Search Results (143)

Background: Gorlin–Goltz syndrome (GGS), also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome, is a rare genetic disorder caused by mutations in the PTCH1, PTCH2, or SUFU genes, leading to an increased risk of neoplasms. Craniofacial anomalies are among the most common features of GGS. This paper aimed to highlight the similarities and differences in clinical presentation across different ages and to emphasize the importance of including all family members in the diagnostic process. The diagnosis can often be initiated by a dentist through routine radiographic imaging. Case Presentation: We present a 17-year longitudinal follow-up of a male patient with recurrent multiple odontogenic keratocysts and other manifestations consistent with GGS. Nearly 20 years later, the patient’s mother presented with similar clinical features suggestive of GGS. Diagnostic imaging, including contrast-enhanced computed tomography (CT), cone-beam CT, magnetic resonance imaging, and orthopantomography, was performed, and the diagnosis was confirmed through genetic testing. Interdisciplinary management included age-appropriate surgical and dermatological treatments tailored to lesion severity. Conclusions: Given the frequent involvement of the stomatognathic system in GGS, dentists play a critical role in early detection and referral. Comprehensive family-based screening is essential for timely diagnosis, improved monitoring, and effective management of this multisystem disorder. Full article

Background/Objectives: Temporomandibular disorders (TMDs) are a group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and related anatomical structures. Although magnetic resonance imaging (MRI) is considered a noninvasive and highly informative imaging modality for assessing TMJ soft tissues, few studies have examined how TMJ structural features observed on MRI findings relate to oral function and craniofacial morphology in female patients with malocclusion. To investigate the associations among TMJ structural features, oral function, and craniofacial morphology in female patients with malocclusion, using MRI findings interpreted in conjunction with a preliminary assessment based on selected components of the DC/TMDs Axis I protocol. Methods: A total of 120 female patients (mean age: 27.3 ± 10.9 years) underwent clinical examination based on DC/TMDs Axis I and MRI-based structural characterization of the TMJ. Based on the structural features identified by MRI, patients were classified into four groups for comparison: osteoarthritis (OA), bilateral disk displacement (BDD), unilateral disk displacement (UDD), and a group with Osseous Change/Disk Displacement negative (OC/DD (−)). Occlusal contact area, occlusal force, masticatory efficiency, tongue pressure, and lip pressure were measured. Lateral cephalometric analysis assessed skeletal and dental patterns. Results: OA group exhibited significantly reduced occlusal contact area (p < 0.0083, η² = 0.12) and occlusal force (p < 0.0083, η² = 0.14) compared to the OC/DD (−) group. Cephalometric analysis revealed that both OA and BDD groups had significantly larger ANB angles (OA: 5.7°, BDD: 5.2°, OC/DD (−): 3.7°; p < 0.0083, η² = 0.21) and FMA angles (OA: 32.4°, BDD: 31.8°, OC/DD (−): 29.0°; p < 0.0083, η² = 0.17) compared to the OC/DD (−) group. No significant differences were observed in masticatory efficiency, tongue pressure, or lip pressure. Conclusions: TMJ structural abnormalities detected via MRI, especially osteoarthritis, are associated with diminished oral function and skeletal Class II and high-angle features in female patients with malocclusion. Although orthodontic treatment is not intended to manage TMDs, MRI-based structural characterization—when clinically appropriate—may aid in treatment planning by identifying underlying joint conditions. Full article

Obstructive sleep apnea syndrome (OSAS) in children and adolescents is a prevalent and multifactorial disorder associated with significant short- and long-term health consequences. While adenotonsillectomy (AT) remains the first-line treatment, a substantial proportion of patients—especially those with obesity, craniofacial anomalies, or comorbid conditions—exhibit persistent or recurrent symptoms, underscoring the need for individualized and multimodal approaches. This review provides an updated and comprehensive overview of current and emerging treatments for pediatric OSAS, with a focus on both surgical and non-surgical options, including pharmacological, orthodontic, and myofunctional therapies. A narrative synthesis of recent literature was conducted, including systematic reviews, randomized controlled trials, and large cohort studies published in the last 10 years. The review emphasizes evidence-based indications, mechanisms of action, efficacy outcomes, safety profiles, and limitations of each therapeutic modality. Adjunctive and alternative treatments such as rapid maxillary expansion, mandibular advancement devices, myofunctional therapy, intranasal corticosteroids, leukotriene receptor antagonists, and hypoglossal nerve stimulation show promising results in selected patient populations. Personalized treatment plans based on anatomical, functional, and developmental characteristics are essential to optimize outcomes. Combination therapies appear particularly effective in children with residual disease after AT or with specific phenotypes such as Down syndrome or maxillary constriction. Pediatric OSAS requires a tailored, multidisciplinary approach that evolves with the child’s growth and clinical profile. Understanding the full spectrum of available therapies allows clinicians to move beyond a one-size-fits-all model, offering more precise and durable treatment pathways. Emerging strategies may further redefine the therapeutic landscape in the coming years. Full article

