Untangling Zebrafish Genetic Annotation: Addressing Complexities and Nomenclature Issues in Orthologous Evaluation of TCOF1 and NOLC1.

Treacher Collins syndrome (TCS) is a genetic disorder affecting facial development, primarily caused by mutations in the TCOF1 gene. TCOF1, along with NOLC1, play important roles in ribosomal RNA transcription and processing. Previously, a zebrafish model of TCS successfully recapitulated the main characteristics of the syndrome by knocking down the expression of a gene on chromosome 13 (coding for Uniprot ID B8JIY2), which was identified as the TCOF1 orthologue. However, database updates renamed this gene as nolc1 and the zebrafish database (ZFIN) identified a different gene on chromosome 14 as the TCOF1 orthologue (coding for Uniprot ID E7F9D9). NOLC1 and TCOF1 are large proteins with unstructured regions and repetitive sequences that complicate alignments and comparisons. Also, the additional whole genome duplication of teleosts sets further difficulty. In this study, we present evidence that endorses that NOLC1 and TCOF1 are paralogs, and that the zebrafish gene on chromosome 14 is a low-complexity LisH domain-containing factor that displays homology to NOLC1 but lacks essential sequence features to accomplish TCOF1 nucleolar functions. Our analysis also supports the idea that zebrafish, as has been suggested for other non-tetrapod vertebrates, lack the TCOF1 gene that is associated with tripartite nucleolus. Using BLAST searches in a group of teleost genomes, we identified fish-specific sequences similar to E7F9D9 zebrafish protein. We propose naming them "LisH-containing Low Complexity Proteins" (LLCP). Interestingly, the gene on chromosome 13 (nolc1) displays the sequence features, developmental expression patterns, and phenotypic impact of depletion that are characteristic of TCOF1 functions. These findings suggest that in teleost fish, the nucleolar functions described for both NOLC1 and TCOF1 mediated by their repeated motifs, are carried out by a single gene, nolc1. Our study, which is mainly based on computational tools available as free web-based algorithms, could help to solve similar conflicts regarding gene orthology in zebrafish.

[20q11.2 microdeletion syndrome: a phenotypic spectrum expansion. Case report]. / Síndrome de microdeleción 20q11.2: ampliación del espectro fenotípico. Reporte de un caso.

Background: 20q11.2 microdeletion syndrome [ORPHA: 444051] is a rare disease, since 16 patients have been reported in literature worldwide. Prevalence ratio is < 1:1,000,000 individuals. Haploinsufficiency on GDF5, SAMHD1 and EPB41L1 genes is important due to phenotypic manifestations in patients. Clinical features can be grouped into craniofacial abnormalities, limb abnormalities, neurological and perinatal disorders. The aim of this report is to present a clinical case of 20q11.21-q11.23 microdeletion, to describe clinical manifestations found, to compare them with features reported in literature, and to contribute to the phenotypic spectrum expansion. Clinical case: 5-year-old female patient who presented hypotonia, psychomotor retardation, microcephaly, facial dysmorphia, pectus excavatum, thoracolumbar scoliosis, right hip subluxation, camptodactyly and clinodactyly. Karyotype test was normal and SNP microarray test reported deletion of chromosomal region 20q11.21-q11.23. Conclusions: It was presented a 20q11.2 microdeletion syndrome confirmed case that shares the features reported in literature, in addition to previously unreported features, such as blepharoptosis, pectus excavatum, scoliosis and hip dysplasia. Interdisciplinary management is important to improve the patient's condition (in her 3 spheres), in order to achieve her best possible health status.

