Evaluación fonoaudiológica clínica de la alimentación y la deglución en lactantes menores con hipoplasia 0 aplasia cóndilo-mandibular: Scoping review / Clinical speech therapy evaluation of feeding and swallowing in young infants with hypoplasia or aplasia of the mandibular condyle: A scoping review

Introducción: Los síndromes craneofaciales congénitos han sido ampliamente descritos debido a su naturaleza precursora de alteraciones en el sistema cráneo-cérvico-mandibular; específicamente las malformaciones a nivel cóndilo-mandibular, como la hipoplasia o aplasia de estas estructuras, comprometen una de las funciones vitales para el ser humano: la alimentación. Con el objetivo de establecer una guía de práctica clínica, se proponen lineamientos que promuevan la práctica fonoaudiológica basada en la evidencia. Pacientes y métodos: Se realiza una revisión sistemática de tipo scoping review en las principales bases de datos biomédicas, en búsqueda de artículos científicos dirigidos a la evaluación de la alimentación y deglución en lactantes menores con hipoplasia y aplasia cóndilo-mandibular asociadas a síndromes craneofaciales. Resultados:Se seleccionaron 37 artículos de tipo ensayo clínico aleatorizado, estudio de casos, estudio ecológico, metaanálisis y revisión sistemática, cuyo contenido es presentado y organizado dentro de un formato de evaluación que busca la obtención de información anatomofuncional de los lactantes menores para el desarrollo de su evaluación clínica. Conclusiones: Se resalta una reducida cantidad y difusión de evidencia fonoaudiológica al aplicar los parámetros de búsqueda, encontrando que los criterios de evaluación específicos ante esta patología no difieren en gran medida a los de la población pediátrica en general.(AU)

Introduction: Congenital craniofacial syndromes have been widely described due to their precursor nature of alterations in the cranio-cervico-mandibular system; specifically, condyle-mandibular malformations such as hypoplasia or aplasia of these structures, compromise one of the vital functions for humans, nutrition. In order to establish a clinical practice guide, guidelines that promote evidence-based speech therapy practice are proposed. Patients and methods: A scoping review is carried out in the main biomedical databases, in search of scientific articles aimed at evaluating feeding and swallowing in newborn and young infants with condyle-mandibular hypoplasia and aplasia associated with craniofacial syndromes. Results: Thirty-seven articles of a randomized clinical trial, case study, ecological study, meta-analysis, and systematic review were selected, this content is presented and organized using an evaluation format that seeks to obtain anatomical and functional information on newborn and young infants for the development of a clinical assessment. Conclusions: A reduced amount and dissemination of speech therapy evidence is highlighted when applying the search parameters, finding that the specific evaluation criteria for this pathology do not differ greatly from those of the pediatric population in general.(AU)

Morphometric analysis of the size-adjusted linear dimensions of the skull landmarks revealed craniofacial dysmorphology in Mid1-cKO mice.

BACKGROUND: The early craniofacial development is a highly coordinated process involving neural crest cell migration, proliferation, epithelial apoptosis, and epithelial-mesenchymal transition (EMT). Both genetic defects and environmental factors can affect these processes and result in orofacial clefts. Mutations in MID1 gene cause X-linked Opitz Syndrome (OS), which is a congenital malformation characterized by craniofacial defects including cleft lip/palate (CLP). Previous studies demonstrated impaired neurological structure and function in Mid1 knockout mice, while no CLP was observed. However, given the highly variable severities of the facial manifestations observed in OS patients within the same family carrying identical genetic defects, subtle craniofacial malformations in Mid1 knockout mice could be overlooked in these studies. Therefore, we propose that a detailed morphometric analysis should be necessary to reveal mild craniofacial dysmorphologies that reflect the similar developmental defects seen in OS patients. RESULTS: In this research, morphometric study of the P0 male Mid1-cKO mice were performed using Procrustes superimposition as well as EMDA analysis of the size-adjusted three-dimensional coordinates of 105 skull landmarks, which were collected on the bone surface reconstructed using microcomputed tomographic images. Our results revealed the craniofacial deformation such as the increased dimension of the frontal and nasal bone in Mid1-cKO mice, in line with the most prominent facial features such as hypertelorism, prominent forehead, broad and/or high nasal bridge seen in OS patients. CONCLUSION:  While been extensively used in evolutionary biology and anthropology in the last decades, geometric morphometric analysis was much less used in developmental biology. Given the high interspecies variances in facial anatomy, the work presented in this research suggested the advantages of morphometric analysis in characterizing animal models of craniofacial developmental defects to reveal phenotypic variations and the underlining pathogenesis.

