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Background. Traumatic dental injuries represent nearly 5% of children and adolescents’ injuries leading to serious medical and psychological issues. This current study aims to evaluate the prevalence of dental trauma and its potential association with different predisposing factors among 12-and 15-year-old schoolchildren in Lebanon. Materials and Methods. 7902 schoolchildren, 3806 male and 4096 female aged 12 years (n = 3985) and 15 years (n = 3917), were recruited by a stratified multistaged randomized cluster sampling method from public and private schools and were clinically examined in a national cross-sectional study. WHO criteria were used to assess anterior permanent teeth; the nature of trauma, the tooth involved, the size of the incisal overjet, and the type of the lip coverage were furthermore assessed. Data regarding age, sex, and causes of TDI were recorded through a structured questionnaire. Results. The prevalence of dental trauma to anterior teeth was 10.9%. Maxillary central incisors (83.7%) were commonly affected. The most common type of injury was enamel fracture (68.3%), falls being the main reason (52.5%). Increased overjet (OR = 2.32, p = 0.034), deficient lip coverage (OR = 5.73, p = 0.019), and gender (OR = 5.36, p ≤ 0.001) were significant predisposing factors for dental trauma. Conclusion. This research highlighted many predisposing factors for dental trauma that affect commonly the anterior teeth. Based on these results, the implementation of strategic preventive measurements targeting especially the identified risk groups remains crucial.

The integrity of the mammalian epidermis depends on a balance of proliferation and differentiation in the resident population of stem cells 1 . The kinase RIPK4 and the transcription factor IRF6 are mutated in severe developmental syndromes in humans, and mice lacking these genes display epidermal hyperproliferation and soft-tissue fusions that result in neonatal lethality 2 – 5 . Our understanding of how these genes control epidermal differentiation is incomplete. Here we show that the role of RIPK4 in mouse development requires its kinase activity; that RIPK4 and IRF6 expressed in the epidermis regulate the same biological processes; and that the phosphorylation of IRF6 at Ser413 and Ser424 primes IRF6 for activation. Using RNA sequencing (RNA-seq), histone chromatin immunoprecipitation followed by sequencing (ChIP–seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) of skin in wild-type and IRF6-deficient mouse embryos, we define the transcriptional programs that are regulated by IRF6 during epidermal differentiation. IRF6 was enriched at bivalent promoters, and IRF6 deficiency caused defective expression of genes that are involved in the metabolism of lipids and the formation of tight junctions. Accordingly, the lipid composition of the stratum corneum of Irf6 −/− skin was abnormal, culminating in a severe defect in the function of the epidermal barrier. Collectively, our results explain how RIPK4 and IRF6 function to ensure the integrity of the epidermis and provide mechanistic insights into why developmental syndromes that are characterized by orofacial, skin and genital abnormalities result when this axis goes awry. Signalling between the transcription factor IRF6 and the kinase RIPK4, in particular the phosphorylation of IRF6 by RIPK4, regulates epidermal differentiation and lipid metabolism, thereby maintaining the function of the epidermal barrier.

Background How deformities associated with unilateral lesser-form cleft lip progress with age remains one of the most pressing concerns for patients and their families. This study aimed to preoperatively assess the characteristics and severity of labial and nasal deformities across different age groups of patients with unilateral lesser-form cleft lip. Methods We conducted a retrospective analysis of patients with unilateral lesser-form cleft lip who received treatment at a single center between 2018 and 2023. The severity of labial and nasal deformities was evaluated through photogrammetric measurements of linear and angular parameters. Differences in deformity severity across age groups were assessed using one-way ANOVA with post-hoc testing. The correlations between ages and the severity of deformities were analysed using Spearman correlation analysis. Results A total of 194 patients aged 2 months to 33 years (mean age: 9.11 ± 8.81) were included. Significant differences were observed in index A (lateral lip height), K (nasal width), L (alar width), M (alar convexity), and N (subalar width) in the one-way ANOVA test. For the subsequent post-hoc tests, non-significant differences in index A, while significant differences in index K, L, M, and N were observed between specific age groups. Notably, no differences were observed between the pairwise comparisons of age groups that were older than 9–12 years. Positive correlations were observed between ages and index K, L, and N while negative correlation was observed between ages and index M. (r K = 0.645, r L = 0.308, r M =−0.363, and r N = 0.427 with all p value < 0.000). Conclusions Without surgical intervention, labial deformities showed no statistically significant differences across age groups. In contrast, the severity and asymmetry of nasal deformities progressed rapidly in patients younger than 9–12 years. Age was significantly correlated with the severity of nasal deformities—including nasal width, alar width, alar convexity, and subalar width. Timely surgical intervention is therefore recommended for patients with unilateral lesser-form cleft lip, particularly those presenting with nasal deformities, to prevent further progression. Trial registration Not applicable since this study did not involve clinical intervention.

