Higher maternal age is associated with higher occurrence of cleft lip/palate in neonates under intensive care

Aim: To assess the prevalence of cleft lip and/or cleft palate (CL/P) and associated variables in neonates admitted to neonatal intensive care units (ICU). Methods: Medical charts for neonates born and admitted to the ICU between 2012 and 2018 were reviewed. Obstetric and neonatal variables were collected by a trained researcher. In the case group, all neonates with CL/P were included. The control group was formed by matching sex, prematurity and month of birth using random number generation. Neonates with congenital malformations were excluded from the control group. Adjusted logistic regression was used (p<0.05). Results: The prevalence of CL/P was 0.43% (n=15). Five cases were excluded, as pairing was not possible. Twenty neonates were included in the control group. In the final multivariate model, CL/P was only associated with increased maternal age. For each year of increase in maternal age, neonates had a 35.2% higher chance of presenting CL/P (95% confidence interval: 1.021­1.792). Conclusions: Higher maternal age was associated with higher occurrence of CL/P in neonates admitted to the ICU. No other neonatal or maternal independent variables were associated with CL/P. Due to missing data, interpretation of study results must be approached with caution

Dental treatment before surgery in a patient with cleft lip and palate: case report / Efeito do Cissus quadrangularis na cicatrização de fraturas em animais de laboratório

Introduction: orofacial clefts are common congenital malformations with an important social, psychological, and economic impact. The treatment of this condition may include different surgical procedures that previously require an adequate oral condition. Case report: we report a case of dental treatment before palatoplasty in a male patient of 17 years-old with bilateral cleft lip and palate and lesion in the jugal mucosa. Final considerations: the adequacy of the oral environment is a fundamental step in the treatment of patients with orofacial clefts and aims to restore oral health regardless of the degree of complexity of the dental treatment through the reduction of the pathogenic microbiota, elimination of retentive niches, instructions on diet and adequate oral hygiene and constant patient motivation.

Objetivos: as fissuras orofaciais são malformações congênitas comuns, com importante impacto social, psicológico e econômico. O tratamento dessa condição pode incluir vários procedimentos cirúrgicos que requerem previamente uma adequada condição bucal. Relato de caso: Relatamos o caso de tratamento odontológico prévio a palatoplastia em um paciente do gênero masculino de 17 anos de idade, com fissura transforame incisivo bilateral e lesão em mucosa jugal. Considerações finais: A adequação do meio bucal é uma etapa fundamental no tratamento de pacientes com fissuras orofaciais e visa restabelecer a saúde bucal independente do grau de complexidade do tratamento odontológico por meio da redução da microbiota patogênica, eliminação de nichos retentivos, orientações sobre dieta e higiene bucal adequada e motivação constante do paciente.

Surgical effects of rehabilitation protocols on dental arch occlusion of children with cleft lip and palate

Aim: to evaluate the surgical effects of two rehabilitation protocols on dental arch occlusion of 5-year-old children with or without cleft lip and palate. Methods: this is a retrospective longitudinal study the sample comprised 45 digitized dental casts divided into followed groups: Group 1 (G1) ­ children who underwent to cheiloplasty (Millard technique) at 3 months and to one-stage palatoplasty (von Langenbeck technique) at 12 months; Group 2 (G2) ­ children who underwent to cheiloplasty (Millard technique) and two-stage palatoplasty (Hans Pichler technique for hard palate closure) at 3 months and at 12 months to soft palate closure (Sommerlad technique); and Group 3 (G3) ­ children without craniofacial anomalies. Linear measurements, area, and occlusion were evaluated by stereophotogrammetry software. Shapiro-Wilk test was used to verify normality. ANOVA followed by posthoc Tukey test and Kruskal-Wallis followed by posthoc Dunn tests were used to compared groups. Results: For the measures intercanine distance (C-C'), anterior length of dental arch (I-CC'), and total length of the dental arch (I­MM'), there were statistical differences between G1x G3 and G2xG3, the mean was smaller for G1 and G2. No statistically significant differences occurred in the intermolar distance and in the dental arch area among groups. The occlusion analysis revealed significant difference in the comparison of the three groups (p=0.0004). Conclusion: The surgical effects of two rehabilitation protocols affected the occlusion and the development of the anterior region of the maxilla of children with oral clefts when compared to children without oral clefts.

Planificación quirúrgica de colgajo faríngeo a medida para insuficiencia velofaríngea secundaria a fisura de paladar: reporte de caso y revisión de literatura / Surgical planning of a tailor-made pharyngeal flap for velopharyngeal insufficiency secondary to a cleft palate: case report and literature review

Resumen La insuficiencia velofaríngea (IVF) es una de las principales secuelas estructurales tras la palatoplastía primaria en casos de fisura de paladar. La IVF se caracteriza por la ausencia de tejido suficiente para lograr un cierre adecuado del mecanismo velofaríngeo durante el habla, lo que conlleva a una resonancia hipernasal y la emisión nasal de aire durante la producción de sonidos orales. Al respecto, el tratamiento ideal para corregir la IVF es quirúrgico, dentro de los cuales el colgajo faríngeo de pedículo superior es uno de los procedimientos más utilizados en nuestro país. Para su realización es fundamental determinar el ancho necesario, lo cual puede ser determinado mediante una videofluoroscopía multiplano (VFMP). Por esto, con el objetivo de potenciar el trabajo multidisciplinario en la corrección quirúrgica de la IVF, a continuación, se presentan los procedimientos de evaluación fonoaudiológica, videonasofaríngoscopía flexible y videofluoroscopía multiplano utilizados para la planificación quirúrgica de un colgajo faríngeo en un adolescente chileno diagnosticado con IVF secundaria a fisura palatina operada. Además, se describe el uso de la VFMP en la planificación quirúrgica del colgajo faríngeo mediante una revisión de literatura.

