Metopic synostosis: Defining the temporal sequence of normal suture fusion and differentiating it from synostosis on the basis of computed tomography images

Only the metopic suture normally fuses during early childhood; all other cranial sutures normally fuse much later in life. Despite this, metopic synostosis is one of the least common forms of craniosynostosis. The temporal sequence of normal physiologic metopic suture fusion remains undefined and controversial. Therefore, diagnosis of metopic synostosis on the basis of computed tomography images alone can prove misleading. The present study sought to determine the normal sequence of metopic suture fusion and characterize both endocranial and ectocranial suture morphology. An analysis of computed tomography scans of 76 trauma patients, ranging in age from 10 days to 18 months, provided normative craniofacial data that could be compared to similar data obtained from the preoperative computed tomography scans of 30 patients who had undergone surgical treatment for metopic synostosis. Metopic suture fusion was complete by 6 to 8 months in all nonsynostotic patients, with initiation of suture fusion evident as early as 3 months of age. Fusion was found to commence at the nasion, proceed superiorly in progressive fashion, and conclude at the anterior fontanelle. Although an endocranial ridge was not commonly seen in synostotic patients, an endocranial metopic notch was virtually diagnostic of premature suture fusion and was seen in 93 percent of synostotic patients. A metopic notch was not seen in any nonsynostotic patient. The morphologic and normative craniofacial data presented permit diagnosis of metopic synostosis based on computed tomography images obtained beyond the normal fusion period.     

A morphogenetic classification of craniofacial malformations

A new classification of malformations of the face and cranium is proposed, based on embryologic studies and observations concerning a great number of patients seen by the authors. First of all, one should distinguish between cerebral craniofacial (with brain and/or eyes involved) and craniofacial malformations. Craniofacial malformations may be characterized by dysostosis and by synostosis. Malformations with dysostosis may be produced by transformation as well as differentiation defects. Synostosis is always caused by a differentiation defect. A new nomenclature is introduced.     

Solvent-dehydrated calvarial allografts in craniofacial surgery

Craniofacial surgery almost always requires the use of bone grafting. Although autografts are the standard procedure for bone grafting, it is sometimes not possible to harvest bone, and autografts have particular risks. The use of allograft bone provides a reasonable alternative to meet the need for graft material. Solvent dehydration is a multistage procedure in which human cadaveric bone is processed by osmotic exchange baths and gamma sterilization. This processing avoids the risk of infection transmission, decreases antigenicity, and does not weaken the mechanical properties of the bone. Solvent-dehydrated, gamma-irradiated human calvarial bone allografts were used for reconstruction of craniofacial deformities in 24 patients between 1988 and 2002. Resorption of the allografts and results of the surgical intervention were evaluated with plain radiographs and three-dimensional computed tomography 12 months after surgery, in 21 patients. Serologic tests for human immunodeficiency virus-1 antibody, hepatitis B surface antigen, and hepatitis C antigen were also performed. Biopsy specimens were taken from the allografts. Average follow-up in this group was 30 months (range, 8 to 60 months), and results of serologic tests were negative in all patients. Seventy-one percent of the patients (15 of 21) showed no resorption, with partial and complete allograft fusion. One patient had nearly total graft loss and the remaining five patients had 10 to 25 percent graft resorption. Rigid fixation of the allograft, contact with the dura and periosteum, and prevention of dead spaces around the allograft are the most important factors in achieving a satisfactory result. In solvent-dehydrated bone allografts, sterilization and antigenic tissue cleaning are achieved after several steps with a minimal dose of radiation. The result is a nonantigenic, sterile mechanical scaffold that can tolerate external forces. Although autografts are the standard in craniofacial surgery, solvent-dehydrated calvarial bone allografts produced successful results in selected cases.     

Delayed cranial vault reconstruction for sagittal synostosis in older children: an algorithm for tailoring the reconstructive approach to the craniofacial deformity

An algorithm for the management of sagittal synostosis in older children who underwent delayed cranial vault reconstruction is presented. This algorithm tailors the surgical approach to the specific craniofacial deformity present in each case. The scaphocephalic deformity characteristic of sagittal synostosis varies significantly when presentation is delayed beyond the first year of life, the time during which reconstruction is usually performed. Sixteen patients with sagittal synostosis who presented after 12 months of age, and were a mean of 3.2 years of age at the time of cranial vault reconstruction, were reviewed. Four patients demonstrated preoperative symptoms and objective findings indicative of increased intracranial pressure, including frequent headaches and emesis, papilledema, or digital markings on computed tomographic scan. Each of the 16 patients underwent either (1) single-stage total vault reconstruction with or without concomitant fronto-orbital expansion; (2) two-stage total vault reconstruction with anterior two-thirds vault expansion followed by transverse occipital expansion and recession a mean of 8.7 months later; or (3) anterior two-thirds vault reconstruction with or without fronto-orbital expansion. In each case, the extent of the scaphocephalic deformity determined the procedure used. The presence of severe frontal bossing associated with transverse restriction of the orbitotemporal region was an indication for fronto-orbital expansion in addition to vault reconstruction, whereas significant occipital protrusion was an indication for transverse posterior vault expansion and recession in addition to anterior two-thirds vault reconstruction. Excellent aesthetic results were obtained in all cases regardless of the type of reconstruction performed. However, it is essential that the extent of the deformity be carefully evaluated preoperatively to permit selection of the appropriate technique for reconstruction.     

