Primary acalvaria with open-lip schizencephaly in indigenous South Papuan surviving newborn: a rare case report.

BACKGROUND: Acalvaria, or acrania, is a rare congenital cranial vault defect with neurocranium absences, including complete or part of calvaria flat bones, dura mater, and associated muscles, but with a still present in the central nervous system, skull base, facial bones, and skin-covered the defect. It is a sporadic incidence without apparent genetic factors confirmed. Acalvaria is often misdiagnosed as anencephaly; the distinguishable difference is that anencephaly has an absence (partial or complete) of the brain tissue, including the skull and scalp. Acalvaria is considered a fatal anomaly with a low survival rate, and only a few cases of extended survival have been reported until now. To the best of the author's knowledge, no acalvaria case has been published in Papua, and only one reported case of the coexistence of acalvaria with schizencephaly in Brazil (2018). CASE REPORT: Herein, we present a case of an indigenous South Papuan living newborn with primary acalvaria and open-lip schizencephaly in a frontoparietal region. A male newborn baby was born from a 39-year-old female Marind-Anim tribe patient with a 38th week of gestation, with no previous history of miscarriage, is not a consanguineous marriage, and had an unremarkable medical history during this pregnancy. Post-natal physical examinations showed an irregularly shaped head with 11.5 cm diameter concave of the right side, with a soft brain-like consistency palpable and the absence of half right frontoparietal calvarium covered with a presence of scalp and hair. Cranial 2-dimension ultrasonography shows an absence of half right frontoparietal calvaria bone with a complete presence of scalp and periosteum covering the defect with a fluid accumulation (anechoic) below the periosteum. A transverse axis view shows a complete structure but hypoplasia of brain cortex with visible slightly dysgenesis of gyrus and sulcus in both hemispheres convincing the acalvaria condition not anencephaly. A fluid accumulation above brain parenchyma of the frontoparietal region happened to be a cerebrospinal fluid coming from a wide-open cleft extending from the left lateral and fourth ventricles to the cerebral cortex, suggesting a typical condition of open-lip schizencephaly. Further health follow-ups until 6 months old showed still normal physical and behavioral development with no sign of complications. CONCLUSIONS: No standard acalvaria treatment is being established; conservative and supportive therapy is mostly taken considering their low survival rate. With the advancement of medical technology nowadays, surgical approaches, including scalp defect closure, bone graft, and 3D-printed defect filling, are being performed and have succeeded in a few cases. Long-term follow-up is required to monitor their neuro-psychological development and complication incidences that need further intervention.

Feminization of the Forehead: A Scoping Literature Review and Cohort Study of Transfeminine Patients.

BACKGROUND: Facial feminization may be performed to alleviate gender dysphoria among transfeminine patients. The upper third of the face has several characteristics, including hairline shape and position, brow position, and forehead protrusion, that may confer feminine identity. The purpose of this study is to conduct a scoping literature review of techniques performed for forehead feminization and to additionally study clinical outcomes within an institutional cohort. METHODS: A systematic literature review was conducted to review articles that discussed techniques and clinical outcomes associated with procedures performed for feminization of the upper third of the face. A retrospective review of patients undergoing such procedures by the senior author was then conducted. Variables collected included demographic factors, operative details, and postoperative outcomes such as complications, revisions, and re-operations. RESULTS: Initial review yielded sixty-seven articles. Title and abstract review followed by standardized application of inclusion and exclusion criteria resulted in a total of twenty-two studies for analysis. Priorities of forehead feminization entail frontal bossing reduction, frontonasal angle widening, orbital contouring, brow lifting, and hairline advancement. Eighty-five patients were included for analysis. The majority were of Caucasian race (56%) and had type 3 forehead classification (92%). The average planned setback of the anterior table was 4.12 mm. CONCLUSIONS: The core tenets of the feminization of the forehead lie in the overall creation of a harmonic curvature of the forehead with other facial features. Our multi-pronged analysis presents an updated review of these principles, which may help plastic surgeons in performing procedures to feminize the upper third of the face. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Unreported variant foramen of the frontal bone: the latero-orbital foramen.

