Open Sutures Research Articles

Teratogenic effects of voriconazole (anti-fungal drug) on Swiss albino mice

Antifungals are a class of drugs that target the treatment of invasive fungal infections. This includes polyenes, triazoles, and echinocadins. Among these, azoles are being extensively used nowadays. Triazoles have become standard for the azoles and have replaced amphotericin B as the first line of defence for fungal infections. With the increased cases of fungal infection, which affect a majority of the population at different stages and situations, one such section of the population is pregnant females. The rate and susceptibility of fungal infections are particularly higher in pregnant females, as the immunity of the mother is highly compromised. Systemic fungal infections like invasive aspergillosis, esophageal candidiasis, and candidemia are being treated with new age triazole antifungals like voriconazole. Prolonged and high concentrations of this drug are associated with various developmental anomalies. With this aim, teratogenic studies were performed on pregnant female mice during gestation and the weaning/lactation period to observe the effects of voriconazole at different dosages (8 mg/kg b.w., 10 mg/kg b.w., and 20 mg/kg b.w.). Pregnant dams were subjected to 20 mg/kg b.w. Voriconazole had a small litter size and a high number of resorptions. Craniofacial defects in the form of reduced ossification and widely open sutures, the presence of the 14th rib, asymmetry in the sternebrae, and the absence of ossified distal phalanges were some of the skeletal anomalies which were significant in the foetus and pups subjected to both 10 mg/kg b.w. and 20 mg/kg b.w. doses of voriconazole.

Targeting of C-ROS-1 Activity Using a Controlled Release Carrier to Treat Craniosynostosis in a Preclinical Model of Saethre-Chotzen Syndrome

Saethre-Chotzen syndrome (SCS) is one of the most prevalent craniosynostosis, caused by a loss-of-function mutation in the TWIST-1 gene, with current treatment options relying on major invasive transcranial surgery. TWIST-1 haploinsufficient osteogenic progenitor cells exhibit increased osteogenic differentiation potential due to an upregulation of the transmembrane tyrosine kinase receptor, C-ROS-1, a TWIST-1 target gene known to promote bone formation. The present study assessed the efficacy of suppressing C-ROS-1 activity using a known chemical inhibitor to C-ROS-1, crizotinib, to halt premature coronal suture fusion in a preclinical mouse model of SCS. Crizotinib (1 μM, 2 μM, or 4 μM) was administered locally over the calvaria of Twist‐1del/+ heterozygous mice prior to coronal suture fusion using either a nonresorbable collagen sponge (quick drug release) or a resorbable sodium carboxymethylcellulose microdisk (slow sustained release). Coronal suture fusion rates and bone parameters were determined by μCT imaging and histomorphometric analysis of calvaria postcoronal suture fusion. Results demonstrated a dose-dependent increase in the efficacy of crizotinib to maintain coronal suture patency, with no adverse effects to brain, kidney, liver, and spleen tissue, or blood cell parameters. Moreover, crizotinib delivered on microdisks resulted in a greater efficacy at a lower concentration to reduce bone formation at the coronal suture sites compared to sponges. However, the bone inhibitory effects were found to be diminished by over time following cessation of treatment. Our findings lay the foundation for the development of a pharmacological nonsurgical, targeted approach to temporarily maintain open coronal sutures in SCS patients. This study could potentially be used to develop similar therapeutic strategies to treat different syndromic craniosynostosis conditions caused by known genetic mutations.

A clinical case of trisomy on chromosome 18 (Edwards Syndrome)

Edwards syndrome (trisomy on chromosome 18) is a genetic disorder caused by the presence of an extra copy of the eighteenth chromosome in humans. It is the second most common chromosomal disorder after Down syndrome. The frequency of Edwards syndrome among newborns is 1:5000–1:7000. The ratio of boys to girls is 1:3. The karyotype of sick girls and boys is 47, XX+18, 47, XY+18, and 47, XY+18, respectively. Patients are born with low birth weight (about 2 kg), they have delayed growth and development, mental retardation, wide fontanels at birth and open cranial sutures, the thorax is wider and shorter than normal, the mandible and mouth opening are small. The eye slits are narrow and short, the auditory orifices are deformed and sometimes absent. There are defects of the heart and large vessels, hypoplasia of the cerebellum and corpus callosum. 5–10% survive to the age of one year, all survivors are profound oligophrenics [1–4].

