Quantitative Morphologic Analysis of Cranial Vault in Twist1+/- Mice: Implications in Craniosynostosis.

BACKGROUND: The haploinsufficiency in the TWIST1 gene encoding a basic helix-loop-helix transcription factor is a cause of one of the craniosynostosis syndromes, Saethre-Chotzen syndrome. Patients with craniosynostosis usually require operative release of affected sutures, which makes it difficult to observe the long-term consequence of suture fusion on craniofacial growth. METHODS: In this study, we performed quantitative analysis of morphologic changes of the skull in Twist1 heterozygously-deleted mice (Twist1+/-) with micro-computed tomographic images. RESULTS: In Twist1+/- mice, fusion of the coronal suture began before postnatal day 14 and progressed until postnatal day 56, during which morphologic changes occurred. The growth of the skull was not achieved by a constant increase in the measured distances in wild type mice; some distances in the top-basal axis were decreased during the observation period. In the Twist1+/- mouse, growth in the top-basal axis was accelerated and that of the frontal cranium was reduced. In the unicoronal suture fusion mouse, the length of the zygomatic arch of affected side was shorter in the Twist1+/- mouse. In one postnatal day 56 Twist1+/- mouse with bilateral coronal suture fusion, asymmetric zygomatic arch length was identified. CONCLUSION: The authors'results suggest that measuring the length of the left and right zygomatic arches may be useful for early diagnosis of coronal suture fusion and for estimation of the timing of synostosis, and that more detailed study on the growth pattern of the normal and the synostosed skull could provide prediction of the risk of resynostosis. CLINICAL RELEVANCE STATEMENT: The data from this study can be useful to better understand the cranial growth pattern in patients with craniosynostosis.

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.

Prmt1 regulates craniofacial bone formation upstream of Msx1.

Protein arginine methylation has been recently identified as an important form of post-translational modification (PTM). It is carried out by the protein arginine methyltransferase (PRMT) family of enzymes, which in mammals consists of nine members. Among them, PRMT1 is the major arginine methyltransferase and participates in transcription, signal transduction, development and cancer. The function of PRMT1 in craniofacial development remains unclear. We generated Wnt1-Cre;Prmt1fl/fl mice with cranial neural crest (CNC)-specific deletion of Prmt1 and compared CNC-derived craniofacial bones from newborn control and Wnt1-Cre;Prmt1fl/fl mice. The size, surface area and volume of the premaxilla, maxilla, palatine bone, frontal bone, and mandible were analyzed using three-dimensional (3D) micro-computed tomography (microCT). We found that Prmt1 deficiency led to alterations in craniofacial bones including the premaxilla, maxilla, palatine bone, frontal bone, and mandible, as well as defects in the incisor and alveolar bone, recapitulating changes seen in Msx1-deficient mice. We further determined that Prmt1 depletion resulted in significant downregulation of Msx1 in calvaria-derived preosteoblast and primordium of frontal bone and mandible. Our study reveals critical roles of PRMT1 in the formation of CNC-derived craniofacial bones and suggests that Prmt1 is an upstream regulator of Msx1 in craniofacial bone development.

Recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB for localized bone regeneration. Histologic and radiographic outcomes of a rabbit study.

