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.

Cleft Lip and Palate Midfacial Hypoplasia: Criteria to Choose the Treatment.

ABSTRACT: A series of skeletal and dentoalveolar/occlusal criteria were proposed for choosing the treatment modality for the management of midface hypoplasia in cleft lip/palate patients, focusing on functional improvement, aesthetics, and minimizing the risk of recurrence and secondary alterations. For which, 42 patients with nonsyndromic cleft lip/palate, all with previous primary lip/palate surgeries and without previous osteotomies, were analyzed. Orthognathic surgery (OS) (n = 24) and maxillary distraction osteogenesis (n = 18) with anterior segmental osteotomies (segmental distraction osteogenesis [SD]), alveolar transport disc (TD), and midface total distraction osteogenesis (TDO) by modified Le Fort III osteotomy was done.The average of maxillary advancement for OS was 5.58 ±â€Š0.83 mm, for SD 9.4 ±â€Š0.89 mm, for TD 8.00 ±â€Š1.00 mm, and for TDO was 8.13 ±â€Š1.55 mm.In the presence of infraorbital and/or zygomatic hypoplasia, TDO was performed using skeletal anchorage, with the requirement of occlusal stability in dental cast in occlusion. In short maxillary arch without dental cast feasibility in occlusion, hypodontia/agenesis or absence of premaxilla, TD and SD was performed. There was only 1 mm of recurrence in 1 patient of each group. Changes in speech were detected in 2 patients in the OS group (8.3%). Orthognathic surgery can be indicated for advancements ≤7 mm not requiring orbito-zygomatic advancement, whereas distraction osteogenesis can be indicated for advances >8 mm with or without the need for orbito-zygomatic advancement, in addition with other dentoalveolar factors and velopharyngeal function.

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.

Estudio Retrospectivo de Fisuras Labio-Máxilo-Palatina en Chile, 12 Años de Seguimiento

RESUMEN: Describir el perfil epidemiológico de los pacientes con FLMP no sindrómica de acuerdo a los factores que involucran a la madre. Estudio de tipo observacional, retrospectivo y analítico a partir de los datos de los casos de FLMP no sindrómicos. Se clasifico el tipo de FLMP y las variables que involucran a la madre. Fueron evaluadas 236 fichas completas de pacientes. Un 56,60 % pertenecen al sexo masculino y 43,40 % al sexo femenino. El mayor porcentaje nació el año 2011 (15,57 %), la FLP es la más prevalente (44,92 %), el 26,67 % de las madres tenía entre 21-25 años al momento del parto, un 80,50 % y 87,50 % consumió alcohol y tabaco respectivamente durante primer trimestre del embarazo, y un 41,33 % se desempeñó en rubro agrícola. Pueden ser considerados como factores de riesgo durante el embarazo: estrés post catástrofe natural, enfermedades crónicas, consumo de fármaco, hábito tabáquico y alcohólico y exposición a pesticidas.

ABSTRACT: The objective of the study was to describe the epidemiologic profile of patients with non-syndromic cleft palate according to factors that involve the mother. Observational, retrospective and analytical study from data obtained of non-syndromic cleft lip palate cases. The type of cleft lip and palate (CLP) and the variables that involve the mother were classified. In this analysis 236 fulfilled clinical records from patients were evaluated; 56,60 % correspond to male and 43,40 % to female. Most births occurred in 2011 (15,57%), cleft palate is the most prevalent (44,92 %), at the moment of birth mothers were 21-25 years old (26,67 %), most of the mothers consumed alcohol or tobacco during the first trimester of pregnancy (80,50 % and 87,50 %, respectively), and 41,33% worked in agriculture related jobs. In conclusion post natural catastrophe stress, chronic diseases, consumption of drugs, smoking and alcohol habits and exposure to pesticides can be considered as a risk factor for having a child with CLP.

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.