New Genetic Variants of RUNX2 in Mexican Families Cause Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures with bulging calvaria, hypoplasia, or aplasia of clavicles permitting abnormal opposition of the shoulders; wide public symphysis; short middle phalanx of the fifth fingers; and vertebral, craniofacial, and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The gene responsible for CCD is the Runt-related transcription factor 2 (RUNX2) gene. We characterize the clinical, genetic, and bioinformatic results of four CCD cases: two cases within Mexican families with six affected members, nine asymptomatic individuals, and two sporadic cases with CCD, with one hundred healthy controls. Genomic DNA analyses of the RUNX2 gene were performed for Sanger sequencing. Bioinformatics tools were used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652delTA; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability-related, and structural alterations in the RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. Moreover, the proband 1 presented clinical data not previously reported that could represent an expanded phenotype of severe expression.

Cranial osteology and a new diagnosis of the late Permian pareiasaur Nanoparia luckhoffi (Broom, 1936) from the Karoo Basin of South Africa, and a consolidated pareiasaurian phylogeny

Pareiasaurs were an enigmatic and diverse group of parareptilian herbivores of the middle and late Permian. Nanoparialuckhoffi was erected in 1936 but remains the least well-known member of four “dwarf” pareiasaurs that comprise Pumiliopareiasauria. After new preparation of the holotype, we present the first detailed cranial description of Nanoparialuckhoffi and a new diagnosis for the taxon based on seven autapomorphies: (1) an additional bone on the posterior margin of the cheek flange between the squamosal and quadratojugal; (2) a pyramidal-shaped parietal; (3) a very short, square lacrimal; (4) paired prepalatal foramina positioned anterolaterally on the internal premaxillary palatal flange; (5) notch on anteromedial border of the choana; (6) a ventral flange formed by the lateral margin of the internal tabulars; and (7) tabulars that extend posteriorly further than the supratemporals. We find evidence supporting a juvenile ontogenetic state for the holotype, including small skull; unossified open cranial sutures; an unossified dorsal braincase; and fewer marginal teeth than most pareiasaurs. An updated phylogeny recovers Nanoparia as a sister taxon to Provelosaurusamericanus from Brazil and remains a constituent member of Pumiliopareiasauria. Keywords: Nanoparia, Pumiliopareiasauria, Pareiasauria, Parareptilia, late Permian, Gondwana.

A comparative study on laparoscopic and open surgical approaches for perforated peptic ulcer repair: efficacy and outcomes analysis.

This study aimed to compare the clinical outcomes of the clinical outcomes of laparoscopic and open sutures for peptic ulcer perforation (PPU). PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies from inception to March 31, 2023. Odds ratios (OR) and 95% confidence intervals (Cl) were also calculated. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. This study was performed using the Stata (V.16.0) software. A total of 29 studies involving 17,228 patients were included in this study. In terms of postoperative outcomes, the laparoscopic group had a shorter postoperative hospital stay(MD = -0.29, 95%CI = -0.44 to -0.13, P = 0.00), less blood loss (MD = -0.45, 95%CI = -0.82 to -0.08, P = 0.02), fewer wound infection (OR = 0.20, 95%CI = 0.17 to 0.24, P = 0.00), fewer pneumonia (OR = 0.59, 95%CI = 0.41 to 0.87, P = 0.01), fewer respiratory complications(OR = 0.26, 95%CI = 0.13 to 0.55, P = 0.00) and lower postoperative morbidity(OR = 0.51, 95%CI = 0.33 to 0.78, P = 0.00). The laparoscopic group had a lower mortality rate (OR = 0.36, 95%CI = 0.27 to 0.49, P = 0.00) than the open group. We also found that the laparoscopic group had a higher overall complication rate than the open group (OR = 0.45, 95%CI = 0.34 to 0.60, P = 0.00). Laparoscopic repair was associated with a lower risk of mortality than open repair in patients with PPU. Laparoscopic repair may be a better option in patients with PPU.