OBJECTIVES: Improvement in localized bone regeneration is needed to avoid the use of autogenous tissue. For that purpose, the use biologic mediators was proposed. The aim was to test whether or not one of two biologic mediators, recombinant human bone morphogenetic protein-2 (rhBMP-2) or recombinant platelet-derived growth factor (rhPDGF-BB), is superior to the other and to control groups for localized bone regeneration. MATERIALS AND METHODS: Four cylinders (height: 5 mm; diameter: 7 mm) were screwed on the parietal and frontal bones at the cranium in 12 rabbits. The cylinders either received (i) deproteinized bovine bone mineral (DBBM) mixed rhBMP-2 (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB (DBBM/PDGF), (iii) DBBM (DBBM), and (iv) empty control (control). Rabbits were euthanized at 2 and 8 weeks (n = 6, respectively). Conventional histomorphometric and micro-CT analyses were performed. Parametric linear mixed models were applied for the analyses with Bonferroni correction for the multiple group comparisons. RESULTS: The area of bone regeneration (histology; AAHisto ) at 2 weeks peaked for DBBM (41.91%) with statistically significantly greater values compared to DBBM/PDGF and the control group (P < 0.05). At 8 weeks, mean AAHisto values were 96.29% (DBBM/BMP-2), 46.37% (DBBM/PDFG), 39.66% (DBBM), and 35.98% (control) (DBBM/BMP-2 vs. all groups (P < 0.05)). At 8 weeks, bone regeneration was greatest for DBBM/BMP-2 (35.62%) with statistically significant differences compared to all other groups (P < 0.05). The area of bone regeneration (micro-CT; AAm-CT ) at 2 weeks amounted to 43.87% (DBBM/BMP-2), 42.81% (DBBM/PDFG), 48.71% (DBBM), and 0.96% (control). The control group demonstrated statistically significantly less AAm-CT compared to all groups (P < 0.05). At 8 weeks, mean AAm-CT values were 63.65% (DBBM/BMP-2), 50.21% (DBBM/PDFG), 44.81% (DBBM), and 4.57% (control) (P > 0.05). CONCLUSIONS: The use of rhBMP-2 significantly enhanced bone regeneration compared to all other groups including the group with rhPDGF-BB.

The Morphogenesis of Cranial Sutures in Zebrafish.

Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone. Parietal and frontal bones are formed by intramembranous ossification within a layer of mesenchyme positioned between the dermal mesenchyme and meninges surrounding the brain. The supraoccipital bone has an endochondral origin. Cranial bones are separated by connective tissue with a distinctive architecture of osteogenic cells and collagen fibrils. Here we show RNA in situ hybridization for col1a1a, col2a1a, col10a1, bglap/osteocalcin, fgfr1a, fgfr1b, fgfr2, fgfr3, foxq1, twist2, twist3, runx2a, runx2b, sp7/osterix, and spp1/ osteopontin, indicating that the expression of genes involved in suture development in mammals is preserved in zebrafish. We also present methods for examining the cranium and its sutures, which permit the study of the mechanisms involved in suture patency as well as their pathological obliteration. The model we develop has implications for the study of human disorders, including craniosynostosis, which affects 1 in 2,500 live births.

A 3D morphometric follow-up analysis after frontoorbital advancement in non-syndromic craniosynostosis.

OBJECTIVE: Frontoorbital advancement (FOA) in patients with non-syndromic craniosynostosis mainly addresses the aesthetic and functional correction of the frontoorbital region. To help define the operative strategy and any follow-up assessments after surgical correction, objective parameters describing the critical regions of skull deformity are essential. Based on 3D morphometric analysis, new parameters for the documentation of changes of the frontoorbital bandeau were developed in a prospective study. METHODS AND MATERIALS: In a prospective series, 13 children with non-syndromic craniosynostosis (seven metopic, four unilateral coronal, and two bilateral coronal) treated with frontoorbital advancement, underwent detailed morphometric and volumetric evaluation using a 3D light optical scan system (3D-Shape, Erlangen, Germany). Measurements were obtained preoperatively and at 3, 6 and 12 months postoperatively with newly developed parameters generated by cephalometric analysis software (Onyx Ceph, Image Instruments, Chemnitz, Germany). RESULTS: In most patients, frontoorbital advancement resulted in stable long-term results without growth inhibition and with normalization or improvement of ongoing skull development. The mean frontal angle was 145° and the frontoparietal angle 137-140°. The cephalic index was normalized or markedly improved. Head circumference and head height increased significantly (p = 0.001 and p = 0.002, respectively). These changes were confirmed in all postoperative measurements. CONCLUSION: During the 12-month follow-up period all angle parameters proved to be stable and no major impairment of normal skull growth was observed after FOA. The frontoorbital angle is a useful parameter in evaluating long-term outcome. The frontoparietal angle is important for the stability of the frontoparietal region, in which a certain growth inhibition may be observed postoperatively.

Long-term morphological outcomes in nonsyndromic sagittal craniosynostosis: a comparison of 2 techniques.