The Risk of Orofacial Cleft Lip/Palate Due to Maternal Ambient Air Pollution Exposure: A Call for Further Research in South Africa.

Background: Despite being underreported, orofacial cleft lip/palate (CLP) remains in the top five of South Africa's most common congenital disorders. Maternal air pollution exposure has been associated with CLP in neonates. South Africa has high air pollution levels due to domestic burning practices, coal-fired power plants, mining, industry, and traffic pollution, among other sources. We investigated air pollutant levels in geographic locations of CLP cases. Methods: In a retrospective case series study (2006-2020) from a combined dataset by a Gauteng surgeon and South African Operation Smile, the maternal address at pregnancy was obtained for 2,515 CLP cases. Data from the South African Air Quality Information System was used to calculate annual averages of particulate matter (PM) concentrations of particles < 10 µm (PM10) and < 2.5 µm (PM2.5). Correlation analysis determined the relationship between average PM2.5/PM10 concentrations and CLP birth prevalence. Hotspot analysis was done using the Average Nearest Neighbor tool in ArcGIS. Results: Correlation analysis showed an increasing trend of CLP birth prevalence to PM10 (CC = 0.61, 95% CI = 0.38-0.77, p < 0.001) and PM2.5 (CC = 0.63, 95% CI = 0.42-0.77, p < 0.001). Hot spot analysis revealed that areas with higher concentrations of PM10 and PM2.5 had a higher proclivity for maternal residence (z-score = -68.2, p < 0.001). CLP birth prevalence hotspot clusters were identified in district municipalities in the provinces of Gauteng, Limpopo, North-West, Mpumalanga, and Free State. KwaZulu-Natal and Eastern Cape had lower PM10 and PM2.5 concentrations and were cold spot clusters. Conclusions: Maternal exposure to air pollution is known to impact the fetal environment and increase CLP risk. We discovered enough evidence of an effect to warrant further investigation. We advocate for a concerted effort by the government, physicians, researchers, non-government organizations working with CLP patients, and others to collect quality data on all maternal information and pollutant levels in all provinces of South Africa. Collaboration and data sharing for additional research will help us better understand the impact of air pollution on CLP in South Africa.

Gene-environment interactions in the pathogenesis of common craniofacial anomalies.

Craniofacial anomalies often exhibit phenotype variability and non-mendelian inheritance due to their multifactorial origin, involving both genetic and environmental factors. A combination of epidemiologic studies, genome-wide association, and analysis of animal models have provided insight into the effects of gene-environment interactions on craniofacial and brain development and the pathogenesis of congenital disorders. In this chapter, we briefly summarize the etiology and pathogenesis of common craniofacial anomalies, focusing on orofacial clefts, hemifacial microsomia, and microcephaly. We then discuss how environmental risk factors interact with genes to modulate the incidence and phenotype severity of craniofacial anomalies. Identifying environmental risk factors and dissecting their interaction with different genes and modifiers is central to improved strategies for preventing craniofacial anomalies.

Augmentation of bone morphogenetic protein signaling in cranial neural crest cells in mice deforms skull base due to premature fusion of intersphenoidal synchondrosis.

