Search Results (445)

Objectives: The aims of this study were to explore the genetic variants identified by Next-Generation Sequencing (NGS) in patients presenting syndromic/non-syndromic cleft palate (CP) associated with tooth agenesis (TA) and to describe the observed phenotype–genotype correlations. Methods: A systematic review exploring PubMed, Scopus and Web of Science was conducted. Data extraction and bias assessment were performed. Results: From 227 screened articles, 8 studies were included. Second premolars were the most frequently missing teeth, followed by central incisors in non-syndromic CP cases. Genetic variants were most commonly reported in IRF6, FGFR1, NOTCH2, CTNND1, ZFHX4 and AXIN2. Several mutations in these genes were associated with syndromic forms such as Pierre Robin Sequence, Kallmann syndrome, and Van der Woude syndrome. Conclusions: This study suggests a potential shared genetic pathway between CP and TA and supports further exploration of TA as a possible clinical indicator of syndromic cases. NGS emerges as a valuable exploratory tool for identifying such associations, though validation in larger patient cohorts remains necessary. Full article

Background: Tooth auto-transplantation (TAT) is a surgical procedure in which a person’s own tooth is extracted and repositioned in the recipient site. The aim of the study is to evaluate the clinical outcomes, treatment strategies, and methodological characteristics, and to propose a preliminary management algorithm of TAT in patients with cleft lip and/or palate (CLP). Methods: A search of the literature was conducted in PubMed, Google Scholar, ClinicalKey, Web of Science, and Cochrane Library databases until 21 June 2026. The systematic review was written according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Risk-of -bias was assessed by the Joanna Briggs Institute (JBI) tool. Results: Five case series and three case reports were included, with four “low” and four “moderate” JBI reporting-quality ratings (reflecting reporting completeness, not low risk of bias). They presented data about 23 patients and 27 TAT cases. The majority of patients (n = 16) received secondary alveolar bone graft with iliac bone. The most common donor teeth were mandibular premolars (n = 20). The most frequent recipient sites were the maxillary 2nd premolar (n = 9) and maxillary incisors (n = 15). Twenty-six teeth (96.3%) survived, and one tooth (3.7%) was extracted. Conclusions: TAT appears to be a promising treatment option in carefully selected CLP patients; however, further high-quality studies are needed with the application of our proposed algorithm. Full article

Cleft lip and palate (CL/P) are among the most common congenital craniofacial anomalies, arising from disruptions in facial development during early embryogenesis. These conditions show significant clinical and genetic heterogeneity and are broadly classified into syndromic and nonsyndromic forms. The objective of this review is to summarize current knowledge on the embryological, genetic, and molecular mechanisms underlying CL/P and to highlight their clinical implications. A comprehensive review of the literature was conducted, focusing on studies in developmental biology, human genetics, and genomics related to CL/P. Emphasis was placed on both syndromic and nonsyndromic forms, including findings from genome-wide association studies, gene mutation analyses, and investigations of gene–environment interactions. Syndromic clefting is frequently associated with pathogenic variants in genes such as IRF6, TP63, and TBX22, which play key roles in epithelial differentiation, transcriptional regulation, and palatal development. In contrast, nonsyndromic CL/P results from complex interactions between multiple genetic variants and environmental factors. Genome-wide association studies have identified numerous susceptibility loci, many located in noncoding regulatory regions active during craniofacial development. Environmental influences, including maternal nutrition, smoking, alcohol exposure, and folate metabolism, have been shown to significantly modify risk. CL/P is a multifactorial condition involving intricate interactions between genetic and environmental factors. Advances in genomics and developmental biology have enhanced understanding of its etiology and are contributing to improved risk assessment, diagnosis, and the development of future precision medicine approaches. Full article

