Introdução: A insuficiência velofaríngea (IVF) é um sinal clínico da Síndrome Velocardiofacial (SVCF), sendo a cirurgia uma opção do tratamento. Objetivo: avaliar indivíduos com sinais clínicos de SVCF, comparativamente a indivíduos com fissura de palato isolada (FPI) e a indivíduos com fissura de palato submucosa (FPSM), visando verificar diferenças entre os grupos em relação à fala e a função velofaríngea antes da cirurgia; redução ou eliminação da hipernasalidade, articulação compensatória, escape de ar nasal e falha velofaríngea, bem como redução ou normalização da nasalância após a cirurgia, além de diferenças entre os grupos quanto aos resultados cirúrgicos relacionado à fala e à função velofaríngea. Modelo/Participantes: Estudo prospectivo envolvendo 75 indivíduos de ambos os sexos, avaliados nos períodos pré e pós-operatório (em média 18 meses) para a correção da IVF, distribuídos em três grupos: com sinais clínicos da SVCF (n=25), com fissura de palato isolada (FPI) reparada e sem sinais de síndrome (n=25) e com fissura de palato submucosa (FPSM) não operada e sem sinais de síndrome (n=25). Local de execução: Hospital de Reabilitação de Anomalias Craniofaciais, Universidade de São Paulo. Variáveis: A fala foi avaliada por três juízes por meio da avaliação perceptivoauditiva e considerando-se a opinião da maioria, quanto aos aspectos hipernasalidade, hiponasalidade e articulação compensatória, além da avaliação do escape de ar nasal e da nasometria, adotando como adequados os valores de nasalância _27%; a função velofaríngea foi avaliada a partir da nasoendoscopia, que determinou a presença e o tamanho da falha velofaríngea. Na análise dos dados utilizou-se o coeficiente de concordância Kappa e os testes Kruskal-Wallis ANOVA, Wilcoxon, McNemar e Qui-quadrado, adotando-se como significantes o valor de p<0,05. Resultados: Após a cirurgia, verificou-se melhora/redução significativa em 20%, 31% e 36% dos pacientes do grupo SVCF, em 24%, 30% e 18% do grupo FPI e em 24%, 30% e 30% do grupo FPSM quanto a hipernasalidade, nasalância e função velofaríngea, respectivamente. Em termos de resolução dos sintomas, as proporções obtidas após a cirurgia foram 28%, 19% e 8% no grupo SVCF, 48%, 41% e 32% no grupo FPI e 20%, 40% e 25% no grupo FPSM para hipernasalidade, nasalância e função velofaríngea, respectivamente. Conclusão: antes da cirurgia não houve diferença entre os grupos quanto a fala para os aspectos hipernasalidade, articulação compensatória e escape de ar nasal, bem como quanto ao tamanho da falha velofaríngea, mas em relação à nasalância, o grupo SVCF apresentou valores maiores que os do grupo FPI, não diferindo do grupo FPSM; a cirurgia reduziu a hipernasalidade, a nasalância e a falha velofaríngea em todos os grupos, reduziu o escape de ar nasal e normalizou a nasalância nos grupos FPI e FPSM, não reduzindo ou eliminando a articulação compensatória em todos os grupos; já, a eliminação da hipernasalidade ocorreu nos grupos SVCF e FPI e da falha velofaríngea no grupo FPI; e não há diferença entre os grupos em relação aos resultados cirúrgicos relacionado à fala quanto aos aspectos hipernasalidade, nasalância, escape de ar nasal e articulação compensatória, bem como relacionado à função velofaríngea. / Introduction: Velopharyngeal insufficiency (VPI) is a clinical sign of the Velocardiofacial Syndrome (VCFS), and surgery is among the treatment options. Objective: To evaluate individuals with clinical signs of VCFS, compared to individuals with isolated cleft palate (ICP) and individuals with submucous cleft palate (SMCP), aiming to analyze the differences between groups regarding speech and velopharyngeal function before surgery; reduction or elimination of hypernasality, compensatory articulation, nasal air escape and velopharyngeal gap, as well as reduction or normalization of nasalance after surgery, besides differences between groups according to the surgical outcomes related to the speech and velopharyngeal function. Design/Participants: Prospective study involving 75 individuals of both genders, evaluated prior and pos surgery (in the average of 18 months) for VPI correction, divided into three groups: with clinical signs of VCFS (n=25), with operated isolated cleft palate without signs of syndromes (ICP) (n=25), and with unoperated submucous cleft palate without signs of syndromes (n=25). Setting: Hospital for Rehabilitation of Craniofacial Anomalies, University of de São Paulo. Main outcome measures: The speech was evaluated by three examiners using the auditory perceptual evaluation and considering the opinion of the majority, addressing the aspects of