A Clinical Study Of 31 Individuals With Midline Facial Defects With Hypertelorism And A Guideline For Follow-up.

In order to contribute to clinical delineation of midline facial defects with hypertelorism (MFDH) and to etiologic diagnosis of the isolated form, 31 patients with MFDH unaffected by known syndromic associations were evaluated. Group A included patients personally examined by the authors, while Group B included those previously evaluated by other geneticists. Among the 14 patients from Group A, there were 7 with distinct pictures of multiple congenital anomalies. In Group B, 5 of the 17 patients also exhibited a distinct pattern of defects. Among isolated MFDH, there was association with anomalies of the skull and facial bones (13/14), otorhinologic (11/16), central nervous system (9/16), and ocular (6/7), and audiologic (3/16); 1/3 of the cases had a relevant gestational intercurrences. Isolated FNM may have involvement of environmental components in some cases; the possibility of a syndromic picture should be extensive investigated. Follow-up of such patients must include the examinations herein performed.65396-40

Craniofacial anomalies: description and evaluation of treatment under the Brazilian Unified Health System

The first initiative for treating craniofacial anomalies under the Brazilian Unified Health System was in 1993. An important step was the creation of the Reference Network for Craniofacial Treatment. There are now 29 services listed in this Network. The current study aimed to describe and assess the general characteristics of healthcare in this Network. Data were colleted by a questionnaire, sent to the centers. Response rate was 86.2%. The results showed an increase in services in Southeast Brazil, in universities, and in relation to cleft lip and palate; public financing was prevalent; team composition was largely in accordance with North American standards; routine care occurred in 90%; and 70% used clinical protocols. The Network's name does not appear to entirely reflect its scope. The results show the need to review the Network's definition, aims, and achievements and the standards for inclusion of craniofacial centers.A primeira iniciativa para incluir a atenção às anomalias craniofaciais no SUS ocorreu em 1993. Um importante avanço foi a criação da Rede de Referência no Tratamento de Deformidades Craniofaciais (RRTDCF), atualmente com 29 centros credenciados. Os objetivos deste estudo foram descrever e avaliar as características gerais da atenção às anomalias craniofaciais nos centros que integram a referida rede. Foi utilizado questionário semi-estruturado, remetido por correio. Obteve-se 86,2% de respostas. Os resultados demonstram agregação de centros no Sudeste, em universidades e na área de fissuras labiopalatais; financiamento predominantemente público; equipes constituídas principalmente de acordo com parâmetros norte-americanos; atendimento de rotina em cerca de 90% e utilização de protocolos em cerca de 70% dos centros. A denominação da RRTDCF não parece corresponder à sua abrangência. Os achados sugerem necessidade de revisão da definição, objetivos e abrangência da RRTDCF e dos critérios de credenciamento de centros.91392

Developmental aspects of oral language in craniosynostosis

BACKGROUND: aspects of language development in craniosynostosis. Craniosynostosis (premature fusion of the cranial sutures) has an incidence of 0.4 to 1/1.000 newborns. Etiology for this congenital anomaly includes environmental and genetic factors. Regarding the form of presentation, it can occur in its isolated form or associated to other congenital anomalies. For this last group, acrocephalosyndactilies are observed. These are genetically determined conditions which present phenotypic similarity, including the following syndromes: Saethre-Chotzen, Apert, Crouzon e Pfeiffer. As all of these conditions affect the craniofacial development, it is possible to find anatomic and functional interferences which determine language delays and/or deficits. AIM: to revise the literature concerning aspects related to normal verbal language development and to describe the main characteristics associated to this condition in children who present Apert, Crouzon, Pfeiffer and Saethre-Chotzen syndromes. A systematic review on syndromic craniosynostosis and oral language was performed, consulting Medline, Lilacs and other important references on this theme. CONCLUSION: several manifestations related to hearing and language have been detected in individuals with syndromic craniosynostosis. The most important are alterations in the sound conduction system, leading to hearing losses, and consequently interfering in language acquisition and development. For this reason, speech-language diagnosis and early intervention are recommended in order to eliminate or minimize damages in language acquisition and development.TEMA: aspectos sobre o desenvolvimento de linguagem oral em craniossinostoses sindrômicas. As craniossinostoses (fusão precoce das suturas cranianas) apresentam incidência em torno de 0,4 a 1/1.000 nativivos. Estas podem ocorrer devido a fatores ambientais ou genéticos. Com relação à forma de apresentação, estas podem ocorrer de maneira isolada ou associada a outros defeitos congênitos. Neste último grupo, destacam-se as acrocefalossindactilias, condições geneticamente determinadas, que apresentam similaridade fenotípica, sendo estas as síndromes de Saethre-Chotzen, Apert, Crouzon e Pfeiffer. Diante destas condições complexas que envolvem o arcabouço craniofacial, é possível encontrar interferências anatômicas e funcionais que determinem atrasos e/ou desvios de linguagem. OBJETIVO: revisar a literatura acerca dos aspectos fonoaudiológicos relacionados ao desenvolvimento normal da linguagem oral e descrever as principais características associadas a ela apresentadas por crianças com síndromes de Apert, Crouzon, Pfeiffer e Saethre-Chotzen. Foi realizada revisão sistemática de estudos sobre as craniossinostoses sindrômicas e dados referentes a linguagem oral nestes casos. Para isso, utilizou-se pesquisa na base de dados Medline e Lilacs, assim como outras publicações importantes para a conclusão do artigo. CONCLUSÃO: diversas manifestações relacionadas à audição e linguagem podem estar presentes em craniossinostoses sindrômicas. Destacam-se as alterações do sistema de condução do som, levando à perda auditiva, o que conseqüentemente prejudica a aquisição e desenvolvimento pleno da linguagem. Deste modo, recomenda-se o diagnóstico e tratamento fonoaudiológico adequados e precoces, eliminando ou minimizando os prejuízos para a aquisição e desenvolvimento da linguagem oral.21322