Estudio Comparativo de Crecimiento Estaturo Ponderal y Acceso a Lactancia Materna Durante el Primer Año de Vida de Niños con Fisura Labio Máxilo Palatina versus Niños sin Fisura / Comparative Growth and Development Study in Children with Cleft Lip Palate Fissure versus Children without Fissure

RESUMEN: La fisura labio máxilo palatina (FLMP) es un problema de salud pública en Chile. Consiste en la falta de fusión del labio y/o los procesos palatinos, generando un desequilibrio músculo esqueletal que impide el desarrollo facial normal. Afectando algunas funciones vitales como respiración, succión y deglución pudiendo ocasionar problemas nutricionales. Evaluar el crecimiento estaturo ponderal y acceso a lactancia materna de niños con fisura labio máxilo palatina (FLMP) comparados con niños sin fisura durante el primer año de vida. Estudio de tipo observacional, analítico de cohorte retrospectivo a partir de los datos provenientes de entrevistas a las madres de niños con FLMP no sindrómica atendidos durante el año 2017 y niños sin FLMP perteneciente a la misma región. En niño/as sin FLMP predomina la lactancia materna exclusiva y en niños/as con FLMP lactancia mixta (47,7 %) y uso exclusivo de leche de fórmula (33.3 %). Los niños/ as con FLMP durante el primer año de vida pesan en promedio 0,45 Kg y miden 1,11 cm menos que los niños/as sin fisura. Los niños/as con FLMP reciben menos lactancia materna y tienen un menor crecimiento estaturo ponderal que los niños/sin FLMP durante el primer año de vida, siendo el peso el parámetro de crecimiento más afectado.

ABSTRACT: The maxillary cleft lip and palate fissure (CLPF) is a public health problem in Chile. It involves the lack of fusion of the lip and / or the palatal processes, generating a skeletal muscle imbalance that prevents normal facial development, further affecting vital functions such as breathing, sucking and swallowing. It may also cause nutritional problems. An observational, analytical, retrospective cohort study was carried out, to assess the growth in weight status of breastfeeding infants with maxillary CLPF, and compare it with children without fissure during the first year of life. The study was based on data obtained in 2017, from interviews with mothers of infants with non-syndromic CLPF, and those without CLPF from the same region in Chile. In children without CLPF, exclusive breastfeeding predominated, while children with CLPF received mixed breastfeeding (47.7 %) and exclusive use of formula milk (33.3 %). During the first year of life, infants with CLPF weighed an average of 0.45 kg and measured 1.11 cm less, than children without fissures. Children with CLPF received less breastfeeding and ranked lower in weight and growth than children / without CLPF during the same time period, with weight being the most affected growth parameter.

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.

Espectro de dismorfosis dentofaciales: estudio restrospectivo de 23 años en hospital tipo I de alta complejidad Chile / 23 years of dentofacial deformities patients treated in a tertiary referral hospital in chile. retrospective study

RESUMEN: Objetivo: Determinar los tipos de dismorfosis dentofaciales (DDF) operados en el Hospital Clínico San Borja Arriarán, Santiago, Chile (HCSBA) entre los años 1993 - 2015 y su distribución por sexo y edad al momento de la intervención quirúrgica. Material y Método: Estudio retrospectivo, el criterio de inclusión fue diagnóstico de DDF (clases II o III esqueletal) no asociado a síndrome. La edad de los pacientes se describió con promedio y desviación estándar y el sexo con porcentajes. Análisis estadístico se realizó mediante test de Proporciones, T de Student, prueba Exacta de Fisher y modelo multivariado. Se consideró un valor p<0,05 como significativo. Resultados: De 1.008 pacientes operados por el equipo de cirugía oral y máxilofacial entre 1993 - 2015, 570 (56,5%) fueron intervenidos por cirugía ortognática para corrección de DDF. 76 (13,3%) por DDF tipo II y 494 (86,7%) por DDF tipo III. El mayor porcentaje fueron 366 mujeres (64,2%), la edad promedio fue 26,9 (DS 10,8) años en clase II y 22,8 (DS 6,8) años en clase III. Todas estas diferencias fueron estadísticamente significativas. El rango de edad con mayor porcentaje de operaciones fue entre los 20 - 30 años (55,6%). Conclusión: La DDF más frecuentemente operada es la DDF III y el mayor porcentaje son mujeres entre los 20 - 30 años.