SURGICAL EXPOSURE OF TEETH IN CLEIDOCRANICAL DYSPLASIA UNDER PROCEDURAL SEDATION:- CASE REPORT

Cleidocranial Dysplasia (CCD) is a rare autosomal dominant condition which is mainly characterised by skeletal abnormalties like hypoplastic or aplastic clavicles, increase in transverse diameter of the cranium, delayed closure of fontanelles with presence of open sutures and skeletal changes in maxilla and mandible. 2,4 These patients usually presents with delayed exfoliation of deciduous teeth, delayed or failed eruption of the permanent dentition with multiple supernumerary teeth, protruding mandible and mid- face retrusion.2 We present a case report of a 16 year old girl undergoing multiple surgical exposure of impacted permanent teeth under conscious sedation so as to move them in normal occlusion with orthodontic traction

The Bat Child

Case Report A short stature 10 year old boy with pes planus, mild hearing loss, failure of exfoliation of the primary dentition, anterior hyperdontia, malocclusion and open anterior fontanelle was observed in Pediatric Orthopedics consultation, and presenting the following alterations (image). Discussion This child has cleidocranial dysplasia (CCD). Is an autosomal dominant disease caused by an heterozygous loss-of-function mutation in the RUNX2 gene, encoding transcription factor CBFA1, on chromosome 6p21, which plays an important role in osteogenesis and differentiation of osteoblasts. The main clinical features include persistently open skull sutures, hypoplasia or aplasia of the clavicles permitting abnormal facility in opposing the shoulders, short middle phalanx of the fifth fingers, dental anomalies (supernumerary teeth, failure of exfoliation of the primary dentition and malocclusion), pes planus, upper respiratory complications, recurrent otitis media, hearing loss and often vertebral malformation (scoliosis). Conclusion The clinical diagnosis of CCD was made during pregnancy, through the detection of aplasia of the clavicles in fetu, in association with the mother having short stature (1.32 meters), persistence of primary teeth and open anterior fontanelle. With 10 years of age, he underwent mendilioma study which revealed the mutation in the RUNX2 gene (c. 747 del (p.(Arg251 Alafs*7))) classified as a pathogenic variant.

A new juvenile Yamaceratops (Dinosauria, Ceratopsia) from the Javkhlant Formation (Upper Cretaceous) of Mongolia.

