Infants, toddlers and young children with cleft lip and palate (CLP) often present with multiple risk profiles due to the complex interaction between genotypical, phenotypical and environmental risk factors influencing their communication development at different ages. Current research recommends the need for a comprehensive early communication intervention (ECI) approach to the treatment of young children with CLP. The areas of strength and weakness in communication development and the factors influencing children with CLP at specific age-group intervals are under-emphasized. The aim of this study was to identify and describe the age-specific risk factors and assets which could influence the communication development of young children with CLP visiting a university-based ECI clinic, the Clinic for High-Risk Babies (CHRIB). Furthermore, the developmental areas of strength and weakness in the child with CLP at three specific age-group intervals, ranging from 1 month to 48 months were described. A retrospective, descriptive, between-subject developmental design with a correlation approach was employed. Purposive sampling was implemented as a non-randomized sampling method and 227 participants were included in the study. The data was extracted from the CHRIB database and analyzed by means of basic descriptive and advanced inferential statistical methods. Extensive data processing of all the potential factors that could have an influence on the early communication developmental areas of children with CLP was performed. A final analysis of the most important associations was performed in the SPSS. The findings revealed that expressive and receptive language and listening skills presented as the most vulnerable communication areas across all three age-groups. The cumulative effect of the risk factors was the greatest in the *[12;24) months age-group since this age group presented with the highest frequency of delayed communication development. The majority of participants in all three age-groups presented with areas of strength, which include age-appropriate cognitive skills, pragmatic development, gestural development and gross motor development. Low birth weight presented as a persistent phenotypical risk factor which influenced the development of functions related to language use in the [1;12) and [12;24) months age groups, and gross motor development and receptive language in the *[12;24) months age group. The environtypical factors such as education and occupation of the mother, as well as the type of day care, indicated significant associations with listening skill development in the [1;12) months group and with the development of functions relating to language use in the [12;24) months age group. Parent-child interaction showed recurrent significant associations with receptive and expressive language across the three age groups. The findings indicated that young children with CLP have unique communication profiles at different age intervals and that these age-specific risk factors and assets should be recognized to ensure a comprehensive approach to ECI services to these young children and their families. / Dissertation (MCommunication Pathology)--University of Pretoria, 2011. / Speech-Language Pathology and Audiology / Unrestricted

Orientadores: Ricardo Della Coletta, Ana Lucia Carrinho Ayroza Rangel / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-26T13:40:24Z (GMT). No. of bitstreams: 1 Moreira_HelenaraSalvatiBertolossi_D.pdf: 1239702 bytes, checksum: 4e6973ffe9eab3d15e1180f4b76d52d2 (MD5) Previous issue date: 2014 / Resumo: As fissuras lábio-palatinas não-sindrômicas (FL/PNS) representam as malformações faciais mais comuns em seres humanos e são causadas por uma combinação de fatores genéticos e ambientais sob um modelo de herança multifatorial. O objetivo deste estudo foi caracterizar o perfil epidemiológico (características clínicas, demográficas e ambientais) dos indivíduos afetados por FL/PNS residentes na região oeste do estado do Paraná na busca por fatores de risco para o desenvolvimento das FL/PNS e também verificar a associação de polimorfismos em genes que codificam enzimas do sistema do reparo do DNA na susceptibilidade das FL/PNS. Para a primeira parte do estudo, foram coletadas 194 amostras de saliva de pacientes com FL/PNS e seus pais, sendo que os mesmos foram entrevistados com um questionário, contendo perguntas relacionadas aos pacientes com fissura e aos seus genitores, visando levantar dados referentes aos aspectos ambientais relacionados às fissuras. A segunda parte do estudo envolveu a análise dos polimorfismos rs1136410 no gene ADPRT, rs1052133 no gene OGG1, rs1800734 no gene