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PubMed1996

A prospective study of the relationship between strabismus and head posture in patients with frontal plagiocephaly.

A prospective study was performed on 16 unoperated patients with frontal plagiocephaly to characterize the relationship between strabismus and abnormal head posture. Serial eye examinations were performed preoperatively and for 24 to 46 months following fronto-orbital advancement. In 14 patients (88 percent), preoperative clinical examination and CT scan indicated coronal plagiocephaly (synostotic); unicoronal synostosis was documented during fronto-orbital advancement in all these patients. Ten patients had abnormal head posture on preoperative examination, 9 of whom had strabismus at some time during the study. These 9 patients all had unicoronal synostosis with ipsilateral strabismus and a contralateral head tilt. All had eye muscle findings consistent with superior oblique paresis, although in 2 patients these signs first developed following fronto-orbital advancement. Strabismus resolved spontaneously in 2 patients between 2 and 8 months following fronto-orbital advancement; the remaining 7 patients underwent extraocular muscle surgery following fronto-orbital advancement, with early resolution of strabismus in all cases. The head tilt resolved or improved significantly in all 9 patients following resolution of the strabismus. Two patients had recurrent superior oblique paresis following surgical correction, necessitating secondary strabismus surgery. The present study indicates that extraocular muscle dysfunction is the major cause of abnormal head posture in patients with coronal plagiocephaly and emphasizes the need for long-term ophthalmologic surveillance in these patients.

Child, Preschool↗
PubMed1996

Dynamic cranioplasty for brachycephaly.

In craniofacial surgery, the most common techniques for treatment of brachycephaly have been either to let the forehead float on the brain or to fix it in an advanced position. Since neither of these techniques renders acceptable results with enough consistency, we have developed a different way of addressing the problem. In principle, the design of the operation is to restrict upward and transverse growth of the cranium but to allow anterior and posterior expansion. This is accomplished by producing transverse tension across the skull and letting it expand anteriorly by means of a superiorly hinged fronto-orbital flap and posteriorly by an inferiorly based occipital flap. To prevent upward expansion at the squamosal sutures when still open, these junctions are bridged with miniplates. This surgical technique has brought definite improvement to the results even in some Apert syndrome children. During a 2-year period, we have treated 14 infants with this technique and followed 10 of them with roentgencephalometry, 3 for more than 1 year, and 4 for more than 6 months. The diagnoses were the following: nonsyndromal bicoronal synostosis (4), Apert (7), bicoronal synostosis with midline cleft, Saethre-Chotzen, and Antley-Bixler (1 each). The mean age of surgery was 6.6 months (range 3 to 16 months). There were no major complications.

Acrocephalosyndactylia↗
PubMed1998

A new in utero sheep model for unilateral coronal craniosynostosis.

Several animal models have been designed in the past to analyze the pathophysiology and management of craniosynostosis, very few of which were intrauterine. Those that were interuterine had problems with either a short gestation or limited availability that prevented most researchers from using them in treatment analysis. We desired to create a biologically sound intrauterine model of craniosynostosis, using an animal with a long gestation and an early calvarial bone formation, which was easy to manipulate in utero, that could be created by any researcher studying this disorder. Using biologic data available regarding growth factors thought to be involved in bone growth and cranial suture closure, we developed a new in utero fetal lamb model for the study of craniosynostosis. Ten 70-day gestation fetal lambs (term gestation 140 days) received a midline coronal incision to expose both coronal sutures. The entire right coronal suture was then excised along with a 4-mm bony margin. In each animal, the site was packed with 25 mg of demineralized sheep bone powder augmented with 50 microg of bone morphogenetic protein-2 (BMP-2) and 1 microg of poly-transforming growth factor-beta. The scalp was closed, and the sheep were returned to the uterus until either 90 or 140 days of gestation. Complete fusion of the right coronal suture occurred in all fetuses by 90 days gestation. In every animal, right-sided frontal bone flattening and supraorbital rim elevation were evident. Histologic analysis showed bony synostosis at the suture site without evidence of suture regeneration. By 140 days, this isolated suture fusion led to marked craniofacial abnormalities including right supraorbital rim elevation, significant frontal bone flattening, a decrease in the anterior-posterior length of the cranial vault, and flattening of the cranial base. In conclusion, we have developed a new model for the study of the secondary effects induced by the process of cranial suture fusion, which produces abnormalities seen in naturally occurring cases of isolated right coronal suture synostosis. In addition, this model confirms that isolated coronal suture fusion alone can lead to the multiple cranial and facial abnormalities seen with this disorder, even in the absence of associated cranial base suture fusions.