Background/Objectives: Cleft lip and palate are among the most common congenital craniofacial anomalies and require careful postoperative care after surgical repair. Mothers, as primary caregivers, are expected to manage feeding, wound care, oral hygiene, and the early recognition of complications; however, gaps in postoperative care knowledge may limit safe home care. This pilot study aimed to evaluate the effect of an artificial intelligence (AI)-supported video-based educational intervention on mothers’ knowledge of postoperative care after cleft lip and/or palate surgery. Methods: This single-group quasi-experimental pre–post pilot study was conducted between April and December 2025 in the Plastic, Reconstructive, and Aesthetic Surgery Clinic of a tertiary hospital in Istanbul. Thirty mothers of children aged 0–18 years who underwent cleft lip and/or palate surgery were included. Data were collected using a Demographic Information Form and a Nutrition and Care Knowledge Questionnaire. Mothers completed the questionnaire before and immediately after watching a standardized AI-supported educational video developed by the researchers. Pre- and post-intervention knowledge scores were compared using nonparametric statistical tests. Results: A total of 30 mothers participated in the study. Child-related sociodemographic and clinical variables were recorded to describe the children’s profile. Among the children, 56.7% were female, and 56.7% were aged 0–3 years. Post-intervention knowledge scores increased in the total score and in all subdomains, including postoperative care, feeding, and complication monitoring. The greatest improvement was observed in complication monitoring, which had the lowest baseline scores. Knowledge gains were observed across participant subgroups. Conclusions: This pilot study suggests that AI-supported video-based education may improve mothers’ short-term knowledge of postoperative care after cleft lip and/or palate surgery. However, because of the single-group design, small sample size, and immediate post-test assessment, the findings should be interpreted as preliminary. Larger controlled studies with longer follow-up are needed to examine knowledge retention and the potential effects of this approach on caregiving practices. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is highly prevalent in children with unilateral cleft lip and palate (UCLP) due to maxillary retrusion and upper airway compromise. While palatal morphology may influence pediatric OSA, three-dimensional (3D) evaluations in this population remain limited. This study evaluated palatal dimensions and maxillary widths in UCLP children with and without OSA using cone-beam computed tomography (CBCT) and examined their associations with OSA severity (apnea–hypopnea index, AHI). Methods: Forty CBCT scans of Thai children with non-syndromic UCLP (mean age 8.98 ± 1.99 years) were analyzed. Participants were categorized into OSA (n = 20; AHI ≥ 1) and non-OSA (n = 20; AHI < 1) groups. Reconstructed palatal structures were measured for surface area, volume, height, and transverse maxillary widths. Group differences were assessed using independent t-tests, and associations with AHI were examined via Pearson’s correlation and linear regression (p < 0.05). Results: Children with OSA exhibited significantly reduced palatal surface area, volume, height, and buccal alveolar crest width compared with those without OSA (p < 0.05). Other transverse widths showed no significant intergroup differences. Linear regression identified palatal volume as the only variable independently associated with AHI (β = −0.631, p < 0.001). Conclusions: Children with UCLP and OSA exhibit significantly constricted palatal morphology. Among the measured parameters, reduced three-dimensional palatal volume was the only variable independently associated with increased OSA severity in this sample. Thus, CBCT-based palatal volume assessment may serve as a preliminary screening parameter to help identify OSA risk within multidisciplinary cleft care, though further validation is needed. Full article

Treatment of cleft lip alveolus and/or palate includes surgical repair to treat communication-related outcomes such as velopharyngeal insufficiency and otological dysfunction. Robot-assisted surgery has recently evolved into a promising adjunct to conventional surgery, particularly for complex procedures such as transoral (reconstructive) surgery. This structured literature review aims to investigate whether robot-assisted transoral cleft palate repair enhances communication (i.e., speech and otological) outcomes compared to conventional manual cleft palate surgery. A literature search was performed using PubMed, Embase, the Cochrane Library and Google Scholar. Primary outcomes were the change in cleft speech characteristics and otological disease after robot-assisted cleft palate surgery versus manual cleft palate surgery. The available evidence on communication-related outcomes remains sparse. Six relevant articles were included. In only one study, transoral robotic cleft surgery (TORCS) significantly reduced otitis media with effusion (OME), need for ventilation tubes and hearing threshold within 2 years post-surgery. No postoperative speech or velopharyngeal outcomes were reported. In conclusion, transoral robotic cleft surgery (TORCS) appears safe and feasible for repair of a cleft palate. It provides superior intraoral view and improved surgeon ergonomics. Current drawbacks are the costs and the available tools, the extended surgical duration and the lack of haptic feedback, which limit the current clinical applicability of TORCS. Based on limited clinical evidence, TORCS may support faster recovery of Eustachian tube function and hearing, but no conclusions on speech outcomes can yet be drawn. Full article