MLH1, rs1130409 no gene APEX1, rs861539 no gene XRCC3, rs1801321 no gene RAD51, rs25487, rs25489, rs3213245 e rs1799782 no gene XRCC1 e rs13181 e rs1799793 no gene ERCC2 em 223 trios (pai, mãe e paciente com fissura) pelo teste de desequilíbrio de transmissão (TDT). As amostras utilizadas para a investigação de polimorfismo foram provenientes de 4 Centros diferentes de tratamento da FL/P, composta por 93 trios de Minas Gerais, 74 do Paraná, 34 da Bahia e 22 da Paraíba. Entre os pacientes avaliados, um predomínio de homens, leucodermas e afetados por fissuras lábio-palatinas (FLP) foi observado. Entre as alterações sistêmicas, as otorrinolaringológicas foram significantemente mais prevalentes em fissuras palatinas (FP) em comparação com as fissuras labiais (FL; p=0,013). Mais de 80% das mães dos pacientes com FL/PNS reportaram que não fizeram uso de suplementos vitamínicos durante o primeiro trimestre de gestação. Entre os 12 polimorfismos avaliados, rs3213245 no gene XRCC1 demonstrou uma significante associação com FL (p=0,03) e rs13181 do gene ERCC2 demonstrou tendência de associação com FLP (p=0,06). O haplótipo formado pelos polimorfismos rs25487, rs25489, rs321345 e rs1799782 no gene XRCC1 também foi significantemente associado as FLs (p=0,02). Os resultados deste estudo revelaram o perfil epidemiológico dos pacientes com FL/PNS atendidos no oeste do estado do Paraná e demonstram que os polimorfismos nos genes XRCC1 e ERCC2, que codificam enzimas associadas ao sistema e reparo do DNA, podem estar associados à suscetibilidade ao desenvolvimento das FL/PNS / Abstract: Nonsyndromic cleft lip and palate (NSCL/P) represents the most common facial malformation in humans, and they are caused by a combination of genetic and environmental factors under a multifactorial model of inheritance. The objective of this study was to characterize the epidemiologic profile (clinical, demographical and environmental features) of individuals affected by the NSCL/P in the west of the Paraná state searchingfor risk factors for the development of NSCL/P, and to verify the association of polymorphisms in genes that encode enzymes of the DNA repair system in the susceptibility of the NSCL/P. For the first part of the study, 194 patients with NSCL/P and their parents were interviewed with a questionnaire containing questions associated with the patients with cleft and their parents, addressing points of environmental aspects related to the clefts only in the western of the city of Parana. The genetic study involved the analysis of the polymorphisms rs1136410 in the gene ADPRT, rs1052133 in the gene OGG1, rs1800734 in the gene MLH1, rs1130409 in the gene APEX1, rs861539 in the gene XRCC3, rs1801321 in the gene RAD51, rs25487, rs25489, rs3213245 and rs1799782 in the gene XRCC1 and rs13181 and rs1799793 in the gene ERCC2 in 223 trios (father, mother and the patient with cleft) by the disequilibrium of transmission test (TDT). The sample to the investigation of the polymorphism were from four centers of FL/PNS treatment, composed by 93 trio from Minas Gerais, 74 from Parana, 34 from Bahia and 22 from Paraiba. A predominance of men, leucoderma and affected by cleft lip and palate (CLP) was observed. In relation to systemic alterations, the otorhinolaryngologics were significantly more prevalent in in patients with cleft palate clefts (CP) in comparison with patients affected by cleft lip (CL, p=0.013). More than 80% of the mothers of the NSCL/P patients reported that they did not use vitamin supplements during their first trimester of the pregnancy. Among the 12 polymorphisms, rs3213245 in XRCC1 demonstrated a significant association with the CL (p=0.03) and rs13181 inERCC2 demonstrated atendency of association with CLP (p=0.06). The haplotype formed by XRCC1 polymorphisms rs25487, rs25489, rs321345 and rs1799782 1 was significantly associated with CL (p=0.02). The results of this study show the epidemiologic profile of the patients with NSCL/P assisted in the west of Parana state and demonstrated that polymorphisms in the genes XRCC1 and ERCC2, which encode enzymes of the DNA repair system, may be associated with the susceptibility of the NSCL/P development / Doutorado / Patologia / Doutora em Estomatopatologia