hypernasality, hyponasality and compensatory articulation, as well as evaluation of nasal air escape and nasometry, considering nasalance values _27% as adequate; the velopharyngeal function was evaluated by nasoendoscopy, which determined the presence and size of the velopharyngeal gap. Data were analyzed by the Kappa coefficient of agreement and the statistical tests Kruskal-Wallis ANOVA, Wilcoxon, McNemar and chi-square, at a significance level of p<0.05. Results: In the post surgery period, there was significant reduction in 20%, 31% and 36% for patients in the VCFS group; 24%, 30% and 18% for the ICP group; and 24%, 30% and 30% for the SMCP group in the hypernasality, nasalance and velopharyngeal function, respectively. Concerning the resolution of symptoms, the post surgery proportion obtained were 28%, 19% and 8% for the VCFS group; 48%, 41% and 32% for the ICP group; and 20%, 40% and 25% for the SMCP group for hypernasality, nasalance and velopharyngeal function, respectively. Conclusion: In the prior surgery period, there was no difference in speech between groups concerning the aspects hypernasality, compensatory articulation and nasal air escape, as well as in the extent of velopharyngeal gap. However, concerning the nasalance, the VCFS group exhibited higher values than the ICP group, with no significant difference compared to SMCP group. The surgery reduced the hypernasality, nasalance and velopharyngeal gap in all groups, reduced the nasal air escape and normalized the nasalance in the ICP and SMCP groups, yet the compensatory articulation was not reduced or eliminated in all groups. Conversely, there was elimination of hypernasality in the VCFS and ICP groups and the velopharyngeal gap was eliminated in the ICP group. There was no difference between groups in the surgical outcomes of speech in relation to the aspects hypernasality, nasalance, nasal air escape and compensatory articulation, as well as in relation to the velopharyngeal function.

Objetivo: Descrever as manifestações clínicas de indivíduos com hipótese diagnostica da Sindrome de deleção 22q11 (SD22q11) confirmados por testes genéticos, na primeira avaliação e durante o acompanhamento dos mesmos em avaliações subsequentes para uma melhor definição do curso natural da doença. Local: Laboratório de Genética e Citogenética Humana do HRAC-USP Bauru/SP. Casuística e metodologia: O presente trabalho é retrospectivo e analisou os dados de prontuários de 72 indivíduos cadastrados no HRAC-USP, os quais receberam hipótese diagnóstica da SD22q11 e foram confirmadas por teste genético (MLPA ou FISH). A avaliação envolveu a analise dos dados relatados por todos os setores do HRAC-USP. Resultados e discussão: Foramanalisados 72prontuários deindivíduos com a SD22q11. Constatamos que a idade media dos indivíduos quando do cadastro no HRAC-USP foi de seis anos. Também constatamos que houve um longo período de tempo entre os retornos ao hospital e que, nesses retornos, nem todas as especialidades foram contempladas. Esses fatos prejudicaram a analise da historia natural da anomalia em questão. Com relação às características fenotipicas, observamos a presença de sinais clínicos típicos, como por exemplo: face alongada, lábios finos, hipoplasia alar, anormalidades menores na orelha, dígitos longos e fendas palpebrais, fissuras labiopalatinas, cardiopatias congenitas, dificuldade de aprendizagem, atraso de linguagem e distúrbios comportamentais. A fissura oral foi à manifestação otorrinolaringológica mais frequente, presente em 75% dos pacientes, onde as fissuras submucosas foram as mais frequentes (43%). As características cognitivas como, atraso de fala (87%), dificuldades de aprendizagem (95%) e distúrbios comportamentais (81%), tiveram um resultado significativo, descritas em quase todos os indivíduos. As cardiopatias congênitas estavam presentes em 47,2% dos prontuários analisados. De um modo geral, comparando a frequência dos sinais clínicos encontrados neste trabalho com dados da literatura, constatamos que as frequências encontram-se dentro do esperado. Conclusão: A maioria dos indivíduos cadastrados no HRAC-USP, pertencentes ao grupo de estudo, apresentou idade superior a 06 anos. Portanto, a observação do curso natural da historia da SD22q11 para avaliar características fenotípicas que surgissem ao longo da evolução clinica do indivíduo e que pudessem ajudar no diagnóstico, ficou prejudicada. Mesmo nos casos onde o indivíduo foi cadastrado no HRAC-USP com idade inferior a dois anos, o diagnóstico foi tardio devido a falta de uma ação multidisciplinar e interdisciplinar no hospital. Mesmo não sendo possível avaliar