A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3.

Cleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met [c.1361C>T]; rs41268753; p = 4.08 × 10(-9)) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR = 8.3, 95% CI 4.1-16.8; OR = 2.16, 95% CI 1.43-3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis.

A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10-8), and 19q13 near RHPN2, a gene involved in organizing the actin cytoskeleton (P = 4.17 × 10-8). Other regions reaching genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and 17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group revealed a novel association with a region on 17q23 (P = 2.92 × 10-8) among individuals with European ancestry. This region included several promising candidates including TANC2, an oncogene required for development, and DCAF7, a scaffolding protein required for craniofacial development. In the Central and South American ancestry group, significant associations with loci previously identified in Asian or European ancestry groups reflected their admixed ancestry. In summary, we have identified novel CL/P risk loci and suggest new genes involved in craniofacial development, confirming the highly heterogeneous etiology of OFCs.

Evaluation of a Three-Dimensional Stereophotogrammetric Method to Identify and Measure the Palatal Surface Area in Children With Unilateral Cleft Lip and Palate.

OBJECTIVE: To assess a three-dimensional (3D) stereophotogrammetric method for area delimitation and evaluation of the dental arches of children with unilateral cleft lip and palate (UCLP). Obtained data were also used to assess the 3D changes occurring in the maxillary arch with the use of orthopedic therapy prior to rhinocheiloplasty and before the first year of life. DESIGN: Within the collaboration between the Università degli Studi di Milano (Italy) and the University CES of Medellin (Colombia), 96 palatal cast models obtained from neonatal patients with UCLP were analyzed using a 3D stereophotogrammetric imaging system. MAIN OUTCOME MEASURES: The area of the minor and greater cleft segments on the digital dental cast surface were delineated by the visualization tool of the stereophotogrammetric software and then examined. "Trueness" of the measurements, as well as systematic and random errors between operators' tracings ("precision") were calculated. RESULTS: The method gave area measurements close to true values (errors lower than 2%), without systematic measurement errors for tracings by both interoperators and intraoperators (P > .05). Statistically significant differences (P < .05) were noted for alveolar segment and time. CONCLUSIONS: Maxillary segments have the potential for growth during presurgical orthopedic treatment in the early neonatal period. The cleft segment delimitation on digital dental casts and area measurements by the 3D stereophotogrammetric system revealed an accurate (true and precise) method for evaluating the stone casts of newborn patients with UCLP.

Nasal changes with nasoalveolar molding in Colombian patients with unilateral cleft lip and palate.

PURPOSE: Presurgical nasoalveolar molding (PNAM) is controversial in maxillofacial orthopedics. It supposedly improves the nasal esthetics and function in unilateral cleft lip/palate (UCLP) patients. However, there is no research available in South America to support this claim. The purpose of this study was to evaluate the efficacy of presurgical nasoalveolar molding therapy on morphological changes of the noses of unilateral cleft lip/palate patients in a Colombian sample. METHODS: Seventeen neonate UCLP patients using PNAM received facial impressions at the beginning of treatment; before primary rhinocheiloplasty; and before palatoplasty. A submentovertex photograph of each cast was taken and analyzed by digital photogrammetry. Wilcoxon and Friedman tests were used for within- and between-group comparisons. RESULTS: A statistically significant reduction of cleft nostril width, without significant changes in noncleft nostril width or total nasal width, was found after PNAM. A significant increase in cleft and noncleft nostril height, plus a nonsignificant increase in nostril area in both sides and a nonsignificant uprighting of the columella were found. These changes were maintained or further improved after rhinocheiloplasty. CONCLUSION: The presurgical nasoalveolar molding technique improved nasal tip projection and alar cartilage depression and decreased partially columella deviation before rhinocheiloplasty in South American unilateral cleft lip/palate patients.

Exploración de significados con respectoa la salud bucal de un grupo de gestantes de la ciudad de Medellín, Colombia: ¿hay alfabetización en salud bucal? / Exploration of meanings regarding oral health in a group of pregnant women in Medellín, Colombia: is there oral health literacy?