As fissuras lábio palatinas (FLP) são as malformações faciais mais comuns presentes ao nascimento e correspondem a cerca de 25% de todos os defeitos congênitos. Sua incidência é alta, de aproximadamente 1/700 nascimentos e varia entre os diferentes grupos étnicos. Elas representam um problema relevante de saúde, pois os portadores necessitam para sua reabilitação estética e funcional de uma equipe multidisciplinar, do nascimento e geralmente, até a vida adulta, o que exige um alto custo econômico. A etiologia das FLP não sindrômicas ainda é controversa na literatura, apesar de existirem esforços mundiais para identificar os fatores que causam esta patologia. Nosso trabalho consistiu do estabelecimento e caracterização de 23 linhagens de células tronco adultas (CTA) obtidas de polpa de dentes decíduos (11 indivíduos, sendo 5 controles, 5 portadores de FLP não sindrômica e 1 portador da síndrome de Van der Woude), do músculo orbicular do lábio (5 indivíduos portadores de FLP), do osso medular (2 indivíduos portadores de FLP) e de gordura de lipoaspiração (5 controles), com o objetivo de utilizá-las para ajudar a elucidar os mecanismos etiológicos de origem genética das fissuras lábio palatinas não sindrômicas; bem como para utilizá-las para bioengenharia dos tecidos alterados nesta patologia, especialmente o tecido ósseo. Demonstramos que os protocolos que utilizamos são facilmente reproduzidos e que as diferentes linhagens CTA obtidas tem plasticidade para diferenciação osteogênica “in vitro”, e que as CTA obtidas de polpa de dente e de músculo orbicular do lábio têm plasticidade para se diferenciar “in vitro” em tecido ósseo, muscular, condrogênico e adipogênico. Além disso, em nossos experimentos, demonstramos que estas CTA tem capacidade de regenerar grandes defeitos ósseos em ratos Wistar não imunossuprimidos, nos quais não observamos clinicamente nenhum tipo de rejeição destas células humanas. Utilizamos uma metodologia inédita para estudar a etiopatogenia das FLP, que consistiu da obtenção de RNA das CTA de indivíduos portadores de FLP e de controles para posterior hibridação em lâminas de “microarray” e comparação do perfil de expressão gênica das mesmas. Observamos neste estudo preliminar que 367 genes estão diferencialmente expressos nas amostras, sendo todos mais expressos nas amostras dos portadores de FLP e sugerimos que esta é uma estratégia promissora para estudo da etiopatogenia das FLP. Concluimos que a realização de estudos das CTA de afetados por FLP e de controles são importantes não só para utilização das mesmas em bioengenharia de tecidos, mas também para estudo da etiopatogenia das fissuras. / Clefts involving the lip and palate (CLP) or palate only (CP) represent the most frequent facial malformation during birth and correspond to approximately 25% of all congenital defects. The incidence of this problem is high; corresponding to approximately 1:700 births, but is different among the ethnic groups. Clefts represent a major health problem due to the requirement of a mutidisciplinary team to deal with the esthetical and funcional reabilitation needs of these patients from birth to, in some cases, adult life, resulting in a high treatment cost. There still many controversies about the ethiology of non-syndomic CLP, even though there are researchers all over the world trying to identify the factors causing this pathology. Our work consisted to establish and characterize 23 adult stem cells (ASC) linages obtained from falling teeth dental pulp (5 controls, 5 non-syndomic CLP patients and 1 Van der Woude syndrome patient), orbicular oris muscle (5 non-syndomic CLP patients), bone marrow (2 non-syndomic CLP patients) and adipose tissue (5 controls). The objectives were to use these lineages to help elucidate the genetic mechanisms involved in the development of non-syndomic CLP, as well as, to bioengineer tissues affected by this pathology, mainly bone tissue. The protocols we used are easily reproductible and we demonstrate that our different ASC linages have in vitro plasticity to osteogenic differentiation, as well as, the lineages obtained from dental pulp and orbicular oris muscle have osteogenic, muscular, condrogenic and adipogenic plasticity. Further more our experiments demonstrate that these ASC lineages have the capacity to regenerate major bone defects in non-immunocompromised Wistar rats, which did not develop any kind of rejection against these human cells. We have used a new methodology to study the molecular mechanisms involved in CLP, which consisted in comparing the mRNA expression profile of ASC from non-syndomic CLP patients and controls, using microarrays. We observed that 367 genes were differently expressed between the two groups and all these genes have a higher expression in samples from nonsyndomic CLP patients, thus suggesting that this is a promising strategy to study the molecular mechanisms involved in CLP. In conclusion, studies involving ASC from non-syndomic CLP patients and controls are important not only to tissue bioengineering, but also to elucidate the molecular mechanisms involved in CLP.

