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.     

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.     

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.     

Atelencephalic microcephaly: craniofacial anatomy and morphologic comparisons with holoprosencephaly and anencephaly

This is the first detailed report of the craniofacial anatomy of atelencephaly. Comparisons were made with a control specimen and others with holoprosencephaly, anencephaly, and anencephaly with holoprosencephalic facial features. In the atelencephalic fetus, severe microcephaly, flattened calvaria, and partial synostosis of the metopic suture were apparent. The cranial fossae were much smaller than usual; lesser wings of the sphenoid were folded into a rounded basal mass. Facial features were pronounced, and orbits were hyperteloric, lowset, and rounded. Ethmoidal cartilages, nasal bones, and maxillary structures were distorted and elongated. The secondary palate was displaced inferiorly and cleft. Because major components of the craniofacial complex were generally present, although misshapen, changes in the atelencephalic skull seem to be deformations rather than malformations. Differences in the cranial morphology of associated disorders--holoprosencephaly and anencephaly--can be construed as aberrations of separate developmental fields. Relationships between atelencephaly and these fields are unclear.     

Clinical characteristics of patients with unicoronal synostosis and mutations of fibroblast growth factor receptor 3: a preliminary report.

Clinical teaching dictates that isolated unicoronal synostosis is sporadic in occurrence and is possibly related to intrauterine constraint. Despite this, isolated reports document a familial occurrence. It has previously been recognized that there may be a familial pattern of inheritance. Recently, mutations in fibroblast growth factor receptors (FGFRs) have been implicated in several syndromic craniosynostoses. At the authors' institution, mutations in FGFR3, located at chromosome 4p16, have been found to cause coronal synostosis. Two cases of unicoronal synostosis were found to have the same Pro250Arg missense mutation in FGFR3. This finding suggested that all patients with a diagnosis of unicoronal synostosis be screened for the FGFR3 mutation. Between January and December of 1996, patients with a diagnosis of plagiocephaly at the Children's Hospital of Philadelphia were evaluated for the FGFR3 mutation. Thirty-seven patients with unicoronal synostosis had mutational studies. Two additional patients were known to have the FGFR3 mutation at the onset of the study. Of the 37 patients screened, four were found to have the FGFR3 mutation, for a total of six patients with both unicoronal synostosis and the FGFR3 mutation. All patients with unicoronal synostosis were evaluated for facial dysmorphology and operative outcome. The six patients with the FGFR3 mutation had more severe cranial dysmorphology and were more likely to need surgical revision than those without the FGFR3 mutation. The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly. The clinical, radiologic, and molecular findings will be an important addition to the surgical management and counseling of patients with unicoronal synostosis.     

Trigonocephaly: refinements in reconstruction. Experience with 33 patients

Thirty-three consecutive patients with metopic synostosis treated between January of 1980 and June of 1984 are presented. All patients underwent craniofacial reconstruction by an interdisciplinary team utilizing a detailed remodeling of the supraorbital rims and forehead. Advantages of the current modifications are discussed, as well as an analysis of the results. We believe this represents a significant advance over previous methods not only because of the superior cosmetic results achieved, but also because of its safety and reproducibility. Reoperation rate was less than 10 percent overall and was necessary only in patients with complex cranial vault abnormalities. Mean follow-up was 22.8 months, with no deaths, infections, or damage to visual or cerebral function. Postoperative head circumference demonstrated an immediate increase followed by a normal growth curve.     

Craniofacial and oral manifestations of fetal alcohol syndrome

Six representative patients with fetal alcohol syndrome (FAS) were studied for craniofacial and oral anomalies, dental development, and long-term bodily growth patterns. The craniofacial features observed were reduction of total head size, increased head-body ratio, the existence of upper and middle craniofacial asymmetry and telecanthus in some instances, and the features of a long face syndrome with a large gonial angle. Dental development was mildly to moderately delayed, and enamel anomalies were present. Analysis of growth patterns demonstrated compensatory growth in stature, weight, or head circumference and a delayed bone age in some instances. It is suggested that the semiquantitative score system for fetal alcohol syndrome study may fail to diagnose individual cases and that craniofacial features are more important in diagnosis than seems to have been appreciated in the past.     