Introducción: el síndrome de microdeleción 20q11.2 [ORPHA: 444051] es una enfermedad rara, pues se han reportado 16 casos a nivel mundial. Su prevalencia se estima en < 1:1,000,000 de nacidos vivos. Induce haploinsuficiencia en los genes GDF5, SAMHD1 y EPB41L1, los cuales son de importancia clínica por las manifestaciones fenotípicas. Se caracteriza por anomalías craneofaciales, anomalías de extremidades, alteraciones neurológicas y perinatales. El objetivo de este reporte es presentar un caso de microdeleción 20q11.21-q11.23, describir las manifestaciones clínicas encontradas, compararlo con lo reportado en la literatura y colaborar en la ampliación del espectro fenotípico. Caso clínico: paciente del sexo femenino de 5 años que presentó hipotonía, retraso psicomotor, microcefalia, dismorfias faciales, pectus excavatum, escoliosis toracolumbar, subluxación de cadera derecha, camptodactilia y clinodactilia. La prueba de cariotipo se reportó sin alteraciones y el ensayo de microarreglo de polimorfismos de un nucleótido (SNP) reportó deleción de la región cromosómica 20q11.21-q11.23. Conclusiones: se presentó un caso confirmado de síndrome de microdeleción 20q11.2 que comparte las características reportadas en la literatura, además de características no reportadas previamente, como ptosis palpebral, pectus excavatum, escoliosis y displasia del desarrollo de cadera. Es importante el manejo interdisciplinario para buscar mejoría en la condición de la paciente (en sus 3 esferas), a fin de alcanzar el mejor estado de salud posible.

Morphological description of the temporomandibular joint ligaments in domestic pigs.

The temporomandibular joint (TMJ) ligaments play crucial roles in its function or dysfunction. The objective of this study was to describe the macro and microscopic morphology of these ligaments in domestic pigs, aiming to: (1) expand knowledge about the species; (2) provide anatomical references for advancing veterinary therapy and utilizing pigs as animal models in craniofacial research. Heads of young Sus scrofa domesticus were dissected to identify TMJ ligaments. Fragments of these ligaments were collected and processed for subsequent histological analysis with Haematoxylin and eosin staining. The results were qualitatively described. Pigs exhibited a TMJ reinforced by three individualized capsular ligaments: a lateral ligament, attaching to the ventral margin of the zygomatic process of the temporal bone and the lateral margin of the mandibular neck; a caudomedial ligament, attaching to the retroarticular process of the squamous part of the temporal bone and the caudomedial margin of the mandibular neck and a caudolateral ligament, attaching to the ventral margin of the base of the zygomatic process of the temporal bone and the caudal margin of the mandibular neck. The lateral ligament exhibited a greater constitution of dense irregular connective tissue, while the caudomedial and caudolateral ligaments showed a greater constitution of dense regular connective tissue. It is concluded that the TMJ of pigs presents one more ligament than horses, cattle, dogs, cats and what has been described for pigs themselves. We believe these results may contribute to the improvement of veterinary clinical and surgical therapy overall, as well as provide essential morphological information for a better interpretation and application of interspecies results in craniofacial research using pigs as an experimental model, as in the case of humans.

Sagittal cranial projections dataset extracted from CBCT volumes corrected to natural head position in a mixed ethnicity population.

This dataset features 200 sagittal projection images derived from Cone Beam Computed Tomography (CBCT) scans, corrected according to the Natural Head Position (NHP) guidelines proposed by Fredrik Lundström and Anders Lundström. The images originate from orthodontic patients in Cali, Valle del Cauca, Colombia, encompassing both initial phases and ongoing treatments. The dataset is divided into two groups: 100 images from female subjects (CoF) and 100 from male subjects (CoM), facilitating gender-specific studies. The dataset is accompanied by an Excel file ``Data info.xlsx'' that details the rotation angles in the axial (Yaw), coronal (Roll), and sagittal (Pitch) planes, along with the pixel size and image dimensions. This detailed documentation supports the replication of studies and aids in the interpretation of cephalometric analyses. Corrections made to align the images with NHP standards involve adjustments in the three main anatomical planes using points from the frontozygomatic suture (Fz) in the axial and coronal planes, and sella (S) and nasion (N) for the sagittal plane.

Impact of COVID-19 Pandemic on Cleft Lip/Palate Surgery in Brazil: Assessing the Current Landscape.

OBJECTIVE: This study aims to evaluate the impact of COVID-19 and the current situation for cleft lip/palate treatment surgeries within Brazil's public health system. DESIGN: Our retrospective study analyzed CL/P corrective surgeries in Brazil's health system using DATASUS TabNet data from March 2020 to December 2022, with historical data from January 2016 to February 2020. We employed ARIMA analysis to estimate pandemic-related surgery cancellations. RESULTS: In 2020, 1992 (CI 95%: 989-2995) CL/P surgeries were not conducted due to pandemics, a 44.1% (CI 95%: 28.1-54.2%) decrease compared to expectations for march to December 2020. Between the onset of the pandemic in Brazil and the end of 2022, 10,643 surgeries were performed in the country, representing a 33.8% shortfall compared to the expected number for the period (16,076; 95% CI: 9697-22,456). CONCLUSION: The study highlights COVID-19's impact on CL/P surgeries in Brazil. Post-pandemic, surgeries increased but regional disparities remain, urging collaborative efforts to improve services and support affected patients.