Animals↗
PubMed1998

Investigation of the influences of biomechanical force on the ultrastructure of human sagittal craniosynostosis.

This study presents comparisons of the ultrastructure of synostotic and open portions of synostotic sagittal sutures using histomorphometry, scanning electron microscopy, and microcomputed tomography. By using stereologic and histomorphometric analysis, this study proposes to demonstrate evidence of the influence of biomechanical force on the suture during the process of sagittal craniosynostosis. Finally, we propose to link the pathologic changes transforming normal suture fusion to craniosynostosis with concurrent changes in the polarity of suture fusion initiation. Seven infants (four boys and three girls) with sagittal craniosynostosis, ranging in age from 1.4 to 4.8 months (mean = 3.0 months), underwent sagittal synostectomies. The synostotic bone specimens were sectioned into three regions: an open suture, partial synostosis, and complete synostosis. Microcomputed tomographic and scanning electron microscopic scanning as well as histomorphometry was performed on all specimens to obtain detailed qualitative and quantitative information regarding the trabecular microarchitecture of the synostosed suture. Microcomputed tomographic analysis determined the bone volume fraction, trabecular thickness, trabecular separation, bone surface to bone volume ratio, and anisotropy for all specimens. Our results showed significant differences in all of these quantitative measurements when comparing the complete synostotic suture with the open portion of the synostotic sutures (p < 0.05). Microcomputed tomographic stereologic analysis showed evidence of the influence of biomechanical force on the synostotic and open portions of the synostotic sutures. Results of scanning electron microscopy show a definite qualitative difference in the trabecular pattern of the partial and complete synostotic suture when compared with the open portion of the synostotic sagittal suture. In this study, we performed both qualitative and quantitative comparisons of the ultrastructure of the complete synostotic and nonsynostotic sagittal sutures using stereologic and histomorphometric techniques. We also demonstrated evidence of the influence of biomechanical force on the synostotic sagittal suture. Finally, we established a link between the pathologic changes transforming normal suture fusion to craniosynostosis and concurrent changes in both the vector and direction of suture fusion initiation.

Biomechanical Phenomena↗
PubMed2002

The course of the inferior alveolar nerve in craniofacial microsomia: virtual dissection using three-dimensional computed tomography image analysis.

Computer-assisted medical imaging was used to locate the mandibular foramen and the portion of the inferior alveolar nerve canal at the level of the angle of the mandible in 19 hemimandibles of patients with craniofacial microsomia. The distance from each of these two points to the borders of the mandible was measured. The ratios of these distances to the height, anteroposterior, and buccolingual extents of the mandibular ramus were calculated. These ratios were compared among affected hemimandibles (Pruzansky classification I, n = 4; and Pruzansky classification II, n = 10), unaffected hemimandibles (n = 9), and the hemimandibles of patients with nonsyndromic, sutural synostosis (n = 7). Comparison of mean distance ratios showed that the mandibular foramen was located significantly more proximally in the affected cohort than in either the unaffected or synostosis control groups. The mandibular foramen was also located significantly closer to the buccal cortex of the mandible in the affected cohort when compared with unaffected patients. The distance from the mandibular foramen to the anterior or posterior tables of the mandible divided by the total anteroposterior distance did not vary among the three groups studied. The distance ratios between the inferior alveolar nerve canal at the level of the angle of the mandible and the mandibular borders also did not vary significantly among the groups studied. An inferior alveolar nerve canal could not be identified in any patient with Pruzansky grade III mandibular deficiency. This quantitative, three-dimensional description of points along the proximal path of the inferior alveolar nerve canal in patients with craniofacial microsomia provides useful information to assist the surgeon during osteotomy planning and may help in avoiding injury to the nerve at the time of surgery.

Child↗
PubMed2004

Cenani-Lenz syndactyly in a patient with features of Kabuki syndrome.

We report a 5 9/12-year-old male with Cenani-Lenz syndactyly (CLS). He presented with three malformed digits on each hand and bilateral 2,3 partial cutaneous toe syndactyly. The expression of this presumed autosomal recessive disorder is variable and has been confused with split hand foot malformation (SHFM). Not all CLS patients show the typical 'spoon hand' configuration originally described. Affected CLS patients show a disorganized appearance of the phalanges with some degree of syndactyly/oligodactyly, in addition to metacarpal and carpal fusions. Radioulnar synostosis may be present. Cases lacking radioulnar synostosis may show proximal dislocation of the radial heads. The distal limb anomalies seen in our patient resemble other reported CLS patients. Radiographic evaluation showed a disorganized appearance of the phalanges, a 'kissing delta phalanx' of one proximal phalanx, metacarpal fusions, carpal coalitions and posterior subluxation of the radial heads. Clinical examination revealed features suggestive of Kabuki syndrome including large, prominent ears, sparse, medially flared and arched eyebrows, wide palpebral fissures, long eyelashes, and oligodontia with flat head 'screwdriver-shaped' incisors, in addition to persistent finger and thumb-tip pads. The faces of CLS patients are rarely shown or described. However, some patients in published reports have large, prominent ears. A recent report suggested midfacial dysmorphism in two patients with CLS (). Although the findings of CLS with features of Kabuki syndrome in our patient may be coincidental, the faces of CLS patients need to be carefully evaluated and described to determine if there is a distinctive accompanying facial phenotype.