Abstract Velopharyngeal insufficiency (VPI) is one of the main structural sequelae after primary palatoplasty in cases of cleft palate. VPI is characterized by the absence of sufficient tissue to achieve adequate closure of the velopharyngeal mechanism (VFM) generating hyper-nasal resonance and nasal emission during the production of oral sounds. In cases of cleft palate, the ideal treatment to correct VPI is surgery. The upper pedicle pharyngeal flap is one of the most widely used procedures. To plan it, is essential to determine the appropriate width, which can be determined by means of multiplane videofluoroscopy (MPVF). For this reason, and with the aim of promoting multidisciplinary approach in the surgical correction of VPI, the following procedures such as speech and language evaluation, flexible videonasopharyngoscopy and multiplane videofluoroscopy used for the surgical planning of a pharyngeal flap, in a Chilean adolescent diagnosed with VPI secondary to operated cleft palate, will be presented. In addition, the use of MPVF in pharyngeal flap surgical planning is described through a literature review.

Pharyngeal bulb prosthesis and speech outcome in patients with cleft palate / Obturador faríngeo e resultados de fala em pacientes com fissura palatina

Abstract Introduction: Individuals with cleft palate can present with velopharyngeal dysfunction after primary palatoplasty and require a secondary treatment due to insufficiency. In these cases, the pharyngeal bulb prosthesis can be used temporarily while awaiting secondary surgery. Objective: This study aimed to investigate the outcome of treatment of hypernasality with pharyngeal bulb prosthesis in patients with history of cleft palate presenting with velopharyngeal insufficiency after primary palatal surgery. We hypothesized that the use of the pharyngeal bulb prosthesis is an effective approach to eliminate hypernasality related to velopharyngeal insufficiency in patients with cleft palate. Methods: Thirty speakers of Brazilian Portuguese (15 males and 15 females) with operated cleft palate, ages ranging from 6 to 14 years (mean: 9 years; SD = 1.87 years), participated in the study. All patients were fitted with a pharyngeal bulb prosthesis to manage velopharyngeal insufficiency while they were awaiting corrective surgery to be scheduled. Auditory-perceptual analysis of speech recorded in the conditions with and without pharyngeal bulb prosthesis were obtained from three listeners who rated the presence or absence of hypernasality for this study. Results: Seventy percent of the patients eliminated hypernasality while employing the pharyngeal bulb prosthesis, while 30% still presented with hypernasality. The comparison was statistically significant (p < 0.001). Conclusion: The use of the pharyngeal bulb prosthesis is an effective approach to eliminate hypernasality related to velopharyngeal insufficiency.

Resumo Introdução: Indivíduos com fissura palatina podem apresentar disfunção velofaríngea após a palatoplastia primária e necessitam de um secundário devido à insuficiência velofaríngea. Nesses casos, o obturador faríngeo pode ser usado temporariamente enquanto se aguarda uma cirurgia secundária. Objetivo: Investigar o resultado do tratamento da hipernasalidade com o uso de obturador faríngeo em pacientes com histórico de fissura palatina que apresentam insuficiência velofaríngea após a palatoplastia primária. Nossa hipótese é que o uso do obturador faríngeo seja uma abordagem eficaz para eliminar a hipernasalidade relacionada à insuficiência velofaríngea em pacientes com fissura palatina Método: Participaram do estudo 30 indivíduos falantes do Português Brasileiro (15 homens e 15 mulheres) com fissura palatina operada, de 6 a 14 anos de idade (média: 9 anos; DP = 1,87 anos). Todos os pacientes receberam obturador faríngeo para o tratamento da insuficiência velofaríngea, enquanto aguardavam vaga para a cirurgia secundária. A análise perceptivo-auditiva da fala, realizada nas condições com e sem obturador faríngeo, foi realizada por três ouvintes, quanto à presença e ausência da hipernasalidade. Resultados: 70% dos pacientes eliminaram a hipernasalidade de fala com o uso do obturador faríngeo, enquanto 30% não eliminaram. A comparação foi estatisticamente significante (p < 0,001). Conclusão: O uso temporário do obturador faríngeo é uma abordagem efetiva para eliminar a hipernasalidade decorrente da insuficiência velofaríngea.

Tratamento de ceratocistos na síndrome de Gorlin Goltz / Diagnosis and treatment of oral keratocysts in Gorlin Goltz Syndrome / Tratamento de ceratocistos na Síndrome de Gorlin Goltz

A Síndrome de Gorlin Goltz apresenta características com comprometimento craniofaciais que incluem carcinomas basocelulares, ceratocístos odontogênicos e fenda labial e/ou palatina. Ceratocísticos odontogênico aparecem durante as primeiras décadas de vida, mais comumente na mandíbula, associados a dentes impactados. O diagnóstico precoce possibilita a cura da lesão, minimiza as deformidades ósseas e pode ser concluído com exames como radiográfico e histopatológico. Relato de caso: Com o objetivo descrever o diagnóstico e analisar as possibilidades de tratamento das manifestações faciais da Síndrome de Gorlin Goltz será relatado um caso clínico de uma paciente infantil. A paciente tem um acompanhamento clínico multidisciplinar com geneticista, oncologista e cirurgião-dentista de 6 anos. Apresentou 5 ceratocisticos odontogênicos, carcinomas basocelulares na região do pescoço, calcificação da foice cerebral, ceratose palmo-plantar e macrocefalia. O tratamento para as lesões císticas foi a enucleação, seguida de osteotomia periférica. O defeito ósseo produzido pela enucleação de cisto mandibular foi enxertado com bloco de osso alógeno do banco de tecidos do INTO-RJ. Conclusão: Constata-se que o Cirurgião-dentista é capacitado para fazer o diagnóstico desta síndrome e encaminhar para o tratamento multidisciplinar. O enxerto alógeno é uma opção adequada de reconstrução de cavidades císticas, beneficiando pacientes do Sistema Único de Saúde... (AU)

Gorlin Goltz Syndrome has features with craniofacial involvement that include basal cell carcinomas, odontogenic keratocysts, and cleft lip and/or palate. Odontogenic keratocysts appear during the first decades of life, most commonly in the mandible, associated with impacted teeth. Early diagnosis enables healing of the lesion, minimizes bone deformities and can be completed with exams such as radiographic and histopathological exams. Case report: In order to describe the diagnosis and analyze the treatment possibilities of the facial manifestations of Gorlin Goltz Syndrome, a clinical case of a child patient will be reported.The patient has a multidisciplinary clinical follow-up with a 6-year geneticist, oncologist and dental surgeon. She had 5 odontogenic keratocystic keratocysts, basal cell carcinomas in the neck region, sickle cerebral calcification, palmoplantar keratosis and macrocephaly. The treatment for cystic lesions was enucleation, followed by peripheral osteotomy. The bone defect produced by the enucleation of a mandibular cyst was grafted with an allogeneic bone block from the tissue bank of INTO-RJ. Conclusion: It is concluded that the dentist is trained to make the diagnosis of this syndrome and refer to multidisciplinary treatment. Allogeneic graft is an appropriate option for the reconstruction of cystic cavities, benefiting patients from the Unified Health System... (AU)

