Suture Fusion Research Articles

New method for quantification of the relative severity and (a)symmetry of isolated metopic synostosis

Trigonocephaly is the result of premature fusion of the metopic suture and its severity can vary widely. However, there is no gold standard for quantification of the severity. This study was performed to quantify severity using the Utrecht Cranial Shape Quantifier (UCSQ) and to assess forehead symmetry. Nineteen preoperative non-syndromic trigonocephaly patients (age ≤1 year) were included for the analysis of severity and symmetry. Severity according to the UCSQ was based on the following combined variables: forehead width and relative skull elongation. The UCSQ was compared to the most established quantification methods. A high correlation was found between the UCSQ and visual score (r=0.71). Moderate to negligible correlation was found between the UCSQ and frontal angle, binocular distance, inter-ocular distance, and frontal stenosis. Additionally, correlation between the visual score and these established quantification methods was negligible. Assessment of the frontal peak (a)symmetry (ratio of right to left triangle area in the curve) showed a mean right versus left triangle area ratio of 1.4 (range 0.9–2.4). The results suggest that the UCSQ is appropriate for the quantification of severity based on the high correlation with clinical judgement. Furthermore, a larger triangle area right than left was unexpectedly found, indicating forehead asymmetry.

Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosynostosis

Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to the premature fusion of skull sutures. CS care requires surgical treatment of variable complexity, aimed at resolving functional and cosmetic defects resulting from the skull growth constrain. Despite significant innovation in the management of CS, morbidity and mortality still exist. Residual cranial defects represent a potential complication and needdedicated management to drive a targeted bone regeneration while modulating suture ossification. To this aim, existing techniques are rapidly evolving and include the implementation of novel biomaterials, 3D printing and additive manufacturing techniques, and advanced therapies based on tissue engineering. This review aims at providing an exhaustive and up-to-date overview of the strategies in use to correct these congenital defects, focusing on the technological advances in the fields of biomaterials and tissue engineering implemented in pediatric surgical skull reconstruction, i.e., biodegradable bone fixation systems, biomimetic scaffolds, drug delivery systems, and cell-based approaches.

Polycystin-1 modulates RUNX2 activation and osteocalcin gene expression via ERK signalling in a human craniosynostosis cell model.

Craniosynostosis refers to the premature fusion of one or more cranial sutures leading to skull shape deformities and brain growth restriction. Among the many factors that contribute to abnormal suture fusion, mechanical forces seem to play a major role. Nevertheless, the underlying mechanobiology‐related mechanisms of craniosynostosis still remain unknown. Understanding how aberrant mechanosensation and mechanotransduction drive premature suture fusion will offer important insights into the pathophysiology of craniosynostosis and result in the development of new therapies, which can be used to intervene at an early stage and prevent premature suture fusion. Herein, we provide evidence for the first time on the role of polycystin‐1 (PC1), a key protein in cellular mechanosensitivity, in craniosynostosis, using primary cranial suture cells isolated from patients with trigonocephaly and dolichocephaly, two common types of craniosynostosis. Initially, we showed that PC1 is expressed at the mRNA and protein level in both trigonocephaly and dolichocephaly cranial suture cells. Followingly, by utilizing an antibody against the mechanosensing extracellular N‐terminal domain of PC1, we demonstrated that PC1 regulates runt‐related transcription factor 2 (RUNX2) activation and osteocalcin gene expression via extracellular signal–regulated kinase (ERK) signalling in our human craniosynostosis cell model. Altogether, our study reveals a novel mechanotransduction signalling axis, PC1‐ERK‐RUNX2, which affects osteoblastic differentiation in cranial suture cells from trigonocephaly and dolichocephaly patients.