Variant foramina of the skull can lead to misdiagnosis on medical imaging and potentially, intraoperative complications if not appreciated. Here, we report an unusual foramen found superior to the frontozygomatic suture. The foramen was located on the left side at the superolateral rim of the orbit, 2.36 cm inferolateral to the supraorbital foramen. It was positioned 2.5 mm superior to the frontozygomatic suture. The foramen had a length of 3.1 mm and a width of 1.3 mm. The internal opening of the foramen was located 1.45 cm superolateral to the zygomaticotemporal foramen. We suggest that this foramen is a pathway for either a branch of the zygomatic nerve or lacrimal nerve and/or their vascular bundles. Although the prevalence of such a finding cannot be confirmed, such a case is of archival value as a comparison for future similar cases.

Sex estimation through geometric morphometric analysis of the frontal bone: an assessment in pre-pubertal and post-pubertal modern Spanish population.

Sex estimates is a key step of biological profile assessment in a forensic or anthropologic context. In this study, the sexual dimorphism of the frontal bone was analyzed to assess the accuracy of sex estimates using a geometric morphometric approach in a pre-pubertal and post-pubertal sample. The shape of the frontal bone was digitized on the lateral cephalograms of 87 pre-pubertal subjects (42 males, mean age 10.14, SD ± 1.48 years; 45 females mean age 10.02, SD ± 1.11 years) and 103 post-pubertal ones (53 males, mean age 29.33 SD ± 11.88 years; 50 females, mean age 26.77 SD ± 11.07 years). A generalized Procrustes analysis (GPA) was performed for shape analyses, filtering the effects of position, rotation, translation, and size. A principal component analysis (PCA) was performed on the GPA transformed variables, and a multiple logistic regression model was used to assess the accuracy of sex estimates. In both age groups, the average size of the centroid was significantly larger in males. The females presented shapes with a shorter distance between P2 (glabella) and P1 (supratoral) and a general narrowing of the structure on the sagittal plane. In the pre-pubertal group, the shape difference was not statistically significant. In the post-pubertal group, the mean shape was significantly different between the sexes. The method displayed a high accuracy for sex estimates (88.7% males, 90.3% females) also when applied in a validation sample (82.6% males and 94.1% females). The described morphometric analysis of the frontal bone is based on a limited number of landmarks, which allows sex estimates with high accuracy in post-pubertal subjects, while it is not applicable in pre-pubertal ones.

Cellular mechanisms of frontal bone development in spotted gar (Lepisosteus oculatus).

BACKGROUND: The cellular and molecular mechanisms initiating vertebrate cranial dermal bone formation is a conundrum in evolutionary and developmental biology. Decades of studies have determined the developmental processes of cranial dermal bones in various vertebrates and identified possible inducers of dermal bone. However, evolutionarily derived characters of current experimental model organisms, such as non-homologous frontal bones between teleosts and sarcopterygians, hinder investigations of ancestral and conserved mechanisms of vertebrate cranial dermal bone induction. Thus, investigating such mechanisms with animals diverging at evolutionarily informative phylogenetic nodes is imperative. RESULTS: We investigated the cellular foundations of skull frontal bone formation in the spotted gar Lepisosteus oculatus, a basally branching non-teleost actinopterygian. Whole-mount bone and cartilage staining and hematoxylin-eosin section staining revealed that mesenchymal cell condensations in the frontal bone of spotted gar develop in close association with the underlying cartilage. We also identified novel aspects of frontal bone formation: enrichment of F-actin, cellular membranes, and E-cadherin in condensing cells, and extension of podia-like structures from osteoblasts to the frontal bone, which may be responsible for bone mineral transport. CONCLUSION: This study highlights the process of frontal bone formation with dynamic architectural changes of mesenchymal cells in spotted gar, an emerging non-teleost fish model system, illuminating supposedly ancestral and likely conserved developmental mechanisms of skull bone formation among vertebrates.