as características fenotípicas surgidas durante a historia natural da doença, constatamos que as manifestações clínicas relatadas nos prontuários cursam com as características da SD22q11 e em frequências que corroboram com as da literatura / To describe clinical manifestations observed in medical records of individuals registered in the hospital with a diagnostic hypothesis of 22q11.2DS confirmed by genetic tests (MLPA OR FISH), since the first assessment in the HRAC-USP and during the follow up of these individuals in subsequent assessments, in order to achieve a better definition to the natural courses of the disease. Local: Laboratory of Human Genetics and Cytogenetics (HRAC-USP Bauru/SP). Methods: This retrospective study analyzed 72 medical records of individuals registered at the HRAC-USP, who were diagnosed with 22q11DS and who had this diagnosis confirmed by a genetic test (MLPA OR FISH). The assessment concerned the analysis of reported data in all sectors of the HRAC-USP. Results and Discussion: 72 medical records of individuals with 22q11DS were analyzed. It was verified that the average age of individuals when registering at the HRAC-USP was six years old. It was also verified that it took a long period of time for these individuals to return to the hospital and, when they did, not all specialties were contemplated. These facts harmed the analysis of the natural history of the anomaly. About the phenotypic characteristics, some typical clinical signs were observed, such as: long face, thin lips, hypoplasia nasal alar, minor abnormalities in the ear, long digits and narrow palpebral fissures, palatal abnormalities, congenital heart defects, learning disabilities, delay speech and behavioral disorders. An oral cleft was the most frequent otorhinolaryngology manifestation, present in 75% of the patients; among which submucous cleft palate were the most frequent (43%). Cognitive features such as, delay speech (87%), learning disabilities (95%) and behavioral disorders (81%) had a significant result, described in almost all individuals. Congenital heart defects were observed at 4% to 48% of individuals with 22q11.2DS, in this study it was observed in 47.2%. In general, comparing the frequency of some clinical signs observed in this study with the literature data, it was verified that the frequencies were within expectations. Conclusion: Most of the individuals registered at the HRAC belonging to the study group were over 6 years old. Therefore, the observation of natural course of the history of 22q11DS to evaluate the phenotypic characteristics that would arise during the clinical evolution of the individual and that could help in the diagnosis was harmed. Even in cases when the individual was registered at the HRAC-USPunder the age of two, the diagnosis was delayed due to lack of a multidisciplinary and interdisciplinary action in the hospital. Even not being possible to measure the phenotypic characteristics that emerged during the natural history of the disease, it was verified that the clinical manifestations reported in the records occur with the 22q11DS characteristics and in frequencies that corroborate with the literature

Neurological abnormalities are associated with emotion processing deficits seen in children with neurodevelopmental disorders. Research suggests that inflammatory mechanisms can negatively impact brain structure and function and are thought to play a role in these processing atypicalities. Children with chromosome 22q11.2 deletion syndrome (22q11.2DS) exhibit emotion processing impairments and associated neural abnormalities. We investigated the roles of inflammatory factors and structural connectivity in relation to emotion processing deficits in 28 children with 22q11.2DS and 33 typically developing children (M = 11.12 years old; SD = 2.17). Results indicate poorer social skills and significantly lower emotion recognition scores in children with 22q11.2DS compared to controls. Additionally, children with 22q11.2DS had higher anisotropic diffusion in right amygdala to fusiform gyrus white matter pathways and lower serum IL-3 concentrations than their typically developing peers. Right amygdala to fusiform gyrus FA values partially mediated the relationship between 22q11.2DS and social skills, as well as the relationship between 22q11.2DS and emotion recognition accuracy. However, there was no indication that IL-3 mediated the relationship between diagnosis and abnormal connectivity. Future studies should employ longitudinal methods to characterize how these connectivity patterns influence social-emotional development as the child ages.

