A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome.

Pfeiffer syndrome (PS) is one of the classic autosomal dominant craniosynostosis syndromes with craniofacial anomalies and characteristic broad thumbs and big toes. We have previously mapped one of the genes for PS to the centromeric region of chromosome 8 by linkage analysis. Here we present evidence that mutations in the fibroblast growth factor receptor-1 (FGFR1) gene, which maps to 8p, cause one form of familial Pfeiffer syndrome. A C to G transversion in exon 5, predicting a proline to arginine substitution in the putative extracellular domain, was identified in all affected members of five unrelated PS families but not in any unaffected individuals. FGFR1 therefore becomes the third fibroblast growth factor receptor to be associated with an autosomal dominant skeletal disorder.

A gene for Crouzon craniofacial dysostosis maps to the long arm of chromosome 10.

Crouzon craniofacial dysostosis (CFD) is an autosomal dominant craniofacial disorder characterized by premature craniosynostosis, shallow orbits and hypoplastic maxilla. To map the gene responsible, we have used a mapping strategy of testing for linkage to known developmental genes. Analysis of a large kindred established linkage between CFD and three loci (D10S190, D10S209 and D10S216) that span a 13 cM region on chromosome 10q. A maximum pairwise lod score of 4.42 (theta = 0) at D10S190 was obtained and the addition of a second kindred produced a combined pairwise lod score of 5.32 (theta = 0) at the same locus. The developmental gene, PAX2, located within this region, is an attractive candidate gene.

Further delineation of the Baller-Gerold syndrome.

Three new patients with the Baller-Gerold syndrome bring the number of reported cases to 20. In addition to craniosynostosis involving various sutures and preaxial reduction defects of variable severity, affected patients may have anal, urogenital, cardiac, central nervous system, and vertebral defects. Autosomal recessive inheritance is supported by the presence of affected sibs and parental consanguinity.

A combined frontoorbital and occipital advancement technique for use in total calvarial reconstruction.

The management of infants with bilateral coronal synostosis and resultant brachyturricephaly poses a significant therapeutic challenge. The application of total calvarial reconstruction to the treatment of this problem has represented a major recent innovation that has substantially improved the cosmetic results in this patient population. However, rigid fixation of the reconstructed calvaria is often required to maintain the correction achieved and to provide protection for the underlying brain. The requirement of extensive fixation constitutes a significant disadvantage for the use of this procedure in infants and young children. In this report, the authors describe an approach to the treatment of this problem that incorporates a series of tongue-in-groove osteotomies to provide increased stability to advancements of both the frontal and occipital regions in conjunction with cranial height reduction, while minimizing the need for metallic fixation. With this approach, the reconstructed skull is sturdy enough to resist the compressive force applied by the weight of the child's head immediately after surgery, but retains the ability to expand progressively. The authors have found the cosmetic results to be extremely gratifying. In this article they present their experience with this technique in seven children.

Development of plagiocephaly in rabbits with unicoronal synostosis.

Human unicoronal synostosis results in plagiocephaly of the cranial vault due to predictable compensatory growth patterns of the contralateral coronal, sagittal, and ipsilateral squamosal sutures. The present study describes the development of plagiocephaly and tests compensatory growth predictions in a naturally occurring rabbit model of uncorrected unicoronal synostosis. Cranial vault and sutural growth data were collected from serial x-ray films in 70 normal rabbits and 19 rabbits with congenital unicoronal synostosis from 1.5 to 18 weeks of age. One-way analysis of variance results revealed that rabbits with unicoronal synostosis had significant (p < 0.05) growth inhibition at both coronal sutures and the contralateral frontonasal suture and a significantly wider (p < 0.05) cranial vault compared to controls. Paired Student's t-tests between affected and unaffected sides of the vault in rabbits with synostosis revealed significant (p < 0.05) asymmetry, with ipsilateral coronal sutures growing less than contralateral ones. Gross qualitative examination of the adult brains revealed severe asymmetry and anteroposterior reduction on the ipsilateral side. These results demonstrate that this congenital rabbit model effectively simulates human cranial vault growth predictions from unicoronal synostosis and produces a plagiocephalic morphology.

Human bites of the lip.

Human bites of the lips are very common. If less than 10 mm in size, they are treated conservatively and if greater, are treated surgically. Many lip bites are treated immediately, when infection is present, surgery is performed a few days later.

Spheno-maxillary meningo-encephalocele. A case report.

A patient is presented who was born with a large swelling on the left side of his face. This was removed by a paediatric surgeon at six weeks of age, and the histology was that of an encephalocele. Based on our findings at a later procedure to correct the child's facial asymmetry resulting from the congenital deformity, we concluded that this was a spheno-maxillary meningo-encephalocele. We have been able to find only one other such meningo-encephalocele reported in the literature.