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.     

Three-dimensional cranial surface reconstructions using high-resolution computed tomography

Until recently, there has been no satisfactory way for anthropologists to visualize intracranial morphology in more than two dimensions without actually "invading" the skull in some manner. Images provided by conventional x-ray and computed tomography (CT) scans are often abstract, flat, two-dimensional representations that fail to reveal three-dimensional relationships. We describe new computer-imaging techniques that reconstruct three-dimensional images from sequential series of narrowly collimated (1-2 mm), high-resolution CT scans of the skull. These computed images represent three-dimensional surface data and can be viewed from any direction. Depth information is encoded in gray scale. In addition, selected portions of the anatomy can be "removed", i.e., made transparent, to allow visualization of previously hidden intracranial morphology. Since the geometric data obtained with the CT scanner are precise, parameters such as linear distances, angles, areas, and volumes can be accurately (and instantaneously) generated. The power and versatility of these computer-imaging techniques are demonstrated by examining living subjects with major craniofacial dysmorphology (Treacher-Collins syndrome and unilateral coronal synostosis); an anthropoid osteological specimen (Gorilla); and a fossil mammal skull.     

The use of hydroxyapatite cement in secondary craniofacial reconstruction.

Sixty-one patients underwent secondary craniofacial reconstruction for contour defects using hydroxyapatite cement over a 3-year period (20-month mean follow-up). There were 56 children, aged 2.2 to 18 years (mean, 10.7 years), 21 boys and 35 girls. This is the first series of pediatric patients in whom the use of hydroxyapatite cement has been reported. There were five adults aged 21 to 46 years (mean, 32 years), 3 men and 2 women. Thirty-one patients underwent reconstruction for secondary orbitocranial defects after surgery for synostosis, 7 after surgery for hypertelorism, 10 for posttraumatic skull defects, and 13 for a variety of other facial skeletal defects. There were seven complications (11 percent), ranging from a retained drain to postoperative seromas, all of which required reoperation without loss of the contour correction. All of the complications occurred in the first 18 months of our study. There has been excellent retention of implant volume with no recurrence of contour defects to date. We have not found any visible evidence of interference with craniofacial growth over the study period. We conclude that hydroxyapatite cement is a versatile and safe biomaterial when used for the correction of secondary craniofacial contour defects in children and adults. The coupling of antibiotics with this biomaterial may have applications in the treatment of osteomyelitis.     

Coronal ring involvement in patients treated for unilateral coronal craniosynostosis

The etiopathology of the clinical entity normally referred to as unilateral coronal synostosis is commonly used to connote unilateral fusion of the frontoparietal suture. However, other sutures in the coronal ring may exhibit synostosis concomitant with or independent from frontoparietal synostosis and give rise to similar clinical phenotypes. This study retrospectively analyzes high-resolution computed tomographic data sets to determine patency of sutures within the coronal ring. Computed tomographic scan digital data from 33 infants who subsequently underwent surgical correction of unilateral coronal synostosis were assessed for sutural patency using Analyze imaging software. The frontosphenoidal suture was subdivided into intraorbital frontosphenoidal and extraorbital frontosphenoidal portions, and the patency of the frontoethmoidal suture was also assessed. Patients were sorted into two groups on the basis of the status of their frontosphenoidal sutures: group 1 had patent frontosphenoidal but synostotic frontoparietal sutures (n = 21) and group 2 had both frontosphenoidal and frontoparietal synostoses. Observer reproducibility was tested. The vertical and horizontal dimensions of the bony orbit and the endocranial base deflection angle were measured with the observer blinded with regard to sutural status group. Frontoethmoidal synostosis was not noted in any patients in either group. Two patients had no frontoparietal suture synostosis with isolated intraorbital frontosphenoidal and extraorbital frontosphenoidal suture closures. Suture diagnosis reproducibility was 99 percent. In group 1, the ipsilateral-to-contralateral vertical orbit dimension ratio averaged 1.11, whereas in group 2 it averaged 1.04 (p < 0.05). The ratio of horizontal orbit measurements was not significantly different between groups. In both groups, the endocranial base was deflected ipsilateral to the synostotic frontoparietal suture, with an average angle of 12 degrees in group 1 and 17 degrees in group 2 (p < 0.005). The extent of synostosis along the coronal sutural ring contributes to the dysmorphology of the orbit and the endocranial base deflection in patients whose clinical phenotypic diagnosis is unilateral coronal synostosis.     