Introducción: en muchas culturas, la madre es la responsable por excelencia del cuidado del bebé, en muchos casos el adulto más significativo, modelo de referencia imitable y transmisora principal de cultura, incluyendo conocimientos y prácticas de salud. El objetivo fue explorar en un grupo de gestantes de la ciudad de Medellín participantes de un programa de intervención, los significados con respecto a la salud bucal propia y de sus hijos. Métodos: el abordaje metodológico fue la etnometodología; se aplicaron entrevistas semiestructuradasque fueron grabadas, transcritas y analizadas, agrupando las respuestas en recurrencias, divergencias, textos significativos y tendencias. Resultados: las gestantes otorgan un significado importante a la boca, relacionado con la supervivencia y la estética; enfatizan en los dientes como parte integrante de la boca y consideran la salud bucal sinónimo de dientes sanos. El concepto de higiene bucal lo representan comohigiene de los dientes, con cepillo y crema dental. La boca de su futuro hijo no es asunto de preocupación, aunque consideran importante su higiene, pero no en etapas tempranas. Conclusiones: la boca como elemento fundamental de supervivencia, es un asunto reconocidopor las entrevistadas. Los cuidados de la boca del bebé, adquieren importancia en relación con la aparición de los dientes. La seda dental, elemento necesario para la higiene de los dientes, no está incorporado en las prácticas de las gestantes, como tampoco una frecuencia del cepillado. La alfabetización en salud propone construir conocimiento que incida positivamente en el fomento y conservación de la salud.

Introduction: in many cultures, mothers are responsible for taking care of their babies, being the mother frequently the most significant adult, a model to follow, and the principal transmitter of culture, including health knowledge and practices. The objective of this study was to explore a group of pregnant women’s perceptions of their own oral health and that of their children. These women were all from Medellín, Colombia, and they were participating in one of the city’s intervention programs. Methods: An ethno-methodologicalapproach was used; therefore, semi-structured interviews were conducted, recorded, transcribed and analyzed, and the responses were classified according to four criteria: recurrence, divergence, tendencies, and significant meanings. Results: pregnant mothers give significant importance to the mouth due to survival and esthetic reasons. They emphasize teeth over other parts of the mouth and think that oral health is synonymous to healthy teeth. The concept of oral hygiene is represented as cleaning the teeth with toothbrush and toothpaste. The mouth of their future child is not a matter of concern, and they consider oral hygiene important but not in early stages. Conclusions: the interviewed mothers recognize the mouth as an essential survival element. Care of the baby’s mouth gains importance as teeth appear.Dental floss, which is considered necessary as a cleaning element, is not used by pregnant women, not is it frequent tooth brushing. The claim of Oral Health Literacy is to build knowledge in order to promote and preserve health.

A retrospective characterization study on patients with oral clefts in Medellín, Colombia, South America / Un estudio retrospectivo de caracterización en pacientes con fisurasorales en Medellín, Colombia, Suramérica

Introduction: the objective of this study was to make a clinical and epidemiological characterization of the patients with cleft lip and/or palate (CLP) who consulted at the Children’s Hospital Clínica Noel Foundation of Medellín, Colombia, South America, between 1985 and 2003. Methods: 919 clinical records were evaluated for a descriptive, longitudinal, retrospective study. A univariate statistical analysis was used for the qualitative variables, and descriptive measures for the quantitative ones. A two-variate statistical analysis was performed in order to determine the association among the qualitative variables with a significance level of 5%. Results: 50.3% of the cases were classified as unilateral and 19.8% as bilateral. Among the unilateral ones, 59.0% were located at the left side and 41.3% at the right side. 3.4% presented cleft lip, 12.4% presented cleft palate, and 12.8% presented cleft soft palate. 1.2% of the sample did not present pathology classification. In terms of gender, males represented 48.0% and females 38.1%; no data was found in 13.9% of the cases. Concerning location, 87.3% of the patients came from the State of Antioquia. As for age at the time of admission to the institution, 44.3% of the children were less than thirty days old. Most parents were between nineteen and thirty years old. Most medical records did not show reports on the father or mother’s family history, diseases during pregnancy or tobacco and alcohol consumption during pregnancy. Conclusions: this study evaluated the clinical records used at the Clínica Noel Foundation. As a result, we recommend to homogenize the professionals who fill in the records and to standardize the instruments in order to generate reliable databases for future research.

