PEMT variants are associated with nonsyndromic cleft lip with or without cleft palate in Chile.

Aim: To assess the association between PEMT variants and nonsyndromic cleft lip with or without cleft palate in Chile and the effects of these variants on global DNA methylation. Subjects & methods: The authors obtained genotypes for nine variants from 247 cases and 453 controls for genotype-phenotype associations. The effect of significant polymorphisms on global DNA methylation (percentage of long interspersed element-1 methylation) was evaluated in a subsample of 95 controls. Results: After multiple comparison corrections, variants rs7649 and rs4646409 were associated with nonsyndromic cleft lip with or without cleft palate. Carriers of risk alleles presented lower DNA methylation levels than noncarriers. Conclusion: According to functional analysis for risk variants from previous reports, the authors infer that a decrease of methyl group availability is occurring in affected subjects.

This study evaluated if variants in the gene named PEMT confers an increased risk for nonsyndromic cleft lip with or without cleft palate in Chile and its possible effects on methylation of DNA, a variable linked to gene expression modulation. The study found that the variants recognized as rs7649 and rs4646409 increase the risk of nonsyndromic cleft lip with or without cleft palate in the Chilean population and decrease DNA methylation. The authors conclude that this gene may be involved in this birth defect. New studies are needed to confirm the relation between this condition and DNA methylation mediated by these genetic variants.

Vitamin B12 Transport Genes and Nonsyndromic Cleft Lip With or Without Cleft Palate in Chile.

The aims of this study were to assess the association between polymorphisms within genes involved in vitamin B12 transport and nonsyndromic cleft lip with or without cleft palate (NSCL/P) and global DNA methylation in Chile. From 247 cases and 453 controls, we obtained variant genotypes for CBLIF, CUBN, AMN, ABCC1, CD320, and TCN2 from a single nucleotide polymorphisms array. Global DNA methylation in 95 controls was obtained through LINE-1 methylation. After multiple comparison corrections, only rs780807 in CUBN remains associated with NSCL/P at dominant model (OR 0.564, p-value = 0.0006, q-value = 0.0450). Carriers of protective allele showed lower levels of DNA methylation than non-carriers (p = 0.0259). Further studies are necessary in order to explain relations with the phenotype and DNA methylation due to the absence of functional evidence for rs780807 in CUBN.

Maternal genotypes of folate/one-carbon metabolism gene variants and nonsyndromic cleft lip with or without cleft palate risk in Chile.

The aim of this study was to evaluate, in a case-control design, the association between maternal genotypes for variants in 23 genes involved in folate/one-carbon metabolism and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a Chilean population. After applying several filters to an Illumina array, we extracted 175 single nucleotide polymorphisms (SNPs) from 150 mothers of NSCL/P cases and 150 control women. Association was evaluated using computed odds ratio (OR) with a 95% confidence interval (95% CI) in additive, recessive, and dominant models. After multiple comparison correction, only SNP rs4451422 (A>C), located 237 bp downstream of the gene encoding the human folylpolyglutamate synthetase (FPGS), maintained a significant association with NSCL/P in the offspring (OR 3.03; 95% CI 1.69-5.26). The variant rs4451422 is associated with a decrease in FPGS expression according to database annotation. Our results lead to a new hypothesis that a lower activity of FPGS enzyme reduces intracellular folate levels and increases the risk of an offspring having NSCL/P.

Genetic variants in S-adenosyl-methionine synthesis pathway and nonsyndromic cleft lip with or without cleft palate in Chile.

BACKGROUND: The S-adenosyl-methionine (SAM) availability is crucial for DNA methylation, an epigenetic mechanism involved in nonsyndromic cleft lip with or without cleft palate (NSCL/P) expression. The aim of this study was to assess the association between single-nucleotide polymorphisms (SNPs) of genes involved in SAM synthesis and NSCL/P in a Chilean population. METHODS: In 234 cases and 309 controls, 18 SNPs in AHCY, MTR, MTRR, and MAT2A were genotyped, and the association between them and the phenotype was evaluated based on additive (allele), dominant, recessive and haplotype models, by odds ratio (OR) computing. RESULTS: Three deep intronic SNPs of MTR showed a protective effect on NSCL/P expression: rs10925239 (OR 0.68; p = 0.0032; q = 0.0192), rs10925254 (OR 0.66; p = 0.0018; q = 0.0162), and rs3768142 (OR 0.66; p = 0.0015; q = 0.0162). Annotations in expression database demonstrate that the protective allele of the three SNPs is associated with a reduction of MTR expression summed to the prediction by bioinformatic tools of its potentiality to modify splicing sites. CONCLUSIONS: The protective effect against NSCL/P of these intronic MTR SNPs seems to be related to a decrease in MTR enzyme expression, modulating the SAM availability for proper substrate methylation. However, functional analyses are necessary to confirm our findings. IMPACT: SAM synthesis pathway genetic variants are factors associated to NSCL/P. This article adds new evidence for folate related genes in NSCL/P in Chile. Its impact is to contribute with potential new markers for genetic counseling.