Unilateral exophthalmos caused by an anterior ethmoidal meningoencephalocele.

A case of unilateral enophthalmos in a 1-year-old child is presented. This was caused by a meningoencephalocele that originated in the anterior cranial fossa and protruded into the orbit through a bony defect at the junction of the frontal and ethmoid bones at the site of the anterior ethmoid canal. This meningoencephalocele was reduced, and the dura was repaired with a temporalis fascia graft. A split calvarial bone graft was inserted into the floor of the orbit, and lateral canthal ligament elevation completed the operative correction.

Breast masses in the augmentation mammaplasty patient: the role of ultrasound.

The detection and evaluation of breast parenchymal abnormalities in the presence of a radiodense implant are often difficult with standard techniques of physical examination and mammography. Breast lesions can be obscured on one or both views by the radiodense implant or concealed within the dense tissue at the prosthesis-breast tissue interface. We investigated the role of ultrasound as an adjunct to mammographic special views, including posterior displacement (Eklund et al.), in previously augmented patients who presented with a clinically palpable mass. The records of 125 consecutive breast augmentation patients seen by us over a 4-year period were retrospectively reviewed. Twenty-six patients presented with a palpable breast abnormality. All 26 patients underwent diagnostic mammograms and sonograms. Findings included 8 parenchymal lesions (4 cysts, 2 fibroadenomas, 1 seroma, 1 breast carcinoma), 8 implant-related irregularities (4 ruptures, 3 bulges, and 1 valve), and normal fibroglandular tissue in 10 patients. Mammography yielded a convincing diagnosis in 7 of 26 patients, whereas ultrasound characterized the abnormality in every case. Ultrasound is a useful adjunct to mammography in evaluating palpable breast abnormalities in the breast augmentation patient. It offers improved visualization of the breast tissue-prosthesis interface, and it is helpful in distinguishing breast parenchymal lesions from palpable irregularities of the implant.

Internal calvarial bone distraction in rabbits with experimental coronal suture immobilization: effects of overdistraction.

This study was designed to assess the effects of overdistraction of an experimentally immobilized coronal suture using an internal appliance on craniofacial growth in rabbits. Fifty-three, 1.5-week-old rabbits were used. Markers were placed on either side of the calvarial sutures. Thirty-nine rabbits had bilateral coronal suture immobilization using methyl methacrylate; 14 rabbits served as normal controls. At 6 weeks of age, the 39 immobilized rabbits were randomly assigned to four groups: (1) immobilized controls (n = 14); (2) suturectomy (n = 6); (3) suturectomy with distraction (n = 9); and (4) suturectomy with overdistraction (n = 10). Lateral head radiographs were taken at 1.5, 6, 12, and 18 weeks of age. Results revealed that, by 18 weeks of age, rabbits with overdistraction exhibited significant compensatory growth abnormalities in the cranial vault, midface, and anterior cranial base compared with the other groups. Results indicate that overdistraction may contribute to craniofacial anomalies through altered growth vectors and compressive tension-stress forces at adjacent sutures and suggest that it may be important to keep "pace" with the growing coronal suture and neurocapsular matrix during distraction to reestablish normal craniofacial morphology.

Age related changes in intracranial volume in rabbits with craniosynostosis.

Neurocapsular growth is highly heritable and determines neurocranial form. Although craniosynostosis alters brain growth direction, resulting in compensatory changes in the neurocranium, it is believed that such compensations occur without reduction in intracranial volume. This hypothesis was tested in a rabbit model with nonsyndromic, familial coronal suture synostosis. Skulls of 56 rabbits (20 normals, 20 with delayed onset synostosis, and 16 with complete synostosis) were scanned using three-dimensional computed tomography at 6 and 18 weeks of age. Intracranial contents were reconstructed, and indirect intracranial volume was calculated. Qualitatively, re-formations of intracranial contents from completely synostosed rabbit skulls exhibited the typical "copper beaten" morphology. Quantitatively, intracranial volume was significantly (p < 0.05) reduced in rabbit skulls with complete synostosis compared with both control rabbit skulls and rabbit skulls with delayed onset synostosis at 6 weeks by 11 percent and 14 percent, respectively). By 18 weeks, intracranial volume in rabbit skulls with synostosis was significantly (p < 0.05) reduced (by 12 percent in complete synostosis and 8 percent in delayed onset synostosis) compared with normal rabbits. Results suggest that in rabbits with uncorrected craniosynostosis, compensatory changes in the neurocranium were not adequate to allow normal expansion of the neurocapsular matrix. Further research is needed to determine whether reduction in intracranial volume was a result of neural tissue deficiency or cerebrospinal fluid (i.e., ventricular or subarachnoid) space compression in this model.

Internal calvarial bone distraction in rabbits with delayed-onset coronal suture synostosis.