Correction of scaphocephaly is one of the principle goals of surgery in sagittal craniosynostosis. Reported relapse in head shape after surgery and continued head growth into late adolescence underscores the need for long-term outcomes to be considered when comparing between different surgical approaches in this condition; yet there are relatively few reports of results to 5 years and beyond in the literature. Therefore, a retrospective review was performed of the anthropometric data of 224 patients with sagittal craniosynostosis who underwent primary surgery between 1994 and 2012. During this period, patients underwent either a modified strip craniectomy (MSC) or calvarial remodeling (CR) procedure. Sixty-two patients were treated by MSC and followed up for a mean of 44 months. One hundred sixty-two patients had CR, with follow-up for a mean of 45 months. Overall, 90 patients were seen up to 5 years, and 47 patients to 9 years or more after surgery. The cephalic index (CI) of MSC-treated patients improved from a mean of 67.0 to 72.7, with 31% achieving a CI greater than 75 at one year. Calvarial remodeling was significantly more effective at correcting the scaphocephalic deformity. Patients treated with CR improved from a mean CI of 66.7 to 76.1. Sixty-two percent of the patients achieved a CI greater than 75. In both groups, outcomes were stable throughout follow-up with no significant relapse up to 14 years after surgery.

Developmental changes in the skull morphology of common minke whales Balaenoptera acutorostrata.

We investigated growth-related and sex-related morphological changes in the skulls of 144 North Pacific common minke whales Balaenoptera acutorostrata. Measurement was conducted at 39 points on the skull and mandible to extract individual allometric equations relating the length and zygomatic width of the skull. The results revealed no significant differences in skull morphology by sex except for width of occipital bone. The size relative to the skull of the anatomical parts involved in feeding, such as the rostrum and mandible, increased after birth. In contrast, the sensory organs and the anatomical regions involved in neurological function, such as the orbit, tympanic bullae, and foramen magnum, were fully developed at birth, and their relative size reduced over the course of development. This is the first study to investigate developmental changes in the skull morphology using more than 100 baleen whale specimens, and we believe the results of this study will contribute greatly to multiple areas of baleen whale research, including taxonomy and paleontology.

The assessment of relationship between the skull base development and the severity of frontal plagiocephaly after bilateral fronto-orbital advancement in the early life.

PURPOSE: The deformation of the skull base in patients with unilateral frontal plagiocephaly (UFP) is well known, but the mechanism is not still clear. We analyzed the skull base in the patients with UFP who underwent fronto-orbital advancement (FOA) in the early life during the last decade. METHODS: We assessed the treatment results and outcome of FOA performed in six patients, four girls and two boys younger than 2 years, in the last decade. Also, the basal cranium's angles were measured by 3D reconstruction images on computed tomography (CT) scan. RESULTS: The mean patients' age at FOAs was 11 months. Two cases were classified as grade 2A, two cases as grade 2B, and two cases as grade 3 (the classification of Di Rocco and Velardi). The ethmoidal axis was deviated a mean of 8.2° to the affected side. The mean angle between the petrosal pyramids and the midline (anterior-petrosal-sagittal angle, APSA) was 75.3° on the affected side and 66.2° on the normal side. The mean difference of APSA was 9.2°. On the follow-up CT images 5 years after surgery, the deviations of the ethmoidal axis clearly decreased, 5.7°, but the differences of APSA did not change, 8.8°. CONCLUSIONS: The midline distortion of anterior skull base should be considered to be spontaneously corrected during the follow-up periods in patients with all types of UFP who underwent FOA, unlike posterior skull base in the patients with grades 2B and 3 classification.

Normal fusion of the metopic suture.

There is some uncertainty as to when normal fusion of the metopic suture occurs. Existing studies have included relatively small numbers and have not used a statistical model to represent any variation in normality. In this study, a total of 337 head computed tomographic scans performed between 2006 and 2009 were retrospectively reviewed after strict exclusion criteria were met. Only patients aged younger than 18 months were included. Assessment was performed by analyzing axial slices of the bony window of the computed tomographic scan by 2 independent investigators. Two separate probit analyses were carried out to estimate the proportion of patients in whom the fusion process would have started and completed. Of 337 patients, 204 (60.5%) were male and 133 were female (39.5%). All patients older than 15 months and 23 days had completely fused metopic sutures. The estimated median age for the start of the fusion process was 4.96 months (95% confidence interval, 3.54-6.76 months), and the estimated median age for the completion of fusion was 8.24 months (95% confidence interval, 7.37-9.22 months). The fusion process completed between 2.05 and 14.43 months of age in 95% of the normal population. The difference between sexes was not significant. In conclusion, there was wide variation in the timing of normal fusion that can complete as early as 2 months of age.