Nonsyndromic orofacial clefts in Chile: LINE-1 methylation and MTHFR variants.

Aim: To evaluate the risk of nonsyndromic orofacial clefts (NSOFCs) associated with LINE-1 methylation, as a marker of global DNA methylation, and the effect of MTHFR functional variants on this variable. Patients & methods: LINE-1 methylation was evaluated by bisulfite modification coupled to DNA pyrosequencing in 95 NSOFC cases and 95 controls. In these subjects, MTHFR genotypes for variants c.C677T (rs1801133) and c.A1298C (rs1801131) were obtained. Results: Middle levels (second tertile) of LINE-1 methylation increase the risk of NSOFCs. In addition, LINE-1 methylation depends on c.A1298C genotypes in controls but not in cases. Conclusion: A nonlinear association between global DNA methylation and NSOFCs was detected in this Chilean population, which appears to be influenced by MTHFR functional variants.

A SHMT1 variant decreases the risk of nonsyndromic cleft lip with or without cleft palate in Chile.

OBJECTIVE: To assess the association between polymorphic variants from SHMT1 and MTHFS genes, involved in the cytoplasmic futile folate cycle, and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Chilean population. SUBJECTS AND METHODS: In a sample of 139 Chilean NSCL/P cases and 278 controls, we obtained the genotypes for nine variants of SHMT1 and MTHFS and the association between them and the phenotype was evaluated using odds ratios (OR) in additive (allele), dominant, and recessive models. RESULTS: After correction for multiple comparisons, only the variant rs1979277 (G > A; p.Leu474Phe) from SHMT1 showed a significant and protective effect for additive (OR 0.60; 95% CI 0.42-0.86; p = .0054, q = 0.0488) and dominant models (OR 0.48; 95% CI 0.29-0.75; p = .0009; q = 0.0081). Our bioinformatic prediction plus functional evidence from previous reports demonstrate that the A allele for this missense variant decreases the enzymatic activity. CONCLUSIONS: Owing to the rs1979277 A allele, which reduces the cytoplasmic SHMT activity and has a higher frequency in controls than in NSCL/P cases, we hypothesized that a low enzyme activity may increase the cytoplasmic concentration of folates and, therefore, explain the protective role against OFCs.

Distracción osteogénica del maxilar y manejo ortodóncico integral en paciente con síndrome de Pfeiffer. Reporte de caso / Maxillary osteogenic distraction and comprehensive orthodontic treatment in a patient with Pfeiffer syndrome. A case report

Síndrome de Pfeiffer es una craneosinostosis de herencia autosómica dominante, cuyas manifestaciones clínicas son tanto a nivel cráneofacial como en extremidades superiores e inferiores. El tratamiento para estos pacientes debe ser efectuado por un equipo multi-disciplinario y representa un gran desafío para los profesionales de la salud. El objetivo de este artículo es exponer el caso de una paciente adolescente diagnosticada con síndrome de Pfeiffer, que presentaba hipoplasia maxilar severa, maloclusión de Clase III y overjet negativo; tratada con distracción osteogénica usando dispositivo RED (rigid external distractor) asociado a aparatología ortodóncica fija. Los resultados cumplieron con las expectativas terapéuticas y estéticas de la paciente, mostrando estabilidad en la evaluación 20 meses post tratamiento. Palabras clave: Acrocefalosindactilia; Ortodoncia; Osteogénesis por distracción; Hueso maxilar (fuente: DeCS BIREME).