Two-dimensional facial photography for assessment of craniofacial morphology in sleep breathing disorders: a systematic review.

PURPOSE: Craniofacial morphology is integral to Sleep Breathing Disorders (SBD), particularly Obstructive Sleep Apnea (OSA), informing treatment strategies. This review assesses the utility of two-dimensional (2D) photogrammetry in evaluating these metrics among OSA patients. METHODS: Following PRISMA guidelines, a systematic review was conducted. PubMed, Embase, and Lilacs databases were systematically searched for studies utilizing 2D photography in SBD. Findings were narratively synthesized. RESULTS: Thirteen studies involving 2,328 patients were included. Significant correlations were found between craniofacial measurements-specifically neck parameters and facial width-and OSA severity, even after BMI adjustment. Ethnic disparities in craniofacial morphology were observed, with photogrammetry effective in predicting OSA in Caucasians and Asians, though data for other ethnicities were limited. Pediatric studies suggest the potential of craniofacial measurements as predictors of childhood OSA, with certain caveats. CONCLUSION: 2D photogrammetry emerges as a practical and non-invasive tool correlating with OSA severity across diverse populations. However, further validation in various ethnic cohorts is essential to enhance the generalizability of these findings.

Incidência de complicações durante os anos iniciais de formação de um serviço de fissuras labiopalatinas / Incidence of complications during the initial years of formation of a cleft lip and palate service

Introdução: A fissura labiopalatina é a malformação congênita craniofacial mais comum. Dificuldades na alimentação, fala e audição são comuns nestes pacientes, necessitando de tratamento multidisciplinar, o que dificulta a criação e manutenção de serviços especializados. A diversidade de classificações e o grande número de técnicas cirúrgicas utilizadas nas cirurgias primárias (queiloplastia e palatoplastia) dificultam a comparação de dados epidemiológicos e de complicações entre os serviços, existindo carência de estudos avaliando centros especializados em fissuras labiopalatinas recém-criados. Método: Foi realizado estudo do tipo coorte prospectiva com pacientes com diagnóstico de fissura labiopalatina submetidos a procedimentos cirúrgicos primários, no Hospital de Clínicas da Universidade Federal de Uberlândia, entre julho de 2017 e fevereiro de 2023. Foram incluídos pacientes menores de 18 anos com acompanhamento pós-operatório de pelo menos 3 meses. Resultados: Participaram do estudo 79 pacientes, que foram submetidos a 115 cirurgias primárias (54 queiloplastias e 61 palatoplastias). Foram relatadas 11 complicações neste período: 2 deiscências em queiloplastia (3,70%), 1 cicatriz hipertrófica em queiloplastia (1,85%), 6 fístulas em palatoplastia (9,83%) e 2 deiscências em palatoplastia (3,28%). A incidência de complicações foi de 9,56% quando analisado o total de cirurgias, sendo 5,55% nos pacientes submetidos a queiloplastia e 13,11% nos pacientes submetidos a palatoplastia. Conclusão: A incidência de complicações durante os anos iniciais de estruturação do serviço foi semelhante a outros estudos da literatura.

Introduction: Cleft lip and palate is the most common congenital craniofacial malformation. Difficulties in eating, speaking, and hearing are common in these patients, requiring multidisciplinary treatment, which makes it difficult to create and maintain specialized services. The diversity of classifications and the large number of surgical techniques used in primary surgeries (cheiloplasty and palatoplasty) make it difficult to compare epidemiological data and complications between services, and there is a lack of studies evaluating newly created specialized centers for cleft lip and palate. Method: A prospective cohort study was carried out with patients diagnosed with cleft lip and palate who underwent primary surgical procedures at the Hospital de Clínicas of the Universidade Federal de Uberlândia, between July 2017 and February 2023. Patients under 18 years of age with follow-up were included. post-operative period of at least 3 months. Results: 79 patients participated in the study, who underwent 115 primary surgeries (54 cheiloplasties and 61 palatoplasties). 11 complications were reported in this period: 2 dehiscences in cheiloplasty (3.70%), 1 hypertrophic scar in cheiloplasty (1.85%), 6 fistulas in palatoplasty (9.83%) and 2 dehiscences in palatoplasty (3.28%). The incidence of complications was 9.56% when analyzing the total number of surgeries, being 5.55% in patients undergoing cheiloplasty and 13.11% in patients undergoing palatoplasty. Conclusion: The incidence of complications during the initial years of structuring the service was similar to other studies in the literature.