Pott's puffy tumor: a need for interdisciplinary diagnosis and treatment.

Pott's puffy tumor (PPT) is an infection of the frontal sinus with subperiosteal and intracranial abscess formation and one of the rare entities in pediatrics. We present a series of four cases of PPT that occurred in two children (6 and 9 years) and in two young adults (17 and 19 years). All patients were treated by an interdisciplinary team of pediatric, neurosurgical, ENT, radiological, and neuroradiological specialists. Antibiotic treatment was combined with single endoscopic surgery in one case and combined endoscopic sinus surgery with an open transcranial approach to drain intracranial abscess formation in three cases. It is important to be aware that PPT occurs in children with the finding of intracranial abscess formation. Therefore, a close interdisciplinary cooperation for successful treatment is needed in this rare disease.

[Pott's Puffy Tumor: a need for interdisciplinary diagnosis and treatment. German Version]. / Pott-Puffy-Tumor: die Notwendigkeit einer interdisziplinären Diagnostik und Behandlung.

Pott's puffy tumor (PPT) is an infection of the frontal sinus with subperiosteal and intracranial abscess formation and one of the rare entities in pediatrics. We present a series of four cases of PPT that occurred in two children (6 and 9 years) and in two young adults (17 and 19 years). All patients were treated by an interdisciplinary team of pediatric, neurosurgical, ENT, radiological, and neuroradiological specialists. Antibiotic treatment was combined with single endoscopic surgery in one case and combined endoscopic sinus surgery with an open transcranial approach to drain intracranial abscess formation in three cases. It is important to be aware that PPT occurs in children with the finding of intracranial abscess formation. Therefore, a close interdisciplinary cooperation for successful treatment is needed in this rare disease.

Association of frontal and maxillary bone fractures and concomitant craniocerebral injuries in patients presenting with head trauma.

Background: Maxillofacial fractures and craniocerebral injuries are common in patients with head trauma. These are injuries with high mortality and morbidity. Therefore, patients with head trauma should be evaluated early with a multidisciplinary approach. Aim: The association between frontal and maxillary bone fractures and concurrent craniocerebral injuries were investigated in patients presenting with head trauma in this study. The data of the patients were analyzed retrospectively. Methods and Material: Age and gender distributions were evaluated in frontal and maxillary fractures. Concomitant craniocerebral injuries were investigated. Craniocerebral injuries were grouped as pneumocephalus, extra-axial, intra-axial injuries and brain edema. Craniocerebral injuries in frontal and maxillary fractures were compared statistically. Results: Frontal bone and maxillary bone fractures were detected in 24% and 95% of the patients. Coexistence of pneumocephalus and intra-axial injuries in frontal bone fracture was statistically significant. The association of frontal posterior wall fractures with pneumocephalus and parenchymal contusion was found to be statistically significant. In addition, the association of craniocerebral injuries were evaluated and statistically significant ones were determined. Conclusion: The presence of maxillofacial fractures in patients presenting with head trauma increases mortality and morbidity. Craniocerebral injuries can be life-threatening and delay the treatment of facial fractures. Upper facial bone fractures are significantly more common in craniocerebral injuries.

A geometric morphometric approach to the study of sexual dimorphism in the modern human frontal bone.

OBJECTIVES: We analyzed the main anatomical traits found in the human frontal bone by using a geometric morphometric approach. The objectives of this study are to explore how the frontal bone morphology varies between the sexes and to detect which part of the frontal bone are sexually dimorphic. MATERIALS AND METHODS: The sample is composed of 161 skulls of European and North American individuals of known sex. For each cranium, we collected 3D landmarks and semilandmarks on the frontal bone, to examine the entire morphology and separate modules (frontal squama, supraorbital ridges, glabellar region, temporal lines, and mid-sagittal profile). We used Procrustes ANOVAs and LDAs (linear discriminant analyses) to evaluate the relation between frontal bone morphology and sexual dimorphism and to calculate precision and accuracy in the classification of sex. RESULTS: All the frontal bone traits are influenced by sexual dimorphism, though each in a different manner. Variation in shape and size differs between the sexes, and this study confirmed that the supraorbital ridges and glabella are the most important regions for sex determination, although there is no covariation between them. The variable size does not contribute significantly to the discrimination between sexes. Thanks to a geometric morphometric analysis, it was found that the size variable is not an important element for the determination of sex in the frontal bone. CONCLUSION: The usage of geometric morphometrics in analyzing the frontal bone has led to new knowledge on the morphological variations due to sexual dimorphism. The proposed protocol permits to quantify morphological covariation between modules, to calculate the shape variations related to sexual dimorphism including or omitting the variable size.