A fissura lábio-palatina não-sindrômica (FLP NS) é uma doença multifatorial, determinada pela interação entre fatores genéticos e ambientais e sua incidência é estimada entre 0,34 e 2,29 a cada 1000 nascimentos. Trata-se de uma embriopatia causada por erros durante a morfogênese orofacial, a qual depende de uma fina regulação de mecanismos como proliferação celular, remodelagem de matriz extracelular, e transição epitélio-mesenquimal. Apesar de intensos esforços para se determinar fatores genéticos e ambientais de susceptibilidade, a etiologia desta malformação permanece pouco compreendida. Vários loci associados às FLP NS vêm sendo identificados por meio de estudos de mapeamento gênico convencionais, entretanto, a grande maioria dos resultados não se replica em diferentes estudos, e não há clareza acerca do efeito funcional das variantes detectadas. Neste contexto, uma abordagem interessante para investigar a etiologia da doença é a análise de expressão gênica, que pode ser utilizada para identificar alterações de vias biológicas que convergem na manifestação do quadro clínico. Em vista disso, neste trabalho nós utilizamos a análise do transcriptoma de células-tronco de polpa dental de pacientes portadores de FLP NS, com o intuito de identificar padrões de expressão relacionados a mecanismos biológicos relevantes para a embriopatogênese da doença. Obtivemos padrões de expressão que sugerem desregulação de mecanismos associados à remodelagem de matriz extracelular e à transição epitélio-mesenquimal. Além disso, ao utilizarmos diferentes condições de cultura celular, verificamos em uma nova amostra de pacientes a desregulação de vias biológicas relacionadas ao reparo de DNA e checkpoint do ciclo celular. Nossos dados revelam a aplicabilidade das células-tronco de polpa dental para este tipo de abordagem, e indicam que tais perfis de expressão podem levar ao acometimento da morfogênese lábio-palatina. Além disso, mostramos pela primeira vez uma conexão entre desregulação de expressão gênica e a documentada maior incidência de formas esporádicas de câncer em famílias segregando a FLP NS. Nossos resultados abrem novas possibilidades para a investigação da etiologia das FLP NS, e ajudarão na compreensão dos eventos embrionários que predispõem a essa malformação. / Non-syndromic cleft lip and palate (NSCL/P) is a multifactorial disease determined by the interplay between genetic and environmental factors, with a variable incidence of 0.34-2.29:1000 births. This malformation arises from errors during lip and palate morphogenesis, which requires tight regulation of biological mechanisms such as cellular proliferation, extracellular matrix remodelling, and epithelial-mesenchymal transition. Albeit much effort has been put into determining the genetic and environmental factors underlying disease susceptibility, the aetiology of NSCL/P remains obscure. Many candidate loci have been identified through conventional gene mapping strategies, however, there is a general lack of reproducibility across studies, and there is no consensus with regard to the functional implications of the identified genetic variants. In this context, an alternative approach resides in assessing differential expression patterns to identify alterations in biological networks that could lead to phenotype manifestation. Here, we analysed the transcriptome of dental pulp stem cells from NSCL/P patients in order to pinpoint dysregulated pathways involved in the embryopathogenesis of the disease. We encountered expression patterns related to dysregulation of extracellular matrix remodelling and epithelial mesenchymal transition. Moreover, by subjecting a novel NSCL/P sample to differential cell culture conditions, we observed abnormal transcription of genes partaking in DNA repair and cell cycle checkpoint pathways. Our results show the applicability of dental pulp stem cells to this strategy and suggest that the observed expression patterns could lead to impairment of lip and palate morphogenesis. Moreover, we described for the first time a connection between abnormal gene expression in these individuals and the elevated occurrence of sporadic cancer types in NSCL/P families. Our results open new possibilities to investigate the aetiology of NSCL/P and provide further insight into the ontogenetic events underlying disease predisposition.

Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2016-10-04T20:52:05Z No. of bitstreams: 1 PERFIL CL?NICO-EPIDEMIOL?G ICO DOS PORTADORES DE FISSURAS .pdf: 1130964 bytes, checksum: 116e81d06957864f0fed433876117d0f (MD5) / Made available in DSpace on 2016-10-04T20:52:05Z (GMT). No. of bitstreams: 1 PERFIL CL?NICO-EPIDEMIOL?G ICO DOS PORTADORES DE FISSURAS .pdf: 1130964 bytes, checksum: 116e81d06957864f0fed433876117d0f (MD5) Previous issue date: 2014-11-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / PURPOSE: Describe the clinical and epidemiological profile of patients with congenital orofacial clefts, residents in the state of Bahia, seen at Anomalies Rehabilitation Center Craniofacial Hospital Santo Antonio in the 2008-2013 period. METHOD: This is an observational and descriptive epidemiological study. The study included patients with orofacial clefts, nonsyndromic, of both sexes and without limitation of age. A simple random sample consisted of 319 records. Information was obtained on sociodemographic profile of the carrier and mother, medication use during pregnancy, clinical and surgical aspects cracks, family history of malformations and consanguinity of the parents. Data were analyzed descriptively using the Statistical Package for Social Sciences version 17.0 on you, where frequency measurements were obtained, mean and standard deviation. RESULTS: It was observed that 51.1% of patients with orofacial clefts were female, 46.2% were in the age group of one year and 54.4% were from the urban area. Most mothers was in the age group between 16 to 25 years during pregnancy and reported medication use in 59.2% of cases, especially vitamins and antibiotic. The cleft transforamen was the most diagnosed (34.4%). At the time of the service registration, it was observed that 90.5% of the subjects had not yet performed the surgical treatment. Family history of cleft was observed in 29.8% of cases and only 7.1% of cases were reported consanguinity between parents. CONCLUSIONS: A slight prevalence of oral clefts was observed in females, less than a year and living in an urban area. Mothers found themselves outside the age range considered risk during pregnancy and were using medication as vitamins and antibiotics that stage. Greater proportion of patients had cleft incisive trans type and have not undergone previous surgical treatment. Family history of orofacial clefts and relations of consanguinity in some of the cases studied was found. / OBJETIVO: Descrever o perfil cl?nico-epidemiol?gico dos portadores de fissuras orofaciais cong?nitas, residentes no estado da Bahia, atendidos no Centro de Reabilita??o de Anomalias Craniofaciais do Hospital Santo Ant?nio, no per?odo de 2008 a 2013. M?TODO: Trata-se de um estudo epidemiol?gico observacional e descritivo. Participaram do estudo portadores de fissuras orofaciais, n?o sindr?micos, de ambos os sexos e sem limita??o de faixa et?ria. A amostra aleat?ria simples foi composta de 319 prontu?rios. Foram obtidas informa??es sobre o perfil sociodemogr?fico do portador e da m?e, uso de medicamentos durante a gesta??o, aspectos cl?nicos e cir?rgicos relacionados as fissuras, hist?rico familiar da malforma??o e consanguinidade dos pais. Os dados foram analisados descritivamente com o uso do Statistical Package for te Social Sciences na vers?o 17.0, onde foram obtidas medidas de frequ?ncia, m?dia e desvio padr?o. RESULTADOS: Observou-se que 51,1% dos portadores de fissuras orofaciais eram do sexo feminino, 46,2% encontravam-se na faixa et?ria menor de um ano e 54,4% eram procedentes na zona urbana. A maioria das m?es encontrava-se na faixa et?ria entre 16 a 25 anos durante o per?odo gestacional e relataram uso de medica??o em 59,2% dos casos, especialmente vitaminas e antibi?ticos. A fissura transforame incisivo foi a mais diagnosticada (34,4%). No momento de cadastro ao servi?o, observou-se que 90,5% dos indiv?duos ainda n?o haviam realizado tratamento cir?rgico. A hist?ria familiar de fissura foi observada em 29,8% dos casos estudados e em apenas 7,1% dos casos foi reportado consanguinidade entre os pais. CONCLUS?ES: Uma leve predomin?ncia de fissuras orofaciais foi observada em indiv?duos do sexo feminino, menores de um ano e residentes em ?rea urbana. As m?es encontravam-se fora da faixa et?ria considerada de risco durante o per?odo gestacional e faziam uso de medica??o como vitaminas e antibi?ticos nessa fase. A maior parcela dos portadores apresentava fissura do tipo transforame incisivo e n?o foram submetidos a tratamento cir?rgico pr?vio. Foi encontrado hist?rico familiar de fissuras orofaciais e rela??es de consanguinidade em alguns dos casos estudados.