Study of pattern of fusion of lambdoid suture using skull radiography and its association with documented age

Abstract Identification is the establishment of identity of a person.It includes age, sex and stature. Forensic practitioners are often faced with cases of age estimation brought by police or sent by court. In the present study we have studied the roentgenogram of patients where age was known. Lambdoid suture in in age group of 20-80 years was studied in roentgenograms. Instances of medico-legal disputes are in refugees, asylum seekers, pensionable age, unknown unidentified persons, dementia, missing or lost cases. We studied the radiographic process of fusion and used Key score to tabulate our findings. We found that the earliest age of commencement of fusion is 34 years and latest is 44 years

Insights and future directions of potential genetic therapy for Apert syndrome: A systematic review.

Apert syndrome is a genetic disorder characterised by craniosynostosis and structural discrepancy of the craniofacial region as well as the hands and feet. This condition is closely linked with fibroblast growth factor receptor-2 (FGFR2) gene mutations. Gene therapies are progressively being tested in advanced clinical trials, leading to a rise of its potential clinical indications. In recent years, research has made great progress in the gene therapy of craniosynostosis syndromes and several studies have investigated its influences in preventing/diminishing the complications of Apert syndrome. This article reviewed and exhibited different techniques of gene therapy and their influences in Apert syndrome progression. A systematic search was executed using electronic bibliographic databases including PubMed, EMBASE, ScienceDirect, SciFinder and Web of Science for all studies of gene therapy for Apert syndrome. The primary outcomes measurements vary from protein to gene expressions. According to the findings of included studies, we conclude that the gene therapy using FGF in Apert syndrome was critical in the regulation of suture fusion and patency, occurred via alterations in cellular proliferation. The superior outcome could be brought by biological therapies targeting the FGF/FGFR signalling. More studies in molecular genetics in Apert syndrome are recommended. This study reviews the current literature and provides insights to future possibilities of genetic therapy as intervention in Apert syndrome.

Intracranial Volume Measured and Correlated to Cephalic Index in Syndromic and Nonsyndromic Anterior Brachycephaly.

Premature fusion of both coronal sutures (anterior brachycephaly) alters skull shape and potentially affects intracranial volume (ICV). Currently little is known about preoperative ICV in anterior brachycephaly. Aim is to measure preoperative ICV and compare this with normative data. Additionally, ICV will be correlated to most used clinical method of quantification: cephalic index (CI). Preoperative patients with anterior brachycephaly (age, ≤12 months) were included and categorized by syndrome (when present). Computed tomography scans were used for ICV measurement by manual segmentation (OsiriX (Fondation OsiriX, Geneva, Switzerland)). Intracranial volume of each subgroup was compared with Lichtenberg normative cranial volume growth curves for controls. Cephalic index was calculated and correlated to ICV using Pearson correlation coefficient. Thirty-four patients with both syndromic and nonsyndromic anterior brachycephaly were included: 17 with Apert syndrome, 6 with Muenke syndrome, 5 with Saethre Chotzen syndrome, 3 with Crouzon, 1 with craniofrontonasal dysplasia, and 2 nonsyndromal. Mean age at preoperative computed tomography scan was 4 months (1-10 months). Mean ICV was 847.31 cm3 (473.91-1459.22 cm3). Nineteen of 34 patients had skull volumes between ±2 SD curves of Lichtenberg, none of the patients had an ICV smaller than -2 SD and 15 of 34 had an ICV larger than +2 SD. Mean ICV in Apert syndrome was 829.85 cm3 (473.91-1061.53 cm3), in Muenke syndrome 942.06 cm3 (768.02-1136.75 cm3), in Saethre Chotzen syndrome 779.72 cm3 (609.21-1002.95 cm3), in Crouzon syndrome 700.57 cm3 (652.31-784.32 cm3), in craniofrontonasal dysplasia 738.97 cm3, and in the nonsyndromal group 1154.64 cm3 (850.07-1459.22 cm3). Apert had a mean greater than +2SD above the mean, the other subgroups had a mean within normal ranges (±2 SD). Correlation between severity of brachycephaly and overall ICV was low (r = 0.42). Mean preoperative ICV in both syndromic and nonsyndromic anterior brachycephaly was 847.31 cm3. Intracranial volume in anterior brachycephaly is in 55.9% between normal ranges (±2 SD). In 44.1% ICV was greater than +2 SD, especially in Apert syndrome (11/16 Apert patients). None of the included patients had a deviant small ICV of less than -2 SD. Additionally, low correlation between ICV and CI (r = 0.42) was found and therefore CI is not suitable for estimating ICV in anterior brachycephaly.