Real-time monitoring of the growth of the nasal septal cartilage and the nasofrontal suture.

INTRODUCTION: The nasal septum is thought to be a primary growth cartilage for the midface and, as such, has been implicated in syndromes involving midfacial hypoplasia. However, this internal structure is difficult to study directly. The aims of this study were to provide direct, continuous measurements of the growth of the nasal septal cartilage and to compare these with similar measurements of the nasofrontal suture to test whether the growth of the cartilage precedes the growth of the suture and whether the growth of the septal cartilage is constant or episodic. METHODS: Ten Hanford minipigs were used. Linear displacement transducers were implanted surgically in the septal cartilage and across the nasofrontal suture. Length measurements of the cartilage and suture were recorded telemetrically each minute for several days. RESULTS: The growth rate of the nasal septal cartilage (0.07% ± 0.03% length/h) was significantly higher than that of the suture (0.03% ± 0.02% length/h) (P = 0.004). The growth of both structures was episodic with alternating periods of growth (5-6 per day) and periods of stasis or shrinkage. No diurnal variation in growth of the cartilage was detected. CONCLUSIONS: These results are consistent with the notion that growth of the septal cartilage might drive growth of the nasofrontal suture. Growth of the midface is episodic rather than constant.

Long follow-up of cranofacial cleft treated by the folded vascularized calvarial bone.

Craniofacial clefts are relatively rare. Tessier proposed a classification of craniofacial clefts. A Tessier no. 10 cranial facial defect is very rare. There are few reports regarding the reconstruction of the orbital rim and roof of a Tessier number 10 cleft. In this paper, we present the reconstruction of the orbital rim and roof by a folded vascularized calvarial bone and the long-term follow-up results.

Biphasic fusion of the murine posterior frontal suture.

BACKGROUND: Craniosynostosis is the premature fusion of cranial sutures early in development. Mice are commonly used to study the mechanisms driving both normal and pathologic cranial suture development. Despite their frequency of use as a model, the time course of bone formation and mineralization during fusion of mouse posterior frontal suture is not well defined. METHODS: To address this, C57Bl/6J mice were euthanized at ages ranging from 6 to 107 days, and the posterior frontal sutures were imaged using micro-computed tomography. Scans were analyzed with an image-processing algorithm that was previously validated with serial histology to quantify both suture fusion and mineral content. The expression profile of genes associated with key developmental time points was examined using real-time polymerase chain reaction in both the bone and the dura. RESULTS: Results demonstrate that the bones of the posterior frontal suture come together during days 10 to 20 and then increase in mineral content and volume between days 21 and 45. The onset of posterior frontal suture fusion was associated with an increase in cartilage-associated genes on day 12. Later mineralization of the suture was associated with an increase in mRNAs for osteoblast differentiation markers, bone morphogenetic proteins, and bone morphogenetic protein inhibitors. CONCLUSIONS: Complete analysis fusion posterior frontal suture shows that it occurs in a discontinuous biphasic manner. The first phase is from days 10 to 20 and involves production of cartilage. A second mineralization phase from days 21 to 45 was seen with both the imaging algorithm and changes in gene expression.

Female adolescent craniofacial growth spurts: real or fiction?

The purpose of the study is to determine whether the various aspects of the craniofacial complex exhibit female adolescent growth spurts. Multilevel polynomial models were used to estimate the growth curves of a mixed-longitudinal sample of 111 untreated females 10-15 years of age. To evaluate the horizontal and vertical movements of the individual landmarks relative to stable structures, the tracings were superimposed on the natural reference structures in the anterior cranial base. The horizontal and vertical growth changes of four landmarks and the changes of three traditional linear measurements were evaluated. Posterior nasal spine (PNS) moved posteriorly at a constant rate of approximately 0.12mm/year. Five measures showed changes in growth velocity (i.e. quadratic growth curves) but not adolescent growth spurts, including the anterior movements of anterior nasal spine (ANS) and pogonion (Pg), the inferior movements of gonion (Go), and the increases in ANS-PNS and condylion to pogonion (Co-Pg). Five measurements, including the inferior movements of ANS, PNS and Pg, the posterior movements of Go, and the increases of Go-Pg exhibited adolescent growth spurts. Peak growth velocities were attained between 11.4 and 12.8 years of age, approximately 0.7-1.4 years earlier in the maxilla than mandible. While the vertical aspects of craniofacial growth exhibit distinct female adolescent growth spurts, with peak rates occurring earlier in the maxilla than mandible, most horizontal aspects of craniofacial growth do not exhibit an adolescent spurt.