Here we report a new articulated skeleton of Yamaceratops dorngobiensis (MPC-D 100/553) from the Khugenetjavkhlant locality at the Shine Us Khudag (Javkhlant Formation, ?Santonian-Campanian) of the eastern Gobi Desert, Mongolia, which represents the first substantially complete skeleton and the first juvenile individual of this taxon. The specimen includes a nearly complete cranium and large portions of the vertebral column and appendicular skeleton. Its skull is about 2/3 the size of the holotype specimen, based on mandibular length. Its juvenile ontogenetic stage is confirmed by multiple indicators of skeletal and morphological immaturity known in ceratopsians, such as the long-grained surface texture on the long bones, the smooth external surface on the postorbital, open neurocentral sutures of all caudal vertebrae, a large orbit relative to the postorbital and jugal, the low angle of the lacrimal ventral ramus relative to the maxillary teeth row, narrow frontal, and straight ventral edge of the dentary. Osteohistological analysis of MPC-D 100/553 recovered three lines of arrested growth, implying around 3 years of age when it died, and verified this specimen’s immature ontogenetic stage. The specimen adds a new autapomorphy of Yamaceratops, the anteroventral margin of the fungiform dorsal end of the lacrimal being excluded from the antorbital fossa. Furthermore, it shows a unique combination of diagnostic features of some other basal neoceratopsians: the ventrally hooked rostral bone as in Aquilops americanus and very tall middle caudal neural spines about or more than four times as high as the centrum as in Koreaceratops hwaseongensis, Montanoceratops cerorhynchus, and Protoceratops andrewsi. The jugal with the subtemporal ramus deeper than the suborbital ramus as in the holotype specimen is also shared with A. americanus, Liaoceratops yanzigouensis, and juvenile P. andrewsi. Adding 38 new scorings into the recent comprehensive data matrix of basal Neoceratopsia and taking into account the ontogenetically variable characters recovered Y. dorngobiensis as the sister taxon to Euceratopsia (Leptoceratopsidae plus Coronosauria). A second phylogenetic analysis with another matrix for Ceratopsia also supported this position. The new phylogenetic position of Y. dorngobiensis is important in ceratopsian evolution, as this taxon represents one of the basalmost neoceratopsians with a broad, thin frill and hyper-elongated middle caudal neural spines while still being bipedal.

Computed Tomography elucidates ontogeny within the basal therapsid clade Biarmosuchia

Biarmosuchia is a clade of basal therapsids that includes forms possessing plesiomorphic ‘pelycosaurian’ cranial characters as well as the highly derived Burnetiamorpha which are characterised by cranial pachyostosis and a variety of cranial bosses. Potential ontogenetic variation in these structures has been suggested based on growth series of other therapsids with pachyostosed crania, which complicates burnetiamorph taxonomic distinction and thus it is essential to better understand cranial ontogeny of the Burnetiamorpha. Here, three new juvenile biarmosuchian skulls from the late Permian of South Africa are described using X-ray micro computed tomography (CT). We found that juvenile biarmosuchians are distinguished from adults by their relatively large orbits, open cranial sutures, and incomplete ossification of the braincase and bony labyrinth. Also, they manifest multiple centres of ossification within the parietal and preparietal bones. CT examination reveals that the holotype of Lemurosaurus pricei (BP/1/816), previously alleged to be a juvenile, shows no evidence of juvenility and is thus probably an adult. This suggests that the larger skull NMQR 1702, previously considered to be an adult L. pricei, may represent a new taxon. This study provides, for the first time, a list of characters by which to recognise juvenile biarmosuchians.

Incidence of persistent metopic suture in Australia: findings from 1034 three-dimensional computed tomography scans.

To investigate the incidence of persistent, open metopic sutures in contemporary Australians aged 24months and older. Metopic suture evaluation was conducted on retrospective cranial/cervical computed tomography scans of patients aged 24 to 252months who presented to the Women's and Children's Hospital in Adelaide, Australia, between 2010 and 2020. Suture ossification was graded according to Lottering scoring system based on 4 stages, on three-dimensional volume-rendered reconstructions (stage 1: fibrous tissue interface, stage 2: commenced fusion, stage 3: complete fusion and stage 4: obliterated suture). The complete persistent sutures were classified as stage 1. Partially closed sutures were classified into stages 2 and 3, while completely closed sutures were defined as stage 4. One thousand thirty-four patients (61.2% male and 38.8% female) were included, with a mean age at scan of 66months. More than half of patients were subject to scanning due to closed-head injuries. The incidence of persistent (completely open) metopic suture was 4.8% (2.3% in males and 2.5% in females). In comparison, a partially closed metopic suture was found in 6.3% of the study cohort, with the remaining sutures located along the metopic suture line, at the glabella, mid-part of the suture, bregma and glabella-bregma areas. The prevalence of persistent metopic sutures in our study of the Australian population is 4.8%, and it is equally distributed between the genders. The pattern of suture closure can commence from any location along the suture line, which is in contrast to the existing literature.

