A Rare Case of Fibrous Dysplasia Presenting With Facial Swelling and Craniofacial Deformity in a 13-Year-Old Girl.

Fibrous dysplasia (FD) is a rare benign skeletal disorder that replaces normal bone with fibrous tissue and immature woven bone. We present a case of a 13-year-old girl with right-sided facial swelling and craniofacial deformity since birth, accompanied by nasal obstruction and difficulty in breathing and swallowing. Computed tomography (CT) imaging revealed an expansile bony lesion with a ground-glass matrix involving multiple craniofacial bones. Histopathological examination confirmed the diagnosis of FD. Management involved regular monitoring and conservative measures, with surgical intervention reserved for symptomatic progression or cosmetic concerns. This case underscores the importance of considering FD in the differential diagnosis of craniofacial asymmetry and highlights the collaborative approach to patient care. Further research is needed to optimize management strategies and outcomes for pediatric patients with FD.

A Case of Trigeminal Neuralgia in an Adult Patient With Lambdoid Synostosis.

Trigeminal neuralgia (TN) is characterized by sudden, brief intense pain in the distribution of the unilateral trigeminal nerve (TGN). Neurovascular compression (NVC) of the TGN is the most common cause of TN. Recent studies have suggested that a structural anomaly of the posterior cranial fossa might be involved in the development of TN, and several studies have documented the association between NVC-related TN and congenital posterior cranial deformities in adults. We present the case of a 56-year-old woman with NVC-related TN and unilateral lambdoid synostosis (ULS), along with a literature review, to investigate the relationship between TN and structural anomalies of the posterior fossa. This is the first report of TN in an adult with ULS. Mild and asymptomatic cases of lambdoid synostosis might have a higher incidence of NVC-related TN in association with posterior cranial fossa deformities.

Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature.

BACKGROUND: Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457). METHODS: This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2. RESULTS: The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved. CONCLUSION: As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.

Mouth breathing induces condylar remodelling and chondrocyte apoptosis via both the extrinsic and mitochondrial pathways in male adolescent rats.

The prevalence of mouth breathing is high in children and adolescents. It causes various changes to the respiratory tract and, consequently, craniofacial growth deformities. However, the underlying mechanisms contributing to these effects are obscure. Herein, we aimed to study the effects of mouth breathing on chondrocyte proliferation and death in the condylar cartilage and morphological changes in the mandible and condyle. Additionally, we aimed to elucidate the mechanisms underlying chondrocyte apoptosis and investigate any variations in the related pathways. Subchondral bone resorption and decreased condylar cartilage thickness were observed in mouth-breathing rats; further, mRNA expression levels of Collagen II, Aggrecan, and Sox 9 were lower in the mouth breathing group, while those of matrix metalloproteinase 9 increased. TdT-mediated dUTP nick end labelling staining and immunohistochemistry analyses showed that apoptosis occurred in the proliferative and hypertrophic layers of cartilage in the mouth breathing group. TNF, BAX, cytochrome c, and cleaved-caspase-3 were highly expressed in the condylar cartilage of the mouth-breathing rats. These results suggest that mouth breathing leads to subchondral bone resorption, cartilage layer thinning, and cartilage matrix destruction, inducing chondrocyte apoptosis via both the extrinsic and mitochondrial apoptosis pathways.

Zebrafish as an experimental model for the simulation of neurological and craniofacial disorders.

Zebrafish have gained momentum as a leading experimental model in recent years. At present, the zebrafish vertebrate model is increasingly used due to its multifactorial similarities to humans that include genetic, organ, and cellular factors. With the emergence of novel research techniques that are very expensive, it is necessary to develop affordable and valid experimental models. This review aimed to highlight some of the most important similarities between zebrafish and humans by emphasizing the relevance of the first in simulating neurological disorders and craniofacial deformity.

Complex craniosynostosis in the context of Carpenter's syndrome.