Craniofacial anomalies (CFAs) are a diverse group of disorders affecting the shapes of the face and the head. Malformation of the cranial base in humans leads CFAs, such as midfacial hypoplasia and craniosynostosis. These patients have significant burdens associated with breathing, speaking, and chewing. Invasive surgical intervention is the current primary option to correct these structural deficiencies. Understanding molecular cellular mechanism for craniofacial development would provide novel therapeutic options for CFAs. In this study, we found that enhanced bone morphogenetic protein (BMP) signaling in cranial neural crest cells (NCCs) (P0-Cre;caBmpr1a mice) causes premature fusion of intersphenoid synchondrosis (ISS) resulting in leading to short snouts and hypertelorism. Histological analyses revealed reduction of proliferation and higher cell death in ISS at postnatal day 3. We demonstrated to prevent the premature fusion of ISS in P0-Cre;caBmpr1a mice by injecting a p53 inhibitor Pifithrin-α to the pregnant mother from E15.5 to E18.5, resulting in rescue from short snouts and hypertelorism. We further demonstrated to prevent premature fusion of cranial sutures in P0-Cre;caBmpr1a mice by injecting Pifithrin-α through E8.5 to E18.5. These results suggested that enhanced BMP-p53-induced cell death in cranial NCCs causes premature fusion of ISS and sutures in time-dependent manner.

Automation of Measurements for Personalized Medical Appliances by Means of CAD Software-Application in Robin Sequence Orthodontic Appliances.

Measuring the dimensions of personalized devices can provide relevant information for the production of future such devices used in various medical specialties. Difficulties with standardizing such measurement and obtaining high accuracy, alongside cost-intensive measuring methodologies, has dampened interest in this practice. This study presents a methodology for automatized measurements of personalized medical appliances of variable shape, in this case an orthodontic appliance known as Tübingen Palatal Plate (TPP). Parameters such as length, width and angle could help to standardize and improve its future use. A semi-automatic and custom-made program, based on Rhinoceros 7 and Grasshopper, was developed to measure the device (via an extraoral scanner digital file). The program has a user interface that allows the import of the desired part, where the user is able to select the necessary landmarks. From there, the program is able to process the digital file, calculate the necessary dimensions automatically and directly export all measurements into a document for further processing. In this way, a solution for reducing the time for measuring multiple dimensions and parts while reducing human error can be achieved.

Alterations in DNA Methylation in Orofacial Clefts.

Orofacial clefts are among the most common craniofacial anomalies with multifactorial etiologies, including genetics and environments. DNA methylation, one of the most acknowledged mechanisms of epigenetics, is involved in the development of orofacial clefts. DNA methylation has been examined in patients with non-syndromic cleft lip with cleft palate (nsCL/P) from multiple specimens, including blood, saliva, lip, and palate, as well as experimental studies in mice. The results can be reported in two different trends: hypomethylation and hypermethylation. Both hypomethylation and hypermethylation can potentially increase the risk of nsCL/P depending on the types of specimens and the specific regions on each gene and chromosome. This is the most up-to-date review, intending to summarize evidence of the alterations of DNA methylation in association with the occurrence of orofacial clefts. To make things straightforward to understand, we have systematically categorized the data into four main groups: human blood, human tissues, animal models, and the factors associated with DNA methylation. With this review, we are moving closer to the core of DNA methylation associated with nsCL/P development; we hope this is the initial step to find a genetic tool for early detection and prevention of the occurrence of nsCL/P.

Protocols in the management of cleft lip and palate: A systematic review: Running Title: Management of Cleft Lip and Palate.

AIM: To identify clinical decisions on surgical as well as non-surgical modalities for the treatment of CLP patients based on randomized controlled trials (RCTs). MATERIALS AND METHODS: PubMed, Ebscohost, and Cochrane Library were searched and 20 articles based on RCTs conducted on cleft patient management were identified. RESULTS: The topics explored were infant orthopedics, lip and palate repair, alveolar bone grafting, and management of cleft maxillary hypoplasia. Nasoalveolar molding (NAM) was found to have great benefits when carried out within one month of birth. Fisher and Mohler's lip repair technique and use of recombinant human bone morphogenetic protein-2 (rh-BMP2) for alveolar bone grafting showed promising results. rh-BMP2 for alveolar bone grafting appears to be a promising alternative to autografts. CONCLUSION: Early commencement of NAM in neonatal life is of great benefit to cleft patients. There is a need for more multicentre collaborations, mainly to identify the ideal surgical technique to reduce the variability in treatment and to ensure that the patient receives appropriate evidence-based treatment.