Orbital teratoma associated with trigonocephaly

A rare case of congenital orbital teratoma that developed concurrently with the clinical findings of metopic sutural synostosis in an infant is presented. A cause-and-effect and/or embryologic relationship between these two cephalic malformations is possible, although coincidental occurrence is equally probable. The proximity of these congenital anomalies permitted complete resolution in a one-stage craniofacial procedure without alteration in the surgical technique.     

Time and natural history: the changing face

There is a considerable body of knowledge on the changing structures of the craniofacial complex in the anthropology literature, which dates back to the late 19th century. This awareness of change in phenotype has not been emphasized in dysmorphology and incorporated into syndrome diagnosis until recently. In contrast to the anthropological data, where serial craniofacial measurements document different rates of growth in the individual structures of the craniofacial complex, awareness of the evolution of phenotype, in dysmorphology, has been based on an appreciation of a changing gestalt. This work has been carried out principally in Noonan syndrome. Noonan syndrome is a cardiofacial syndrome in which affected individuals may be short and mildly mentally retarded. In this autosomal dominant disorder, a marked change of phenotype with age from the newborn period, infancy, childhood, adolescence, and adulthood has been documented. Similar variation with age is likely to be found in many other dysmorphic syndromes. Increasing insight into the evolution of phenotypes should markedly increase the potential for diagnosis.     

Endoscopic craniectomy for early correction of craniosynostosis

Twelve patients between 0.4 and 7.8 months of age were treated by an endoscopic approach to strip craniectomy. Nine patients had sagittal suture involvement. Two patients had a single unilateral lambdoid suture synostosis, and one patient had a combination of a right coronal synostosis and a metopic synostosis. Postoperatively, all patients were placed in cranial remodeling helmets and the results showed that the estimated blood loss ranged from 5 cc to 150 cc, with blood transfusion required in only one patient. All patients were discharged from the hospital by day 2, and all patients had an improvement in their cranial head shape. The specific technique of using the endoscope to aid in performing a strip craniectomy will be discussed. Nine endoscopically treated patients with the diagnosis of sagittal suture synostosis were compared with nine patients treated by using the Marchac remodeling techniques. The mean operative time (1.6 hours versus 3.5 hours), estimated blood loss (43 cc versus 168 cc), hospital costs ($11,671 versus $36,685), and length of stay (1.16 days versus 5.1 days) were less by using the endoscopic technique. All nine patients treated by using the Marchac technique required a blood transfusion, whereas only one patient was transfused in the endoscopically treated group.     

The craniofacial anomalies archive at St. Louis Children's Hospital: 20 years of craniofacial imaging experience.

This article describes how the Craniofacial Imaging Laboratory at the Cleft Palate and Craniofacial Deformities Institute, St. Louis Children's Hospital, Washington University Medical Center, has developed an electronic archive for the storage of computed tomography image digital data that is independent of scanner hardware and independent of units of storage media (i.e., floppy disks and optical disks). The archive represents one of the largest repositories of high-quality computed tomography data of children with craniofacial deformities in the world. Archiving reconstructed image data is essential for comparative imaging, surgical simulation, quantitative analysis, and use with solid model fabrication (e.g., stereolithography). One tertiary craniofacial center's experience in the establishment and maintenance of such an archive through three generations of storage technology is reported. The current archive is housed on an external 35-GB hard drive attached to a Windows-based desktop server. Data in the archive were categorized by specific demographics into groups of patients, number of scans, and diagnoses. The Craniofacial Imaging Laboratory archive currently contains computed tomography image digital data for 1827 individual scans. The earliest scan was done in 1980; the most recently stored scan for the purposes of this report occurred in May of 2000. The average number of scans archived per complete year was 94, with a range of 59 to 138. Of the 1827 total scans, 74 percent could be classified into specific diagnostic categories. The majority of the archive (55 percent) is composed of the following five diagnoses: sagittal synostosis (17 percent), unilateral coronal synostosis (11 percent), hemifacial microsomia (10 percent), plagiocephaly without synostosis (10 percent), and metopic synostosis (7 percent). Storage of computed tomography image data in a digital archive currently allows for continuous upgrading of image display and analysis and facilitates longitudinal and cross-sectional studies, both intramural and extramural. Internet access for clinical and research purposes is feasible, but contingent on protection of patient confidentiality. The future of digital imaging regarding craniofacial computed tomography scan storage and processing is also discussed.     