Calvarial involvement in disseminated rhinosporidiosis - A case report and literature review.

Rhinosporidiosis is a chronic granulomatous infection caused by Rhinosporidium seeberi and mainly involves nasal and ocular mucosa. Bony involvement in rhinosporidiosis is very rare. A young male, previously operated for nasal rhinosporidiosis, presented with two bony swellings on the forehead and multiple subcutaneous lesions on the right lower limb. The diagnosis of disseminated cutaneous rhinosporidiosis with frontal bone involvement was made with the help of fine needle aspiration cytology (FNAC), histopathology, and computed tomography (CT) scan head. Wide excision of the bony lesion was performed. To the best of our knowledge, this is the first radiologically proven case of frontal bone involvement in disseminated rhinosporidiosis. Early diagnosis can be established with a good clinicopathological and radiological correlation. It also emphasizes the importance of CT scan for the evaluation of any subcutaneous skull lesion.

Regional difference in microRNA regulation in the skull vault.

BACKGROUND: The murine calvaria has several membrane bones with different tissue origins (e.g., neural crest-derived frontal bone vs. mesoderm-derived parietal bone). Neural crest-derived frontal bone exhibits superior osteogenic activities and bone regeneration. MicroRNA (miRNA) has been emerged as a crucial regulator during organogenesis and is involved in a range of developmental processes. However, the underlying roles of miRNA regulation in frontal bone and parietal bone is unknown. RESULTS: Total of 83 significantly expressed known miRNAs were identified in frontal bones versus parietal bones. The significantly enriched gene ontology and KEGG pathway that were predicted by the enrichment miRNAs were involved in several biological processes (cell differentiation, cell adhesion, and transcription), and multiple osteogenic pathways (e.g., focal adhesion, MAPK, VEGF, Wnt, and insulin signaling pathway. Focal adhesion and insulin signaling pathway were selected for target verification and functional analysis, and several genes were predicted to be targets genes by the differentially expressed miRNAs, and these targets genes were tested with significant expressions. CONCLUSIONS: Our results revealed a novel pattern of miRNAs in murine calvaria with dual tissue origins, and explorations of these miRNAs will be valuable for the translational studies to enhance osteogenic potential and bone regeneration in the clinic.

Morphometric study of the primary ossification center of the frontal squama in the human fetus.

PURPOSES: Detailed morphometric data on the development of ossification centers in human fetuses is useful in the early detection of skeletal dysplasias associated with a delayed development of ossification centers and their mineralization. Quantitative analysis of primary ossification centers of cranial bones is sporadic due to limited availability of fetal material. MATERIAL AND METHODS: The size of the primary ossification center of the frontal squama in 37 human (16 males and 21 females) spontaneously aborted human fetuses aged 18-30 weeks was studied by means of CT, digital-image analysis and statistics. RESULTS: With neither sex nor laterality differences, the best-fit growth dynamics for the primary ossification center of the frontal squama was modelled by the following functions: y = 13.756 + 0.021 × (age)2 ± 0.024 for its vertical diameter, y = 0.956 + 0.956 × age ± 0.823 for its transverse diameter, y = 38.285 + 0.889 × (age)2 ± 0.034 for its projection surface area, and y = 90.020 + 1.375 × (age)2 ± 11.441 for its volume. CONCLUSIONS: Our findings for the primary ossification center of the frontal squama may be conducive in monitoring normal fetal growth and screening for inherited faults and anomalies of the skull in human fetuses.