Foxc1 controls the growth of the murine frontal bone rudiment by direct regulation of a Bmp response threshold of Msx2.

The mammalian skull vault consists of several intricately patterned bones that grow in close coordination. The growth of these bones depends on the precise regulation of the migration and differentiation of osteogenic cells from undifferentiated precursor cells located above the eye. Here, we demonstrate a role for Foxc1 in modulating the influence of Bmp signaling on the expression of Msx2 and the specification of these cells. Inactivation of Foxc1 results in a dramatic reduction in skull vault growth and causes an expansion of Msx2 expression and Bmp signaling into the area occupied by undifferentiated precursor cells. Foxc1 interacts directly with a Bmp responsive element in an enhancer upstream of Msx2, and acts to reduce the occupancy of P-Smad1/5/8. We propose that Foxc1 sets a threshold for the Bmp-dependent activation of Msx2, thus controlling the differentiation of osteogenic precursor cells and the rate and pattern of calvarial bone development.

Maxillary growth and maturation during infancy and early childhood.

OBJECTIVE: To describe maxillary growth and maturation during infancy and early childhood. MATERIALS AND METHODS: Serial cephalograms (N=210) of 30 subjects (15 females and 15 males) from the Bolton-Brush Growth Study were analyzed. Each subject had a series of six consecutive cephalograms taken between birth and 5 years of age, as well as one adult cephalogram. Twelve maxillary measurements (eight linear and four angular) and seven landmarks were used to characterize maxillary growth. Maturation of the linear measures was described as a percentage of adult status. RESULTS: Maxillary and anterior cranial base size increased in both sexes between 0.4 and 5 years of age. The linear anteroposterior (AP) measures (S-SE, SE-N, ANS-PNS) increased almost as much as the vertical measures (S-PNS, SE-PNS, N-A, N-ANS) over the first 5 years. After 5 years of age there was significantly more vertical than AP growth. The size and shape changes that occurred were greatest between 0.4 and 1 years; yearly velocities decelerated regularly thereafter. Overall linear growth changes that occurred between 0.5 and 5 years of age (a span of 4.5 years) were generally greater than the changes in maxillary growth that occurred between 5 and 16 years (a span of 11 years). The linear measures showed a gradient of maturation, with the AP measures being more mature than the vertical measures. Male maxillae were less mature than female maxillae at every age. CONCLUSIONS: The maxilla undergoes its greatest postnatal growth change during infancy and early childhood, when relative AP growth and maturation are emphasized.

Craniofacial growth in patients with FGFR3Pro250Arg mutation after fronto-orbital advancement in infancy.

BACKGROUND: The facial features of children with FGFR3Pro250Arg mutation (Muenke syndrome) differ from those with the other eponymous craniosynostotic disorders. We documented midfacial growth and position of the forehead after fronto-orbital advancement (FOA) in patients with the FGFR3 mutation. METHODS: We retrospectively reviewed all patients who had an FGFR3Pro250Arg mutation and craniosynostosis. Only patients who had FOA in infancy or early childhood were included. The clinical records were evaluated for type of sutural fusion; midfacial hypoplasia and other clinical data, including age at operation; type of procedures and fixation (wire vs resorbable plate); frequency of frontal readvancement, forehead augmentation, midfacial advancement; and complications. Preoperative and postoperative sagittal orbital-globe relationship was measured by direct anthropometry. Outcome of FOA was graded according to the Whittaker classification as category I, no revision; category II, minor revisions, that is, foreheadplasty; category III, alternative bony work; category IV; redo of initial procedure (ie, secondary FOA). Midfacial position was determined by clinical examination and lateral cephalometry. RESULTS: A total of 21 study patients with Muenke syndrome (8 males and 13 females) were analyzed. The types of craniosynostosis were bilateral coronal (n=15), of which 3 also had concurrent sagittal fusion, and unilateral coronal (n=5). Two patients had early endoscopic suturectomy, but later required FOA. Mean age at FOA was 22.9 months (range, 3-128 months). Secondary FOA was necessary in 40% of patients (n=8), and secondary foreheadplasty in 25% (n=5) of patients. No frontal revisions were needed in the remaining 35% of patients (n=7). Mean age at initial FOA was significantly younger in the group requiring repeat FOA or foreheadplasty compared with patients who did not require revision (P<0.05). Location of synostosis, type of fixation, and bone grafting did not significantly affect the need for revision. Only 30% (n=6) of patients developed midfacial retrusion. CONCLUSIONS: The frequency of frontal revision in patients with Muenke syndrome who had FOA in infancy and early childhood is lower than previously reported. Age at forehead advancement inversely correlated with the incidence of relapse and need for secondary frontal procedures. Midfacial retrusion is relatively uncommon in FGFR3Pro250Arg patients.