Background: Treacher Collins Syndrome (TCS) is a rare, congenital craniofacial syndrome. Its most characteristic feature is mandibular and midface hypoplasia. Due to malformations of the facial skeleton, airway abnormalities can also be observed, predisposing individuals to obstructive sleep apnoea (OSA). OSA in TCS may contribute to significant morbidity, including developmental delays, cardiovascular disorders and reduced quality of life. Objectives: This narrative review aims to present the true prevalence of OSA and the treatment options for TCS patients. Additionally, the pathophysiology and diagnostic tools for this condition were briefly outlined. Methods: The literature search included publications from PubMed, Scopus, Web of Science and Cochrane Library. The chosen period of time for these publications was 2000–2024. Results: The results showed that OSA is a serious problem among TCS patients. Although there is no standardised treatment protocol, the primary methods often include mandibular distraction osteogenesis (MDO) and continuous positive airway pressure (CPAP). Approaches such as hypoglossal nerve stimulation (HNS) need further investigation, especially with longitudinal observations. Conclusions: The development of treatment options seems to be promising, suggesting a favourable outlook for standardising the treatment protocols. Full article

Background/Objectives: Neurodevelopmental disorders (NDDs) represent a clinically diverse group of conditions that affect brain development, often leading to varying degrees of functional impairment. Many NDDs, particularly syndromic forms, are caused by genetic mutations affecting critical cellular pathways. Ribosomopathies, a subgroup of NDDs, are linked to defects in ribosomal function, including those involving the synthesis of diphthamide, a post-translational modification of translation elongation factor 2 (eEF2). Loss-of-function (LoF) mutations in genes involved in diphthamide biosynthesis, such as DPH1, DPH2, and DPH5, result in developmental delay (DD), intellectual disability (ID), and multisystemic abnormalities. DPH5-related diphthamide deficiency syndrome has recently been reported as an ultrarare disorder linked to LoF mutations in DPH5, encoding a methyltransferase required for diphthamide synthesis. Methods: Clinical, neurological, and dysmorphological evaluations were performed by a multidisciplinary team. Brain MRI was acquired on a 3T scanner. Craniofacial abnormalities were assessed using the GestaltMatcher phenotyping tool. Whole exome sequencing (WES) was conducted on leukocyte-derived DNA with a trio-based approach. Bioinformatic analyses included variant annotation, filtering, and pathogenicity prediction using established databases and tools. Results: The affected subject carried a previously reported missense change, p.His260Arg, suggesting the occurrence of genotype–phenotype correlations and a hypomorphic behavior of the variant, likely explaining the overall milder phenotype compared to the previously reported patients with DPH5-related diphthamide deficiency syndrome. Conclusions: Overall, the co-occurrence of short stature, relative macrocephaly, congenital heart defects, variable DD/ID, minor skeletal and ectodermal features, and consistent craniofacial features suggests a differential diagnosis with Noonan syndrome and related phenotypes. Full article

Chronic migraine (CM) is a debilitating neurological disorder, yet the glial-specific mechanisms underlying its pathophysiology in the trigeminal nucleus caudalis (TNC)—a critical hub for craniofacial pain processing—remain poorly understood. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to resolve cell-type-specific transcriptional landscapes in a nitroglycerin (NTG)-induced CM rat model, with a particular focus on microglia and astrocytes. We identified 19 transcriptional clusters representing nine major cell types, among which reactive microglia (NTG-Mic) and astrocytes (NTG-Asts) were markedly expanded. The NTG-Mic displayed a glycolysis-dominant, complement-enriched state, whereas the NTG-Asts exhibited concurrent activation of amino acid transport and cytokine signaling pathways. Pseudotime trajectory analysis revealed bifurcated glial activation paths, with NTG driving both cell types toward terminal reactive states. Intercellular communication inference uncovered suppressed homeostatic interactions (e.g., CSF1-CSF1R) alongside enhanced proinflammatory signaling (e.g., FGF1-FGFR2, PTN-SDC4), particularly affecting neuron–glia and glia–glia crosstalk. Together, these findings define a high-resolution atlas of glial reprogramming in CM, implicating state-specific metabolic–immune transitions and dysregulated glial communication as potential targets for therapeutic intervention. Full article