Bone and Bones↗
PubMed2005

FGFR3 P250R mutation increases the risk of reoperation in apparent 'nonsyndromic' coronal craniosynostosis.

Many patients with a clinical diagnosis of "nonsyndromic" coronal craniosynostosis have been found to be heterozygous for the fibroblast growth factor receptor 3 (FGFR3) mutation Pro250Arg. The phenotype associated with this mutation is variable and lacks highly distinctive features, so it is difficult to diagnose on clinical examination alone. The authors present a retrospective study of 76 patients with isolated coronal synostosis who were operated on in a single dedicated craniofacial unit over 25 years. The authors investigated whether any single factor, including the presence of a FGFR3 Pro250Arg mutation, predisposed to an increased transcranial reoperation rate. Eight patients had repeat transcranial surgery for a functional indication. Heterozygosity for the FGFR3 Pro250Arg mutation, present in 29 patients in the cohort, was the only factor found to have a significant association (P=0.048) with the transcranial reoperation rate. Six patients (20.7%) with the mutation underwent reoperation on the basis of raised intracranial pressure, as compared with two patients (4.3%) without the mutation. This highlights the need for genetic analysis and long-term clinical follow-up in apparently "isolated" coronal synostosis.

Adolescent↗
PubMed2005

Microscopic approach to craniosynostosis.

The purpose of this study is to describe a minimally invasive approach using a microscope and the subsequent helmet therapy. The authors have treated 14 patients with the microscopic technique between May 2001 and November 2003. In this group of patients, there were 3 females and 11 males with an average age of 10.5 weeks and a range of 4 to 28 weeks. The study included 8 patients with sagittal synostosis and 6 patients with other synostoses. In the latter group, there were 3 patients with metopic, one with unicoronal, one with bicoronal, and one with lambdoidal. The approach used limited incisions over the affected sutures. The craniotomy/craniectomy was completed using a 5-mm burr. Postoperative helmet therapy was begun within 2 weeks after surgery. In patients with sagittal synostosis, a mean of 1.5 helmets for a duration of 11.4 weeks was used. In the other groups of patients with craniosynostosis, a mean of 2.3 helmets for a duration of 13.5 weeks was used. A microscopic variation to the "minimally invasive" approach to craniosynostosis is presented. It provides excellent visualization, illumination, and control of the surgical field. When compared with traditional surgery, it results in shorter hospitalization and operative time and decreased blood loss. The authors note that critical to this approach is the postoperative helmet therapy. Early results are encouraging.

Blood Loss, Surgical↗
PubMed1983

Functional status in ulnar deficiency.

Function is the most important consideration in the evaluation of patients with congenital ulnar deficiency. The upper extremity function of 8 patients with ulnar deficiency was evaluated. None of these patients had been treated with surgical procedures directed to the elbow, forearm, or wrist. The functional criteria included: (a) active ranges of elbow, forearm, and wrist motion, (b) power grip, (c) prehension, (d) dexterity, and (e) a patient's activities questionnaire. The averaged total active range of joint motion was 229 degrees or 46% of predicted normal active motion. Power grip averaged 27% of the contralateral extremity, and prehension tests were generally well performed. Timed tests were completed an average of 11.6 s slower than the contralateral control hand. Our patients did not report any deficiencies in bimanual activities. Patients performed most poorly when their congenital anomaly included radiohumeral synostosis or congenital absence, deformity, or contracture of the ipsilateral digits. The radiographic appearances or classification of the ulnar deficiency, in the absence of radiohumeral synostosis, did not correlate well with patient function.

Adolescent↗
PubMed2005

Expression of FGFR-2 and FGFR-3 in the normal human fetal orbit.