Carpenter's syndrome or acrocephalopolysyndactyly type II is a rare genetic autosomal recessive disease, with an incidence estimated at 1 per 1 million births. Common findings of a brachydactyly, polysyndactyly, and a trefoil-like skull with extreme brachycephaly due to fusion of the bilateral coronal, sagittal and lambdoid sutures. We report a 12-month-old male who was referred to our care for evaluation of a craniofacial deformity-a trefoil-like skull, flattened and receding forehead, bulging of temporal bones, hypertelorism, exorbitism, and polysyndactyly in the upper and lower limbs and psychomotor delay. Head computed tomography (CT) with 3D reconstruction revealed craniosynostosis with fusion of the coronal, metopic, and sagittal sutures. Correction of the craniofacial deformity was performed with satisfactory aesthesis of the craniofacial bones at 2 years of follow-up. Early correction of craniofacial deformity in Carpenter's syndrome is usually safe within 6 to 12 months. Venous drainage abnormalities and ectatic emissary veins can lead to significant bleeding and may be detected on MR angiography. Significant skull weakening may lead to bony fragmentation while creating cranial flaps and is best evaluated with 3D CT imaging. Taking these pitfalls into consideration decreases the chances of aborting the surgery and may lead to better overall outcomes.

Hemifacial hypertrophy - Report of 2 cases.

Hemifacial hyperplasia (HH) is a rare congenital condition involving enlargement of one or more tissues of the face. The treatment is surgically challenging and requires expertise. This manuscript aims to report two similar appearing HH but warranting different surgical treatment. A 19-year-old female and a 14-year-old boy presented with right facial asymmetry since birth and sought correction of the same. Surgical treatment was planned. Based on clinical history, diagnosis and imaging, HH was diagnosed. The first case was entirely a soft tissue abnormality that was treated with debulking while the second case had involvement of facial bones, necessitating surgical recontouring. The facial asymmetry was addressed. Healing was uneventful. Though the aesthetical concern and appearance of the two cases of HH were same, the treatment vastly differed. This was based on the source of asymmetry. Proper diagnosis and informed decision are a key for successful surgical outcome.

The perioral muscle continuum affects premaxillary development in Wistar rats.

Craniofacial deformities involve soft tissue and skeletal abnormalities. Facial bone growth is based on congenital defects and iatrogenic factors, in which muscle activity is important. Understanding the effects of muscle function on facial bone growth may help us in clinical treatment. Although there have been some studies, fewer have focused on the effects of perioral muscle continuity on maxillary development, which needs further research. In our study, mimic perioral muscle surgeries were performed in twenty 3-day Wistar rats, which were divided into four equal groups, including five untreated rats as control (Ctrl), five rats by unilateral perioral muscle incision (MI), five rats by unilateral perioral muscle incision combined with muscle stripping (MIMS) and five rats treated by unilateral perioral muscle incision combined with periosteal stripping (MIPS). After six weeks, skulls were imaged and measured by micro-CT scan and hematoxylin-eosin staining. Differences in the rats' premaxilla were analyzed with self-contrasted and group-control studies. Compared with Ctrl group, there were significant premaxillary developmental defects in the affected side of the rats in all three surgical groups. In the affected side, both the width and the length of the premaxilla were less than the unaffected side, particularly in MIMS and MIPS groups. Group-control study showed that the ratio of premaxillary length of affected side to unaffected side had significant differences between MI and MIMS. The conclusion was that complete perioral muscle continuity with intact muscle attachment on the premaxilla is the driving force for the premaxillary development.

Prenatal diagnosis of auriculocondylar syndrome with a novel missense variant of GNAI3: a case report.

BACKGROUND: Auriculocondylar syndrome (ACS) is a rare disorder characterized by micrognathia, mandibular condyle hypoplasia, and auricular abnormalities. Only 6 pathogenic variants of GNAI3 have been identified associated with ACS so far. Here, we report a case of prenatal genetic diagnosis of ACS carrying a novel GNAI3 variant. CASE PRESENTATION: A woman with 30 weeks of gestation was referred to genetic counseling for polyhydramnios and fetal craniofacial anomaly. Severe micrognathia and mandibular hypoplasia were identified on ultrasonography. The mandibular length was 2.4 cm, which was markedly smaller than the 95th percentile. The ears were low-set with no cleft or notching between the lobe and helix. The face was round with prominent cheeks. Whole-exome sequencing identified a novel de novo missense variant of c.140G > A in the GNAI3 gene. This mutation caused an amino acid substitution of p.Ser47Asn in the highly conserved G1 motif, which was predicted to impair the guanine nucleotide-binding function. All ACS cases with GNAI3 mutations were literature reviewed, revealing female-dominated severe cases and right-side-prone deformities. CONCLUSION: Severe micrognathia and mandibular hypoplasia accompanied by polyhydramnios are prenatal indicators of ACS. We expanded the mutation spectrum of GNAI3 and summarized clinical features to promote awareness of ACS.

Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis.

Background: Congenital anomalies are increasingly becoming a global pediatric health concern, which requires immediate attention to its early diagnosis, preventive strategies, and efficient treatments. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (Gnai3) gene mutation has been demonstrated to cause congenital small jaw deformity, but the functions of Gnai3 in the disease-specific microRNA (miRNA) upregulations and their downstream signaling pathways during osteogenesis have not yet been reported. Our previous studies found that the expression of Mir24-2-5p was significantly downregulated in the serum of young people with overgrowing mandibular, and bioinformatics analysis suggested possible binding sites of Mir24-2-5p in the Gnai3 3'UTR region. Therefore, this study was designed to investigate the mechanism of Mir24-2-5p-mediated regulation of Gnai3 gene expression and explore the possibility of potential treatment strategies for bone defects. Methods: Synthetic miRNA mimics and inhibitors were transduced into osteoblast precursor cells to regulate Mir24-2-5p expression. Dual-luciferase reporter assay was utilized to identify the direct binding of Gnai3 and its regulator Mir24-2-5p. Gnai3 levels in osteoblast precursor cells were downregulated by shRNA (shGnai3). Agomir, Morpholino Oligo (MO), and mRNA were microinjected into zebrafish embryos to control mir24-2-5p and gnai3 expression. Relevant expression levels were determined by the qRT-PCR and Western blotting. CCK-8 assay, flow cytometry, and transwell migration assays were performed to assess cell proliferation, apoptosis, and migration. ALP, ARS and Von Kossa staining were performed to observe osteogenic differentiation. Alcian blue staining and calcein immersions were performed to evaluate the embryonic development and calcification of zebrafish. Results: The expression of Mir24-2-5p was reduced throughout the mineralization process of osteoblast precursor cells. miRNA inhibitors and mimics were transfected into osteoblast precursor cells. Cell proliferation, migration, osteogenic differentiation, and mineralization processes were measured, which showed a reverse correlation with the expression of Mir24-2-5p. Dual-luciferase reporter gene detection assay confirmed the direct interaction between Mir24-2-5p and Gnai3 mRNA. Moreover, in osteoblast precursor cells treated with Mir24-2-5p inhibitor, the expression of Gnai3 gene was increased, suggesting that Mir24-2-5p negatively targeted Gnai3. Silencing of Gnai3 inhibited osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization. Promoting effects of osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization by low expression of Mir24-2-5p was partially rescued upon silencing of Gnai3. In vivo, mir24-2-5p Agomir microinjection into zebrafish embryo resulted in shorter body length, smaller and retruded mandible, decreased cartilage development, and vertebral calcification, which was partially rescued by microinjecting gnai3 mRNA. Notably, quite similar phenotypic outcomes were observed in gnai3 MO embryos, which were also partially rescued by mir24-2-5p MO. Besides, the expression of phospho-JNK (p-JNK) and p-p38 were increased upon Mir24-2-5p inhibitor treatment and decreased upon shGnai3-mediated Gnai3 downregulation in osteoblast precursor cells. Osteogenic differentiation and mineralization abilities of shGnai3-treated osteoblast precursor cells were promoted by p-JNK and p-p38 pathway activators, suggesting that Gnai3 might regulate the differentiation and mineralization processes in osteoblast precursor cells through the MAPK signaling pathway. Conclusions: In this study, we investigated the regulatory mechanism of Mir24-2-5p on Gnai3 expression regulation in osteoblast precursor cells and provided a new idea of improving the prevention and treatment strategies for congenital mandibular defects and mandibular protrusion.

Trio cooperates with Myh9 to regulate neural crest-derived craniofacial development.