Introducción: el objetivo de este estudio consistió en caracterizar clínica y epidemiológicamente pacientes con labio y/o paladar hendido (LPH) que consultaron el Hospital Infantil Clínica Noel de Medellín, Colombia, entre 1985 y 2003. Métodos: se evaluaron 919 historias clínicas, para un estudio de tipo descriptivo, longitudinal y retrospectivo. Se realizó un análisis univariado para las variables cualitativas, y medidas descriptivas para las variables cuantitativas. Se realizó análisis bivariado para determinar la asociación entre las variables cualitativas con un nivel de significancia del 5%. Resultados: 50,3% de los casos fueron clasificados como unilaterales y 19,8% como bilaterales. Dentro de los unilaterales, el 59,0% se presentaron al lado izquierdo y el 41,3% al lado derecho. El 3,4% presentó labio hendido, el 12,4% presentó paladar duro hendido, y el 12,8% presentó paladar blando hendido. El 1,2% de la muestra no incluía clasificación de la patología. En cuanto al sexo, los hombres representaron 48,0% y las mujeres 38,1%; no se encontraron datos en el 13,9%. El 87,3% de los pacientes provenían del departamento de Antioquia. La edad predominante de ingreso a la Fundación fue antes de treinta días de nacido. La mayoría delos padres estaban entre diecinueve y 30 años de edad. La mayoría de las historias clínicas no tenían reporte acerca de historia familiar de la madre y el padre, enfermedades sufridas durante el embarazo o consumo de cigarrillo y bebidas alcohólicas durante el embarazo. Conclusiones: este estudio permitió evaluar la historia clínica usada en la Fundación Clínica Noel. Se sugiere calibrar los profesionales que diligencian los registros, y estandarizar los instrumentos para generar una base de datos confiable para futuras investigaciones.

Rehabilitación temprana de los maxilares en pacientes con labio y paladar hendido bilateral utilizando un dispositivo ortopédico dinámico intraoral, cinta adhesiva labial y gingivoperiosteoplastia: estudio piloto experimental / Early maxillary rehabilitation of bilateral cleft lip and palate patients using an intraoral dynamic orthopedic appliance, lip tape adhesion and gingivoperiosteoplasty: experimental pilot study

Introducción: el objetivo fue corroborar la respuesta ortopédica de los componentes alveolares al dispositivo ortopédico dinámico intraoral propuesto en el estudio piloto realizado por el mismo grupo investigador, combinado con la utilización de una cinta adhesiva sobre el labio y la gingivoperiosteoplastia (GPP) en una población colombiana. Métodos: denueve pacientes con LPHB entre los cinco y diez meses de edad, se seleccionaron seis pacientes, cuatro hombres y dos mujeres. Se les implantó el dispositivo dinámico y la cinta adhesiva durante un promedio de 3,5 semanas. Después de obtener el resultado ortopédico se les realizó la GPP y la rinoqueiloplastia primaria. Se obtuvieron modelos maxilares antes y después del tratamiento ortopédico, donde se tomaron medidas directamente con un calibrador digital y se compararon entre sí. Se evaluó la formación ósea cualitativamente con tomografías computarizadas, seis meses después de realizada la GPP. Se les hizo análisis estadístico descriptivo. Resultados: en todos los pacientes se logró retracción óptima de la premaxila. Cuatro de los seis pacientes requirieron expansión anterior. Hubo neoformación ósea en los ocho sitios donde se realizó la GPP. Conclusiones: el uso del dispositivo ortopédico dinámico y la cinta adhesiva sobre el labio permite disminuir las discrepancias entre los segmentos maxilares enpacientes con LPHB. La gingivoperiosteoplastia hecha en este esquema de tratamiento actúa como un procedimiento osteoinductor que propicia la neoformación ósea. Se corroboraron los hallazgos del estudio piloto realizado por el mismo grupo investigador y representa una opción terapéutica para pacientes con LPHB en nuestra comunidad.