Rheological behavior of thermoreversible k-carrageenan/nanosilica gels

The rheological behavior of silica/κ-carrageenan nanocomposites has been investigated as a function of silica particle size and load. The addition of silica nanoparticles was observed to invariably impair the gelation process, as viewed by the reduction of gel strength and decrease of gelation and melting temperatures. This weakening effect is seen, for the lowest particle size, to become slightly more marked as silica concentration (or load) is increased and at the lowest load as particle size is increased. These results suggest that, under these conditions, the particles act as physical barriers to polysaccharide chain aggregation and, hence, gelation. However, for larger particle sizes and higher loads, gel strength does not weaken with size or concentration but, rather, becomes relatively stronger for intermediate particles sizes, or remains unchanged for the largest particles, as a function of load. This indicates that larger particles in higher number do not seem to increasingly disrupt the gel, as expected, but rather promote the formation of stable gel network of intermediate strength. The possibility of this being caused by the larger negative surface charge found for the larger particles is discussed. This may impede further approximation of neighboring particles thus leaving enough inter-particle space for gel formation, taking advantage of a high local polysaccharide concentration due to the higher total space occupied by large particles at higher loads.FCT - PTDC/QUI/67712/2006FEDE

Angular Analysis Of Corpus Callosum In 18 Patients With Frontonasal Dysplasia.

Considering the rarity of the frontonasal dysplasia (FD) and the few reports about it in a large casuistry using magnetic resonance image (MRI), we describe the results of the angular analysis of the corpus callosum of 18 individuals with FD (7 male, 11 female), using an easily-reproductive method. Group I had 12 individuals with isolated form and Group II had 6 individuals with FD syndromic with unknown etiology. The results are presented in set. Comparing with the control group, patients with FD presented alpha angle increase and beta and gamma angles reduction (p<0.05). Alpha and gamma angles express the relationship between the anterior portion of corpus callosum and the floor of 4th ventricle. Considering the embryonary development, these findings would occur secondarily to failure during the development of nasal capsula. Thus, angular anomaly in corpus callosum would be a usual finding, and not fortuitous in patients with FD.62195-

Análise angular do corpo caloso em 18 pacientes com displasia frontonasal

Considering the rarity of the frontonasal dysplasia (FD) and the few reports about it in a large casuistry using magnetic resonance image (MRI), we describe the results of the angular analysis of the corpus callosum of 18 individuals with FD (7 male, 11 female), using an easily-reproductive method. Group I had 12 individuals with isolated form and Group II had 6 individuals with FD syndromic with unknown etiology. The results are presented in set. Comparing with the control group, patients with FD presented alpha angle increase and beta and gamma angles reduction (p<0.05). Alpha and gamma angles express the relationship between the anterior portion of corpus callosum and the floor of 4th ventricle. Considering the embryonary development, these findings would occur secondarily to failure during the development of nasal capsula. Thus, angular anomaly in corpus callosum would be a usual finding, and not fortuitous in patients with FD.Considerando a raridade da displasia frontonasal (DF) e os poucos estudos sobre esta condição clínica usando ressonância magnética (RM), descrevemos os resultados da análise angular do corpo caloso em 18 indivíduos com DF (7 homens, 11 mulheres), usando um método de fácil reprodução. O Grupo I foi formado por 12 indivíduos com DF isolada e o Grupo II, por 6 portadores de DF sindrômica de etiologia desconhecida. Não houve diferença entre os grupos, e os dados são apresentados em conjunto. Comparando com o grupo controle, houve aumento significativo do ângulo alfa e redução dos ângulos beta e gama (p<0,05) Os ângulos alfa e gama expressam a relação entre a porção anterior do corpo caloso e do piso do 4º ventrículo. Esses achados radiológicos poderiam ocorrer secundariamente à falência do desenvolvimento da cápsula nasal. Assim, as anomalias angulares no corpo caloso poderiam ser um achado usual, e não fortuito, na DF.19519

Testing criteria for 22q11.2 deletion syndrome: preliminary results of a low cost strategy for public health