Trio is a unique member of the Rho-GEF family that has three catalytic domains and is vital for various cellular processes in both physiological and developmental settings. TRIO mutations in humans are involved in craniofacial abnormalities, in which patients present with mandibular retrusion. However, little is known about the molecular mechanisms of Trio in neural crest cell (NCC)-derived craniofacial development, and there is still a lack of direct evidence to assign a functional role to Trio in NCC-induced craniofacial abnormalities. Methods:In vivo, we used zebrafish and NCC-specific knockout mouse models to investigate the phenotype and dynamics of NCC development in Trio morphants. In vitro, iTRAQ, GST pull-down assays, and proximity ligation assay (PLA) were used to explore the role of Trio and its potential downstream mediators in NCC migration and differentiation. Results: In zebrafish and mouse models, disruption of Trio elicited a migration deficit and impaired the differentiation of NCC derivatives, leading to craniofacial growth deficiency and mandibular retrusion. Moreover, Trio positively regulated Myh9 expression and directly interacted with Myh9 to coregulate downstream cellular signaling in NCCs. We further demonstrated that disruption of Trio or Myh9 inhibited Rac1 and Cdc42 activity, specifically affecting the nuclear export of ß-catenin and NCC polarization. Remarkably, craniofacial abnormalities caused by trio deficiency in zebrafish could be partially rescued by the injection of mRNA encoding myh9, ca-Rac1, or ca-Cdc42. Conclusions: Here, we identified that Trio, interacting mostly with Myh9, acts as a key regulator of NCC migration and differentiation during craniofacial development. Our results indicate that trio morphant zebrafish and Wnt1-cre;Triofl/fl mice offer potential model systems to facilitate the study of the pathogenic mechanisms of Trio mutations causing craniofacial abnormalities.

Association of Dysplastic Coronoid Process with Long-Face Morphology.

Vertical malocclusion is a developmental condition, resulting from complex interactions among multiple etiological factors during the growth period. As a tricky dentofacial deformity clinically, long-face (LF) morphology is characterized by excessive vertical facial growth with severe disarrangement of jaws and teeth. Since the improvement of LF patients on facial profile and occlusion is often difficult and lacks long-term stability, it becomes important to unravel the etiology of LF pattern formation for early prevention and treatment. In the current studies, we identified a transgenic mouse model that exhibited a dysplastic coronoid process and LF morphology. Although the mutant mice exhibited jaw structures and occlusion comparable to controls at birth, they all acquired typical LF morphology with anterior open bite during postnatal growth, resembling clinical features of the selected skeletal class III patients. Since the coronoid process provides an insertion site for the temporalis attachment, we examined the initial development and differentiation of the temporalis and found identical results in both control and mutant mice before E17.5 when the temporal muscle makes attachment to the coronoid process. However, thereafter, we observed altered orientation and reduced size of the cross-sectional area of the temporalis in mutant mice, which persisted to the weaning stage. Biomechanical analysis and simulation modeling further support the idea that altered morphology of the coronoid process may impair the efficiency of the vertical temporalis contraction and appears to correlate with LF formation. Consistently, we present evidence that a dysplastic mandibular coronoid process was also seen in some human patients with skeletal III LF morphology. Taken together, the results presented in this study establish an association of the craniofacial bony structures with vertical patterning, which will have implications in earlier prediction for clinical precaution and intervention.

Achondroplasia and Macular Coloboma.

Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia.

Evaluating aesthetics of the nasolabial region in children with cleft lip and palate: professional analysis and patient satisfaction.

Cleft lip and palate is one of the most common deformities of the craniofacial region, and treatment of this deformity is essential for social reintegration. One of the major goals of surgery and treatment of craniofacial deformities is to improve the aesthetic appearance of the face, and thereby improve the patient's social acceptability. Here, we present a critical review of the criteria for aesthetic evaluation of the nasolabial region in cleft patients by assessing publications with the highest level of evidence, including professional evaluation, and patient satisfaction. The findings indicate treatment of this condition represents a major challenge for multidisciplinary team care.