Supratentorial vs infratentorial posterior calvarial distraction osteogenesis for the increase of ICV in children with syndromic or multi-suture craniosynostosis: a retrospective cohort study

PurposeCraniosynostosis is the premature and pathological fusion of calvarial sutures. One modality of surgical treatment of syndromic craniosynostosis is posterior calvarial distraction (PCD). This can be either supratentorial or infratentorial. Currently, supratentorial PCD may be regarded as safer but produces a smaller increase in calvarial volume compared to infratentorial PCD. This study quantifies and compares the effectiveness of supratentorial and infratentorial PCD to help guide surgical decision-making.MethodsThe CT and/or MRI scans of 47 cases of craniosynostosis who underwent PCD from the Birmingham Children’s Hospital (BCH) were converted to sagittal series multi-planar reformatted (MPR) scans for the manual calculation of ICV. The 47 cases were classified as having undergone either supratentorial or infratentorial PCD using lateral plain film radiographs, with 28 and 32 pairs of pre- and post-operative CT/MRI scans reviewed respectively.ResultsA statistically significant difference between supratentorial and infratentorial PCD was observed for the increase in supratentorial volume (STV) (P = 0.0458) and total intracranial volume (TICV) (P = 0.0437), but not for the increase in infratentorial volume (ITV) (P = 0.0697). The relationship for each volume trended towards convergence but was not achieved before the physical limit of 30 mm distraction had been reached. Intraclass correlation coefficient values for agreement of MRI and CT scans for STV, ITV and total ICV were 0.852, 0.864 and 0.854 respectively.ConclusionOur evidence suggests that supratentorial PCD is more effective for increasing ICV in a clinical setting. CT and MRI imaging modalities are acceptably clinically interchangeable for calculating ICV in craniosynostosis.

Anthropometric changes in the skull base in children with sagittal craniosynostosis submitted to surgical correction.

Studies have examined the impact of fusion of the sagittal suture in the skull base while others have evaluated the growth of the skull base before and after surgery. This study aims to perform the anthropometric measures of the skull base in children with scaphocephaly to evaluate the influence of surgical repair in the remodeling of the skull base and anthropometric measures. Twenty-one children with diagnosis of scaphocephaly were operated between April 2007 and October 2008, and anthropometric measures at the skull base were performed before and after a year of surgery. The measures were the cranial index (CI), distance between the crista galli and tuberculum sellar (CG-TS), distance between the crista galli and the internal auditory meatus (CG-IAM), distance between the oval foramen (OF-OF), distance between the internal auditory meatus (IAM-IAM), the angle of the skull base (Â1), and the angle between the nasion, center of sella, and basion (Â2). There was a normalization of the CI in all children, confirming an appropriate cranial remodeling. The CG-TS measure evaluated the anterior skull base, with proportional growth of 12.5%. The mediolateral growth was observed by the increase of OF-OF measures by 8.5% and IAM-IAM by 9.5%. The CG-TS measure grew by 7.2%. There was no statistical difference in the angles analyzed. Surgical treatment of scaphocephaly led to remodeling of the skull base, confirmed by the changes of anthropometric measures taken before and after a year of surgery.

Emissary veins and pericerebral cerebrospinal fluid in trigonocephaly: do they define a specific subtype?