El Síndrome de Gorlin Goltz tiene características con compromiso craneofacial que incluyen carcinomas de células basales, queratoquistes odontogénicos y labio leporino o paladar hendido. Los queratoquistes odontogénicos aparecen durante las primeras décadas de vida, más comúnmente en la mandíbula, asociados con dientes retenidos. El diagnóstico precoz permite la curación de la lesión, minimiza las deformidades óseas y se puede concluir con exámenes como exámenes radiográficos e histopatológicos. Reporte de caso: Con el fin de describir el diagnóstico y analizar las posibilidades de tratamiento de las manifestaciones faciales del Síndrome de Gorlin Goltz, se reportará un caso clínico de un paciente infantil. El paciente tiene un seguimiento clínico multidisciplinario con un genetista, oncólogo y cirujano dentista de 6 años. Presentó 5 queratocísticos odontogénicos, carcinomas basocelulares en la región del cuello, calcificación de la hoz cerebral, queratosis palmoplantar y macrocefalia. El tratamiento de las lesiones quísticas fue la enucleación, seguida de una osteotomía periférica. El defecto óseo producido por la enucleación de un quiste mandibular se injertó con un bloque óseo alogénico del banco de tejidos de INTO-RJ. Conclusión: Parece que el odontólogo está capacitado para realizar el diagnóstico de este síndrome y derivar al tratamiento multidisciplinario. El injerto alogénico es una opción adecuada para la reconstrucción de cavidades quísticas, beneficiando a los pacientes del Sistema Único de Salud... (AU)

Depressão pós-parto em mães de bebês sem e com fissuras labiais, palatinas e labiopalatinas / Postpartum depression in mothers of babies without and with cleft lip and/or palate / Depresión postparto en las madres de bebés sin y con labio y/o paladar hendido

Depressão pós-parto (DPP) é um transtorno que afeta a saúde da mulher e a qualidade da relação mãe-bebê. Este estudo comparou a DPP de mães de bebês sem e com fissuras labiais, palatinas e labiopalatinas, e identificou as variáveis preditoras da DPP considerando a amostra como um todo. Participaram 120 mães, sendo 60 de bebês com fissuras e 60 de bebês sem condição de risco. Para a coleta foram utilizados: protocolo de entrevista e Escala de Depressão Pós-Parto de Edimburgo (EDPE). Resultados apontaram maior incidência de DPP em mães de bebês sem fissura (30%) do que em mães de bebês com fissura (20%). Porém, não houve diferenças estatisticamente significativas entre os grupos. As variáveis que explicaram a ocorrência de DPP foram: menor escolaridade materna, menor número de filhos, ausência de fissura no bebê, maior idade do bebê, e menor condição socioeconômica.

Postpartum depression (PPD) is a disorder that affects women's health and the quality of the mother-baby relationship. This study compared the PPD of mothers of babies without and with cleft lip and/or palate, and identified the predictor variables of PPD considering the sample as a whole. 120 mothers participated, 60 of babies with clefts and 60 of babies without risk condition. For data collection, were used the interview protocol and the Edinburgh Postnatal Depression Scale (EPDS). Results showed a higher incidence of PPD in mothers of babies without cleft (30%) than in mothers of babies with clefts (20%). However, there were no statistically significant differences between groups. The variables that explained the occurrence of PPD were: lower maternal education, fewer children, absence of cleft in the baby, older age of the baby, and lower socio economic status.

La depresión posparto (DPP) es un trastorno que afecta la salud de la mujer y la calidad de la relación madre-bebé. Este estudio comparó la DPP de madres de bebés sin y con labio y/o paladar hendido, e identificó las variables predictoras de DPP considerando la muestra en su conjunto. Participaron 120 madres, 60 de bebés con hendiduras y 60 de bebés sin condiciones de riesgo. Para la recolección de datos se utilizó el protocolo de entrevista y la Edinburgh Postnatal Depression Scale (EPDS). Los resultados mostraron una mayor incidencia de DPP en madres de bebés sin hendidura (30%) que en madres de bebés con hendidura (20%). Sin embargo, no hubo diferencias estadísticamente significativas entre los grupos. Las variables que explicaron la ocurrencia de DPP fueron: menor educación materna, menor número de hijos, ausencia de hendidura en el bebé, mayor edad del bebé y menor nivel socioeconómico.

Palatoplasty in children: nursing diagnoses and interventions related to the immediate postoperative period / Palatoplastía en niños: diagnósticos e intervenciones de enfermería referentes al postoperatorio inmediato / Palatoplastia em crianças: diagnósticos e intervenções de enfermagem referentes ao pós-operatório imediato

Abstract Objective: To identify the main nursing diagnoses and interventions in children in the immediate postoperative period of palatoplasty. Method: Documentary and retrospective study, developed in a Brazilian public and tertiary hospital, between August and September 2020. Children who underwent only palatoplasty, between January and December 2019, aged between 10 and 24 months, were included. Those with medical syndromes and/or comorbidities were excluded. The Theoretical Framework of Basic Human Needs and the NANDA International and Nursing Interventions Classification Taxonomies were used. Data underwent descriptive statistical analysis. Results: The sample consisted of 126 children. Psychobiological needs such as oxygenation, hydration, nutrition, elimination, cutaneous-mucosal and physical integrity, pain and environmental perception predominated. Based on them, nine nursing diagnoses, with four focusing on the problem and five on risk, as well as 17 interventions, were identified. Conclusion: The use of standardized languages to identify affected human needs and, based on them, diagnoses and interventions, favored clinical reasoning for the construction and organization of clinical nursing practice.