Calvarial sutural abnormalities: metopic synostosis and coronal deformation--an anatomic, three-dimensional radiographic, and pathologic study

The purposes of this study were (1) to evaluate the histologic differences between synostotic versus deformational suture abnormalities and (2) to correlate these histologic findings with anatomic and three-dimensional computed tomographic (CT) scans. We examined three infants with premature metopic synostosis; one infant also had microcephaly trisomy 13 and curious overriding of the coronal sutures. The three-dimensional CT scans demonstrated obliteration of the metopic suture inferiorly. Histologic sections of this suture showed complete bony stenosis. The same pattern was found in all three infants, including the two infants with trigonocephaly who did not have trisomy 13 or microcephaly. In the trisomy 13 infant, the overlapped inferior coronal suture was obliterated on CT examination. However, histologic sections in this region showed a merging of bone; there was no synostosis. In summary, three-dimensional CT re-formation correlated with metopic suture histology. "Stenotic" fusion existed in all infants with trigonocephaly, those with normal and abnormal karyotypes, with and without microcephaly. However, three-dimensional CT re-formation of the trisomic infant showed opacification of the coronal suture in the areas of greatest overlap, whereas histology revealed a curious bone remodeling pattern, possibly a precursor to "deformational" craniosynostosis.     

Tracing craniosynostosis to its developmental stage through bone center displacement.

In metopic and coronal suture synostosis, the involved bone centers are abnormally situated just next to the affected suture. Bone centers are the starting point of ossification during embryogenesis from which bone growth spreads radially. In this paper, we describe a similar observation for sagittal suture synostosis, with both parietal bone centers located almost completely cranially. The (reduced) distance between the bone centers of a synostotic suture reflects the time during embryogenesis at which fusion took place. We suggest that in craniosynostosis the bone centers arise in their normal position, and initial outgrowth is undisturbed until the bone fronts meet. It is during this developmental stage that fusion occurs instead of suture formation. Due to the fusion, growth can only occur at the free bony rims from then on. The bone centers remain located at a fixed distance from one another in the middle of the fused bones, becoming relatively more displaced with time. This implies that the distance between the involved bone centers directly indicates the developmental period during which sutural growth was arrested. The same phenomenon of bone center displacement is found in types of craniosynostosis with and without fibroblast growth factor receptor (FGFR) or TWIST gene mutations.     

Tissue expansion in the reconstruction of Tessier craniofacial clefts: a series of 17 patients

Tessier craniofacial clefts are among the most surgically challenging examples of craniofacial dysmorphology. These clefts are characterized by hypoplasia of soft-tissue and skeletal elements throughout the three-dimensional extent of the cleft. Whereas bone grafting and craniofacial osteotomies have been successful toward correcting the underlying skeletal abnormalities, the ultimate success of these reconstructions has been limited by the deficiency of skin and soft tissue. This deficiency demands reconstruction ideally with tissue of like texture, consistency, and, especially in the face, color. Craniofacial tissue expansion was used toward reconstructing these facial clefts with like-quality tissue, allowing for tension-free reconstruction after osteotomy and bone grafting. Seventeen patients with Tessier craniofacial clefts underwent preoperative craniofacial soft-tissue expansion in the surgical management of their clefts. Tissue expansion was used in the primary correction of facial clefts in eight patients, with nine patients undergoing expansion before secondary surgery. In this series, tissue expansion has evolved as an important element in overcoming the skin and soft-tissue deficiency associated with these clefts, allowing for tension-free closure and improved aesthetic results in these surgically challenging patients.     