O objetivo deste trabalho foi investigar a ocorrência de mutações na sequência de nucleotídeos do gene AMELX, candidato a defeitos na formação do esmalte dentário, em indivíduos com e sem fissura labiopalatina. Para análise do gene proposto, foi coletado saliva de 165 indivíduos, que foram divididos em 4 grupos: Grupo 1 - composto por 46 indivíduos com fissura labiopalatina e malformação dentária; Grupo 2 - composto por 34 indivíduos com fissura labiopalatina e sem malformação dentária; Grupo 3 - composto por 34 indivíduos sem fissura labiopalatina e com malformação dentária e Grupo 4 - composto por 51 indivíduos sem fissura labiopalatina e malformação dentária. Foi realizada a extração do DNA genômico das amostras de saliva, seguido da PCR e sequenciamento direto. Cada mutação identificada no sequenciamento foi confirmada repetindo-se a reação de sequenciamento da fita antisenso. Após a coleta dos dados no Software SeqScape® 2.6, estes foram devidamente analisados por meio de gráficos e tabelas. Das amostras submetidas ao sequenciamento genético, obteve-se um aproveitamento de 95%, 90%, 89%, 88%, 94% e 100% destas amostras dos éxons 2, 3, 4, 5, 6 e 7, respectivamente. Dos 990 fragmentos sequenciados (seis éxons em 165 amostras de saliva), 918 fragmentos (93%) foram analisados. Detectou-se alteração na sequência de bases em 37 destes fragmentos (4%), sendo 14 no Grupo 1 (1,5%), 12 no Grupo 2 (1,3%), quatro no Grupo 3 (0,4%) e sete no Grupo 4 (0,7%), dos tipos missense e silenciosa, distribuídas nos éxons 2, 6 e 7 do gene AMELX, em oito distintos locais no cromossomo X. De acordo com os resultados obtidos do sequenciamento direto do gene AMELX, foi possível concluir que foram encontradas mutações na sequência de nucleotídeos do gene AMELX, em indivíduos com e sem fissura labiopalatina e malformação dentária. Observou-se ainda que a mutação localizada na posição 75 do éxon 6 esteve presente em todos os grupos estudados, sugerindo que, apesar de ser uma mutação silenciosa, pode ser um polimorfismo novo, a ser catalogado, pois foi detectado em 26 indivíduos, do total de 165, representando 16%. Entretanto, este estudo não pode afirmar que estas mutações alteraram diretamente o fenótipo dos pacientes dos grupos estudados. / The aim of this study was to investigate the occurrence of mutations in the AMELX candidate gene involved in enamel formation, in patients with and without cleft lip and palate and dental malformation. For gene analysis proposed was collected saliva from 165 patients who were divided in 4 groups: Group 1 - 46 individuals with cleft lip and palate and dental malformation, Group 2 - 34 individuals with cleft lip and palate without dental malformations; Group 3 - 34 individuals without cleft lip and palate with dental malformations and Group 4 - 51 individuals without cleft lip and palate and dental malformation. Next, genomic DNA was extracted from this saliva, followed by PCR and direct DNA sequencing. All samples with mutations were sequenced twice; once using the forward primer and a second time using the reverse primer. After data analysis with Software SeqScape® 2.6, the data were collated. Of the 165 samples, 95%, 90%, 89%, 88%, 94% and 100% of the samples were successfully sequenced from exons 2, 3, 4, 5, 6 and 7 respectively. Overall, of the 990 total sequenced exons (six exons in 165 samples of saliva), 918 exons (93%) were able to be completely sequenced and analyzed. Mutations were detected in 37 of the fragments (4%), more specifically, 14 in Group 1 (1.5%), 12 in Group 2 (1.3%), four in Group 3 (0.4%) and seven in Group 4 (0.7%), which included only missense and silent mutations, distributed throughout exons 2, 6 and 7 in the AMELX gene in eight different locations on chromosome X. According to the results obtained from direct sequencing of protein-coding exons of the AMELX gene, mutations were found in the nucleotide sequence of the AMELX gene in individuals with and without cleft lip and palate and dental malformation. It was also observed that the mutation in position 75 of exon 6 was present in all groups, suggesting that, though a silent mutation, may be a new polymorphism to be cataloged: it was found in 26 patients, the total of 165, representing 16%. However, this study cannot confirm that these mutations directly altered the phenotypes of the patients in the groups tested.