Apert syndrome: neurosurgical outcomes and complications following posterior vault distraction osteogenesis.

PURPOSE: Posterior vault distraction osteogenesis (PVDO) has been utilized during the past 15 years to treat a variety of clinical features commonly presented by patients with Apert syndrome. The objective of this study is to determine the efficacy of PVDO in addressing both elevated intracranial pressure (ICP) and ectopia of the cerebellar tonsils (ECT) in young Apert patients. In addition, we aimed to determine the prevalence of hydrocephalus in Apert syndrome patients who underwent PVDO. METHODS: A retrospective study was made with a cohort of 40 consecutive patients with syndromic craniosynostosis (SC), previously diagnosed with Apert syndrome, who underwent PVDO between 2012 and 2022, and thereafter received at least 1 year of follow-up care. Demographic data and diagnosis, along with surgical and outcome data, were verified using medical records, clinical photographs, radiologic examination, and interviews with the parents of all cohort patients. RESULTS: The average patient age when PVDO was performed was 12.91 ± 10 months. The average posterior advancement distance achieved per patient was 22.68 ± 5.26 mm. The average hospital stay per patient was 3.56 ± 2.44 days. The average absolute and relative blood transfusion volumes were 98.47 ml and 17.63 ml/kg, respectively. Although five patients (14%) presented ECT preoperatively, this condition was completely resolved by PVDO in three of these five patients. One of the three patients whose ECT had completely resolved presented syringomyelia postoperatively, requiring subsequent extra dural foramen magnum decompression. All of the remaining four patients were asymptomatic for ECT for at least 1 year of follow-up, and none of these four patients required any additional treatments to address ECT. Two patients presented hydrocephalus requiring ventriculoperitoneal shunt placement. CONCLUSIONS: This study demonstrates that PVDO both reduces diagnosed elevated ICP symptoms and is partially effective in treating ECT in Apert syndrome patients. Hydrocephalus in Apert syndrome is an uncommon feature. The effectiveness of PVDO in addressing hydrocephalus is uncertain.

Association of clinical indicators in TMJ, craniofacial, occlusal, and upper airway changes with symptoms of pediatric obstructive sleep apnea and mouth-breathing.

OBJECTIVE: To assess the association between self-reported symptoms of pediatric OSA and clinical signs in MB children. METHODS: Seventy-three MB children aged 7-14 years answered an interview questionnaire on OSA symptoms in childhood, focusing on chewing, nasal, and sleep disturbances. MB children were checked for changes on the craniofacial, occlusion, TMJ, upper airway, and body posture by a multi-disciplinary team, consisting of medical residents, dental, and psychology postgraduate students. Multiple logistic regression analysis verified the association between clinical signs and self-reported symptoms. RESULTS: Reported symptoms of chewing disturbance as TMD noise, muscle pain, and morning headache were significantly associated with the presence of lip incompetence and Class II malocclusion. Sleep disturbances as snoring, waking up at night, daytime sleepiness, and sleeping with the mouth open were significantly associated with the presence of hypertrophic tonsils and obstructive Mallampati score. CONCLUSION: Symptoms of pediatric OSA were found in mouth-breathing children, which should be carefully investigated in order to prevent OSA in the future.

Determination of mandibular distraction osteogenesis most suitable parameters. An experimental study.