Pfeiffer ́s syndrome is an autosomal dominantly inherited craniosynostosis, its clinical features are both at craniofacial level and upper and lower limbs. The treatment must be carried out by a multidisciplinary team and represents a great challenge for health profes-sionals. The aim of this article is to present the case of a teenage patient diagnosed with Pfeiffer ́s syndrome, who had severe maxillary hypoplasia, class III malocclusion and negative overjet; treated by osteogenic distraction with a RED (rigid external distractor) associated with fixed orthodontic appliances. The results reached the patient's therapeutic and esthetic expectations and showed stability at 20 months posttreatment. Keywords: Acrocephalosyndactylia; Orthodontics; Distraction osteogenesis; Maxilla (source: MeSH NLM).

Modelo de ficha clínica ortodóntica en pacientes con fisura labio palatina / Application of a novel orthodontic medical record in cleft lip and palate patients

La ficha clínica es un documento médico legal que permite el registro de la información de un paciente y su problema de salud. En la Unidad de Malformaciones Craneofaciales de la Universidad de Chile, se ha utilizado por 33 años un modelo único de ficha clínica dental utilizado específicamente para la atención ortodóntica en pacientes con fisura labio palatina. El objetivo de este trabajo, es exponer una ficha clínica ortodóntica utilizada con finalidades tanto de documento clínico y docencia. Palabras clave: Ficha clínica; Ortodoncia; Labio hendido; Fisura del paladar (fuente: DeCS BIREME).

The medical record is a medico-legal document that allows the registration of a patient and his/her health problem. During the last 33 years, a unique model of orthodontic medical record has been used specifically for orthodontic care in patients with cleft palate at the Craniofacial Malformation Unit of the University of Chile. The objective of this work is to present an orthodontic medical record that can be used for both, clinical and teaching purposes. Keywords: Medical record; Orthodontics; Cleft lip; Cleft palate (source: MeSH NLM).

Clasificación anatómica: una propuesta para categorizar las fisuras labiopalatinas / Anatomical classification: a proposal to categorize cleft lip and palate

El origen de una clasificación para las fisuras labiopalatinas se remonta desde comienzos del siglo XX. Muchos de los sistemas propuestos por diversos autores no han prosperado, principalmente debido a su complejidad para memorizar y registrar. Esta nota científica resume las clasificaciones de fisuras labiopalatinas más populares entre los profesionales de la salud y además propone una nueva, basada en aspectos anatómicos y morfológicos de las fisuras en los pacientes, la Clasificación Anatómica. Esta clasificación, diseñada y utilizada por la Unidad de Malformaciones Craneofaciales de la Universidad de Chile, busca entregar una solución a esta problemática, categorizando las fisuras, de manera simple y descriptiva, según los tejidos comprometidos (labio, paladar, labiopalatinas), si su manifestación clínica es poco prevalente (atípicas) o si se encuentran asociadas a algún síndrome (sindrómicas). Palabras clave: Fisura del paladar; Labio leporino; Clasificación (fuente: DeCS BIREME).

The origin of cleft lip and palate classification dates back to the early twentieth century. Many of the systems proposed by different authors have not prospered, mainly because of their complexity in memorizing and recording. This scientific note summarizes the most popular cleft lip and palate classifications among health professionals and also proposes a new one, based on anatomical and morphological features of the patient ́s cleft; the Anatomical Classification. This classification, designed and used by the Craniofacial Mal-formations Unit of the University of Chile, seeks to provide a solution to this problem, categorizing the clefts, in a simple and descriptive manner, according to the tissues invol-ved (lip, palate, lip and palate), if its clinical manifestation is not that prevalent (atypical) or if they are associated with some syndrome (syndromic). Keywords: Cleft palate; Cleft Lip; Classification (source: MeSH NLM).

Manejo no quirúrgico de fisura alveolar severa en paciente adulta mediante tratamiento ortodóncico fijo. Reporte de caso / Non-surgical management of severe alveolar fissure through orthodontic treatment in an adult patient. Case report

La fisura labio alveolo palatina es la malformación congénita más común entre las anomalías craneofaciales. Debido a sus múltiples alteraciones, impacta directamente en la calidad de vida del paciente. Su manejo es interdisciplinario y el tratamiento debe iniciar-se desde el nacimiento. El objetivo de este caso clínico es mostrar el manejo ortodóncico integral de una paciente adulta con fisura alveolo palatina unilateral no tratada de 18 mm de ancho, que acude a la consulta porque deseaba una solución estética y funcional, pero sin someterse a una cirugía. A través de un tratamiento con ortodoncia fija multibrackets se logró contactar los rebordes alveolares del defecto óseo, obteniendo resultados positivos en relación a la estética dental y funcionalidad. Palabras clave: Adultos; Fisura del paladar; Ortodoncia.