Introduction: the purpose of this study was to corroborate the orthopaedic alveolar results of dynamic orthopaedic devices used in the pilot study by the same research group, combined with the use of an adhesive tape over the lip and gingivoperiostioplasty in a Colombian population. Methods: 6 patients with complete bilateral cleft lip and palate, 4 males and 2 females were selected out of 9 patients between five and ten months of age. The dynamic orthopaedic device and the adhesive tape were used during an average time of 3.5 weeks. After obtaining the orthopaedic result, the gingivoperiostioplasty and rhinoplasty were performed. Comparisons between before and after treatment casts were analyzed with an electronic digital calliper. The boneformation was evaluated with a dental CT scan after a period of 6 months. Descriptive statistical analysis was used. Results: every patient after orthopaedic treatment retracted the premaxilla, four of the six patients studied required anterior alveolar expansion. There was bone formation in the 8 sites where the gingivoperiostioplasty was performed. Conclusion: the use of the dynamic orthopaedic device and the adhesive tape over the lip decreased the discrepancies in maxillary segments of bilateral cleft lip and palate patients. The gingivoperiosteoplasty performed in this protocol serves as an osteo-inductor suitable for bone formation. This study corroborates the pilot study by the same research group and represents a practical option for the treatment in cases with protrusion of the premaxilar in our community.

Rehabilitación temprana del paciente con labio y paladar hendido bilateral utilizando un dispositivo ortopédico y gingivo-periosteoplasty: pilot study / Early rehabilitation of bilateral cleft lipand palate patients using an orthopaedic appliance and gingivo-periosteoplasty: pilot study

Introducción: la reposición de la premaxila en los casos de labio y paladar hendido bilateral (LPHB) por medio de dispositivos intraorales ha sido un aspecto controvertido en su tratamiento. En este estudio se presenta una propuesta terapéutica de ortopedia dinámica intraoral temprana para nuestra comunidad. El objetivo fue evaluar los resultados obtenidos por el uso de un dispositivo intraoral muco-óseo-soportado, acompañado de la cirugía de gingivoperiosteoplastia como parte del cierre primario del labio en los casos de LPHB completo. Métodos: se evaluaron 4 sujetos de 20 semanas de nacidos con LPHB completo, 3 hombres y una mujer. A todos los pacientes se les implantó un dispositivo intraoral muco-óseo-soportado. Después de obtener el resultado ortopédico se les realizó la gingivoperiosteoplastia y la rinoqueiloplastia primaria. Se compararon los modelos del arco maxilar, antes y después del tratamiento ortopédico mediante mediciones digitales a las cuales se les realizo análisis estadístico descriptivo y se evaluó la formación ósea con tomografías computarizadas, 6 meses después de realizada la gingivoperiosteoplastia. Resultados: en cada uno de los pacientes se logró una retracción de la premaxila y una alineación alveolar satisfactoria. Hubo formación ósea en 3 de los 6 sitios en los que se realizó la gingivoperiosteoplastia. Conclusiones: la ortopedia dinámica intraoral temprana con este tipo de dispositivo mejora la posición de la premaxila y de los segmentos laterales en los casos de LPHB y propicia la neoformación ósea en el sitio de la fisura cuando se acompaña de la gingivoperiosteoplastia. Los resultados sugieren que este dispositivo ortopédico intraoral es una opción terapéutica para pacientes con LPHB en nuestra comunidad.

Odontología para bebés / Dentistry for babies

El proyecto de la odontología para bebés se constituyó como respuesta a las necesidades de la comunidad en educación y atención en salud oral en el grupo etario de 0 a 5 años de edad. Dicho programa concientiza a las personas para entender que la salud bucal hace parte de la salud general, y al mismo tiempo, genera el trabajo participativo (profesionales-comunidad), posibilita el autocuidado y el mantenimiento de la salud, propicia el trabajo interdisciplinario y multiprofesional, cambia la mentalidad del motivo de consulta curativo al educativo/preventivo y, por ende, disminuye la prevalencia de caries dental en la población menor