Sutural effects of fronto-occipital cranial modification

Maya adult crania from the site of Lamanai, Belize provide a retrospective means of examining growth processes in the cranial vault. The Lamanai population practiced fronto-occipital deformation which is found to be significantly associated with premature sagittal synostosis and wormian bones of the lambdoidal suture. The undeformed members of the population also exhibit an abnormally high frequency of sagittal synostosis, but a significantly lower frequency than the deformed sample. It is suggested that the deforming apparatus creates tensile forces on the sagittal suture during the peak period of growth of the parietals, and that these forces might induce an adaptive response important in producing premature sagittal synostosis. The undeformed sample may have an increased congenital risk of sagittal synostosis created by their natural brachycephalic morphology in utero. The frequency patterning of wormian bones suggests a mixture of genetic and environmental causes in which tensile forces may also play a role. © 1996 Wiley-Liss, Inc.     

Craniofacial growth of fetal Macaca nemestrina: A cephalometric roentgenographic study

The prenatal growth of the macaque craniofacial skeleton is described using lateral radiographs of 82 fetal and 25 neonatal Macaca nemestrina whose known gestational ages range from 50 to 186 days. The ossification sequence of the craniofacial bones resembles that in the human fetus. During gestation, the macaque neurocranium loses its round, globular shape, becoming flattened and elongated in an anteroposterior direction. In contrast, the morphologic pattern of the face is established early in fetal life, and little change takes place during the remaining prenatal period. The macaque craniofacial dimensions develop along the general skeletal growth pattern, unlike the human craniofacial dimensions, which follow an intermediate pattern between the neural and general skeletal patterns. However, despite minor differences, the macaque and human fetal faces follow the same basic patterns of growth.     

Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent

Prenatal ethanol exposure is the leading preventable cause of congenital mental disability. Whereas a diagnosis of fetal alcohol syndrome (FAS) requires identification of a specific pattern of craniofacial dysmorphology, most individuals with behavioral and neurological sequelae of heavy prenatal ethanol exposure do not exhibit these defining facial characteristics. Here, a novel integration of MRI and dense surface modeling-based shape analysis was applied to characterize concurrent face-brain phenotypes in C57Bl/6J fetuses exposed to ethanol on gestational day (GD)7 or GD8.5. The facial phenotype resulting from ethanol exposure depended upon stage of insult and was predictive of unique patterns of corresponding brain abnormalities. Ethanol exposure on GD7 produced a constellation of dysmorphic facial features characteristic of human FAS, including severe midfacial hypoplasia, shortening of the palpebral fissures, an elongated upper lip, and deficient philtrum. In contrast, ethanol exposure on GD8.5 caused mild midfacial hypoplasia and palpebral fissure shortening, a shortened upper lip, and a preserved philtrum. These distinct, stage-specific facial phenotypes were associated with unique volumetric and shape abnormalities of the septal region, pituitary, and olfactory bulbs. By demonstrating that early prenatal ethanol exposure can cause more than one temporally-specific pattern of defects, these findings illustrate the need for an expansion of current diagnostic criteria to better capture the full range of facial and brain dysmorphology in fetal alcohol spectrum disorders.     

Masticatory function and post-pleistocene evolution in Nubia

The present research focuses on craniofacial variation in Nubia over approximately 10,000 years. Samples were grouped according to their temporal location and subsistence pattern, and represent a transition from a hunting-gathering adaptation (Mesolithic) to a transitional hunting-gathering-agricultural adaptation (A-C Group) and finally to a fully agricultural adaptation (Meroitic/X-Group/Christian). The purposes were: (1) to compare the Mesolithic sample with the later Nubian populations; and (2) to evaluate further the hypothesis that change in Nubian craniofacial morphology was due to changing functional demands associated with the progressive change in subsistence adaptation and associated behavior. The results tend to support recent views that the Nubian Mesolithic population is probably ancestral to later Nubian groups, and that the masticatory-functional hypothesis can best account for craniofacial change among the Nubians since 12,000 B.P. According to this hypothesis systematic reduction in functional demand placed on the masticatory complex from the Mesolithic led, secondarily, to an alteration of the growth of the maxillomandibular complex such that the face became progressively less robust and more inferoposteriorly located relative to the cranial vault. Both the increase in the height of the vault relative to its length, producing a more “globular” appearance, and the reduction in dental size were tertiary, compensatory responses to altered facial size and position.