Pycnodysostosis- a rare disorder with distinctive craniofacial dysmorphia. A case report

Pycnodysostosis is a rare autosomal recessive condition caused by the mutation of CTSK gene. CTSK regulates the activity of Cathepsin K which is responsible for osteoclast-mediated bone resorption. This mutation causes the bones to become dense, sclerotic, brittle, and thus, prone to fracture. Affected individuals have normal cognitive development and life expectancy, however, the quality of life depends on the early diagnosis of the condition. The patient presents with striking clinical (short stature, brachydactyly) and radiological (frontal and parieto-occipital bossing, open sutures, and fontanelles, acro-osteolysis of terminal phalanges) features making the diagnosis clinico-radiographic. In atypical or mild cases with overlapping features, gene mapping is advocated. A plethora of dental anomalies and characteristic craniofacial dysmorphia puts the dentist in a position to diagnose such a case.

Identification of differentially expressed proteins between fused and open sutures in sagittal nonsyndromic craniosynostosis during suture development by quantitative proteomic analysis.

Nonsyndromic craniosynostosis (NCS), the premature fusion of cranial sutures, results in an abnormal skull shape and is associated with a significant morbidity. Proteomics is a promising tool for disease characterization and biomarker discovery; we aimed to identify biologically relevant differentially expressed proteins for NCS. Label-based quantitative proteomic profiling using TMT was performed on protein extracted from mesenchymal stem cells, osteoblasts and bone tissue of five open and five fused sutures of sagittal NCS (sNCS) and analyzed using quantitative LC-MS/MS based bottom-up proteomics. Differential protein abundance between open and fused sutures was determined to identify biologically relevant proteins of interest. Proteins were validated in an independent sample set by western blot and immunohistochemistry. We observed 838 differentially expressed proteins between open and fused sutures of sNCS. Decorin, lumican, and asporin were significantly downregulated while COL4A1 and TGFβ1|1 were upregulated in fused compared to open sutures. The majority of significantly differentially expressed proteins between open and fused sutures were observed in the proteomes of osteoblasts suggesting that protein changes contributing to premature sagittal suture fusion occur predominantly at the osteoblast level. Our findings suggest a possible ineffective ECM deposition at the osteoblast cell stage.

The ontogenetic pattern of neurocentral suture closure in the axial skeleton of Hyperodapedontinae (Archosauromorpha, Rhynchosauria) and its evolutionary implications

AbstractUnderstanding the ontogeny of a taxon is a crucial step to properly elucidate its taxonomy and evolution. However, aside from histological data, osteological criteria for assessing maturity are considered lineage specific or controversial. The sequence of neurocentral suture closure of the axial skeleton of extant crocodilians, which occurs in a posterior–anterior sequence, is a non‐destructive method used to determine maturity in extinct reptiles. However, its use in extinct archosaurs not closely related to crocodilians is debatable, as the ancestral condition of Archosauria is unknown and variation occurs in timing and sequence orientation within the clade. We have assessed the pattern of neurocentral suture closure of Hyperodapedontinae rhynchosaurs, an early archosauromorph clade distantly related to archosaurs. Unlike extant crocodilians, they exhibit an anterior–posterior sequence neurocentral suture closure. Relative size and other ontogenetic markers suggest that neurocentral closure in the Hyperodapedontinae correlates with aging, although closed sutures were rare in the sample. A high number of open or partially open sutures in mature individuals indicate that they remained open during most of their life. Our study indicates that: (1) the delayed neurocentral closure may be a paedomorphic heterochronic process in Hyperodapedontinae, as it contrasts with the fully closed neurocentral sutures of early diverging non‐hyperodapedontine rhynchosaurs; (2) the assumption that open neurocentral sutures indicates immaturity in extinct reptiles is not always correct; and (3) the delayed closure may have originated independently in several archosauromorph lineages, but the ancestral condition of Archosauria probably follows the crocodilian closure pattern.