Recent studies have identified a subpopulation of craniosynostotic individuals who exhibit progressive or delayed-onset synostosis and mild craniofacial growth abnormalities. These individuals may be good candidates for nonextirpation, distraction osteogenesis therapy. The present study was designed to test this hypothesis by using internal calvarial bone distraction in a rabbit model with familial delayed-onset craniosynostosis. Data were collected from 159 rabbits: 71 normal controls, 72 with delayed-onset coronal suture synostosis, 8 with delayed-onset coronal suture synostosis and coronal suturectomy, and 8 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the frontonasal, coronal, and anterior lambdoidal sutures. At 25 days of age, correction was accomplished through either a 5-mm-wide suturectomy or distraction osteogenesis. An internal distraction appliance was fixed to the frontal and parietal bones and percutaneously and intermittently activated at an average of 0.10 mm/day for 42 days (4.11 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis had significantly (p < 0.01) reduced coronal suture growth rates (0.04 mm/day) compared with the other three groups (0.07 mm/day). Rabbits with suturectomy and rabbits with distraction showed similar coronal suture responses. However, from 42 to 84 days of age, rabbits with distraction showed reduced growth at the vault sutures and abnormal growth patterns in cranial vault width, cranial vault shape, and cranial base angulation compared with the other three groups. Results demonstrated that, although the normal coronal suture growth rate was maintained in rabbits with delayed-onset synostosis using intermittent distraction osteogenesis, normal adult craniofacial structure was not achieved. Such anomalous growth was probably a result of altered growth vectors and compressive forces at adjacent sutures during distraction. These findings suggest that distraction osteogenesis without corticotomy may be a treatment alternative in individuals with progressive, delayed-onset synostosis, but that internal appliances that generate low-level, continuous distractive forces should be investigated and developed.

Degradation kinetics of biodegradable DL-polylactic acid biodegradable implants depending on the site of implantation.

A recently developed biodegradable system made of DL-polylactic acid (DL-PLA) for internal fixation of non-weight-bearing bones of the craniofacial skeleton was investigated. The plates were used for rigid fixation of experimental nasal bone fractures in 20 New Zealand white rabbits. In addition, prebent plates were placed in subcutaneous pockets in the backs of the animals. The material was removed after 7, 14, 28, and 42 days, and bending angles, plate stability, molecular weights (MW), and histologic analyses were studied. A significant decrease of MW over time and a difference in MW loss, showing a faster degradation subcutaneously, were observed. Plate stability did not decrease during the interval of 6 weeks, but a loss of bending angle was found in all prebent implants. This effect was caused by memory of DL-PLA. The results suggest that memory of biodegradable materials should be investigated before clinical application and that degradation rates differ according to the site of implantation.

Restitution of facial form in a patient with hemifacial microsomia. A case report.

Hemifacial microsomia involves unilateral underdevelopment of the ear, mandible and associated structures. This report describes an approach to early surgical restoration of function to improve growth, illustrated with a case report.

Le Fort III osteotomy to correct dish-face deformity resulting from facial trauma.

Untreated craniofacial fractures may result in a deformity similar to that which results from underdevelopment of the maxilla. Such a deformity can be corrected by osteotomy simulating Le Fort type III fracture lines. This operation necessitates careful pre-operative planning which incorporates a feasibility study with the combined use of dental study casts, cephalometric radiography and life-size photographic reproductions. A case history which describes the management of late complications of a malunited class III fracture is given.

Le Fort III osteotomy in Crouzon's disease.

The features of Crouzon's disease are craniostenosis and maxillary hypoplasia. A patient with Crouzon's disease is presented, on whom Le Fort III osteotomy and osteotomy of the mandible were performed, involving the insertion of 9 bone grafts to maintain the correction and to improve the facial appearance.

Vascularized fronto-orbital advancement.

Fronto-orbital advancement is the procedure of choice for correction of fronto-orbital recession resulting from coronal synostosis in children. However, long-term follow-up evaluations often reveal "undercorrection" of the deformity with development of recurrent recession of lateral supraorbital regions. One factor that may contribute to this process is devascularization of the fronto-orbital bar during its reshaping and advancement. If subsequent revascularization is suboptimal, excessive resorption or inadequate growth of the bar may lead to supraorbital recession. On the basis of studies of temporal bone grafts, which have shown that vascularized grafts are superior to free bone grafts in terms of bone graft survival, we postulated that maintaining vascularization of the fronto-orbital bar would favor better healing and growth that would translate to more favorable aesthetic results. Herein, we review the vascular anatomy of the fronto-orbital region and report the application in six patients of a technique for fronto-orbital advancement that preserves a significant portion of this blood supply. Technical caveats involved in the successful application of this approach are discussed. The attachment of the periosteum to the lateral two thirds of the supraorbital bar allows additional stability. This prevented the use of plates and screws in these patients.