Background/Objectives: This cross-sectional analytical study investigated the relationship between the craniofacial morphology, condylar displacement, and degenerative changes in the temporomandibular joints (TMJs) in adult patients with class II skeletal malocclusion. To compare cephalometric variables, joint space dimensions, and centric slide measurements between patients with and without CBCT-confirmed TMJ degenerative alterations. Methods: Sixty adults with class II malocclusion were divided into two equal groups (n = 30) based on the presence or absence of TMJ degenerative changes on CBCT. Joint spaces were measured, condylar displacement was evaluated using a condylar position indicator (CPI), and cephalometric analysis was performed in both maximal intercuspation and centric relation. Statistical comparisons were performed using t-tests, chi-squared tests, and Pearson’s correlation analysis. Significance was set at p < 0.05. Results: Patients with degenerative TMJ changes exhibited significantly greater overjet (p = 0.0001) and a trend toward increased ANB angles (p = 0.055). The superior joint space was reduced on the right side (p = 0.031). Condylar displacements ≥ 2 mm were more frequent in the affected group and correlated with sagittal cephalometric discrepancies (45% vs. 24% in controls). Conclusions: Aggravated skeletal class II malocclusion with increased overjet could be associated with TMJ degenerative changes. CR-based cephalometry and CBCT evaluation may aid in diagnostic assessment, but longitudinal studies are needed to confirm the clinical relevance. Full article

Background: Even with advanced management involving pharmacologic and ventilatory strategies, respiratory dysfunction increases morbidity and reduces the quality of life. This narrative review examines how craniofacial and cervical manipulative interventions—including nasomaxillary skeletal expansion, breathing re-education, and structural techniques—may holistically optimize airway function by enhancing neurological and lymphatic dynamics, modulating vagal tone, reducing pharyngeal collapsibility, and supporting immune regulation across diverse clinical settings. Objectives: To explore manual techniques that influence respiratory and autonomic function and to evaluate their reported clinical efficacy and supporting evidence, particularly in the context of airway disorders such as asthma and pneumonia. Methods: A narrative review of the literature from PubMed and Google Scholar was conducted using search terms related to airway function and osteopathic manipulative techniques (OMTs). The inclusion criteria spanned 2010–2025 English-language peer-reviewed full-text articles on airway function, OMT, and emergency airway maneuvers. Clinical trials, observational studies, and reviews were included; non-peer-reviewed content and animal studies (unless mechanistically relevant) were excluded. Chapman’s reflexes related to respiratory function were incorporated to highlight somatic–visceral correlations. Key Findings: The techniques reviewed included frontal lift, vomer manipulation, maxillary and zygomatic balancing, and cervical adjustments. Thoracic OMT methods, such as diaphragm doming and lymphatic pump techniques, were also addressed. Emergency techniques, such as the BURP and Larson maneuvers, prone positioning, and high-frequency chest wall oscillation, were presented as comparative strategies to OMTs for acute airway management. Conclusions: Craniofacial and cervical manipulations can be a promising adjunct for enhancing airway function. However, the current literature displays heterogeneity and lack of large-scale randomized trials, which emphasize the necessity for standardized research and the establishment of clinical guidelines with the collected evidence. Full article

Background/Objectives: Orofacial clefts are congenital anomalies that cause substantial morbidity and mortality. This study aimed to investigate temporal and geographic trends in mortality among Brazilian individuals with orofacial clefts listed as the underlying cause of death on death certificates. Methods: A retrospective cross-sectional study was conducted using data from the Department of Informatics of the Brazilian Unified Health System (DATASUS) from 1996 to 2023. Results: The mortality information system registered 987 deaths related to orofacial clefts, with 880 patients under 1 year of age. There was a downward trend in annual mortality rates from 1996 to 2019, followed by an increase from 2020 to 2023. The main associated cause of death was respiratory and cardiovascular disorders. The mortality rate for infants under 1 year with orofacial clefts showed greater variation than did the mortality rate of children who died of other causes. The reduction in mortality rates from 1996 to 2019 occurred during the expansion and strengthening of DATASUS and its coordination with other levels of healthcare. The rise in mortality between 2020 and 2023 coincided with a reduction in surgical procedures due to the COVID-19 pandemic. Conclusions: This study revealed a decline in deaths from orofacial clefts in Brazil over several decades. These findings emphasize the importance of addressing preventable causes of death, including respiratory infections and malnutrition. High mortality within the first year of life—particularly among newborns under 28 days—highlights a critical shortage of pediatricians and its impact on care for individuals with craniofacial anomalies. Full article