RESUMEN Objetivo: identificar los principales diagnósticos e intervenciones de enfermería en niños en postoperatorio inmediato de palatoplastía. Método: estudio documental y retrospectivo, desarrollado en un hospital público y terciario brasileño, entre agosto y septiembre de 2020. Se incluyeron niños sometidos exclusivamente a palatoplastía, que realizaron la cirugía entre enero y diciembre de 2019, con edad entre 10 y 24 meses. Se excluyeron aquellos con síndromes y/o comorbidades clínicas. Se utilizó el Referencial Teórico de las Necesidades Humanas Básicas y las Taxonomías NANDA Internacional y la Nursing Interventions Classification. Los datos fueron sometidos al análisis estadístico descriptivo. Resultados: la muestra constó de 126 niños. Predominaron las necesidades psicobiológicas: oxigenación, hidratación, nutrición, eliminación, integridad cutáneo-mucosa y física, percepción dolorosa y ambiental. A partir de eso se identificaron 9 diagnósticos de enfermería, siendo 4 con enfoque en el problema y 5 de riesgo, además de 17 intervenciones. Conclusión: la utilización de lenguajes estandarizado en la identificación de las necesidades humanas afectadas y, a partir de ellas los diagnósticos e intervenciones, favoreció el raciocinio clínico para que se construyese y se organizase la práctica clínica de enfermería.

RESUMO Objetivo: identificar os principais diagnósticos e intervenções de enfermagem em crianças em pós-operatório imediato de palatoplastia. Método: estudo documental e retrospectivo, desenvolvido em um hospital público e terciário brasileiro, entre agosto e setembro de 2020. Foram incluídas crianças submetidas exclusivamente a palatoplastia, que realizaram a cirurgia entre janeiro e dezembro de 2019, com idade entre 10 e 24 meses. Excluíram-se aquelas com síndromes e/ou comorbidades clínicas. Utilizou-se o Referencial Teórico das Necessidades Humanas Básicas e as Taxonomias NANDA Internacional e da Nursing Interventions Classification. Os dados foram submetidos a análise estatística descritiva. Resultados: a amostra constou de 126 crianças. Predominaram as necessidades psicobiológicas: oxigenação, hidratação, nutrição, eliminação, integridade cutâneo-mucosa e física, percepção dolorosa e ambiental. A partir delas foram identificados 9 diagnósticos de enfermagem, sendo 4 com foco no problema e 5 de risco, além de 17 intervenções. Conclusão: a utilização de linguagens padronizadas na identificação das necessidades humanas afetadas e, a partir delas os diagnósticos e intervenções, favoreceu o raciocínio clínico para a construção e organização da prática clínica de enfermagem.

Manejo ortopédico prequirúrgico de labio y paladar hendido unilateral: Reporte de casos con diferentes abordajes / Tratamento ortopédico pré-cirúrgico de fissura labiopalatina unilateral: relato de casos com diferentes abordagens / Presurgical orthopedic management of unilateral cleft lip and palate: Report of cases with different approaches

Pese a los avances de cirugía reconstructiva, el labio y paladara hendido unilateral (LPHU) representa un reto quirúrgico complejo cuando la brecha es mayor a 10 mm. En países de recursos limitados, la distancia geográfica, falta de centros de referencia multidisciplinarios, recursos económicos de las familias y actualmente, la pandemia; limita el acceso de pacientes al tratamiento prequirúrgico. El presente estudio descriptivo reporta 2 casos de LPHU completo, de similar tamaño por inspección visual profesional, sexo masculino, no asociados a síndrome. El propósito del mismo es hacer una revisión de dos técnicas de ortopedia prequirúrgica: Placa de Ortopedia Funcional Maxilar (OFM)-Moldeado Nasal (MN); y el Retractor Nasal (RN)-Taping, como alternativa de tratamiento a distancia. El paciente con placa OFM-MN fue tratado en el 2015, presencial, el paciente con RN-Taping, en el 2021 por telemedicina y un promotor de salud capacitado. Los resultados de simetría nasal y maxilar se midieron con software ImageJ, a través de 4 mediciones lineales y una angular, basadas en el método descrito por Barillas y de mediciones lineales realizadas a los modelos de yeso como las propuestas por Mazaheri. Las técnicas descritas para ambos pacientes lograron disminuir el ancho de la hendidura y moldear el cartílago alar del lado hendido. La técnica OFM-MN mostró ventajas en el desarrollo del arco maxilar promoviendo aumento de volumen de hueso y desarrollo en los tres planos del espacio sin colapso del arco. La técnica RN-Taping, restringió el arco maxilar, sin embargo, podría ser una alternativa de tratamiento a distancia.

Apesar dos avanços na cirurgia reconstrutiva, a fenda labiopalatina unilateral (LPHU) representa um desafio cirúrgico complexo quando o gap é maior que 10 mm. Em países com recursos limitados, distância geográfica, falta de centros de referência multidisciplinares, recursos econômicos das famílias e, atualmente, a pandemia; limita o acesso do paciente ao tratamento pré-cirúrgico. O presente estudo descritivo relata 2 casos de LPHU completa, de tamanho semelhante por inspeção visual profissional, do sexo masculino, não associada à síndrome. Seu objetivo é revisar duas técnicas ortopédicas pré-cirúrgicas: Placa Ortopédica Funcional Maxilar (OFM) - Moldagem Nasal (MN); e o Retrator Nasal (RN)-Taping, como alternativa de tratamento remoto. O paciente com placa OFM-MN foi atendido em 2015, pessoalmente, o paciente com RN-Taping, em 2021 por telemedicina e promotor de saúde treinado. Os resultados da simetria nasal e maxilar foram medidos com o software ImageJ, por meio de 4 medidas lineares e uma angular, com base no método descrito por Barillas e medidas lineares feitas nos modelos de gesso como os propostos por Mazaheri. As técnicas descritas para ambos os pacientes foram capazes de reduzir a largura da fenda e moldar a cartilagem alar do lado da fenda. A técnica OFM-MN apresentou vantagens no desenvolvimento do arco superior, promovendo aumento do volume ósseo e desenvolvimento nos três planos do espaço sem colapso do arco. A técnica RN-Tapingrestringiu a arcada superior, porém pode ser uma alternativa para tratamento remoto.