Runx2 function in cells of neural crest origin during intramembranous ossification.

Runt-related transcription factor 2 (Runx2), also known as core binding factor 1 (Cbfa1), is a multifunctional transcription factor and an essential master gene controlling osteoblast differentiation. We previously demonstrated the in vivo functions of Runx2 in mesoderm-derived cells. However, no studies have been conducted on Runx2 function during the differentiation of neural crest (NC)-derived cells in vivo. Wingless-type MMTV integration site family member 1 (Wnt1) is expressed in the NC, and Wnt1-Cre efficiently targets craniofacial NC-derived cells. Runx2 deficiency in cells of the Wnt1 lineage (referred henceforth as Runx2wnt1-/- within mice) resulted in defective ossification in certain regions, primarily in the anterior half of the craniofacial bones, including the frontal bone, jugal bone, squamous temporal bone, mandible, maxilla, and nasal bone. The skeletal analysis also revealed that heterozygous Runx2wnt1+/- embryos had an impaired closure of the frontal bone at the metopic suture and lacked the secondary palate in spite of otherwise normal ossification. This result suggests that ossification at the central part of the frontal bone is more dependent on Runx2 expression in comparison to other areas. These results indicate that Runx2 is indispensable not only for mesoderm-derived cells but also for NC-derived cells to differentiate during intramembranous ossification after migration to their destination from the neural plate border. Moreover, this implies that there are different levels of dependency on Runx2 expression for successful ossification between NC-derived cells that have migrated to different locations.

Sex estimation using external morphology of the frontal bone and frontal sinuses in a contemporary Czech population.

Sex estimation is a task of utmost importance in forensic anthropology and bioarcheology. Along with the pelvic bone, the skull is the most important source of sexual dimorphism. On the human skull, the upper third of the face (i.e., the frontal bone) is one of the most significant sexually dimorphic structures useful in anthropological research, especially when studied by methods of virtual anthropology. This study was focused on sex estimation using the form and shape of the external surface of the frontal bone with or without the inclusion of its sinuses. The study sample consisted of 103 cranial CT images from a contemporary Czech population. Three-dimensional virtual models of the frontal bones and sinuses were analyzed using geometric morphometrics and multidimensional statistics: coherent point drift-dense correspondence analysis (CPD-DCA), principal component analysis (PCA), and support vector machine (SVM). The whole external frontal surface was significantly different between males and females both in form and shape. The greatest total success rate of sex estimation based on form was 93.2%, which decreased to 86.41% after crossvalidation, and this model identified females and males with the same accuracy. The best estimation based on shape reached a success rate of 91.26%, with slightly greater accuracy for females. After crossvalidation, however, the success rate decreased to 83.49%. The differences between sexes were significant also in the volume and surface of the frontal sinuses, but the sex estimation had only 64.07% accuracy after crossvalidation. Simultaneous use of the shape of the frontal surface and the frontal sinuses improved the total success rate to 98.05%, which decreased to 84.46% after crossvalidation.

A rare case: sclerosing osteomyelitis of the frontal bone.

The patient presented in this study had a form of chronic sclerosing osteomyelitis (CSO) that is rarely reported in calvarial bones and has never been reported in the frontal bone in the literature. We aimed to contribute to the literature with this case study. In this study, we report a 14-year-old girl who presented with swelling and pain in the frontal bone and underwent treatment due to CSO. The patient had no history of trauma and chronic infection. We conclude that CSO should be considered in the differential diagnosis of the patients presenting with cranial swelling whose diagnosis cannot be established based on the radiological findings.

Fgfr1 conditional-knockout in neural crest cells induces heterotopic chondrogenesis and osteogenesis in mouse frontal bones.