The FaceBase Consortium: a comprehensive program to facilitate craniofacial research

The FaceBase Consortium consists of ten interlinked research and technology projects whose goal is to generate craniofacial research data and technology for use by the research community through a central data management and integrated bioinformatics hub. Funded by the National Institute of Dental and Craniofacial Research (NIDCR) and currently focused on studying the development of the middle region of the face, the Consortium will produce comprehensive datasets of global gene expression patterns, regulatory elements and sequencing; will generate anatomical and molecular atlases; will provide human normative facial data and other phenotypes; conduct follow up studies of a completed genome-wide association study; generate independent data on the genetics of craniofacial development, build repositories of animal models and of human samples and data for community access and analysis; and will develop software tools and animal models for analyzing and functionally testing and integrating these data. The FaceBase website (http://www.facebase.org) will serve as a web home for these efforts, providing interactive tools for exploring these datasets, together with discussion forums and other services to support and foster collaboration within the craniofacial research community.     

Computerized tomography using a modified orthogonal tangent correction algorithm.

A modified orthogonal tangent correction algorithm is presented for computerized tomography. The algorithm uses four X-rays scans spaced 45 degrees apart, to reconstruct a transverse axial image. The reconstruction procedure is interative in which image matrix elements are corrected by alternately matching the two sets of orthogonal scan data. The algorithm has been applied to phantom data as well as to video recorded fluoroscopic data.     

The effect of growth hormone therapy on craniofacial growth and dental maturity in children with Down syndrome.

Craniofacial growth was evaluated 3 years after termination of growth hormone (GH) therapy in ten Down syndrome (DS) children. The control group consisted of 16 age-matched children with DS. The treatment started at 6-9 months of age, and the duration was 36 months. There were no statistically significant differences in craniofacial development between DS children treated with GH or DS children not treated. In conclusion, the results of this study indicate that GH therapy for 36 months in children with DS did not change the craniofacial morphology compared to a group of DS children not given GH.     

Scaling relationships between craniofacial sexual dimorphism and body mass dimorphism in primates: implications for the fossil record

Craniofacial remains (the most abundant identifiable remains in the fossil record) potentially offer important information about body size dimorphism in extinct species. This study evaluates the scaling relationships between body mass dimorphism and different measures of craniofacial dimorphism, evaluating taxonomic differences in the magnitude and scaling of craniofacial dimorphism across higher taxonomic groups. Data on 40 dimensions from 129 primate species and subspecies demonstrate that few dimensions change proportionally with body mass dimorphism. Primates show general patterns of greater facial vs. neurocranial and orbital dimorphism, and greater dimorphism in lengths as opposed to breadths. Within any species, though, different craniofacial dimensions can yield very different reconstructions of size dimorphism. There are significant taxonomic differences in the relationships between size and craniofacial dimorphism among primate groups that can have a significant impact on reconstructions of body mass dimorphism. Hominoids tend to show lower degrees of facial dimorphism proportional to size dimorphism than other primates. This in turn implies that strong craniofacial dimorphism in Australopithecus africanus could imply very strong body size dimorphism, conflicting with the relatively modest size dimorphism inferred from postcrania. Different methods of estimating the magnitude of size dimorphism from craniofacial measurements yield similar results, and yield comparatively low percent prediction errors for a number of dimensions. However, confidence intervals for most estimates are so large as to render most estimates highly tentative.     

Head posture and craniofacial morphology

The associations between craniofacial morphology and the posture of the head and the cervical column were examined in a sample of 120 Danish male students aged 22–30 years. Two head positions were recorded on lateral cephalometric radiographs, one determined by the subject's own feeling of a natural head balance (self balance position), and the other by the subject looking straight into a mirror (mirror position). Craniofacial morphology was described by 42 linear and angular variables, and postural relationships by 18 angular variables. A comprehensive set of correlations was found between craniofacial morphology and head posture. The correlations were similar for both head positions investigated. Of the postural variables, the position of the head in relation to the cervical column showed the largest set of correlations with craniofacial morphology. Extension of the head in relation to the cervical column was found in connection with large anterior and small posterior facial heights, small antero-posterior craniofacial dimensions, large inclination of the mandible to the anterior cranial base and to the nasal plane, facial retrognathism, a large cranial base angle, and a small nasopharyngeal space. The possible role of functional factors in mediating the relationship between morphology and posture was discussed.     