No description available.

No description available.

Craniofacial malformations arise from developmental defects in the head, face, and neck and account for one third of congenital defects at birth. Clinical phenotypes such as DiGeorge Syndrome, the most common microdeletion condition, illustrate a developmental link between cardiovascular and craniofacial morphogenesis. Moreover, recent fate mapping studies in mice and zebrafish support this notion through identification of a multipotent progenitor in the cardiopharyngeal field that gives rise to the heart, branchiomeric muscles, and pharyngeal arch (PA) arteries. NKX2-5 is a key cardiac transcription factor associated with human congenital heart disease and mouse models of Nkx2-5 deficiency highlight critical roles in cardiac development. In zebrafish, nkx2.5 and nkx2.7 are paralogous genes in the NK4 family expressed in cardiomyocytes and PAs. Despite the shared cellular origins of cardiac and craniofacial tissues, the function of NK4 factors in head and neck patterning has not been elucidated. Here, we demonstrate that Nkx2.7 serves as a previously unappreciated, crucial regulator of craniofacial muscle and cartilage formation. Our studies reveal a unique requirement for nkx2.7 in PA1- and PA2-derived branchiomeric muscle and cartilage elements for which nkx2.5 cannot compensate. Moreover, molecular evolutionary analysis of NK4 genes reveals that nkx2.5 and nkx2.7 are ohnologs resulting from two rounds of vertebrate whole genome duplications with an early split between them, underscoring the concept that these genes play independent roles during development. The distinct mechanistic function of nkx2.7 is elucidated by cell counting experiments that uncover the requirement of nkx2.7 in specification of PA1 and PA2 branchiomeric muscle progenitors. Furthermore, single cell RNA-sequencing performed on microdissected PA tissues from wild-type and nkx2.7-/- embryos identifies decreased expression of the ventral neural crest gene signature essential for cartilage and jaw joint morphogenesis. Together, our studies shed light on an evolutionarily conserved, unique function of Nkx2.7 in vertebrate craniofacial development and have the potential to advance our understanding of the etiologies and therapeutic interventions for patients with congenital deformities of the head and neck.

Stress and anxiety negatively impact the working memory system by competing for executive resources. Broad memory deficits have been reported in individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS). We investigated anxiety and physiological stress reactivity in relation to visuospatial working memory impairments in 20 children with 22q11.2DS and 32 typically developing children (M = 11.10 years, SD = 2.95). Results indicate reduced post-stress RSA recovery and overall increased levels of cortisol in children with 22q11.2DS. Additionally, anxiety mediated the relationship between 22q11.2DS and visuospatial working memory impairment. However, there was no indication that stress response physiology mediated this association. Results suggest that anxiety exacerbates impaired working memory in children with 22q11.2DS. Thus, treatment and intervention methods for children with 22q11.2DS should address anxiety related symptomology.