Despite the advances in reconstructive surgery, unilateral cleft lip and palate (UCLP) represents a complex surgical challenge when greater than 10 mm. In low resource settings, distance, lack of multidisciplinary centers, low income and currently, the pandemic; limits patients to access to presurgical treatment. This study reports 2 cases of complete UCLP, similar in size by professional visual inspection, male, not associated with any syndromes. The purpose is to review two presurgical orthopedic techniques: Maxillary Functional Orthopedic Plate (MFO) -Nasal Molding (NM) and Nasal Retractor (NR) -Taping as a teledentistry alternative. The patient with the FMO-NM plate was treated in 2015, in person; the NR-Taping patient, in 2021, by telemedicine and a trained health promoter. The results of nasal and maxillary symmetry were measured with ImageJ software, through 4 linear measurements and one angular, based on the method described by Barillas and linear measurements made on the plaster models such as those proposed by Mazaheri. The techniques described for both patients were able to reduce the width of the cleft and mold the alar cartilage on the cleft side. The OFM-MN technique showed advantages in the development of the maxillary arch by guiding growth and development in the three planes of the space without collapse of the arch. The NR-Taping technique restricted the maxillary arch but is an alternative to remote treatment

Qualitative Assessment of Surgical Repair of Three Types of Unilateral Cleft Lip

Abstract Objective: To assess the effect of the three types of unilateral cleft lip (UCL) [cleft lip only, cleft lip and alveolus, and cleft lip alveolus and palate] on the outcome of the repair. Material and Methods: This study was a case series of effect of types of UCL on the outcome of the repair. Fifteen subjects each were in three UCL phenotypes groups. Evaluation of the scar, lip, and nose was done qualitatively by both parents/guardians and professionals using a modified form of the criteria described by Christofides et al. (2006). Results: In the assessment of the surgical scar, the parents found a difference between the three types of cleft in terms of texture, shape, and width of the scar and presence of columella deviation. The professional assessors, however, only found the three types of cleft to be different in the presence of alar flattening. Conclusion: Differences truly exist in the outcome of surgical repair of the three types of unilateral cleft lip, especially in the aesthetics of the nose and in the width and shape of the residual lip scar. Thus, it is important to consider this in the assessment of UCL repair because putting the subtypes together might have a negative impact on the assessment.

Evaluation of palatal volume in children with cleft lip and palate: a comparison of two surgical protocols / Avaliação volumétrica do palato em crianças com fissura labiopalatina: comparação de dois protocolos cirúrgicos

Objective: Compare the palatal volume in children with unilateral cleft lip and palate before and after two surgical protocols. Material and Methods: Retrospective data collection was performed in a specialized hospital. The sample comprised 120 digitized dental models divided into, Group 1 (G1) ­ participants submitted to cheiloplasty at 3 months (Millard technique) and one-step palatoplasty at 12 months (von Langenbeck technique); Group 2 (G2) ­ participants submitted to cheiloplasty (Millard technique) and hard palate closure (Hans Pichler technique) at 3 months and soft palate closure at 12 months (Sommerlad technique). The dental models were evaluated at Time 1 (T1): before primary plastic surgeries, Time 2 (T2): 1st post-surgical phase, and Time 3 (T3): 2nd post-surgical phase. The volume was measured through stereophotogrammetry system software. Parametric and non-parametric statistical tests were applied (α=5%). Results: The intragroup analysis revealed that G1 had a statistically significant increase in volume at T2 followed by a reduction at T3 (p=0.003); G2 showed a statistically significant increase of dental arch volume between T1 and T2 (p=0.001). There was no statistically significant difference in the intergroup and gender analyses (p>0.05). Conclusion: The surgical protocol influenced the palatal volume of children with unilateral cleft lip and palate. This study suggested that two-step palatoplasty protocol has a tendency to be more appropriate.(AU)

Objetivo: Comparar o volume palatino em crianças com fissura unilateral de lábio e palato antes e após dois protocolos cirúrgicos. Material e Métodos: A coleta de dados retrospectiva foi efetuada em um hospital especializado. A amostra foi composta por 120 modelos dentários digitalizados divididos em, Grupo 1 (G1) ­ participantes submetidos a queiloplastia aos 3 meses de vida (técnida de Millard) e a palatoplastia em única etapa aos 12 meses (técnica de von Langenbeck); Grupo 2 (G2) ­ participantes submetidos a queiloplastia (técnica de Millard) e fechamento do palato duro (técnica de Hans Pichler) aos 3 meses de vida e fechamento do palate mole aos 12 meses (técnica de Sommerlad). Os modelos dentários foram avaliados em Tempo 1 (T1): antes das cirurgias plásticas primárias, Tempo 2 (T2):1ª fase pós-cirúrgica e Tempo 3 (T3): 2ª fase pós-cirúrgico. O volume foi mensurado por meio do software do sistema de estereofotogrametria. Testes estatísticos paramétricos e não-paramétricos foram utilizados (α=5%). Resultados: As análises intragrupos indicaram que G1 apresentou aumento estatisticamente significante em T2 seguido de redução em T3 (p=0.003). G2 apresentou crescimento estatisticamente significativo do volume palatino entre T1 e T2 (p=0.001). Não houve diferença estatisticamente significante nas análises intergrupos e entre gêneros (p>0.05). Conclusão: O protocolo cirúrgico influenciou o volume palatino das crianças com fissura unilateral de lábio e palato. Este estudo sugeriu que o protocolo da palatoplastia em duas etapas possui uma tendência de ser mais apropriado.(AU)

Éxito de la ortopedia prequirúrgica en pacientes con labio fisurado y paladar hendido ­ Revisión de alcance / Sucesso pré-cirúrgico em ortopedia em pacientes com fissura de labio e palato - Revisão da abordagem / Pre-surgical orthopedics success in patients with cleft lip and cleft palate - Scoping review