SIMULTANEOUS OPERATIONS DURING UMBILICAL AND PARAUMBILICAL HERNIA REPAIR: POSSIBLE OR NECESSARY?

The aim of the study was to determine the possibility and effectiveness of simultaneous surgical interventions in umbilical and paraumbilical hernia repair. Material and methods: 148 case histories were analyzed concerning patients who were routinely admitted to the surgical department of the Kharkiv Regional Council's Municipal Non-Profit Enterprise «Regional Clinical Hospital» between 2017 and 2019, and who underwent umbilical and paraumbilical hernia repair simultaneously with operations related to some other surgical pathology (group 1, n = 67) or in separate interventions (group 2, n = 81). All patients were routinely operated after a set of mandatory and additional general clinical, laboratory and instrumental research conducted in accordance with the existing guidelines. The structure and results of surgical interventions related to the underlying disease and simultaneous operations were studied. Results: Simultaneous operations were performed for comorbid cholecystolithiasis, diaphragmatic esophageal hernia with gastroesophageal reflux, inguinal hernia, white line hernia, benign diseases of the uterus and uterine appendages et al. The frequency of complications and recurrences of hernia in patients with simultaneous and isolated of umbilical hernia repair did not differ significantly. The outcome of the operation mostly depended on the method of operation (postoperative complications were most often observed in open sutures repair and were absent in laparoscopic hernia repair). Additional risk factors were weight gain and diabetes. Conclusions: Summarizing the data obtained, it can be concluded that application of modern endovideoscopic techniques in surgery makes simultaneous surgical interventions not only possible but also necessary in the presence of concomitant abdominal pathology that requires surgical treatment.

CLEIDOCRANIAL DYSOSTOSIS: OROFACIAL CHANGES IN A 26-YEAR-OLD WOMAN

Cleidocranial dysostosis (CCD) is an inherited autosomal dominant syndrome due to the heterozygous mutation of the RUNX2 gene, which is often the same in men and women. The diagnosis is based on clinical and radiographic features, which include images of the skull, thorax, pelvis, and hands. The present study aims to present a case report of CCD in a 29-year-old feoderm woman. During intraoral examination permanent nonerupted teeth, deep palate, prominent mandible, maxillary hypoplasia, and vertical occlusion dimension were observed. Panoramic radiographs and computed tomography scan of the conical bundle showed several nonerupted teeth and multiple supernumerary teeth. Wormian bones and persistent open sutures were observed on the lateral radiograph of the head. The shoulder radiograph shows the absence of right and left clavicles. In view of the complexity of the treatment an interdisciplinary discussion is necessary, taking into account age and economic condition.