Plasticity of the endocranial base in nonsyndromic craniosynostosis

Limited in vivo data exist on the dysmorphology of the cranial base in nonsyndromic craniosynostosis. Few studies have documented the effect of calvarial surgery for synostosis on endocranial morphology. Previous work has suggested that the dysmorphology of the endocranial base is diagnostically specific for metopic, sagittal, and unicoronal sutures. The purpose of this study was to further evaluate the endocranial base in infants with nonsyndromic craniosynostosis by testing the hypothesis that the dysmorphology is, to some degree, a secondary deformation rather than a primary malformation. Three questions were addressed: (1) Can individuals reliably identify affected suture-specific endocranial-base morphology using standard templates? (2) Does calvarial surgery in infancy for craniosynostosis affect the perception of endocranial-base morphology? and (3) Does calvarial surgery in infancy for nonsyndromic craniosynostosis normalize the endocranial base?In this study, three-dimensional volumetric reconstructions from archived computed tomography digital data were processed using the ANALYZE imaging software. Dysmorphology was assessed by nine independent, blinded skilled observers who reviewed two separate sets of images of endocranial bases. Both sets contained images from the same patients: one set contained preoperative images, and the other contained images of the endocranial base 1 year after calvarial surgery. Observers were asked to sort each set into four suture-specific diagnostic groups: normal, unicoronal, metopic, and sagittal. Each set contained 10 patients with unicoronal synostosis, 10 with metopic synostosis, 10 with sagittal synostosis, and four normal patients. Seventy-eight percent of the total number of preoperative images were correctly sorted into the suture-specific diagnostic group, whereas only 55 percent of the total number of postoperative images were correctly matched. With regard to the individual sutures, the results were as follows (data are presented as preoperative accuracy versus postoperative accuracy): metopic, 76 percent versus 44 percent; sagittal, 58 percent versus 34 percent; unicoronal, 100 percent versus 79 percent; and normal, 83 percent versus 72 percent. Although 36 of 306 total images per group (12 percent) actually represented normal patients, the observers called 72 of 306 normal (24 percent) in the preoperative set versus 110 of 306 normal (36 percent) in the postoperative set. In conclusion, (1) the endocranial dysmorphology of nonsyndromic craniosynostosis is recognizably specific to the affected suture; (2) calvarial surgery for nonsyndromic craniosynostosis normalizes the endocranial base qualitatively with regard to the diminished ability of raters to identify the primary pathology; and (3) the documented postoperative changes in endocranial base morphology after calvarial surgery for nonsyndromic craniosynostosis in infancy indicates that a major component of that dysmorphology is a secondary deformity rather than a primary malformation.     

Fetal alcohol syndrome: an examination of craniofacial dysmorphology in Macaca nemestrina

The purpose of this investigation was to evaluate the craniofacial features in nonhuman primate models exposed in utero to moderate and high weekly binge doses of ethanol. While the high-dosed animal did have unusual craniofacial dysmorphology, she did not exhibit the typical facial pattern seen in human fetal alcohol syndrome. The high-dosed specimen displayed a scaphocephalic head shape secondary to synostosis of the sagittal suture. The brain of this monkey was grossly abnormal and microcephalic.     

Efficacy of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition

It has been reported that radiotherapy-induced craniofacial deformities can occur in 66 to 100 percent of survivors of childhood head and neck cancers. Recent interest in the effectiveness of radioprotectors in the protection of normal tissue against radiation injury led us to investigate a possible role of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition. Therefore, the objective of this study was to use the radioprotective agent amifostine (Ethyol, WR-2721) as a probe to determine the effectiveness of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition after single-dose orthovoltage radiation to the infant rabbit orbital-zygomatic complex. Seven-week-old male New Zealand white rabbits were randomized into three groups (n = 10 each): group 1, 0 Gy (sham radiation); group 2, 35-Gy single-dose orthovoltage radiation; and group 3, 35-Gy single-dose orthovoltage radiation and amifostine (300 mg/kg intravenously, given 20 minutes before radiation). Serial radiographs and computed tomographic scans were obtained for cephalometric analysis, bone volume, and bone density measurements until skeletal maturity at 21 weeks. Significant (p < 0.05) reductions in orbital-zygomatic complex linear bone growth, bone volume, and bone density were observed after 35-Gy radiation compared with nonirradiated controls. No significant differences were noted between groups in cephalometric analysis of the nontreated (nonirradiated) left orbital-zygomatic complex, indicating no crossover effect from the radiation beam. However, pretreatment with amifostine, 20 minutes before 35-Gy radiation, resulted in significant (p < 0.05) preservation of linear bone growth, bone volume, and bone mineral density in the rabbit orbital-zygomatic complex compared with controls. This study demonstrated for the first time the effectiveness of a radioprotector in the prevention of radiation-induced craniofacial bone growth inhibition, and it paves the way for investigation into the pathogenic mechanism and prevention of radiotherapy-induced craniofacial deformities.