The premature fusion of the metopic suture may be associated with the presence of emissary veins (EV) and abnormally large pericerebral cerebrospinal fluid (CSF) spaces which suggest an associated focal disturbance in CSF dynamics. The incidence of such findings and their potential significance in terms of management of the disease have not been fully elucidated. The aim of this study is to investigate whether these phenomena identify specific subtypes of trigonocephaly. In such a direction, we evaluated the volume of the pericerebral CSF spaces and their relationship to the morphology ("Ω," "V," or flat type) of the prematurely fused metopic suture and to the value of the interfrontal angle value on the grounds of computed tomographic (CT) scan examinations. The preoperative brain CT scans of 74 children (52 boys, 22 girls) with trigonocephaly who had undergone fronto-orbital remodeling were evaluated. The volume of the pericerebral CSF spaces and the value of the interfrontal angle were calculated. The type of intracranial notch was studied and classified according to its shape on the preoperative CT scan: a groove "Ω," a ridge/"V" ridge or absent when flat and evidence of emissary veins related to the abnormally fused suture. Preoperatively, an endocranial metopic groove or ridge was seen in 70% of the children. Emissary veins were identified in 34 of 74 patients (45%), at a mean distance of 2.04 cm (1.18-2.94 cm) from the nasion. The presence of large pericerebral CSF spaces significantly correlated with the presence of EV (p < 0.05), with the "Ω" type (p < 0.05) and with interfrontal angles under 134° (p < 0.005). Metopic suture early fusion shows an association between EV, pericerebral CSF spaces, and the "Ω" groove appearance of the suture. This association identifies a specific subgroup in which the presence of emissary veins and large pericerebral CSF spaces is an indicator of local venous hypertension due to the sagittal sinus constriction within an osseous groove created by the abnormal suture fusion process. The implications for the surgical management and long-term results as compared to trigonocephalic children with small or absent normal peripheral spaces and EV are still to be determined.

Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis

Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1+/- mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.

Síndrome de Pfeiffer tipo 2: relato de um caso

OBJECTIVE: Report a rare case of Pfeiffer’s syndrome type 2 in a male newborn. CASE REPORT: Newborn male, preterm term of 33 weeks and 2 days, serial ultrasound suggesting presence of craniosynostosis and other abnormalities such as irregular and narrow vertebrae, pachygium, and ventriculomegaly in the second trimester, being confirmed later with magnetic resonance imaging. There was no need for obstetrical medications and maneuvers for the birth. Apgar score 4, heart rate less than 100bpm, precarious respiratory evolution, orotracheal intubation, umbilical venous catheterization and orogastric tube were required. With 2 hours of life presented bradycardia along with hemodynamic instability evolved to a cardiorespiratory arrest with no success in cardiopulmonary resuscitation. He passed away 3 hours after birth. COMMENTS: Pfeiffer’s syndrome is rare, being type 2 the most lethal because it has a clover-shaped skull. It is associated with the genetic mutations in fibroblast growth receptors FGFR1, FGFR2, and FGFR3. Premature fusion of the cranial sutures prevents normal skull growth by interfering with the shape of the face and head. The prognosis is associated with the severity of the anomalies and the early diagnosis through the gestational and family history, through detailed physical examinations and images (three-dimensional ultrasonography and MRI). The patient should have multidisciplinary treatment at birth.

Neuro-Ophthalmological Manifestations of Craniosynostosis: Current Perspectives.