Lacrimal drainage anomalies in 3p deletion syndrome.

3p deletion syndrome or deletion 3p25-pter syndrome is an exceptionally rare genetic disorder characterized by deletion of the distal segment of the short arm of chromosome 3. There are less than a hundred reported cases worldwide. Clinical characteristics include severe physical and mental retardation, trigonocephaly, micrognathia, and diffuse hypotonia. The common ocular manifestations include congenital ptosis and canthal anomalies. To the best of the authors' knowledge, no lacrimal drainage anomalies have been reported earlier. The present case describes proximal lacrimal drainage anomalies in a patient with 3p deletion syndrome. The patient was successfully managed with membranotomy and punctal and canalicular dilatation, resulting in a complete resolution of epiphora.

Pierre Robin Sequence and 3D Printed Personalized Composite Appliances in Interdisciplinary Approach.

This paper introduces a complex novel concept and methodology for the creation of personalized biomedical appliances 3D-printed from certified biocompatible photopolymer resin Dental LT Clear (V2). The explained workflow includes intraoral and CT scanning, patient virtualization, digital appliance design, additive manufacturing, and clinical application with evaluation of the appliance intended for patients with cranio-facial syndromes. The presented concept defines virtual 3D fusion of intraoral optical scan and segmented CT as sufficient and accurate data defining the 3D surface of the face, intraoral and airway morphology necessary for the 3D design of complex personalized intraoral and extraoral parts of the orthopedic appliance. A central aspect of the concept is a feasible utilization of composite resin for biomedical prototyping of the sequence of marginally different appliances necessary to keep the pace with the patient rapid growth. Affordability, noninvasiveness, and practicality of the appliance update process shall be highlighted. The methodology is demonstrated on a particular case of two-year-old infant with Pierre Robin sequence. Materialization by additive manufacturing of this photopolymer provides a highly durable and resistant-to-fracture two-part appliance similar to a Tübingen palatal plate, for example. The paper concludes with the viability of the described method and material upon interdisciplinary clinical evaluation of experts from departments of orthodontics and cleft anomalies, pediatric pneumology and phthisiology, and pediatric otorhinolaryngology.

Cat-Eye Syndrome: A Report of Two Cases and Literature Review.

Cat-eye syndrome is a rare genetic disease that involves the proximal long (q) arm of chromosome 22. The classic clinical triad includes coloboma of the iris, ears, and anal malformations. This syndrome was named "cat eye" due to the vertical coloboma of the iris. However, the spectrum of clinical manifestations is variable, and the iris coloboma may be absent in 40-50% of cases. Association with congenital heart disease is also frequent and its diagnosis should raise suspicion of a genetic condition. We describe two cases of male infants affected by the cat-eye syndrome, of which no one presented the classic clinical triad. One of them had unpredictable complications that led to prolonged neonatal intensive care unit stay. Although having distinct phenotypes, the diagnosis in both cases was made through nonobstructive total anomalous pulmonary venous return, anal imperforation, and craniofacial anomalies. Iris coloboma was an important clue only in one of them. Prenatal diagnosis is a challenge, such that a genetic study is essential for a final diagnosis in the absence of the classic triad.

Dental and Craniofacial Manifestation of Axenfeld-Rieger Syndrome: A Case Report.

Axenfeld-Rieger syndrome (ARS) is an autosomal dominant syndrome with a prevalence estimated at 1:50000 to 1:100000 in newborns. It is mainly characterized by ocular, craniofacial, and dental abnormalities. From the pediatric dentist's point of view, early diagnosis of the syndrome from the ocular, craniofacial, and dental manifestation can prevent further abnormalities and ocular complications such as glaucoma. This case report presents a brief description of ARS with the characteristics of craniofacial and dental findings.

Role and mechanism of BMP4 in bone, craniofacial, and tooth development.