Background: Congenital tooth agenesis is a common dental anomaly in individuals with orofacial clefts and may be related not only to cleft type but also to skeletal growth characteristics. This study aimed to investigate whether the number of congenitally missing permanent teeth is associated with cleft type, sex, and sagittal and vertical skeletal patterns in non-syndromic cleft patients. Materials and Methods: A retrospective cross-sectional analysis was conducted on 60 patients aged ≥17 years (36 males, 24 females; mean age 19.5 ± 1.8 years) with surgically repaired cleft lip and/or palate, based on clinical records collected over a long-term follow-up period. Sagittal (Class I, II, III) and vertical (normal, deep bite, open bite) skeletal patterns were extracted from available orthodontic records based on routine cephalometric assessment. The number of congenitally missing permanent teeth, excluding third molars, was recorded. Statistical analysis included non-parametric tests and Poisson regression. Results: The distribution of missing teeth deviated significantly from normality according to the Shapiro–Wilk test (p < 0.001). In the Poisson regression model, sex (p = 0.011) and cleft type (p < 0.001) were significantly associated with the number of congenitally missing teeth, whereas sagittal skeletal pattern (p = 0.338) and vertical skeletal pattern (p = 0.281) were not significant predictors. Conclusions: In this retrospective record-based analysis, the number of congenitally missing teeth appeared most consistently associated with cleft type, while sex showed a model-dependent association in the adjusted regression analysis. Full article

Cleft lip with or without cleft palate (CL/P) is one of the most common congenital craniofacial anomalies worldwide and presents significant functional, esthetic, and psychosocial challenges. Despite advances in multidisciplinary care and surgical reconstruction, complications such as impaired wound healing, scar formation, and growth disturbances warrant the development of novel regenerative and surgical strategies, which heavily rely on animal models at the pre-clinical stage. For the current narrative review, the literature search was performed by combining cleft phenotype terms with modeling-approach terms in six databases and was supplemented by manual review of reference lists from full-text articles. The included articles were summarized based on cleft type and the methods for cleft induction (chemically induced, genetically engineered, and surgically created). Particularly, chemical teratogens such as retinoic acid, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), corticosteroids, and 6-aminonicotinamide have been widely used to induce cleft phenotypes and elucidate environmental influences on palatogenesis, whereas genetic models have clarified the roles of key molecules and signaling pathways, including Sonic hedgehog (SHH), bone morphogenetic protein (BMP), and transforming growth factor-β (TGF-β), in the development of lip and palate. Meanwhile, the surgical models have focused on the alveolar cleft in skeletally mature animals for evaluating novel grafting materials. By comparing the strengths and limitations of existing models, this review highlights opportunities for improving experimental design and translational relevance in future cleft research. Overall, despite a wide range of CL/P animal models available, few replicate clinically relevant defect anatomy and the postnatal craniofacial deformation observed in CL/P patients, underscoring the need for the development of new models. Full article