Craniosynostosis, a premature fusion of cranial sutures that can be isolated or syndromic, is a congenital defect with a broad, multisystem clinical spectrum. The visual pathway is prone to derangements in patients with craniosynostosis, particularly in syndromic cases, and there is a risk for permanent vision loss when ocular disease complications are not identified and properly treated early in life. Extensive advancements have been made in our understanding of the etiologies underlying vision loss in craniosynostosis over the last 20 years. Children with craniosynostosis are susceptible to interruptions in visual input arising from strabismus, refractive errors, and corneal damage; any of these aberrations can result in understimulation of the visual cortex during childhood neurodevelopment and permanent amblyopia. Elevated intracranial pressure resulting from abnormal cranial shape or volume can lead to papilledema and, ultimately, optic atrophy and vision loss. A pediatric ophthalmologist is a crucial component of the multidisciplinary care team that should be involved in the care of craniosynostosis patients and consistent ophthalmologic follow-up can help minimize the risk to vision posed by such entities as papilledema and amblyopia. This article aims to review the current understanding of neuro-ophthalmological manifestations in craniosynostosis and explore diagnostic and management considerations for the ophthalmologist taking care of these patients.

Midpalatal suture density ratio: Assessing the predictive power of a novel predictor of skeletal response to maxillary expansion

Rapid maxillary expansion (RME) is a common orthodontic treatment to correct maxillary transverse deficiency; however, the inability to determine the precise timing of fusion of the midpalatal suture creates difficulty for clinicians to prescribe the appropriate treatment, surgical or nonsurgical expansion. The purpose of this study was to assess the predictive power of the midpalatal suture density ratio (MPSD) for a skeletal response to RME. Pre- and posttreatment cone-beam computed tomography scans were obtained from 78 orthodontic patients aged from 8 to 18years treated with RME. MPSDs were calculated from pretreatment scans, and a prediction was made for the amount of skeletal expansion obtained at the level of the palate after comprehensive orthodontic treatment. Predicted values were compared with actual outcomes as assessed from posttreatment scans, followed by regression analyses to investigate correlations between MPSD and skeletal expansion and equivalence testing to analyze the performance of the predicted measurements. The MPSDs were not statistically significantly (P>0.05) correlated with the amount of skeletal expansion achieved. In addition, the predicted skeletal expansion using MPSD was not statistically equivalent to the skeletal expansion achieved using an equivalence margin of ±0.05. The results suggest that the MPSD obtained from pretreatment cone-beam computed tomography scans were not correlated well enough with the amount of skeletal expansion achieved to be an effective predictor of the amount of long-term skeletal expansion after RME.

Resident Commentary: Is There a Significant Difference in Relapse and Complication Rate of Surgically Assisted Rapid Palatal Expansion Using Tooth-Borne, Bone-Borne, and Orthodontic Mini-Implant-Borne Appliances (Ploder et al, 2020)?

Resident Commentary: Is There a Significant Difference in Relapse and Complication Rate of Surgically Assisted Rapid Palatal Expansion Using Tooth-Borne, Bone-Borne, and Orthodontic Mini-Implant-Borne Appliances (Ploder et al, 2020)?

Determination of age from the cadaver’s skull–evidence from a cross-sectional study from central India

Introduction: Cranial suture closure is one trait that has been used since the 16th century for age estimation after the 2nd decade of life. To determine the pattern of cranial vault suture closure in relation to age among dead bodies of subjects (3rd to 5th decades of life) and identify any relationship between progression of the union of cranial suture and age. Materials and Methods: We conducted a cross-sectional observational study from January 2016 to June 2017 involving 500 cadavers. Cadavers were studied for ectocranial and endocranial closure pattern for sagittal-coronal and lambdoid sutures. Spearman coefficient was utilized to assess the correlation between the age of the subject and the stage of fusion of cranial sutures. Results: We noted that the process of endocranial fusion of cranial suture was more regular than ectocranial. The coronal suture was the first to fuse. Conclusion: No definite correlation was found to exist between age and suture closures. Keywords: Age, Skull, Cadaver, India.

Craniosynostosis

Craniosynostosis is a condition of one or more of the fibrous sutures in an infant skull prematurely fuses by turning into bone (ossification).1 Premature fusion of cranial sutures may have an effect on cranial shape an less frequently on brain growth.2 There is a changing in the growth pattern of the skull and the skull can’t expand perpendicular to the fused suture, craniosynostosis can lead to abnormal head shape and abnormal facial features and results in increased intracranial pressure leading possibly to visual difficulty, sleeping impairment, eating problem, or impaired mental status with a significant reduction in IQ. Keywords: Preterm labor, IUGR, Hydrocephalus, Fetal anomalies, Increase intracranial pressure.