Resumen: Kerr McNeil, protesista escocés introdujo la ortopedia maxilar neonatal hace más de dos siglos, fue así que sugirió inicialmente que la reposición de los segmentos maxilares mediante aparatos ortopédicos producía una maxila aparentemente normal. Se han descrito distintos tipos de aparatología ortopédica prequirúgica, divididos en tres categorías: activos, semiactivos y pasivos. Objetivo: Realizar una búsqueda de la literatura en bases de datos indexadas sobre el éxito de la ortopedia prequirúrgica en pacientes con labio fisurado y paladar hendido. Metodología: Se realizó una búsqueda computarizada en las siguientes bases de datos electrónicas: PUBMED, SCIENCEDIRECT, PROQUEST, COCHRANE, OVIDSP SCOPUS, Y MEDLINE. Los buscadores booleanos utilizados en las diferentes bases de datos fueron OR, AND, NOT. Resultados: Trece artículos cumplieron con los criterios de elegibilidad y se incluyeron en esta revisión, 4 son estudios observacionales descriptivos longitudinales y prospectivos, 5 son reportes de casos clínicos, 1 es en estudio retrospectivo, 1 es una revisión Cochrane, 2 son casos y controles; el uso de la ortopedia dependía del caso de extensión y severidad según la fisura labiopalatina y el tiempo de uso debía ser desde el momento del nacimiento del bebé hasta los 3 meses de vida. Conclusión:La ortopedia prequirúrgica es exitosa si se usa desde el momento del nacimiento y hasta los tres meses de vida, ofreciendo resultados satisfactorios y de manera eficaz disminuyendo la hendidura palatina, la deformidad nasal y la fisura labial antes de practicar la queilorrafia y la palatorrafia.

Resumo: Kerr McNeil, um protesista escocês introduziu a ortopedia maxilar neonatal há dois séculos, estabelecendo o conceito de uso de peças ortopédicas para produzir uma maxila mais natural. Três tipos diferentes de ortopedia pré-cirúrgica foram descritos. São eles: ativo, semi-ativo e passivo. Objetivo: Realizar uma pesquisa em dados indexados sobre o sucesso do tratamento ortopédico pré-cirúrgico em pacientes com quadro de fissura labiopalatina. Metodologia: Foi realizada pesquisa informatizada em bancos de dados eletrônicos como: PUBMED, SCIENCEDIRECT, PROQUEST, COCHRANE, OVIDSP SCOPUS e MEDLINE. As pesquisas booleanas utilizadas nas bases de dados múltiplas foram OR, AND, NOT. Resultados: Treze artigos atenderam aos padrões de elegibilidade e foram incluídos nesta revisão. 4 (quatro) deles são estudos observacionais descritivos, longitudinais e prospectivos. 5 (cinco) são relatórios clínicos, 1 (um) é um estudo retrospectivo, 1 (um) é uma revisão Cochrane e 2 (dois) são casos clínicos e check ups. A implantação do tratamento ortopédico dependeu do tipo de extensão dos casos e da gravidade da fenda palatina. Conclusão: a ortopedia pré-cirúrgica tem sucesso se implementada ao nascimento até os 3 meses de idade. Assegura resultados satisfatórios diminuindo consideravelmente a fenda palatina, a malformação nasal e a fenda labial antes da realização dos procedimentos de Queilorrafia e Palatorrafia

Kerr McNeil, Scottish prosthetic introduced the Neonatal maxillary orthopedics two centuries ago setting the concept of using orthopedic parts to. Three different types of pre-surgical orthopedics have been described. These are: active, semi-active and passive. Objective: Perform a research in indexed data regarding the success of pre-surgical orthopedics treatment in patients with a condition of cleft lip and cleft palate. Methodology: A computer based research was performed at electronic data bases such as: PUBMED, SCIENCEDIRECT, PROQUEST, COCHRANE, OVIDSP SCOPUS, and MEDLINE. The Booleans researches used in the multiples data bases were OR, AND, NOT. Findings: Thirteen papers met the eligibility standards and were included in this review. 4 (four) of them are descriptive, longitudinal and prospective observational studies. 5 (five) are clinic reports, 1 (one) is a retrospective study, 1 (one) is a Cochrane review, and 2 (two) are clinic cases and check ups. The orthopedics treatment implementation depended on the kind of extension cases and severity of the cleft palate. Conclusion: the pre-surgical orthopedics is successful if it is implemented at birth up to 3 months of age. It assures satisfactory results decreasing considerably cleft palate, nasal malformation, and cleft lip before performing Cheilorrhaphy and Palatorrhaphy procedures. Key words: Cleft lip, cleft palate, orthopedic surgery, palatal obturators, nose deformities

A Systematic Review of the Role of Mitochondria in Cleft Pathology: A Forgotten General?

ABSTRACT@#Orofacial clefts (OFC) are one of the most common birth defects that affects the lip, palate, or lip and palate of an infant. The deterioration of clefts is multifactorial involving multiple genes, various interactions from environmental factor and most forgotten, mitochondrial abnormality. The aim of this review is to highlight the importance of mitochondrial activity related to non-syndromic OFC deformity. Despite its important role in cells, the study on mitochondrial activity in cleft pathology was scarce and almost forgotten compared to other genetic investigations. This systematic review was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. The literature search was done via the following databases: Google Scholar, Pubmed and Scopus with a total of nine studies of mitochondrial abnormalities were included. We hypothesise that mitochondria play an important role in early craniofacial development. A decreased in its function or activity may result in cleft lip formation. Hence, we would like to shed light on the remarkable role of mitochondria activity in the pathogenesis of non-syndromic OFC.

Mechanism of cleft palate in C57BL/6N mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin / 中华口腔医学杂志