BACKGROUND: Distraction osteogenesis is a process of induced bone generation. Various protocols have been described for the management of the latency period, distraction speed and consolidation period, with greater or lesser success. OBJECTIVE: To better understand the process of mandibular distraction and establish the determining factors and their optimal times. MATERIAL AND METHODS: Twenty-seven dogs were studied, which had 54 distractors placed and that underwent unidirectional, bilateral mandibular distraction osteogenesis. The distraction processes were applied using six variants, two for each factor: latency period, distraction period and distraction speed. The changes were examined by means of bone biopsies and X-rays of the area at 0, 7, 14, 21, 45 and 55 days of the process. RESULTS: The most efficient osteogenic distraction parameters were a latency period of five days, a consolidation period of six weeks, distraction speed of 1 mm/day for distances of less than 20 mm, and 3 mm/day for longer distances. CONCLUSIONS: The sequential histological study allowed to observe the appearance of cellular elements (osteocytes, osteoclasts, osteoid matrix, trabeculate, etc.) and their participation in granulation tissue, newly-formed bone and compact mature bone.

ANTECEDENTES: Respecto a la distracción osteogénica (generación ósea inducida), con mayor o menor éxito han sido descritos diversos protocolos para el manejo del período de latencia, velocidad de distracción y período de consolidación. ­. OBJETIVO: Entender mejor el proceso de la distracción mandibular y establecer los factores determinantes y sus tiempos óptimos. MATERIAL Y MÉTODOS: Se estudiaron 27 perros sometidos a distracción osteogénica unidireccional, bilateral de la mandíbula. Los procesos de distracción se aplicaron con seis variantes, dos por cada factor (período de latencia, período de distracción y velocidad de distracción). Se estudiaron los cambios mediante biopsias del hueso y radiografías de la zona a los 0, 7, 14, 21, 45 y 55 días del proceso. RESULTADOS: Los parámetros de distracción osteogénica más eficientes fueron período de latencia de cinco días, período de consolidación de seis semanas, 1 mm diario de velocidad de distracción para distancias menores a 20 mm y 3 mm diarios para distancias mayores. CONCLUSIONES: El estudio histológico secuencial permitió observar la aparición de los elementos celulares (osteocitos, osteoclastos, matriz osteoide, trabeculado, etcétera) y su participación en el tejido de granulación, el hueso neoformado y el hueso maduro compacto.

Cephalometric Evaluation in Patients with Obstructive Sleep Apnea undergoing Lateral Pharyngoplasty.

Introduction Lateral pharyngoplasty (LP) has shown promising results. Craniofacial deformity reduces the pharyngeal space, contributing to the etiopathogenesis. The analysis of craniofacial features can be performed using cephalometry. Objective To verify if craniofacial deformity is associated with worse polysomnographic data in patients with obstructive sleep apnea (OSA), and to verify if the preoperative cephalometric parameters can interfere with the surgical success of the LP. Methods The study included 21 patients with OSA aged between 18 and 65 years who underwent LP in a university hospital from 2015 to 2019. Polysomnography was performed postoperatively, after a minimum period of 6 months from the surgical procedure. In addition, a cephalometric evaluation was performed to assess craniofacial deformity, and to correlate it with the polysomnographic results. Results The mean and median of all polysomnographic respiratory parameters improved postoperatively, especially the apnea-hypopnea index (AHI), which went from 40.15 to 16.60 events per hour ( p = 0.001). Of the 21 patients, 15 showed improvements in the AHI postoperatively. As for the cephalometric evaluations, we found that the longer the distance between the hyoid bone and the mandibular plane, the greater the patient's preoperative AHI ( p = 0.011). When assessing whether cephalometric changes related to craniofacial deformities influence the surgical outcome of LP, no correlation was found for any cephalometric measurement. Conclusion The longer the distance between the hyoid bone and the mandibular plane, the greater the preoperative AHI, and LP was an effective OSA treatment. Cephalometric variables are not able to modify or determine the success of LP in apneic patients in the population assessed.

Health-Related Quality of Life in Mexican Children and Adolescents with Non-Syndromic Craniosynostosis.

OBJECTIVE: Assess the Health-Related Quality of Life in children and adolescents with non-syndromic craniosynostosis and compare it with participants without craniosynostosis. DESIGN: Non-experimental, cross-sectional design. SETTING: The assessment was done remotely and the instrument was sent via chat or email. PATIENTS/PARTICIPANTS: Participants (ages 8-17) with non-syndromic craniosynostosis (n = 27) and without craniosynostosis (n = 26). MAIN OUTCOME MEASURE(S): We used an adapted version for the Mexican population of the Health-Related Quality of Life Questionnaire for Children and Adolescents -KIDSCREEN-52. RESULTS: All scores were in the average clinical range and both groups scored similarly in all domains except those with craniosynostosis were significantly lower in the Social Support and Peers domain (rpb = 0.48). CONCLUSIONS: Children and adolescents with non-syndromic craniosynostosis reported similar Health-Related Quality of Life as the control group, except for the Social Support domain, which should be investigated in future studies.