OBJECTIVE: This review aimed to present an overview of the effect of bone morphogenetic protein 4 (BMP4) on craniofacial and skeletal development, particularly the specific role of BMP4 in tooth development. DESIGN: The search for this narrative review was conducted in PubMed, Web of Science, Embase, and ScienceDirect using relevant keywords, including checking reference lists of journal articles by hand searching. RESULTS: Mutations or deletions of BMP4 cause tissue development defects in mice and humans, such as fragile bone, craniofacial deformity, cleft lip and palate, tooth development stagnation, and abnormal structure. CONCLUSIONS: BMP4 is a reliable and vital candidate to regulate the development of bones, craniofacies, and teeth. It also has high clinical application potential.

What's Shape Got to Do With It? Examining the Relationship Between Facial Shape and Orofacial Clefting.

Nonsyndromic orofacial clefts belong to a class of congenital malformations characterized by a complex and multifactorial etiology. During early facial development, multiple factors can disrupt fusion leading to a cleft; this includes the shape of the embryonic face. The face shape hypothesis (FSH) of orofacial clefting emerged in the 1960s, influenced by morphological differences observed within affected families, comparative studies of mouse models, and advances in modeling genetic liability for complex traits in populations. For the past five decades, studies have documented changes in the shape or spatial arrangement of facial prominences in embryonic mice and altered post-natal facial shape in individuals at elevated risk for orofacial clefting due to their family history. Moreover, recent studies showing how genes that impact facial shape in humans and mice are providing clues about the genetic basis of orofacial clefting. In this review, I discuss the origins of the FSH, provide an overview of the supporting evidence, and discuss ways in which the FSH can inform our understanding of orofacial clefting.

Split orthodontic airway plate: An innovation to the utilization method of conventional orthodontic airway plate for neonates with Robin sequence.

Since the emergence of neonatal infant orthodontics for treatments of cleft lip and palate with or without Robin sequence (RS) in Europe in the 1950s, advancements in design and scope of its application have been remarkable. As the first institution to adopt orthodontic airway plate (OAP) treatment in the United States in 2019, we saw a need for innovation of the original design to streamline the most labor-intensive and time-consuming aspects of OAP utilization. A solution is introduced using a systematic split expansion mechanism to re-size the OAP periodically to accommodate the neonate's maxillary growth. To date, seven RS patients have received this modified treatment protocol at our institution. Each patient completed full treatment using only one OAP. This innovative utilization method is aptly named the split orthodontic airway plate (S-OAP). Details of the S-OAP and its modifications from conventional OAP are reported.

Gnas Loss Causes Chondrocyte Fate Conversion in Cranial Suture Formation.

Calvaria development is distinct from limb formation. Craniosynostosis is a skull deformity characterized by premature cranial suture fusion due to the loss of the GNAS gene and, consequently, its encoded protein Gαs. This birth defect requires surgery, with potential lethal consequences. So far, hardly any early-stage nonsurgical interventions for GNAS loss-related craniosynostosis are available. Here, we investigated the role of the Gnas gene in mice in guarding the distinctiveness of intramembranous ossification and how loss of Gnas triggered endochondral-like ossification within the cranial sutures. Single-cell RNA sequencing (scRNA-seq) of normal neonatal mice cranial suture chondrocytes showed a Hedgehog (Hh) inactivation pattern, which was associated with Gαs signaling activation. Loss of Gnas evoked chondrocyte-to-osteoblast fate conversion and resulted in cartilage heterotopic ossification (HO) within cranial sutures and fontanels of the mouse model, leading to a skull deformity resembling craniosynostosis in patients with loss of GNAS. Activation of ectopic Hh signaling within cranial chondrocytes stimulated the conversion of cell identity through a hypertrophy-like stage, which shared features of endochondral ossification in vivo. Reduction of Gli transcription activity by crossing with a loss-of-function Gli2 allele or injecting GLI1/2 antagonist hindered the progression of cartilage HO in neonatal stage mice. Our study uncovered the role of Gαs in maintaining cranial chondrocyte identity during neonatal calvaria development in mice and how reduction of Hh signaling could be a nonsurgical intervention to reduce skull deformity in craniosynostosis due to loss of GNAS.