A mixed longitudinal anthropometric study of craniofacial growth of Colombian mestizos 6-17 years of age.

The purpose of this study was to evaluate the craniofacial growth of Colombian mestizos. Four age cohorts, including a total of 458 children and adolescents (262 males and 216 females), were included in this mixed-longitudinal study. The cohorts were first measured at ages 6, 9, 12, and 15 and every year thereafter for 3 years. Eight anthropometric measurements were taken, including three cranial (head perimeter, head width, and head length), two craniofacial (maxillary and mandibular length), and three facial (face height, bizygomatic width, and bigonial width). Multilevel analyses showed that all dimensions increased between 6 and 17 years of age. The cranium grew less than the craniofacial, which in turn grew less than the facial dimensions. In addition, vertical dimensions showed more growth than antero-posterior dimensions, which in turn grew more than transverse dimensions. None of the measurement showed statistically significant growth differences between subjects with normal occlusion and Class I or Class II malocclusions. Males were generally larger than females and showed greater growth rates. Except for facial width, whose yearly velocities decreased regularly with age, an adolescent growth spurt was evident for most of the male measurements. Yearly velocities for females followed a simpler decelerating pattern. The results provide reference data for Colombian mestizos, for whom normative data of other ethnic groups are not applicable. While occlusion had little or no effect, there were gender differences, as well as important growth differences between cranial and facial measurements.

Craniofacial growth, maturation, and change: teens to midadulthood.

Despite the attainment of several adult cranial dimensions relatively early in childhood, skeletal maturity and, by consequence, adult form are typically defined by the eruption of the third molars around 17 years of age. This in turn serves as the division between subadults and adults, which is then applied to population studies of biological variation. Specifically, comparative data sets of adult measurements are not directly applied to individuals who do not have complete skeletal growth, as it is believed that the confounding effects of allometry may skew the results. The present study uses geometric morphometrics techniques to investigate the appropriateness of this division with respect to three-dimensional anatomical landmarks. Twenty-six landmarks were collected from a single population of 24 crania partitioned into 4 age groups spanning late adolescence to midadulthood. Generalized Procrustes and multivariate statistical analyses were performed on the landmark data. Results showed no significant morphological differences between the teen and young adult age groups, whereas significant shape and size differences were found in older adults relative to their younger cohorts. Moreover, no growth-related shape variation (ie, allometry) was detected within the sample. These findings suggest that adult form is attained several years earlier than commonly thought and corroborate other research that suggest that subtle changes in cranial morphology continue throughout adulthood.

A novel anthropometric chart for craniofacial surgery.

Various indices and measurements of the growing cranial vault exist, but there is no single head-shape chart specific to craniofacial surgery. The authors have produced a reliable head-shape chart that will enable accurate charting of patients with craniosynostosis both in the preoperative and postoperative period.One thousand eighty-two participants were used to obtain normal anthropometric measurements, specifically the ear-to-ear measurement and the glabella-to-external occipital protuberance measurement. Both male and female participants aged 6 months to 25 years were used to obtain these measurements. These measurements were correlated with the cephalic index as described by Farkas according to the different age groups.A head-shape chart has been created for males and females using the normal ear-to-ear measurements and the cephalic index that define both qualitative and quantitative elements of the growing skull. Craniofacial surgeons may find this chart useful for managing patients with craniosynostosis. This chart is also useful in the assessment of how the skull grows after surgery.