A MOUTH FULL OF TEETH: A CASE REPORT

<h3>Background</h3> An increase in the number of teeth is termed <i>supernumerary teeth</i>.¹^,² These teeth can be present both unilaterally or bilaterally, in one jaw, or in both jaws.² In the maxilla, the anterior region is the most common location, and a solitary tooth in the midline is referred to as <i>mesiodens</i>. However, supernumerary teeth are more often seen in the mandible, especially in the premolar region, and are referred to as <i>peridens</i>.¹^,² Supernumerary teeth distal to the molars are referred to as <i>distodens</i>.² This type of dental anomaly is commonly associated with developmental disorders, such as Gardner syndrome and cleidocranial dysplasia.²^,³ The excess number of teeth affects both the primary and permanent dentitions. It more commonly affects the permanent dentition and usually interferes with the eruption pattern, leading to malposition, crowding, ectopic eruption, and malocclusion.¹^,² <h3>Clinical and Radiographic Presentation</h3> A 9-year-old female with multiple impacted supernumerary teeth was referred by an orthodontist requesting a cone beam computed tomography (CBCT) scan for evaluation of impacted teeth. According to the clinic notes from the orthodontist, the patient was not complaining of any pain and had not been previously diagnosed with any medical disorder. There was no concerning medical history reported for the patient. The family history revealed that the patient's mother was deaf. The CBCT scan revealed multiple impacted permanent and supernumerary teeth in the jaws. On the basis of the radiologist's recommendation, the patient was referred to the University of Iowa Hospital and Clinic for genetic tests to rule out a possible underlying disorder. <h3>Differential Diagnosis</h3> Cleidocranial dysplasia, Gardner syndrome, Apert syndrome, and Crouzon syndrome were considered. <h3>Diagnosis and Management</h3> The CBCT scan revealed 19 impacted supernumerary teeth, apart from the impacted permanent teeth. The scan also showed a dentigerous cyst around the unerupted permanent mandibular right first molar. The image revealed multiple open sutures. A chest radiograph revealed marked variations in the clavicles bilaterally. On genetic testing, in addition to the findings from the scan, led to the diagnosis of cleidocranial dysplasia. The patient is currently scheduled for systematic removal of the supernumerary teeth as part of the comprehensive treatment plan. <h3>Discussion</h3> This case demonstrates the crucial role and importance of interpretation of CBCT volumes by a radiologist and the immense benefit of interdisciplinary care provided to a patient. CBCT is an excellent imaging tool to evaluate the location of teeth and aids in the treatment plan by revealing incidental findings that could be life changing for a patient and by enabling better patient care and outcomes.

A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis.

Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10-8): rs781716 (P = 4.71 × 10-9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10-8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10-9; OR = 0.34), located ~ 155kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10-8, OR = 0.45; P = 3.31 × 10-8, OR = 0.45; P = 1.09 × 10-8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10-8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10-6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821-55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

A study on differences in the obliteration of cranial sutures and their clinical significance

Introduction: There are very few studies on the patency of cranial sutures, and this study analyzes the difference in sutural patency. The objective was to study the difference in the patency of coronal, sagittal, and lambdoid sutures in Indian human adult skulls. Material and Methods: This study involved 120 Indian human adult skulls. The suture patency was graded in accordance to a classification proposed by Sabini and Elkowitz on a scale of 0–4. An open suture was classified as 0; fused but not obliterated as 1; and Grades 2, 3, and 4 represented 50%, and 100% of obliteration, respectively. Results: The lambdoid sutures were observed to be the most patent and least obliterated. Grade 1 sutures were observed to be 44.71% in lambdoid, 8.4% in sagittal, and 7.3% in coronal sutures. Grade 2 sutures were observed to be 42.6% in lambdoid, 49.3% in sagittal, and 46.7% in coronal sutures. Grade 3 sutures were observed to be 10.1% in lambdoid, 32.1% in sagittal, and 36.2% in coronal sutures. Grade 4 sutures were observed to be 2.6% in lambdoid, 10.2% in sagittal, and 9.8% in coronal sutures. No open sutures were observed. Discussion and Conclusion: Lambdoid sutures are more patent than coronal and sagittal sutures. This can be attributed to the presence of more muscular contractile forces acting on the lambdoid suture when compared with other sutures. The mechanisms involved in suture closure are complex and involve genetic and environmental factors, age, and tissue interactions. Therefore, more advanced research is essential for a clearer insight on this subject, which has immense clinical implications in neuroscience.

Cleidocranial dysplasia – A case report discussing the clinical and radiological manifestations

Cleidocranial dysplasia (CCD) is a generalized skeletal disorder characterized by typical clinical and radiological abnormalities which include open cranial sutures and fontanelle, presence of Wormian bones, characteristic abnormalities of the clavicle and pelvic bones, and dentition. We report a teenage boy who presented for the evaluation of short stature. He was detected to have CCD based on his clinical examination and radiographic findings. An early diagnosis and treatment directed at correcting the dental and orthopedic abnormalities are imperative to obtain an optimal cosmetic and functional outcome in these patients.