Objective: To explore the molecular mechanism of cleft palate in mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Methods: The pregnant mice were randomly divided into TCDD-treated group (n=42) and control group (n=42). TCDD-treated group was given by gavage a single dose of TCDD (64 μg/kg) at 8: 00 AM on gestation day 10 (GD10) and the control group was given by gavage the isopyknic corn oil. At GD13-GD15, the fetal mice palate development was observed by HE staining. The mouse embryonic palatal mesenchymal cell proliferation was detected by 5-bromo-2-deoxyuridine (BrdU) immunofluorescence. The localization and expression of maternally expressed gene3 (MEG3) in mouse embryonic palatal mesenchymal cells was detected by situ hybridization and real-time PCR (RT-PCR). The key protein expressions of transforming growth factor-β (TGF-β)/Smad signaling pathway in mouse embryonic palatal mesenchyme were analyzed by Western blotting. The interaction of MEG3 and TGF-β receptor Ⅰ (TGF-βRⅠ) was examined by RNA binding protein immunoprecipitation (RIP). Results: At GD13 and GD14, compared with the control group, the ratio of BrdU-positive cells in the palatal mesenchyme of TCDD-treated fetuses decreased significantly (GD13, t=6.66, P=0.003; GD14, t=6.56, P=0.003). However, at GD15, the ratio of BrdU-positive cells was significantly increased (t=-5.98, P=0.004). MEG3 was mainly expressed in the nuclei of fetal mouse palatal mesenchymal cells, and the expression of MEG3 in TCDD group was significantly increased at GD13, GD14 and GD15(GD13, t=39.28, P=0.012; GD14, t=18.75, P=0.042; GD15, t=28.36, P=0.045). At GD14, TCDD decreased the levels of p-Smad2 and Smad4 in embryonic palate mesenchymal cells (p-Smad2, t=9.48, P=0.001;Smad4, t=63.10, P=0.001), whereas the expression of Smad7 was significantly increased at GD14 (t=30.77, P<0.001). The results of the RIP experiment showed that the amount of TGF-βRⅠ-bound MEG3 in mouse embryonic palatal mesenchymal cells in the TCDD group (23.940±1.301) was higher than that in the control group (8.537±1.523)(t=24.55, P<0.001). Conclusions: MEG3 is involved in the suppression of mouse embryonic palatal mesenchymal cell proliferation, functioning at least in part via interacting with the TGF-βRⅠ protein and thereby suppressing Smad signaling in the context of TCDD induced cleft palate.

Association study between haplotypes of WNT signaling pathway genes and nonsyndromic oral clefts among Chinese Han populations / 北京大学学报(医学版)

OBJECTIVE@#To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios.@*METHODS@#The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07).@*RESULTS@#After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4).@*CONCLUSION@#This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

Exploring the association between de novo mutations and non-syndromic cleft lip with or without palate based on whole exome sequencing of case-parent trios / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design.@*METHODS@#Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database.@*RESULTS@#A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes.@*CONCLUSION@#Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.

Psychosocial repercussions experienced by parents who care for infants with syndromic orofacial clefts / Repercussões psicossociais vivenciadas por pais cuidadores de lactentes com fissura orofacial sindrômicos

Abstract Objectives: to understand the psychosocial implications experienced by caregiving parents, resulting from the care of the child with cleft lip and/or palate associated with the syndrome. Methods: a cross-sectional and qualitative study, guided by the Consolidated Criteria for Reporting Qualitative Research tool, carried out between January and May 2019. Data collection was carried out through semi-structured interviews that were audio-recorded and transcribed in full. Thematic content analysis was used as the methodological framework and Symbolic Interactionism as the theoretical framework. Results: the participants were 16 caregiving parents. Four categories were listed: implications for diagnosis and treatment initiation, implications for financial issues and paid activities, implications for the care process, and implications for access to health resources. Conclusion: it was found that psychosocial implications experienced by these informal caregivers are multifaceted and complex, and that knowing them will enable planning and implementation of actions that contribute, in addition to the children's rehabilitation process, to the health and quality of life of those who care.

Resumo Objetivos: compreender as implicações psicossociais vivenciadas por pais cuidadores, decorrentes do cuidado do filho com fissura de lábio e/ou palato associada à síndrome. Métodos: estudo transversal, qualitativo, norteado pela diretriz Consolidated Criteria for Reporting Qualitative Research, realizado entre janeiro e maio de 2019. A coleta de dados realizou-se através de entrevista semiestruturada, que foi audiograda e transcrita na íntegra. Utilizou-se como referencial metodológico a Análise de Conteúdo Temática e como referencial teórico, o Interacionismo Simbólico. Resultados: participaram 16 pais cuidadores. Foram elencadas quatro categorias: implicações diante do diagnóstico e início do tratamento, implicações relacionadas às questões financeiras e de atividades remuneradas, implicações relacionadas ao processo de cuidar e implicações referentes ao acesso aos recursos de saúde. Conclusão: percebeu-se que as implicações psicossociais vivenciadas por esses cuidadores informais são multifacetadas e complexas, e conhece-las viabilizará o planejamento e a implementação de ações que contribuam, além do processo reabilitador das crianças, à saúde e qualidade de vida daqueles que cuidam.

Three-Dimensional paladar shutter fisurated in pediatric patient / Obturador tridimensional de paladar fisurado en paciente pediátrico

ABSTRACT: Palatal fissure is one of the congenital craniofacial malformations with the highest incidence worldwide, which compromises both the aesthetic and functional part, thus altering the vital functions: chewing, phonation, hearing and swallowing. The literature indicates that this anomaly occurs in 25% individually and 50% when associated with the cleft lip. One of the characteristics of these patients is the presence of notable malnutrition, caused by difficulty feeding, because they cannot exert enough pressure to suck breast or bottle milk; In addition, oral-nasal communication will lead to food entering the nostrils, causing regurgitation until possible bronchial aspiration. Given this problem, it is necessary to use an acrylic device capable of momentarily sealing the palatal fissure, in order to prevent the diversion of food and restore the sucking reflex in the infant. The objective of this study is to determine the effectiveness of the Three-dimensional Cleft Palate Shutter in a pediatric patient who attended the National Foundation of Maxillofacial Rehabilitation (FUNARMAF) in June 2019. The methodological design corresponds to an analytical - synthetic study since it was based on the analysis of a single case of a 5-month-old female patient, with a Unilateral Palatal Fissure (right), giving her the treatment. Results show that a closure of the oral-nasal communication was obtained, re-establishing the suction reflex. In all, it was observed that the use of this device is effective in patients with lip-palatal fissure since it acts as an adjuvant in breastfeeding and feeding the baby.