Most facial bones, including frontal bones, are derived from neural crest cells through intramembranous ossification. Fibroblast growth factor receptor 1 (Fgfr1) plays a pivotal role in craniofacial bone development, and loss of Fgfr1 leads to cleft palate and facial cleft defects in newborn mice. However, the potential role of the Fgfr1 gene in neural crest cell-mediated craniofacial development remains unclear. To investigate the role of Fgfr1 in neural crest cells, we analyzed Wnt1-Cre;Fgfr1flox/flox mice. Our results show that specific knockout of Fgfr1 in neural crest cells induced heterotopic chondrogenesis and osteogenesis at the interface of the anterior portions of frontal bones. We observed that heterotopic bone formation continued through postnatal day 28, whereas heterotopic chondrogenesis lasted only through the embryonic period. In summary, our results indicate that loss of Fgfr1 in neural crest cells leads to heterotopic chondrogenesis and osteogenesis.

Physiological Signatures of Dual Embryonic Origins in Mouse Skull Vault.

BACKGROUND/AIMS: The mammalian skull vault is a highly regulated structure and consists of several membrane bones of different tissue origins (e.g. neural crest derived frontal bone and mesoderm derived parietal bone). Although membrane bones form through intramembranous ossification, neural crest derived frontal bone has superior osteoblast activity and bone regeneration ability, triggering a novel conception for craniofacial reconstruction and bone regeneration called endogenous calvarial regeneration. However, a comprehensive landscape of the genes and signaling pathways involved in this process is not clear. METHODS: Transcriptome analysis within the two bone elements is firstly performed to determine the physiological signatures of differential gene expressions in mouse skull vault. RESULTS: Frontal bone tissues and parietal bone tissues maintain tissue origin through special gene expression similar to neural crest vs mesoderm tissue, and physiological functions between these two tissues are also found in differences related to proliferation, differentiation and extracellular matrix production and clustered signaling pathways. CONCLUSION: Our data provide novel insights into the potential gene regulatory network in regulating the development of neural crest-derived frontal bone and mesoderm-derived parietal bone.

3D-Microarchitectural patterns of Hyperostosis frontalis interna: a micro-computed tomography study in aged women.

Although seen frequently during dissections and autopsies, Hyperostosis frontalis interna (HFI) - a morphological pattern of the frontal bone thickening - is often ignored and its nature and development are not yet understood sufficiently. Current macroscopic classification defines four grades/stages of HFI based on the morphological appearance and size of the affected area; however, it is unclear if these stages also depict the successive phases in the HFI development. Here we assessed 3D-microarchitecture of the frontal bone in women with various degrees of HFI expression and in an age- and sex-matched control group, hypothesizing that the bone microarchitecture bears imprints of the pathogenesis of HFI and may clarify the phases of its development. Frontal bone samples were collected during routine autopsies from 20 women with HFI (age: 69.9 ± 11.1 years) and 14 women without HFI (age: 74.1 ± 9.7 years). We classified the HFI samples into four groups, each group demonstrating different macroscopic type or stage of HFI. All samples were scanned by micro-computed tomography to evaluate 3D bone microarchitecture in the following regions of interest: total sample, outer table, diploe and inner table. Our results revealed that, compared to the control group, the women with HFI showed a significantly increased bone volume fraction in the region of diploe, along with significantly thicker and more plate-like shaped trabeculae and reduced trabecular separation and connectivity density. Moreover, the inner table of the frontal bone in women with HFI displayed significantly increased total porosity and mean pore diameter compared to controls. Microstructural reorganization of the frontal bone in women with HFI was also reflected in significantly higher porosity and lower bone volume fraction in the inner vs. outer table due to an increased number of pores larger than 100 µm. The individual comparisons between the control group and different macroscopic stages of HFI revealed significant differences only between the control group and the morphologically most pronounced type of HFI. Our microarchitectural findings demonstrated clear differences between the HFI and the control group in the region of diploe and the inner table. Macroscopic grades of HFI could not be distinguished at the level of bone microarchitecture and their consecutive nature cannot be supported. Rather, our study suggests that only two different types of HFI (moderate and severe HFI) have microstructural justification and should be considered further. It is essential to record HFI systematically in human postmortem subjects to provide more data on the mechanisms of its development.