ABSTRACT: Objective: To determine main characteristics of dentofacial deformities (DDF) patients treated with orthognathic surgery at San Borja Arriarán Clinical Hospital, Santiago, Chile (HCSBA) during the last 23 years. Materials and methods: This is a retrospective study, the cases are registered in the electronic database of the oral and maxillofacial service of the HCSBA between 1993 - 2015. Inclusion criteria were patients with a diagnosis of DDF (skeletal class II or III) - not associated with syndromes- who went under orthognathic surgery since 1993 to 2015. Characteristics analysed included: type of DDF, sex and age. Results were described using percentage, mean and standard deviation. Proportion, Student's Ttest, Exact Fisher Test and a multivariate model were utilized for statistical analysis. A p-value <0.05 was considered significant. Results: A total of 1.008 patients were surgically treated. During this period 570 (56,5%) patients underwent orthognathic surgery to correct DDF, 76 (13.3%) for DDF type II and 494 (86.7%) for DDF type III. Most patients intervened were women 366 (64.2%). The mean age was of 23.3 years; 26.9 (SD 10.8) years in class II and 22.8 SD (6.8) years in class III. All differences were statistically significant. The age range with the highest percentage of operations was between 20 - 30 years (55.6%). Conclusion: The most frequently operated DDF is type III, the highest percentage being women and young adults between 20 - 30 years.

Treatment of Maxillary Hypoplasia in Cleft Lip and Palate: Segmental Distraction Osteogenesis With Hyrax Device.

The objective of this work is to describe a segmental maxillary distraction osteogenesis (SDO) with segmental Lefort I with an inexpensive device.Four patients who presented severe class III and maxillary hypoplasia due to cleft lip and palate sequel were treated. A SDO was performed using a dental-anchored Hyrax device, achieving enlargement of the upper jaw without altering speech, with adequate and stable occlusion. Dental implants in a new formed bone were installed.The authors can conclude that SDO is a good treatment alternative for patients with maxillary hypoplasia. It preserves velopharyngeal function and is a stable treatment, maintaining the overjet achieved with distraction osteogenesis, without changes in posterior occlusion. The open bite generated with tooth-borne devices can be solved with temporary anchorage devices and intermaxillary elastics during consolidation phase. Modified Hyrax device allows expanding and moving forward the maxillary arch, with a low cost.

Infant multiple mandibular fracture: case report / Fractura múltiple mandibular en infante: reporte de caso

Infant facial fracture incidence is low. Most reported cases affect the jaw and are single fractures. We present a twenty-two-month old patient, who had a high-energy car accident. Among other injures, she suffered a multiple mandibular fracture: bicondylar, left body and right parasymphyseal. Stable internal fixation of parasymphyseal and body mandibular fracture was performed on the third day. Condylar fractures had a functional treatment with switching elastic traction to prevent ankylosis. Computed tomography (CT) showed mandibular condyles remodelling after six months. Clinical examination showed that mandibular movement ranges were preserved without alteration. Successful treatment of paediatric patients is based on the achievement of an adequate anatomic reduction and the stability of the fracture, allowing opportune form and function recovery, in order to assure further development of dental and facial structures...

La incidencia de fracturas faciales en infantes es baja. Los casos reportados muestran que afectan principalmente a la mandíbula y corresponden a fracturas únicas. Presentamos una paciente de 22 meses de edad, que sufre accidente automovilístico. Resulta entre otros, con múltiples frac-turas mandibulares: bicondílea, de cuerpo izquierdo y parasinfisiaria derecha. Al tercer día se realiza fijación interna estable en fractura parasinfisiaria y de cuerpo mandibular y tratamiento funcional de las frac-turas condíleas a través de tracción elástica alterna-da, para prevenir la anquilosis. Tomografía computa-da a los seis meses muestra remodelación de los cóndilos mandibulares. Al examen clínico los rangos de movimiento mandibular están conservados y sin alteración. El éxito del tratamiento en pacientes pediátricos se basa en obtener una adecuada reducción anatómica y estabilidad de la fractura, que permita recuperar oportunamente forma y función, asegurando el futuro desarrollo de las estructuras dentarias y faciales.

Diplopia y epistaxis como complicación de la técnica anestésica al nervio maxilar superior / Diplopia and epistaxis, clinical complications to maxillary nerve anesthesic technique

La segunda rama del nervio Trigémino puede ser fácilmente bloqueada por vía intraoral. La técnica más usada consiste en entrar por el agujero Palatino Posterior, atravesando el conducto del mismo nombre con una aguja y depositando una solución de anestésico local en la parte más alta de la fosa Pterigopalatomaxilar, por donde emerge desde en endocráneo, vía agujero Redondo Mayor el nervio Maxilar Superior. Las indicaciones, contraindicaciones, técnica y consideraciones anatómicas se presentan, seguidas de una comparación entre agujas de 3.1 cm y 4.1 cm de longitud en relación con las complicaciones de Diplopia y Epistaxis