The transcription of the main gene associated with Treacher-Collins syndrome (TCOF1) is regulated by G-quadruplexes and cellular nucleic acid binding protein (CNBP).

Treacle ribosome biogenesis factor 1 (TCOF1) is responsible for about 80% of mandibular dysostosis (MD) cases. We have formerly identified a correlation between TCOF1 and CNBP (CCHC-type zinc finger nucleic acid binding protein) expression in human mesenchymal cells. Given the established role of CNBP in gene regulation during rostral development, we explored the potential for CNBP to modulate TCOF1 transcription. Computational analysis for CNBP binding sites (CNBP-BSs) in the TCOF1 promoter revealed several putative binding sites, two of which (Hs791 and Hs2160) overlap with putative G-quadruplex (G4) sequences (PQSs). We validated the folding of these PQSs measuring circular dichroism and fluorescence of appropriate synthetic oligonucleotides. In vitro studies confirmed binding of purified CNBP to the target PQSs (both folded as G4 and unfolded) with Kd values in the nM range. ChIP assays conducted in HeLa cells chromatin detected the CNBP binding to TCOF1 promoter. Transient transfections of HEK293 cells revealed that Hs2160 cloned upstream SV40 promoter increased transcription of downstream firefly luciferase reporter gene. We also detected a CNBP-BS and PQS (Dr2393) in the zebrafish TCOF1 orthologue promoter (nolc1). Disrupting this G4 in zebrafish embryos by microinjecting DNA antisense oligonucleotides complementary to Dr2393 reduced the transcription of nolc1 and recapitulated the craniofacial anomalies characteristic of Treacher Collins Syndrome. Both cnbp overexpression and Morpholino-mediated knockdown in zebrafish induced nolc1 transcription. These results suggest that CNBP modulates the transcriptional expression of TCOF1 through a mechanism involving G-quadruplex folding/unfolding, and that this regulation is active in vertebrates as distantly related as bony fish and humans. These findings may have implications for understanding and treating MD.

Determinación de los parámetros idóneos de la distracción osteogénica de la mandíbula. Estudio experimental / Determination of mandibular distraction osteogenesis most suitable parameters. An experimental study

Resumen Antecedentes: Respecto a la distracción osteogénica (generación ósea inducida), con mayor o menor éxito han sido descritos diversos protocolos para el manejo del período de latencia, velocidad de distracción y período de consolidación. Objetivo: Entender mejor el proceso de la distracción mandibular y establecer los factores determinantes y sus tiempos óptimos. Material y métodos: Se estudiaron 27 perros sometidos a distracción osteogénica unidireccional, bilateral de la mandíbula. Los procesos de distracción se aplicaron con seis variantes, dos por cada factor (período de latencia, período de distracción y velocidad de distracción). Se estudiaron los cambios mediante biopsias del hueso y radiografías de la zona a los 0, 7, 14, 21, 45 y 55 días del proceso. Resultados: Los parámetros de distracción osteogénica más eficientes fueron período de latencia de cinco días, período de consolidación de seis semanas, 1 mm diario de velocidad de distracción para distancias menores a 20 mm y 3 mm diarios para distancias mayores. Conclusiones: El estudio histológico secuencial permitió observar la aparición de los elementos celulares (osteocitos, osteoclastos, matriz osteoide, trabeculado, etcétera) y su participación en el tejido de granulación, el hueso neoformado y el hueso maduro compacto.

Abstract Background: Distraction osteogenesis is a process of induced bone generation. Various protocols have been described for the management of the latency period, distraction speed and consolidation period, with greater or lesser success. Objective: To better understand the process of mandibular distraction and establish the determining factors and their optimal times. Material and methods: Twenty-seven dogs were studied, which had 54 distractors placed and that underwent unidirectional, bilateral mandibular distraction osteogenesis. The distraction processes were applied using six variants, two for each factor: latency period, distraction period and distraction speed. The changes were examined by means of bone biopsies and X-rays of the area at 0, 7, 14, 21, 45 and 55 days of the process. Results: The most efficient osteogenic distraction parameters were a latency period of five days, a consolidation period of six weeks, distraction speed of 1 mm/day for distances of less than 20 mm, and 3 mm/day for longer distances. Conclusions: The sequential histological study allowed to observe the appearance of cellular elements (osteocytes, osteoclasts, osteoid matrix, trabeculate, etc.) and their participation in granulation tissue, newly-formed bone and compact mature bone.