Background: Cleft lip with or without cleft palate (CL ± P) is a common congenital anomaly requiring a multidisciplinary team approach from birth into adulthood. Many patients undergo multiple secondary procedures on the lip, nose, and alveolus, representing a substantial long-term “burden of care” for families and health systems. The relationship between preoperative cleft severity and the cumulative number of surgical interventions into late adolescence remains insufficiently characterized. Methods: A retrospective cohort study was conducted on 166 patients with cleft lip ± cleft palate treated at a single tertiary cleft center. All patients underwent primary cheiloplasty, with or without concomitant gingivoperiosteoplasty (GPP), and had follow-up extending to a mean age of 18 years. Preoperative nasolabial deformity was graded into four categories (mild, moderate, severe, and very severe) using standardized photographic assessment. The primary outcome was the total number of cleft-related surgical interventions on the lip, nose, and alveolus, including the primary operation and all subsequent corrective procedures. Associations between preoperative severity and surgery counts were analyzed using the Kruskal–Wallis test and Bonferroni-adjusted pairwise comparisons. Results: All 166 patients underwent a primary procedure, either cheiloplasty alone (n = 86; 51.8%) or cheiloplasty combined with GPP (n = 80; 48.2%). A second surgical intervention was performed in 111 patients (66.8%), yielding 138 procedures, most commonly GPP with bone grafting (n = 54), corrective cheiloplasty (n = 48), GPP without graft (n = 23), and rhinoplasty (n = 12). A third intervention was performed in 48 patients (28.9%; 70 procedures), predominantly rhinoplasty and additional cheiloplasties, and a fourth intervention in 13 patients (7.8%; 17 procedures), mostly staged rhinoplasty and lip revisions. Overall, 56 patients (33.7%) had only one (primary) operation, 50 (30.1%) had two, 27 (16.3%) had three, 18 (10.8%) had four, 13 (7.8%) had five, and one patient (0.6%) had six surgical interventions. The total number of operations differed significantly across severity grades (Kruskal–Wallis p < 0.001). Patients with mild and moderate severity had significantly fewer surgeries than those with severe or very severe deformities (all p ≤ 0.023), whereas differences between mild vs. moderate and severe vs. very severe were not significant. Conclusions: In this cohort of patients with cleft lip followed to a mean age of 18 years, two-thirds required at least one secondary procedure, and nearly one-fifth underwent four or more surgeries. Higher preoperative severity was strongly associated with greater surgical burden, particularly when comparing mild or moderate deformities to severe and very severe clefts. These findings underline the importance of preoperative severity assessment for family counseling, expectation management, and the design of treatment protocols aimed at minimizing the long-term burden of care while preserving functional and esthetic outcomes. Full article

Objectives: A comprehensive diagnosis and treatment were carried out in 104 newborns, including 48 children diagnosed with unilateral cleft lip and palate (UCLP) and 56 patients diagnosed with bilateral cleft lip and palate (BCLP). The control group consisted of 116 medical records and diagnostic models of jaws from newborns with UCLP/BCLP, which were analysed before and after orthodontic correction using a removable facebow with headgear attachment. Methods: All newborns (n = 104) underwent orthodontic correction to reposition of the alveolar process fragments in UCLP and intermaxillary bone in BCLP using mini-implants and elastic traction devices/springs, followed by primary cheiloplasty. Cheiloplasty was performed one month after fragment alignment had been achieved. Results: Statistical analysis showed that orthodontic correction using mini-implants and elastic traction was highly effective. In the UCLP group, normalised alignment of alveolar fragments was achieved in 97.9% of cases (p = 0.0000000016); in the BCLP group, normalised positioning of the intermaxillary bone was observed in 96.42% (p = 0.00000000007). A direct comparison between the treatment and control groups revealed consistent significance across all diastasis measurements, supporting the clinical advantage of fixed orthodontic approaches. Conclusions: The clinical data and statistical analysis indicate that the fixed orthodontic appliance combined with mini-implants and elastic traction is effective. This approach normalises alveolar and intermaxillary positioning and provides optimal preoperative conditions for primary cheiloplasty and subsequent uranoplasty. It also shortens rehabilitation duration and leads to stable aesthetic and functional results. Full article