The labial-alveolar-palatal cleft is the most common congenital malformation among craniofacial anomalies. Due to its multiple alterations, it directly impacts the quality of life of patients. Its management is interdisciplinary and the treatment must start from birth. The aim of this case report is to show the integral orthodontic management of an adult patient with an untreated unilateral alveolar cleft of 18 mm wide, who came to the Dental office pursuing an aesthetic and functional solution without undergoing surgery. Through a fixed orthodontic multibrackets treatment it was possible to contact the alveolar ridges of the bone defect, obtaining positive results in relation to esthetics and function. Keywords: Adults; Cleft palate; Orthodontics

Puente adhesivo temporal como solución estética en paciente con fisura de labio y paladar / Temporary adhesive bridge as aesthetic solution in patient with cleft lip palate

RESUMEN: Las dificultades por ausencia de una pieza dentaria anterior en un paciente con fisura de labio y paladar operado y en período de crecimiento requieren una solución estética inmediata posterior al retiro de aparatología fija de ortodoncia y en espera de una solución definitiva, sin embargo, ante escenarios como éste son útiles materiales de restauración que cumplan con indicaciones como rapidez en el trabajo, de tipo adhesivos reforzados con fibras de polietileno, altamente estéticos, manipulables y útiles en moldeabilidad. Se presenta un caso donde se utilizó resina compuesta, una cinta reforzada de fibra de polietileno, para la realización de un puente de reposición temporal de dos piezas dentarias anteriores en un paciente con diagnóstico de fisura de labio y paladar unilateral como una solución muy estética, no invasiva, provisional en espera del término del crecimiento para una rehabilitación definitiva.

ABSTRACT: There are several therapeutic alternatives for the rehabilitation of absent permanent teeth, but these alternatives are limited when the piece has an im-portant aesthetic component and must be performed in developing patients. Such is the case of patients with cleft palate, in which it is essential to use a highly es-thetic material and to rehabilitate edentulous spaces, usually an incisor, once the orthodontic treatment is completed and as a temporary solution in waiting of a de-finitive rehabilitation in these situations, restorative materials reinforced with poly-ethylene fibers are useful. In this case, a reinforced tape of polyethylene fiber was used as a temporary replacement bridge of two anterior teeth in a patient with a diagnosis of cleft lip and unilateral palate as an esthetic, non-invasive and temporary solution until his grow for a definitive rehabilitation.

Tratamiento integral de fisura palatina con injerto de lengua: reporte de caso / Sinus floor elevation with a lateral window technique and simultaneous dental implants placement: case report

RESUMEN: La fisura labio palatina (FLP) es una alteración del desarrollo, congénita, de etiología desconocida. La fístula oronasal es la complicación más común de la reparación del paladar con fisura. Los problemas más comunes incluyen hipernasalidad al hablar y el pase de fluidos y comida hacia la cavidad nasal. El caso corresponde a un paciente de 16 años de edad, sexo masculino, con fístula buconasal de 2,1 cm de diámetro mayor en sentido transversal, como secuela de FLP unilateral derecha. Además relata problemas en la alimentación, traspaso de fluidos a la cavidad nasal, problemas de habla por insuficiencia velo faríngea (IVF) valor 9, alteraciones en sus relaciones interpersonales y baja autoestima. Se realizó el injerto de lengua en fístula buconasal, tratamiento de ortodoncia y rehabilitación oral para dar solución estética y funcional. El éxito del tratamiento integral le permitió al paciente mejorar sus relaciones sociales debido a una mayor autoestima.

ABSTRACT: The cleft lip and palate (CLP) is a developmental and congenital anomaly of unknown etiology. The oronasal fistula is the most common complication of the cleft palate reparation. The most common problems are hypernasality on speech and the passage of fluids and food to the nasal cavity. This case is about a sixteen- year-old boy with a 2,1 cm diameter oronasal fistula due to a right unilateral CLP sequel. He also presented alimentation problems, fluid passage to the nasal cavity, speech defects by velopharyngeal insufficiency (VFI), relationships problems and low self-esteem. A tongue graft in the oronasal fistula, orthodontic treatment and oral rehabilitation were made to give an aesthetic and functional solution. The success of the treatment allowed the patient to improve his relationships due to a greater self-esteem.