Assessing ontogenetic maturity in extinct saurian reptiles.

Morphology forms the most fundamental level of data in vertebrate palaeontology because it is through interpretations of morphology that taxa are identified, creating the basis for broad evolutionary and palaeobiological hypotheses. Assessing maturity is one of the most basic aspects of morphological interpretation and provides the means to study the evolution of ontogenetic changes, population structure and palaeoecology, life-history strategies, and heterochrony along evolutionary lineages that would otherwise be lost to time. Saurian reptiles (the least-inclusive clade containing Lepidosauria and Archosauria) have remained an incredibly diverse, numerous, and disparate clade through their ~260-million-year history. Because of the great disparity in this group, assessing maturity of saurian reptiles is difficult, fraught with methodological and terminological ambiguity. We compiled a novel database of literature, assembling >900 individual instances of saurian maturity assessment, to examine critically how saurian maturity has been diagnosed. We review the often inexact and inconsistent terminology used in saurian maturity assessment (e.g. 'juvenile', 'mature') and provide routes for better clarity and cross-study coherence. We describe the various methods that have been used to assess maturity in every major saurian group, integrating data from both extant and extinct taxa to give a full account of the current state of the field and providing method-specific pitfalls, best practices, and fruitful directions for future research. We recommend that a new standard subsection, 'Ontogenetic Assessment', be added to the Systematic Palaeontology portions of descriptive studies to provide explicit ontogenetic diagnoses with clear criteria. Because the utility of different ontogenetic criteria is highly subclade dependent among saurians, even for widely used methods (e.g. neurocentral suture fusion), we recommend that phylogenetic context, preferably in the form of a phylogenetic bracket, be used to justify the use of a maturity assessment method. Different methods should be used in conjunction as independent lines of evidence when assessing maturity, instead of an ontogenetic diagnosis resting entirely on a single criterion, which is common in the literature. Critically, there is a need for data from extant taxa with well-represented growth series to be integrated with the fossil record to ground maturity assessments of extinct taxa in well-constrained, empirically tested methods.

Pharmacological targeting of KDM6A and KDM6B, as a novel therapeutic strategy for treating craniosynostosis in Saethre-Chotzen syndrome

BackgroundDuring development, excessive osteogenic differentiation of mesenchymal progenitor cells (MPC) within the cranial sutures can lead to premature suture fusion or craniosynostosis, leading to craniofacial and cognitive issues. Saethre-Chotzen syndrome (SCS) is a common form of craniosynostosis, caused by TWIST-1 gene mutations. Currently, the only treatment option for craniosynostosis involves multiple invasive cranial surgeries, which can lead to serious complications.MethodsThe present study utilized Twist-1 haploinsufficient (Twist-1del/+) mice as SCS mouse model to investigate the inhibition of Kdm6a and Kdm6b activity using the pharmacological inhibitor, GSK-J4, on calvarial cell osteogenic potential.ResultsThis study showed that the histone methyltransferase EZH2, an osteogenesis inhibitor, is downregulated in calvarial cells derived from Twist-1del/+ mice, whereas the counter histone demethylases, Kdm6a and Kdm6b, known promoters of osteogenesis, were upregulated. In vitro studies confirmed that siRNA-mediated inhibition of Kdm6a and Kdm6b expression suppressed osteogenic differentiation of Twist-1del/+ calvarial cells. Moreover, pharmacological targeting of Kdm6a and Kdm6b activity, with the inhibitor, GSK-J4, caused a dose-dependent suppression of osteogenic differentiation by Twist-1del/+ calvarial cells in vitro and reduced mineralized bone formation in Twist-1del/+ calvarial explant cultures. Chromatin immunoprecipitation and Western blot analyses found that GSK-J4 treatment elevated the levels of the Kdm6a and Kdm6b epigenetic target, the repressive mark of tri-methylated lysine 27 on histone 3, on osteogenic genes leading to repression of Runx2 and Alkaline Phosphatase expression. Pre-clinical in vivo studies showed that local administration of GSK-J4 to the calvaria of Twist-1del/+ mice prevented premature suture fusion and kept the sutures open up to postnatal day 20.ConclusionThe inhibition of Kdm6a and Kdm6b activity by GSK-J4 could be used as a potential non-invasive therapeutic strategy for preventing craniosynostosis in children with SCS.Graphical abstractPharmacological targeting of Kdm6a/b activity can alleviate craniosynostosis in Saethre-Chotzen syndrome. Aberrant osteogenesis by Twist-1 mutant cranial suture mesenchymal progenitor cells occurs via deregulation of epigenetic modifiers Ezh2 and Kdm6a/Kdm6b. Suppression of Kdm6a- and Kdm6b-mediated osteogenesis with GSK-J4 inhibitor can prevent prefusion of cranial sutures.