Complex Craniosynostosis in Pitt-Hopkins Syndrome: Case Report in Twins.

INTRODUCTION: Pitt-Hopkins syndrome (PTHS) is a rare genetic syndrome associated with neurodevelopmental disorders and craniofacial dysmorphisms caused by variations in the TCF4 transition factor. The aim of this article was to report the case of two twin infants diagnosed with PTHS, confirmed by the identification of a heterozygous pathogenic variant in the TCF4 gene through DNA extracted from a buccal swab. CASE PRESENTATION: Both infants presented with craniofacial asymmetry with a metopic crest and cranial deformity. During the diagnostic investigation, computed tomography with three-dimensional reconstruction of the skull showed premature fusion of the left coronal and metopic sutures in both twins. They underwent craniofacial reconstruction at the 9th month of age using a combination of techniques. The postoperative outcomes were satisfactory in both cases. CONCLUSION: To the best of our knowledge, this is the first case report to describe the occurrence of complex craniosynostosis (CCS) in children with PTHS. Further studies are needed to determine whether the co-occurrence of PTHS and CCS described here indicates an association or is explained by chance.

The role of upper airway and facial skeleton anatomy in the evolution of obstructive sleep apnea: an 8-year follow-up.

PURPOSE: To evaluate the role of anatomic alterations of the upper airway and facial skeleton in the evolution of obstructive sleep apnea (OSA) in a prospective population-based study with an 8-year follow-up. METHODS: This was a population-based, longitudinal, prospective study, which took place from 2007 to 2015 at the Instituto do Sono, Sao Paulo, Brazil. In 2007, type I polysomnography (PSG), otorhinolaryngological examination, and collection of anthropometric measurements of all volunteers were performed. Volunteers were classified according to their anatomical features of the upper airway and facial skeleton. After 8 years, volunteers were invited for reevaluation. The relationship between anatomical characteristics and polysomnographic evolution was evaluated. RESULTS: The study included 554 patients. After 8 years of follow-up, there was an increase in neck circumference and body mass index of the participants. There was a worsening in all polysomnographic parameters analyzed, with an increase in the apnea-hypopnea index, a decrease in minimum saturation values, and an increase in the percentage of sleep time with peripheral oxyhemoglobin saturation <90%. There was no statistical relationship between the anatomical findings considered unfavorable and the worsening of polysomnographic parameters. CONCLUSIONS: In a sample of the general population, after 8 years, we did not find any relationship between upper airway and facial skeleton characteristics and the progression of OSA.

Can intraoral and facial photos predict obstructive sleep apnea in the general and clinical population?

STUDY OBJECTIVES: This study aimed to evaluate and compare measurements of standardized craniofacial and intraoral photographs between clinical and general population samples, between groups of individuals with an apnea-hypopnea index (AHI) ≥ 15 and AHI < 15, and their interaction, as well as the relationship with the presence and severity of obstructive sleep apnea (OSA). METHODS: We used data from 929 participants from Sleep Apnea Global Interdisciplinary Consortium, in which 309 patients from a clinical setting and 620 volunteers from a general population. RESULTS: AHI ≥ 15 were observed in 30.3% of the total sample and there were some interactions between facial/intraoral measures with OSA and both samples. Mandibular volume (p < 0.01) and lateral face height (p = 0.04) were higher in the AHI ≥ 15 group in the clinical sample compared to the AHI ≥ 15 group in the general population and AHI < 15 group in the clinical sample. When adjusted for sex and age, greater mandible width (p < 0.01) differed both in the clinical and in the general population samples, reflecting AHI severity and the likelihood of OSA. The measure of smaller tongue curvature (p < 0.01) reflected the severity and probability of OSA in the clinical sample and the higher posterior mandibular height (p = 0.04) showed a relationship with higher AHI and higher risk of OSA in the general population. When adjusted for sex, age, and body mass index, only smaller tongue curvature (p < 0.01) was associated with moderate/severe OSA. CONCLUSIONS: Measures of greater tongue and mandible were associated with increased OSA risk in the clinical sample and craniofacial measurement was associated in the general population sample.