Nasoalveolar molding (NAM) has gained wide acceptance and evidence in cleft therapy. However, standardized treatment protocols and experiences recorded from European centres are lacking. The results of 40 infants with cleft lip and palate treated with presurgical NAM according to the Grayson technique were analyzed. Standardized parameters of cleft width and nasal symmetry were measured in pre- and posttreatment plaster casts and in digitalized 3-dimensional STL models. Statistical analyses were performed by using Student's t-test in a per-protocol manner. 27 out of 40 infants completed NAM and were analyzed. In 13 patients NAM was either temporarily interrupted or terminated prematurely due to skin irritations or lack of parental support. These cases were excluded from statistical analysis, resulting in a drop-out rate of 32.5%. Intersegmental alveolar distance (ISAD), intersegmental lip distance (ISLD), nostril height (NH), nostril width (NW) and columella deviation angle (CDA) were significantly changed in unilateral cleft lip and palate (UCLP) (n = 8). In unilateral cleft lip (UCL) (n = 9), only ISLD, NH and CDA were significantly changed. ISAD of the right and left side, ISLD of the right and left side, premaxilla deviation angle, nostril height and columella length were changed significantly in bilateral cleft lip and palate (BCLP) cases (n = 10). NAM is a suitable presurgical treatment modality. A positive effect has been seen in UCLP and BCLP infants, as compared with their birth status.

There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum.

Purpose: Mutations in the transcription factor IRF6 cause allelic autosomal dominant clefting syndromes, Van der Woude syndrome, and popliteal pterygium syndrome. We compared the distribution of IRF6 coding and splice-site mutations from 549 families with Van der Woude syndrome or popliteal pterygium syndrome with that of variants from the 1000 Genomes and National Heart, Lung, and Blood Institute Exome Sequencing Projects. Methods: We compiled all published pathogenic IRF6 mutations and performed direct sequencing of IRF6 in families with Van der Woude syndrome or popliteal pterygium syndrome. Results: Although mutations causing Van der Woude syndrome or popliteal pterygium syndrome were nonrandomly distributed with significantly increased frequencies in the DNA-binding domain ( P = 0.0001), variants found in controls were rare and evenly distributed in IRF6 . Of 194 different missense or nonsense variants described as potentially pathogenic, we identified only two in more than 6,000 controls. PolyPhen and SIFT (sorting intolerant from tolerant) reported 5.9% of missense mutations in patients as benign, suggesting that use of current in silico prediction models to determine function can have significant false negatives. Conclusion: Mutation of IRF6 occurs infrequently in controls, suggesting that for IRF6 there is a high probability that disruption of the coding sequence, particularly the DNA-binding domain, will result in syndromic features. Prior associations of coding sequence variants in IRF6 with clefting syndromes have had few false positives. Genet Med 2013:15(5):338–344

Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.

Van der Woude syndrome (VWS) is a rare congenital malformation characterized by lower lip pits among patients with a lip and/or palate cleft. It is transmitted by an autosomal dominant inheritance with variable expressivity. The study group consisted of 24 consecutive patients (13 males and 11 females) with VWS operated on at a single center between 2009 and 2022. They suffered from: bilateral cleft lip and palate - 6 patients; unilateral cleft lip and palate - 9 patients; cleft lip - 1 patient; and isolated cleft palate - 8 patients. In 16 (66%) cases pits of lower lip occurred on both side of midline, while in 8 (34%) the pits were detected unilaterally. The primary cleft repairs were performed according to one-stage principle at the mean age of 8.6 months (SD 1.4, range 6-12). In all patients lower lip pits repairs were performed after the primary cleft repairs as a separate procedure at the mean age of 37 months (SD 11.3 range 14-85). The mean number of all primary repairs of the syndrome-both cleft defect and lower lip pits repairs-was 2.46. Nine patients (37.5%) required additional secondary corrections of the lower lip due to the poor aesthetic post-operative outcome. The frequent need for secondary corrections of residual lower lip deformities indicates the considerable difficulties in obtaining a satisfactory outcome of the repairs to lip pits caused by VWS. The average number of the primary surgical interventions in evaluated material remained low.

Congenital lip sinus is a rare entity with upper lip sinus being rarer than the lower lip sinus. It can be an isolated entity or associated with cleft lip, palate or Van der Woude syndrome. Syndromic association requires proper evaluation and aggressive surgical treatment. Preoperative delineation of the sinus tract with ultrasound sonography or MRI is mandatory. Simple excision is sufficient in cases of isolated sinuses. In this article, we report an infant with upper lip sinus managed successfully with simple excision and reviewed the literature.