Craniofacial Deformity in a Patient with Dyke-Davidoff-Masson Syndrome: A Case Report

PURPOSE: The Dyke-Davidoff-Masson syndrome is a rare disease entity that was first reported in 1993, and it is characterized by not only the cerebral hemiatrophy that is accompanied by the ipsilateral ventriculomegaly and ipsilateral compensatory osseous hypertrophy, but also the overgrowth of the paranasal sinuses. No studies have attempted to examine it from perspectives of the skull deformity and plastic surgery. Here, we report our case with a review of the literatures. METHODS: A 45-year-old man with Dyke-Davidoff-Masson visited our medical institution with nasal bone fracture. Based on the previously taken brain MRI scans, we measured the degree of craniofacial deformity, and the horizontal distance, which is based on the margin of the skull, as well as the falx cerebri. RESULTS: We made a comparison of the degree of craniofacial deformity. This showed that the mean horizontal distance on the axial view was shorter by approximately 28.46%, as compared with that of the left unaffected side. CONCLUSION: The Dyke-Davidoff-Masson is characterized by a concurrent presence of the atrophy of the cerebral hemisphere, with the cranial deformity. For the reconstruction of the bone and soft-tissue deformity with Dyke-Davidoff-Masson syndrome, it is needed to perform objective assessments.

Craniofacial Deformity in a Patient with Dyke-Davidoff-Masson Syndrome: A Case Report

PURPOSE: The Dyke-Davidoff-Masson syndrome is a rare disease entity that was first reported in 1993, and it is characterized by not only the cerebral hemiatrophy that is accompanied by the ipsilateral ventriculomegaly and ipsilateral compensatory osseous hypertrophy, but also the overgrowth of the paranasal sinuses. No studies have attempted to examine it from perspectives of the skull deformity and plastic surgery. Here, we report our case with a review of the literatures. METHODS: A 45-year-old man with Dyke-Davidoff-Masson visited our medical institution with nasal bone fracture. Based on the previously taken brain MRI scans, we measured the degree of craniofacial deformity, and the horizontal distance, which is based on the margin of the skull, as well as the falx cerebri. RESULTS: We made a comparison of the degree of craniofacial deformity. This showed that the mean horizontal distance on the axial view was shorter by approximately 28.46%, as compared with that of the left unaffected side. CONCLUSION: The Dyke-Davidoff-Masson is characterized by a concurrent presence of the atrophy of the cerebral hemisphere, with the cranial deformity. For the reconstruction of the bone and soft-tissue deformity with Dyke-Davidoff-Masson syndrome, it is needed to perform objective assessments.

The reconstruction of posttraumatic craniofacial deformity using modified lefort II and III osteotomy and autogenous iliac bone graft

Cranial Cephalometric Measurement using Newly Devised Caliper and Computer Program

The measurement and visualization of the roundness of the cranial circumference has not been attempted by the simple measurement device. That's why there has been a tendency that the morphologic cranial deformity can be diagnosed with accuracy only by the experienced physician. The accurate understanding of the roundness of the cranial circumference, however, is essential for the diagnosis and the decision of the treatment principle in cranofacial morphological deformity. Current methods, such as simple physical examination and/or the photography, are not enough to accurately express the roundness of the cranial circumference. In order to develop the new method of measurement, authors selected 16 points from the axial cutting plane of the cranium. These points can be selected under the same principle even though the axial plane changes. After measuring the distance of 16 points, the values are put into computer program. In conclusion, authors can retrieve the x, y coordinates of the 16 points and can show the intuitive roundness of the circumference of the selected axial plane of the cranium. This measurement tool will be helpful not only for the identification of the severity of the morphologic cranial deformity, but for the classification and the assessment of the result of the surgery.

Establishment and application of craniofacial three-dimensional visualization model / 实用口腔医学杂志

Objective:To establish a three-dimensional visualization model of craniofacial hard and soft tissues with data based on CT. It could be used in clinic as diagnosis and operation simulation. Methods:Original data of patients' craniofacial hard and soft tissues by CT scanning was transferred into the system. After 2-D and 3-D image preprocessing, advanced Marching Cubes Algorithm (Marching Tetrahedron Algorithm) was used for surface fitting;3-D volume rendering was accomplished by footprint method. Results: The whole craniofacial frame and its surface could be observed clearly in reconstructed 3-D Model. Furthermore, the 3-D Model could be seen from any sight angle and sectioned in any direction and place. Doctors could observe the characters of craniofacial deformity for more details. Conclusion: The problems of X-ray reflection of metal brackets, control of X-ray dosage and time spending in 3-dimensional visualization model reconstruction were solved. This model could be used in clinic for diagnosis and operation simulation.