Craniofacial Orthodontic Experience in CODA-Accredited Orthodontic Residency Programs.

To evaluate orthodontic care for patients with craniofacial anomalies (CFA) by identifying orthodontic residents' preparedness to treat certain conditions and willingness to receive more training in CFA.A 12-question survey was sent through the American Association of Orthodontics (AAO) organization to orthodontic residents. Questions were primarily designed to obtain information on the frequency with which they dealt with patients with CFA in their training, specific craniofacial conditions that orthodontic residents feel comfortable treating.A total of 150 participants out of 1066 responded. Of the 150 responses, 35% were first-year residents, 43% second year, and 22% were third-year residents. Thirty nine percent of residents saw 3 or more CFA patients during their residency followed by 24% that saw no patients with CFA. Forty five percent reported that 1 to 3 hours of lecture time was devoted to CFA per month. Sixty percent felt their training in CFA was not sufficient to feel comfortable treating these patients in practice. Specifically, 62% felt comfortable treating Down syndrome, 84% unilateral cleft lip and/or palate, and 64% bilateral cleft lip and/or palate, while the majority did not feel comfortable treating Pierre Robin sequence (68%), Cleidocranial dysplasia (65%), Crouzon syndrome (75%), Pfeiffer syndrome (80%), Treacher Collins syndrome (76%), Apert syndrome (76%), CHARGE syndrome (84%), and DiGeorge sequence (84%). Seventy eight percent of residents reported that they would like more training in treating craniofacial.Orthodontic residents did not feel comfortable treating patients with CFA. Majority of the residents felt that they would like to learn more about CFA.

Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases.

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect at the junction between the lobe and helix, known as a "Question Mark Ear" (QME). Several additional features, originating from the first and second branchial arches and other tissues, have also been reported. ACS is genetically heterogeneous with autosomal dominant and recessive modes of inheritance. The mutations identified to date are presumed to dysregulate the endothelin 1 signaling pathway. Here we describe 14 novel cases and reassess 25 published cases of ACS through a questionnaire for systematic data collection. All patients harbor mutation(s) in PLCB4, GNAI3, or EDN1. This series of patients contributes to the characterization of additional features occasionally associated with ACS such as respiratory, costal, neurodevelopmental, and genital anomalies, and provides management and monitoring recommendations.

Tissue Augmenting Palatoplasty for the Treatment of Velopharyngeal Insufficiency.

PURPOSE: Persistent velopharyngeal insufficiency (VPI) following primary palatoplasty remains a difficult problem to treat. This study evaluates speech outcomes following revision palatoplasty with tissue augmentation using buccal myomucosal flaps (BMF) as an alternative to pharyngoplasty for patients with VPI. METHODS: A retrospective single-center review of revision palatoplasty with tissue augmentation at a tertiary pediatric hospital Cleft-Craniofacial Center between January 2017 and March 2021 was conducted. Patients with a history of previous palatoplasty, a diagnosis of persistent or recurrent VPI, and comprehensive pre- and postoperative speech evaluations who underwent revision palatoplasty with BMF were included. RESULTS: Twenty patients met inclusion criteria (35% female, 20% syndromic). Mean age at the time of revision palatoplasty with BMF was 9.7 years. Preoperatively, all patients had stigmatizing speech and received the recommendation for speech surgery; the mean Pittsburgh Weighted Speech Score (PWSS) was 14.3 ± 4.9. The mean postoperative PWSS at the most recent assessment was 4.2 ± 2.3, representing a statistically significant improvement from preoperative scores (P < .001). Mean follow-up time was 8.9 months. Following revision palatoplasty with BMF, only one patient has received the recommendation for further speech surgery. No complications were noted. CONCLUSION: In patients with VPI following primary palatoplasty, revision palatoplasty with tissue augmentation offers an alternative to pharyngoplasty. This approach preserves dynamic velopharyngeal function, improves speech outcomes, and should be considered an option when treating patients with post-primary palatoplasty VPI.