Orofacial Deformities in 3 Related Rhesus Monkeys (Macaca mulatta) Resembling Human Binder's Syndrome.

Binder's syndrome is a rare congenital deformity characterized by midface hypoplasia, particularly around the nasomaxillary area. Genetic etiology or developmental failure caused by prenatal exposure to teratological agents has been considered. In this article, we present 3 related rhesus monkeys born with orofacial deformities similar to those found in infants with the Binder phenotype. For the first time, a primate biomodel for this condition is presented. The clinical description and association with management and environmental factors are discussed. These findings reinforce the knowledge about the relationship between possible vitamin K metabolism interference and Binder's syndrome.

Risk factors and characteristics of the birth of patients with craniofacial microsomia, a case-control study.

BACKGROUND: Craniofacial microsomia (CM) is characterized by changes in the first and second branchial arches. It is a clinical condition whose etiology is still uncertain, but studies have shown that genetic, nutritional, and environmental factors can result in disorders of blastogenesis of the branchial arches. This study evaluates gestational aspects, focusing on possible risk factors associated with CM. METHODS: This is a case-control study conducted with patients monitored at a medical genetics service and compared to a control group of patients without evidence of malformations, born in a mother and child hospital, both located in Porto Alegre, Southern Brazil. Mothers' data were obtained using questionnaires and by reviewing medical records. The sample consisted of 43 patients with CM (cases) and 129 patients without evidence of malformations (controls), paired by sex, totaling three controls for each case. Data analysis was performed using the two-tailed Fisher's exact test, Pearson's chi-square test, and the t-test. RESULTS: We identified several factors associated with the development of CM, including the use of abortion methods by the mothers of these babies (p = .001), maternal diabetes (p = .009), advanced maternal age (p = .035), and a history of vaginal bleeding (p < .001). Furthermore, these patients exhibited a tendency to be born prematurely (p = .027), with low birth weight (p = .007), and lower Apgar scores (p = .003) when compared to healthy infants. Using a multivariate model, the use of abortion methods (p = .003) and vaginal bleeding (p = .032) remained independently associated with craniofacial microsomia. CONCLUSIONS: We have identified several risk factors for the development of CM, including a propensity for premature birth, low birth weight, and respiratory difficulties. Additionally, women of advanced maternal age and/or those who used abortion methods and/or have diabetes have a higher risk of giving birth to a baby with CM. This information can be valuable in clinical practice, especially for the prevention of future cases.

Cephalometric Evaluation in Patients with Obstructive Sleep Apnea undergoing Lateral Pharyngoplasty

Abstract Introduction Lateral pharyngoplasty (LP) has shown promising results. Craniofacial deformity reduces the pharyngeal space, contributing to the etiopathogenesis. The analysis of craniofacial features can be performed using cephalometry. Objective To verify if craniofacial deformity is associated with worse polysomnographic data in patients with obstructive sleep apnea (OSA), and to verify if the preoperative cephalometric parameters can interfere with the surgical success of the LP. Methods The study included 21 patients with OSA aged between 18 and 65 years who underwent LP in a university hospital from 2015 to 2019. Polysomnography was performed postoperatively, after a minimum period of 6 months from the surgical procedure. In addition, a cephalometric evaluation was performed to assess craniofacial deformity, and to correlate it with the polysomnographic results. Results The mean and median of all polysomnographic respiratory parameters improved postoperatively, especially the apnea-hypopnea index (AHI), which went from 40.15 to 16.60 events per hour (p = 0.001). Of the 21 patients, 15 showed improvements in the AHI postoperatively. As for the cephalometric evaluations, we found that the longer the distance between the hyoid bone and the mandibular plane, the greater the patient's preoperative AHI (p = 0.011). When assessing whether cephalometric changes related to craniofacial deformities influence the surgical outcome of LP, no correlation was found for any cephalometric measurement. Conclusion The longer the distance between the hyoid bone and the mandibular plane, the greater the preoperative AHI, and LP was an effective OSA treatment. Cephalometric variables are not able to modify or determine the success of LP in apneic patients in the population assessed.