NAA10 (N-alpha-acetyltransferase 10) is a pivotal enzyme in eukaryotic cells, serving as the catalytic subunit of the NatA complex, which is responsible for the N-terminal acetylation of approximately 40–50% of the human proteome. Beyond its canonical role in co-translational N-terminal acetylation, NAA10 also acetylates internal lysine residues of various proteins and exerts non-catalytic regulatory functions through diverse protein–protein interactions. Pathogenic variants in NAA10 are linked to a spectrum of developmental disorders, most notably Ogden syndrome, which is characterized by neurodevelopmental delay, cardiac defects, and craniofacial anomalies. In cancer, NAA10 is frequently overexpressed or genomically amplified, where its dysregulation correlates with tumor aggressiveness and poor prognosis. Functional studies implicate NAA10 in regulating cell cycle progression, apoptosis, migration, and other hallmarks of cancer. In this review, we summarize the structure, molecular mechanisms, and physiological functions of NAA10, as well as its roles in human diseases and cancer. We present in silico pan-cancer analyses that highlight its clinical significance and potential downstream pathways. Furthermore, we discuss the therapeutic potential and challenges of targeting NAA10 in cancer, and propose future research directions to better understand its multifaceted roles in health and disease. Full article

This case study presents the long-term management of a 14-year-old male diagnosed with 18q deletion syndrome, also known as de Grouchy Syndrome, highlighting the challenges of treating rare chromosomal disorders in rural Romania. Background and Clinical Significance: 18q deletion syndrome, also known as de Grouchy syndrome, is a chromosomal disorder caused by the deletion of a part of the long arm of chromosome 18. This syndrome is seen in one out of 10,000 live births. The main features of the syndrome are short stature, hearing loss, hypotonia, mental retardation, endocrine disorders, and autoimmunity. Case Presentation: The patient’s condition was initially suspected at birth due to abnormal features and was later confirmed through genetic testing, revealing a 46,XY,del(18) karyotype. Key clinical features include craniofacial dysmorphism, delayed growth, congenital cardiac anomalies, developmental delay, severe neurological impairment, and multiple comorbidities such as endocrine dysfunction, dental anomalies, and orthopedic deformities. Despite early interventions such as cardiac surgery, the patient’s management has been challenged by limited access to specialized care. Conclusions: The case underscores the importance of timely genetic testing, early multidisciplinary care, and the role of family support in managing complex disorders. This report also addresses the gaps in healthcare accessibility in rural settings and emphasizes the need for improved infrastructure and genetic services. By comparing this case with the existing literature, the study explores the variability in clinical presentations of 18q deletion syndrome and advocates for more precise genetic testing to better understand its phenotypic spectrum. The patient’s ongoing challenges with medical and socio-economic factors emphasize the critical need for coordinated care and family support in managing rare genetic conditions. Full article

Background/Objectives: Temporomandibular disorder (TMDs) patients often present limited mouth opening (LMO). A key diagnostic cutoff is a mouth opening threshold >40 mm. However, this universal cutoff may not accurately reflect gender anatomical variations. This study investigates gender-specific differences in maximum mouth opening (MMO) to propose revised diagnostic criteria for LMO. Methods: A five-year prospective study was conducted from 1 August 2019 to 1 May 2024 in a Portuguese TMDs department. The patients’ gender, MMO, and LMO complaints with clinical validation were recorded. Statistical analyses, including Generalized Additive Models (GAMs) and Generalized Linear Models (GLMs), assessed the relationship between MMO and LMO, with gender-stratified comparisons. Results: In this study 1045 patients were included. The median (accompanied by the interquartile range [25th percentile–75th percentile]) MMO was lower in females (40 mm [34–45]) than in males (44 mm [40–48]). Patients presenting LMO complaints exhibited significantly reduced MMO values compared to those without LMO complaints (p < 0.001). Gender-specific thresholds emerged: for females, LMO was observed when MMO was ≤35 mm, while in males, LMO symptoms appeared when MMO was ≤38 mm. A “gray zone” of diagnostic uncertainty was identified between 36 and 37 mm for females and 38 and 42 mm for males. Conclusions: In this study we observed the gold standard cutoff for diagnosing MMO in female should be <35mm and for male <38mm. These findings suggest that a single LMO threshold does not account for gender-related anatomical differences, potentially leading to underdiagnosis in females and misclassification in males. Revising diagnostic criteria to incorporate gender-specific thresholds could enhance accuracy, improve early diagnosis, and promote personalized treatment strategies for TMDs patients. Further research incorporating additional variables such as age, dental occlusion, craniofacial structure, and body mass index is recommended to refine these diagnostic guidelines. Full article