The clinical heterogeneity of the 22q11.2 Deletion Syndrome (22q11.2DS - OMIM, #188400 and #192430) is a universal challenge leading to diagnostic delay. The aim of this study was to evaluate a low cost strategy for the diagnosis of this condition based upon clinical criteria previously reported. Health professionals, who collected clinical data, from twelve centers were trained in those criteria, which were summed through an online application (CranFlow).ResultsClinical and laboratorial data of 347 individuals registered from 2008 to 2017 in the Brazilian Database on Craniofacial Anomalies/22q11.2 Deletion Syndrome, were reviewed. They were divided in two groups: (I) 168 individuals investigated before the definition of the criteria and (II) 179 individuals investigated after the criteria application. All of them were investigated for 22q11.2DS by Fluorescent in situ Hybridization (FISH) and/or Multiplex Ligation Probe-dependent Amplification (MLPA), detecting 98 cases with 22q11.2DS. Among the individuals with 22q11.2DS in Group II, 42/53 (79.25%) fulfilled the proposed criteria against 11/53 (20.75%) who did not fulfill them (p<.0001). The association of congenital heart diseases with high predictive value for 22q11.2DS and hypernasal voice were significantly associated to the presence of 22q11.2DS (p=0.0172 and p<.0001, respectively). In addition, 22q11.2DS was confirmed 3.82 more times when the individuals fulfilled the proposed criteria. Of the 249 cases negative for the typical deletion in 22q11.2, Chromosomal Microarray Analysis (CMA) was performed in 132 individuals and detected pathogenic alterations at other genomic regions in 19 individuals, and variants of uncertain clinical significance in 31 cases.ConclusionsTherefore, a locus-specific approach could be used to individuals with positive criteria as a cost-effective alternative for 22q11.2DS diagnosis. The authors discuss advantages and suggest ways of implementing this approach to investigate 22q11.2DS in a public health system14CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP#460422/2014–6; #305985/2017–5Sem informação# 2012/51799–

Cranial nerve cavernous malformations causing trigeminal neuralgia and chiasmal apoplexy: report of 2 cases and review of literature

Objective: To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Subjects and methods: Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. Results: The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Conclusions: Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium.Objetivo: Verificar se a hibridização in situ por fluorescência (FISH) em células de mucosa oral poderia ser empregada para detectar criptomosaicismo com linhagem 45,X em pacientes 46,XY. Sujeitos e métodos: Amostra de 19 jovens saudáveis 46,XY e cinco pacientes com distúrbios da diferenciação do sexo (DDS), quatro 45,X/46,XY e um 46,XY. FISH com sondas específicas para X e Y em núcleos interfásicos de linfócitos e mucosa oral para investigar a proporção de núcleos contendo apenas o sinal do cromossomo X. Resultados: A frequência de núcleos contendo apenas o sinal do X nos dois tecidos dos homens saudáveis não diferiu (p = 0,69). Em todos os pacientes com DDS essa frequência foi significativamente maior, e também não houve diferença entre os dois tecidos (p = 0,38). Conclusões: A investigação de mosaicismo com linhagem 45,X em pacientes com DDS 46,XY ou esterilidade pode ser feita por FISH diretamente em células de mucosa oral

Uso da fish em mucosa oral para investigação de mosaicismo com linhagem 45,x: estudo com homens saudáveis e pacientes com distúrbios da diferenciação do sexo

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOObjective: To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Subjects and methods: Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. Results: The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Conclusions: Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium. © ABE&M todos os direitos reservados.To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Subjects and methods: Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. Results: The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Conclusions: Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium584328334FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2011/50189-7Verificar se a hibridização in situ por fluorescência (FISH) em células de mucosa oral poderia ser empregada para detectar criptomosaicismo com linhagem 45,X em pacientes 46,XY. Sujeitos e métodos: Amostra de 19 jovens saudáveis 46,XY e cinco pacientes com distúrbios da diferenciação do sexo (DDS), quatro 45,X/46,XY e um 46,XY. FISH com sondas específicas para X e Y em núcleos interfásicos de linfócitos e mucosa oral para investigar aproporção de núcleos contendo apenas o sinal do cromossomo X. Resultados: A frequência de núcleos contendo apenas o sinal do X nos dois tecidos dos homens saudáveis não diferiu (p =0,69). Em todos os pacientes com DDS essa frequência foi significativamente maior, e tambémnão houve diferença entre os dois tecidos (p = 0,38). Conclusões: A investigação de mosaicismo com linhagem 45,X em pacientes com DDS 46,XY ou esterilidade pode ser feita por FISHdiretamente em células de mucosa ora

Desequilíbrios genômicos na cardiopatia congênita sindrômica

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. © 2017 Sociedade Brasileira de Pediatria.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 screen935497507FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2008/10596-0, 2008/50421-4, 2009/08756-1, 2011/23794-7149600/2010-0, 471422/2011-8; 471422/2011-8; 2011/23794-7Identificar desequilíbrios genômicos patogênicos em pacientes que apresentam cardiopatias congênitas (CC) e anomalias extracardíacas e exclusão da síndrome de deleção 22q11.2 (SD22q11.2). Foram avaliados por microarray cromossômico (CMA) 78 pacientes neg