RESUMEN: La Fisura Palatina es una de las malformaciones congénitas craneofacial con mayor incidencia a nivel mundial, que compromete tanto la parte estética como funcional, alterando así las funciones vitales: masticación, fonación, audición y deglución. La literatura nos indica que esta anomalía se presenta en un 25 % de forma individual y en un 50 % cuando se asocia al labio leporino. Una de las características de estos pacientes es la presencia de una notable desnutrición, ocasionado por la dificultad para alimentarse, debido a que no pueden ejercer la suficiente presión para succionar la leche materna o del biberón; además la comunicación buco-nasal dará lugar a que los alimentos ingresen a las fosas nasales, ocasionando regurgitaciones hasta provocar una posible bronco-aspiración. Ante esta problemática es necesario el uso de un dispositivo de acrílico capaz de sellar momentáneamente la fisura palatina, con el fin de impedir el desvió de los alimentos y reestablecer el reflejo de succión en el lactante. Objetivo: Determinar la eficacia del Obturador Tridimensional de Paladar Fisurado en un paciente pediátrico que asistió a la Fundación Nacional de Rehabilitación Maxilo-Facial (FUNARMAF) en junio del 2019. Metodología: Analítico - Sintético, ya que se basó en el análisis de un solo caso de una paciente de sexo femenino de 5 meses, con un Fisura Labio Palatina Unilateral (derecha), brindándole el tratamiento. Resultados: Se obtuvo un cierre de la comunicación buco-nasal, reestableciendo el reflejo de succión. Conclusión: se observó que es eficaz el uso de este dispositivo en pacientes con Fisura Labio Palatina ya que actúa como coadyuvante en la lactancia materna y alimentación del bebé.

Use of collaborative learning as atool to evaluate syndromic craniofacial anomalies / Uso da aprendizagem colaborativa como ferramenta para avaliar anomalias craniofaciais sindrômicas

Almost 30% of oral cleftsare associated with other structural abnormalities.However, little is known on orofacial characteristics related tothese cases since they are not systematically reported. To close this gap, we developed a collaborative learning approach supported by an interprofessional team aiming to systematicallydescribe oral findings and impactthe training of future professionals that hopefully will incorporate these descriptionsintotheir clinical practice. The methodological proposal consisted of small group sessions focusing on a particular syndrome or group of syndromes followed by examiningpatients with those conditions. Twenty cases were examined and studied over one semester andaset of conditions to be identified in the orofacial regionwasdefined. Here, we present a guideline that we suggest that dentists and dental institutions use. We also present the advantages of using collaborative learning as a tool in the training of the clinician (AU).

Quase 30% das fissuras orais estão associadas a outras anormalidades estruturais. No entanto, pouco se sabe sobre as características orofaciais relacionadas a esses casos, uma vez que não são relatados de forma sistemática. Para fechar essa lacuna, desenvolvemos uma abordagem de aprendizagem colaborativa apoiada por uma equipe interprofissional com o objetivo de descrever sistematicamente os achados orais e impactar o treinamento de futuros profissionais que, esperançosamente, irão incorporar essas descrições em sua prática clínica. A proposta metodológica consistia em sessões de pequenos grupos enfocando uma determinada síndrome ou grupo de síndromes seguidas de exame de pacientes com essas condições. Vinte casos foram examinados e estudados ao longo de um semestre e foi definido um conjunto de condições a serem identificadas na região orofacial. Aqui, apresentamos uma diretriz que sugerimos que os dentistas e instituições odontológicas utilizem. Também apresentamos as vantagens de usar a aprendizagem colaborativa como uma ferramenta no treinamento do clínico (AU).

The risk of nonsyndromic cleft lip with or without cleft palate and Vax1 rs7078160 polymorphisms in southern Han Chinese / Risco de fenda labial não sindrômica com ou sem fenda palatina e polimorfismo Vax1 rs7078160 em indivíduos da etnia Han do sul da China

Abstract Introduction: Non-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population, Objective: The aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients. Methods: In this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case-control and family-based associations were analyzed. Results: The case-control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p = 0.04) and non-syndromic cleft lip and palate (p = 0.01), but not associated with non-syndromic cleft lip only and nonsyndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG + AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p = 0.04, OR = 2.05, 95% CI: 1.01-4.16) and non-syndromic cleft lip and palate (p = 0.01, OR = 3.94, 95% CI: 1.34-11.54). In addition, we did not detect any transmissiondisequilibrium in rs7078160 (p = 0.68). Conclusion: This study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.

Resumo Introdução: A fenda labial não sindrômica, com ou sem fenda palatina, é um defeito congênito comum em todo o mundo, devido a uma combinação de fatores ambientais e genéticos. O genome-wide association studies relatou que o polimorfismo rs7078160 do Vax1 está intimamente relacionado à fenda labial não sindrômica, com ou sem fenda palatina em populações europeias. Estudos subsequentes mostraram os mesmos resultados nas populações mongol, japonesa, filipina e vietnamita etc. No entanto, pesquisas conflitantes foram relatadas na população chinesa. Objetivo: Investigar a associação entre o polimorfismo rs7078160 e fenda labial não sindrômica, com ou sem fenda palatina, em pacientes do sul da China. Método: Tentamos investigar a distribuição do polimorfismo rs7078160 em 100 trios completos de pacientes (39 pacientes com fenda labial e palatina não sindrômica; 36 pacientes com fenda labial somente, não sindrômica; 25 com fenda palatina somente, não sindrômica e seus pais), da etnia Han do sul da China, e em 60 trios saudáveis selecionados como controle. Reação de polimerase em cadeia e o sequenciamento de Sanger foram uszados para genotipar o polimorfismo rs7078160 do Vax1 e tanto os casos-controle quanto as associações baseadas na família foram analisadas. Resultados: As análises de caso-controle revelaram que o polimorfismo rs7078160 estava significativamente associado a fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04) e fenda labial e palatina não sindrômica (p = 0,01), mas não estava associado a pacientes com fenda labial somente não sindrômica e fenda palatina somente não sindrômica. A composição do genótipo de rs7078160 compreende AA homozigoto mutado, AG heterozigoto e GG homozigoto selvagem. Casos com genótipos AG + AA comparados com GG homozigotos mostraram um risco aumentado de fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04, OR = 2,05, IC de 95%: 1,01 ± 4,16) e fenda labial e palatina não sindrômica (p = 0,01, OR = 3,94, IC 95%: 1,34-11,54). Além disso, não detectamos desequilíbrio de transmissão em rs7078160 (p = 0,68). Conclusão: Este estudo sugere que o polimorfismo rs7078160 foi um fator de risco para fenda labial não sindrômica, com ou sem fenda palatina, e o gene Vax1 está fortemente associado com fenda labial não sindrômica, com ou sem fenda palatina em populações da etnia Han do sul da China.