Orofacial clefts are among the most common congenital craniofacial anomalies in the world. Immunity factors modulate response, inflammation, and healing in clefted tissue. This study aims to evaluate the levels of the pro-inflammatory biomarkers Granulysin, Resistin, FCGR1A, NF-kßp65, and CD68 to describe and understand the morphopathological basis of inflammation. The comparison was done between patient and control samples across milk and mixed dentition age groups. In total, 14 patient samples were analyzed with a total of 10 control samples to form two distinct control groups with milk dentition age and mixed dentition age. Samples were analyzed using light microscopy, and a semi-quantitative method of evaluation and comparison was used to determine the number of immunohistochemically positive structures of patient and control samples. Statistics included Spearman’s correlation and Fisher’s exact test to compare groups and detect significant differences. NF-kßp65 in the milk dentition age group (p = 0.043 for NF-kßp65 in connective tissue, p = 0.017 for NF-kßp65 in salivary glands), and FCGR1A and CD68 in the mixed dentition age group showed statistically significant differences in the expression of palatal tissues compared to the controls (p = 0.016 for FCGR1A in connective tissue, p = 0.048 for CD68 in epithelium). Spearman’s rank correlation revealed eight very strong correlations among several factors and one strong correlation between factors. The presence of many very strong and strong Spearman’s correlations among inflammatory factors in cleft-affected individuals suggests heightened signaling in these pathways. Furthermore, the difference in the inflammatory factor expression at different dentition ages suggests variation in the inflammation character with age. Full article

49,XXXXY syndrome (Fraccaro syndrome) is a rare sex chromosome pentasomy, historically considered a severe variant within the Klinefelter spectrum. It is characterized by intellectual disability, craniofacial dysmorphism, skeletal anomalies, hypogonadism, and congenital cardiac defects. Although neuroimaging abnormalities have increasingly been recognized in 49,XXXXY syndrome, neonatal diagnosis prompted primarily by ventriculomegaly remains rare. We report a neonate with prenatally detected ventriculomegaly in whom postnatal evaluation revealed cleft palate, congenital cardiac defects, bilateral cryptorchidism, and auditory dysfunction. Cranial ultrasonography and brain magnetic resonance imaging demonstrated bilateral ventriculomegaly with colpocephaly and a cavum vergae variant. Cytogenetic analysis confirmed the presence of a 49,XXXXY karyotype. This case highlights ventriculomegaly as a potential early diagnostic clue in 49,XXXXY syndrome and underscores the importance of chromosomal analysis in neonates presenting with structural brain abnormalities associated with multisystem anomalies. Early recognition is important for timely multidisciplinary surveillance and long-term endocrine follow-up. Full article

Background/Objectives: Large language models (LLMs) are increasingly consulted for information about cleft lip and palate (CLP), yet the reliability of their outputs across clinical domains has not been evaluated. This study aimed to compare the quality of CLP-related information generated by GPT-4o and Gemini 2.5 Pro across multiple thematic domains using a validated quality instrument and a reliability-first analytic framework. Methods: Fifty-four standardized CLP questions across six domains were submitted to GPT-4o (OpenAI) and Gemini 2.5 Pro (Google DeepMind) on 25 September 2024 via their public interfaces, using new, history-free sessions and default settings, yielding 108 responses. Three independent, CLP-experienced raters scored each response using the Global Quality Score (GQS; 1–5 scale assessing accuracy, completeness, and clinical usefulness). Before comparing models, we applied a reliability-first filter: only domains where all three raters showed substantial agreement (Fleiss’ kappa [κ] ≥ 0.60) were included in statistical comparisons. Domains that failed this threshold were analyzed qualitatively to identify the source of disagreement. A descriptive taxonomy of errors was developed for low-scoring responses. Results: Three domains met the reliability threshold (General Care Information, General Cleft Information, and Pre-Treatment Information; 30 paired questions). Both models performed at a high and practically equivalent level: GPT-4o median GQS 4.33 (IQR 4.00–5.00) versus Gemini 2.5 Pro 5.00 (IQR 4.00–5.00); the difference was not statistically significant (Wilcoxon V = 139.00, p = 0.691; Hodges–Lehmann median difference 0.00, 95% CI −0.33 to 0.67). Three domains were excluded because rater agreement was insufficient; qualitative review showed this reflected genuine clinical practice variation rather than clear model errors. The most common inaccuracies were overgeneralization of outcomes, outdated surgical timing, and omission of multidisciplinary team roles. Conclusions: Both models provided high-quality CLP information in domains supported by clinical consensus, indicating they may serve as useful adjuncts for general patient and family counseling. Clinicians should, however, verify any treatment-specific content against current institutional protocols before relaying it to patients. Future research should assess readability, alignment with health literacy, and patient comprehension of AI-generated CLP information. Full article

