixos da população, alta incidência de doenças infecciosas e carenciais, escassos recursos para saúde e pesquisa, prática freqüente e sem controle de automedicação, facilidade de obtenção de medicações que deveriam estar submetidas à prescrição médica e, finalmente, proibição legal de interrupção da gestação. Além disso, pode somar-se uma qualidade ambiental precária ou mesmo condições de trabalho insalubres durante a gravidez. No presente trabalho apresentamos as principais metodologias para detecção e monitorização de potenciais teratógenos, com ênfase especial nos programas desenvolvidos no Brasil e América Latina.

Defeitos congênitos em uma regiäo de mineraçäo de carväo / Population risk for birth defects in a coal mining region

Objetivo: Avaliar a relação entre o impacto ambiental decorrente da extração de carvão e sua repercussão na saúde reprodutiva de uma população, residente em pequenas cidades do Sul do Brasil, pela observação da freqüência de defeitos congênitos nos recém-nascidos. Métodos: Foram monitoradas as freqüências de oito defeitos congênitos em 10.391 nascidos vivos, ocorridos no período de janeiro de 1985 a dezembro de 1995 em um hospital localizado no município de São Jerônimo, RS. Destes, foram selecionados oito maiores defeitos congênitos, e a análise de suas prevalências ao nascimento visou reduzir os possíveis erros-diagnósticos. As taxas de defeitos congênitos foram comparadas às de outros hospitais geograficamente próximos e às fornecidas pelo Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC) para a América Latina. Resultados/Conclusões: As freqüências observadas não diferiram das encontradas em hospitais regionais e no ECLAMC. O pequeno número de crianças avaliadas mostra apenas algumas tendências, concluindo serem necessários outros estudos mais profundos

Síndrome de Down: caracteristicas clínicas, perfil epidemiológico e citogenético em recém-nascidos no Hospital de Clínicas de Porto Alegre / Down syndrome: clinical characteristics, epidemiologic and cytogenetic profile in newborns at the Hospital de Clínicas de Porto Alegre

Säo descritas as características dos recém-nascidos com Síndrome de Down no HCPA entre junho 1988 e março de 1995 com relacao a frequencia de achados fenotipicos, perfil citogenetico e fatores de risco, usando controles contemporaneos. A incidencia de Sindrome de Down no HCPA foi de 2,21 por 1000 nascimentos. As caracteristicas mais frequentes foram: fendas palpebrais obliquas, hipotonia muscular, perfil facial achatado, epicanto, clinodactilia e prega simiesca. Os casos foram significativamente diferentes dos controles com relacao a peso ao nascer, idade da mae e do pai e apresentacao ao parto. Dos 39 casos que realizaram cariotipagem, 33 eram trissomias livres, 4 translocacoes e 2 mosaicos. Os dados da casuistica do HCPA sao condizentes com a literatura em relacao ao perfil citogenetico, caracteristicas fenotipicas e fatores associados. O conhecimento das caracteristicas semiologicas mais frequentes na populacao local e importante para realizar um rastreamento adequado