Prótesis y ortodoncia: rehabilitación de fisurado bilateral: caso clínico / Prosthesis and orthodontics: bilateral fissure repair: a clinical case

RESUMEN: El paciente fisurado labiopalatino muestra una falta de fusión de los procesos palatinos presentando una comunicación de la cavidad buconasal, anomalías de forma y/o la agenesia de los dientes cercanos a la fisura y un deficiente crecimiento sagital y transversal maxilar, esto es más complejo en la fisura bilateral, por ser el más severo de los subtipos de fisura. Se dificultan las funciones básicas como comer, hablar y relacionarse con los demás. Su tratamiento requiere del trabajo de un equipo transdisciplinario, coordinado y organizado, conformado por todos aquellos profesionales que colaboren en proporcionar un resultado integral. El objetivo de este artículo es exponer un caso clínico de rehabilitación protésica en conjunto con un tratamiento de ortodoncia en un paciente que presenta labio leporino bilateral y fisura palatina, además de una premaxila móvil, severamente extruida.

ABSTRACT: The cleft lip and palate patient is mainly characterised by the presence of an oronasal communication, malformation or agenesis of the teeth close to the cleft, and deficient sagittal and transverse growth of the maxilla. These patients require various treatments involving a multidisciplinary team, which may include a maxillofacial surgeon, an orthodontist, a speech therapist, a paediatrician, plastic surgeon, a general dentist, a prosthodontist, an ENT specialist, a psychologist, and all those professionals who can help provide functional, aesthetic and psychological improvement. This report describes a case of prosthetic rehabilitation in a patient with cleft lip and palate without alveolar bone in the cleft area, which prevented rehabilitation with an osseointegrated implant, in addition to a mobile and severely extruded pre-maxilla, which required an orthopaedic repositioning.

Técnica alternativa y simple de rehabilitación oral con prótesis removible para una paciente con epidermolisis bullosa distrófica: reporte de caso clínico / Aternative and simple oral rehabilitation technique using a removable prosthesis for a patient with epidermolysis bullosa dystrophica: a case report

La epidermolisis bullosa es una enfermedad de origen genético caracterizada por una marcada fragilidad de la piel y las mucosas, resultando en la aparición de lesiones vesiculobullosas y/o desprendimientos tisulares de aparición espontánea o, más comúnmente, como consecuencia de roce mecánico. La formación de cicatrices con retracción tisular genera a nivel oral obliteración vestibular, anquiloglosia y microstomía, complicándose la rehabilitación odontológica y, en particular, la protésica. El presente artículo describe una alternativa protésica, simple y económica, para una paciente desdentada parcial con epidermolisis bullosa distrófica recesiva.

Epidermolysis bullosa is a rare genetic disease that is characterised by the formation of blisters and erosions on the skin and mucous membranes following minor traction or trauma. Oral manifestations of the disease include obliteration of the vestibule, ankyloglossia, and microstomia. Oral rehabilitation, and prosthetic rehabilitation, in particular, is a challenge. This article describes a simple, inexpensive prosthetic alternative for a partially edentulous patient with recessive dystrophic epidermolysis bullosa.

Tratamiento periodontal y ortodóncico de un caso de periodontitis agresiva, 12 años de seguimiento / Periodontal and Orthodontic Treatment of a case of aggressive periodontitis, 12-year period

Sólo se conocen algunos reportes de casos con un diagnóstico de periodontitis agresiva en niños. La manifestación clínica de esta enfermedad se presenta con la pérdida prematura de los dientes temporales y luego de los definitivos, con un avance rápido. Se presenta un caso clínico tratado en conjunto con periodoncia y ortodoncia, mejorando su oclusión, con 12 años de seguimiento.

There are only some cases of aggressive periodontitis that we are aware of that affect children. This disease´s clinical manifestation appears with the premature loss of the temporary teeth and later of the permanent ones, this process happens rather quickly. We present a clinical case that was worked on by orthodontics as well as periodontics, showing an improvement in its occlusion, with a 12 year follow up.