Noonan syndrome (NS) is a genetic disorder characterized by distinctive craniofacial and skeletal features, short stature, mild to moderate developmental impairment, and multisystem involvement, notably affecting the cardiovascular, musculoskeletal, and endocrine systems. Although abnormalities of the bone matrix, as well as osteopenia and osteoporosis, are well recognized in individuals with NS and other RASopathies, the specific impact of RAS/MAPK pathway dysregulation on bone health remains poorly understood. Objectives: The aim of this study was to evaluate bone turnover and bone remodeling markers in a cohort of children with NS, to gain further insights into the bone status of these patients. Methods: In this cross-sectional, case-control study, we analyzed 28 children (20 males) with a molecular diagnosis of NS and 35 healthy subjects (21 males), matched by age and sex. We assessed markers of bone metabolism and bone turnover (calcium, phosphate, PTH, 25(OH)-vitamin D, osteocalcin, procollagen I N-propeptide-P1NP, bone alkaline phosphatase-BALP, C-telopeptides of type I collagen-CTX) and bone remodeling (RANKL, OPG, and sclerostin). Bone mineralization was measured at the lumbar spine (L2–L4) using dual-energy X-ray absorptiometry (DEXA). Results: Serum CTX levels were significantly higher in NS patients compared to controls (1.8 ± 0.7 vs. 1.3 ± 0.5 ng/mL, p = 0.0004). RANKL levels were higher in NS patients, although the difference did not reach statistical significance. No significant differences were found for OPG, sclerostin, or other markers of bone metabolism between patients and controls. Conclusions: Children with NS exhibit increased bone resorption, as indicated by elevated CTX levels, suggesting a potential imbalance in bone remodeling processes. Further studies are warranted to better define the impact of RAS/MAPK pathway dysregulation on bone health in this population. Full article

Rubinstein–Taybi syndrome (RSTS) is a rare genetic disorder characterized by distinctive craniofacial, limb, and developmental abnormalities, often identified postnatally. Prenatal diagnosis remains challenging due to a scarcity of ultrasound diagnostic markers and a wide range of phenotypic manifestations. We describe the case of a 28-year-old pregnant patient who presented to our center after fetal abnormalities such as aberrant cranial morphology, a shorter femur, and rocker-bottom feet were detected. A comprehensive ultrasound examination at 26 weeks revealed skeletal and craniofacial characteristics suggestive of RSTS, which prompted genetic counseling and molecular karyotyping. Single-nucleotide polymorphism (SNP) array analysis confirmed a loss on chromosome 16p13.3, including the CREB-binding protein (CREBBP) gene, confirming the suspicion. This case emphasizes the importance of genetic testing and sophisticated prenatal imaging in enabling an early and precise diagnosis of RSTS, offering important information on its prenatal phenotype and supporting family counseling. Extensive research becomes vital in establishing precise ultrasound markers for the early detection of RSTS during pregnancy. Full article

Objectives: This narrative review aims to redefine Open Mouth Posture Syndrome (OMPS) as a multifactorial condition with overlapping symptoms and a cyclical pathophysiology. A novel classification system for OMPS subtypes is proposed to standardize research approaches and enhance clinical understanding. Methods: An interdisciplinary literature review was conducted, focusing on structural, functional, and adaptive mechanisms underlying OMPS. Subtype definitions were refined based on recent findings. Results: OMPS is categorized into five subtypes: Obstructive, Habitual, Anatomical, Sleep-Disordered Breathing, and Tongue-Related Pathologies. These subtypes share interconnected etiologies and manifestations, contributing to a feedback loop that complicates diagnosis and management. Conclusions: This classification system lays the foundation for future research and clinical protocols, emphasizing the need for a systematic approach to understanding OMPS. Full article