Social isolation is commonly reported in individuals with isolated cleft lip and palate (ICLP), and is often cited as due to secondary factors of living with a facial malformation. However, the data are mixed, and the literature is biased to self-report studies. This study aimed to go beyond self-report data, and various components of social functioning were examined in a group of males with and without ICLP. The main aim of the study was to assess and compare social motivation in ICLP, and to relate social adjustment to brain structure. It was predicted that males with ICLP would be more likely to be socially isolated; however, self-concept was predicted to be similar to the comparison group (NC). Additionally, males with ICLP were predicted to have reduced social motivation (i.e., social abulia). Finally, volumes of the medial orbitofrontal cortex (mOFC) and the cerebellum were predicted to be related to social outcomes. The sample's age range was 13 - 25 years old, and 20 males with ICLP were compared to a group of 20 NC males. MRI scans were obtained from all the participants. As expected, males with ICLP were more likely to be socially isolated. Against predictions, they also had lower self-concept relative to the NC group. However, self-concept was not related to the extent of facial abnormality in the ICLP group. In line with predictions, the study did provide evidence for social abulia as a mechanism for social isolation, as males with ICLP had a more positive attitude after being socially excluded relative to excluded NC males. Unexpectedly however, the groups responded the same to social pressure, as all participants were more likely to take riskier turns in a driving simulator experiment when someone behind them was honking. Finally, social adjustment was significantly correlated with the volume of the mOFC, and posterior cerebellum white matter. Both correlations suggested that individuals with larger volumes were more likely to be better socially adjusted. In conclusion, the study provided evidence for a potentially different mechanism of social isolation in ICLP, and showed that brain morphology may at least partly underlie social dysfunction as well.

abstract: The purpose of this study is to evaluate the effects of parent training in the Enhanced Milieu Teaching with Phonological Emphasis (EMT+PE) intervention program, using a secure internet-based conferencing software (telepractice), on parent strategy use and child speech and language outcomes for children with repaired cleft lip and/or palate (CL/P). Three participant dyads composed of a parent and child participated in this study. Children ranged in age from 21 to 27 months at the beginning of this study and all had a diagnosis of nonsyndromic CL/P. Participating dyads received three in- person training sessions and three weekly telepractice intervention sessions. Assessment and intervention sessions were administered by a trained Speech Language Pathologist (SLP) and a graduate SLP student clinician. Parents demonstrated a positive intervention effect by significantly increasing their use of EMT+PE intervention strategies during training. Based on preliminary results, parents were able to maintain their increased use of strategies following the conclusion of intervention as well. Telepractice proved to be a valid service delivery model for conducting early intervention sessions and for supporting the early speech and language development for children with CL/P. / Dissertation/Thesis / Masters Thesis Communication Disorders 2020

Cleft lip and palate (CLP) has been determined to be the second most common birth defect in the United States, affecting 1 in every 940 births (Parker et al., 2010). The team approach is the accepted best practice for children with CLP (Kummer, 2020) and the school-based Speech-Language Pathologist (SLP) has an important role to play in assessment and intervention of children with repaired CLP, however there is little research to describe their collaboration. This research aimed to explore and describe the referral practices of school-based SLP’s to CLP teams. A survey titled “Referral to Cleft Lip and Palate Teams: Practice of School-Based Speech Language Pathologist’s” was developed and distributed to members of the American Speech-Language Hearing Association’s (ASHA’s) Special Interest Groups (SIGs) 15 and 16 following an in depth literature review on the topic. A total of 57 practicing school-based SLPs acted as respondents. The results of the survey suggested VPD was the main reason for making a referral to a CLP team (89.72%), which validates the response that clients mostly referred had suspected VPD (89.47%). Making a team referral was not common practice, as 58.7% had never made a CLP team referral in the schools. ENTs (51.06%) were the preferred choice of referral in comparison to a CLP team (25.53%). Barriers to making CLP team referrals varied and obtaining permission from the school was experienced by some respondents (36.36%). Respondents made valuable comments which centered on positive experiences with working with CLP teams (11/56). The process of making referrals to CLP teams and collaboration between school-based SLPs and CLP teams needs to be addressed in graduate training and CE. According to Vallino et al., (2019) such communication enhances care, bridges the perceived gap between school-based SLPs and CLP teams, and will ensure that children with CLP and VPD receive the best care possible.

Children with cleft lip/palate receive team care which typically ends at eighteen. Young adults then need to transition into an adult-centered model of care. A paucity of literature exists regarding their perspective on transition of care experience. This research explores the experiences of young adults with CLP regarding their transition of care process, within the person-centered ICF framework.