A Pilot Study of Identification Genetic Background of Craniosynostosis Cases.

The early fusion of the cranial sutures was described as a craniosynostosis. The early diagnosis and management of craniosynostosis is very important. Environmental factors and genetic abnormalities plays a key role during the development of craniosynostosis. Syndromic craniosynostosis cases are related with autosomal dominant disorders but nearly half of the affected cases carry a new mutation. In this study, in order to identify the genetic etiology of craniosynostosis the authors analyzed 20 craniosynostosis patients by using conventional karyotype, aCGH, sanger sequencing, next generation sequencing (NGS) and Multiplex ligation-dependent probe amplification (MLPA) techniques. The authors identified mutations on FGFR2 and FGFR3 genes which were associated with Muenke syndrome, Crouzon syndrome and skeletal dysplasia syndromes. NGS applied all of the cases and 7 clinical variations in 5 different gene were detected in %20 of cases. In addition to these abnormalities; del(11)(q14.1q22.2), del(17)(q21.31), dup(22)(q13.31) and t(2;16)(q37;p13) have been identified in our cohort which are not previously detected in craniosynostosis cases. Our study demonstrates the importance of detailed genetic analysis for the diagnosis, progression and management of the craniosynostosis.

Analysis of Cranial Base Suture Fusion Patterns.

It is known from both anatomic and radiographic studies that the majority of cranial sutures begin fusing in early adulthood and are fused by late adulthood. However, most of the studies focus on the cranial vault rather than the cranial base. Most clinicians treating patients with craniosynostosis are interpreting the behavior of cranial sutures on CT imaging. Therefore, the purpose of this study was to further clarify the radiographic appearance of cranial base sutures over the natural human life span. Thirty CT scans of the head and face were reviewed for each decade starting at 1 year of life up to age 90. Scans were evaluated for the appearance of the occipitomastoid, petrosoocciptial, sphenosquamous, sphenopetrosal, frontosphenoidal, sphenozygomatic, petrososquamosal, frontoethmoidal, sphenoethmoidal and sphenoccipital sutures. Sutures were categorized as obliterated, present with fusion, present without fusion and unable to visualize. The majority of cranial base sutures are visible up through the eighth decade, although evidence of ossification across the suture starts as early as the second decade. Some sutures such as the occipitomastoid appeared > 90% open even as late as the ninth decade. Other sutures such as the sphenosquamosal and frontozygomatic are mostly fused by that age. Cranial base sutures appear to behave radiographically similar, to the cranial vault sutures in that they largely remain visible throughout adulthood but show varying amounts of ossification. There are some cranial base sutures which appear to remain open throughout life although the significance of this has yet to be determined.