Objective: Implant rehabilitation in grafted alveolar clefts requires a complex staged reconstructive approach, and a clinically important yet underexplored question is which patients require additional pre-implant block regrafting after primary grafting has already been completed. This single-centre retrospective cohort study aimed to evaluate whether a history of maxillary advancement is associated with a reduced likelihood of requiring pre-implant block regrafting (defined here as Re-graft 1), and to describe medium-term implant survival outcomes in a cleft implant cohort. Methods: Forty-two patients with Veau class III or IV cleft palate who underwent implant rehabilitation in grafted alveolar cleft sites between 2011 and 2023 were included. A total of 80 dental implants were evaluated at the implant level; analyses of primary grafting outcomes and the need for Re-graft 1 were performed at the patient level. Mean age at implant placement was 21.07 years (range, 17–38 years); mean follow-up was 83 months. Patients were categorised by maxillary advancement history: distraction osteogenesis (n = 11), orthognathic Le Fort I advancement (n = 9), or no advancement (n = 22). Bergland grades were assigned independently by two attending surgeons from postoperative radiographs. Implant outcomes were classified using the ICOI/Misch four-level scale (success, satisfactory survival, compromised survival, failure). Group comparisons used chi-square and Fisher’s exact tests. Results: Patients with any maxillary advancement history were significantly less likely to require Re-graft 1: 65.0% of patients with advancement did not require Re-graft 1, compared with 27.3% in the no-advancement group (Fisher’s exact p = 0.029; OR = 4.95). Overall implant survival was 93.75%; 58.75% of implants were classified as complete success, and 30.00% as satisfactory survival. Conclusions: In this observational, hypothesis-generating cohort, maxillary advancement history was associated with a lower likelihood of requiring pre-implant block regrafting. Implant rehabilitation showed favorable medium-term survival. These findings are limited by the retrospective single-center design, modest sample size, and absence of multivariable adjustment, and require confirmation in larger prospective studies with standardized regrafting criteria. Full article

This study reports a previously unreported heterozygous MYCN missense variant, c.454G>A (p.Ala152Thr), identified in a child and two affected relatives, with clinical findings consistent with Feingold syndrome type 1, an autosomal dominant developmental disorder most commonly caused by loss-of-function variants in MYCN. The proband presented with a cleft palate, craniofacial dysmorphism, feeding difficulties, hypotonia, and characteristic digital anomalies. Similar features were observed in the father and sibling. Clinical exome sequencing revealed the novel MYCN variant, which was confirmed by Sanger sequencing and demonstrated co-segregation with the phenotype. Although most pathogenic MYCN variants leading to FS1 truncate the protein, this missense change lies within the N-terminal transactivation domain, a region involved in transcriptional regulation and protein stability. The physicochemical alteration introduced at residue Ala152 may plausibly affect MYCN function, consistent with haploinsufficiency as the established disease mechanism. According to the 2024 ACGS Best Practice Guidelines, the variant was classified as a variant of uncertain significance leaning toward pathogenicity. This report expands the mutational spectrum of MYCN, supports the potential clinical relevance of N-terminal missense variation in MYCN, and highlights intrafamilial phenotypic variability in FS1. Full article