AIMS: To demonstrate the expression patterns of two fibroblast growth factor receptors (FGFR-2 and FGFR-3) in the normal human fetal orbit. METHODS: 6 microm orbital slide sections were prepared from 12 week old human fetal material obtained within established ethical guidelines. Radioactive in situ hybridisation techniques were used to demonstrate the expression patterns of FGFR-2 and FGFR-3 within these sections. Only one foetus had appropriate orbital sections taken. RESULTS: FGFR-2 was expressed within the extraocular muscles (EOMs) and the optic nerve sheath and to a lesser degree within the orbital periosteal margins and the cranial sutures. FGFR-3 was expressed a lot within the periosteal margins and cranial sutures but not within either the EOMs or the optic nerve sheath. CONCLUSIONS: FGFR-2 and FGFR-3 are differentially expressed within different orbital components. FGFR-2 gene mutations may be responsible for craniosynostotic syndromes such as Crouzon, Pfeiffer, and Apert, while those in the FGFR-3 gene may cause isolated unicoronal synostosis. EOMs may be histologically abnormal in cases of Apert, Pfeiffer, and Crouzon syndromes but not isolated unicoronal synostosis. The pattern of expression of FGFR-2 in the normal human fetal orbit may explain some of the EOM histological findings seen in some cases of Apert, Pfeiffer, and Crouzon syndromes.

Fibroblast Growth Factor 2↗
PubMed1982

A family study of craniosynostosis, with probable recognition of a distinct syndrome.

A family study was based on 184 consecutive patients who had undergone surgery for craniosynostosis at The Hospital for Sick Children, London, between 1953 and 1976. Of these, 127 were traced and visited and are the probands for this study. Crouzon syndrome was recognised in 16, Apert in 11, Saethre-Chotzen in nine, and Pfeiffer in two. In addition, two probands had Saethre-Chotzen-like facies and bilaterally broad big toes owing to partial or complete duplication of the distal phalanx. This syndrome is distinct from Pfeiffer syndrome, in which the facies more closely resembles that in Crouzon syndrome and in which it is the proximal phalanx of the big toe (and often of the thumb) which is abnormal. It is suggested that this newly recognised syndrome be called after Robinow and Sorauf, who appear to be the first to have described a family with the condition. One proband with coronal stenosis had a mother and brother affected, but no syndrome was recognised in them. Excluding this last case, no non-syndromic proband had an affected parent. The 58 probands with predominantly sagittal synostosis had 106 sibs, none of whom was affected. The 21 probands with predominantly coronal synostosis included one sib pair both affected; the remaining 17 sibs were unaffected. The four probands with predominantly metopic stenosis had 13 unaffected sibs and the four with multiple sutures involved had eight unaffected sibs. One sagittal proband had an unaffected monozygotic twin and another an unaffected dizygotic twin.

Craniosynostoses↗
PubMed2007

Correction of sagittal craniosynostosis using a novel parietal bone fixation technique: results over a 10-year period.

Isolated sagittal synostosis is a common form of craniosynostosis affecting roughly 1 in 5,000 children at birth. This results in a scaphocephalic head shape with a characteristically elongated anterior-posterior dimension and narrowed biparietal diameter. We present our experience with the correction of scaphocephaly due to sagittal synostosis using cranial vault reconstruction with a novel form of parietal bone fixation in 21 patients over 10 years. The medial fixation results in a hinging effect whereby transverse brain growth at the squamoid suture is enhanced. This results in excellent cosmetic results that are immediate and durable without the need for postoperative molding helmets. Furthermore, the complications associated with this procedure are limited.

Bone Wires↗
PubMed1996

Incidence of increased intracranial pressure after early surgical treatment of syndromic craniosynostosis.

The late development of intracranial hypertension after an aesthetically successful cranial vault expansion has been noted anecdotally in children with syndromic synostosis. If untreated, this process can lead to neurological and visual deterioration; however, the frequency of this problem is uncertain. In an attempt to detect this process before the onset of irreversible impairment, the authors have since 1991 incorporated routine ophthalmological evaluations into the multidisciplinary follow-up protocol for all patients with complex craniosynostosis. These examinations were performed at initial evaluation and at 6-month intervals thereafter. The present report focuses on the results in 22 consecutive infants with syndromic synostosis who underwent initial surgery between 1991 and 1994. All but 4 children underwent initial cranial reconstruction at 6-18 months of age. Four patients had papilledema preoperatively which in each instance resolved postoperatively. During the follow-up period, 8 children manifested evidence of late intracranial hypertension at a median of 16.5 months after initial operation(s): 4 developed asymptomatic papilledema, 1 had progressive proptosis, and 3 had other subtle clinical signs of increased intracranial pressure (ICP). Further evaluation disclosed a Chiari 1 malformation in 2 children; 4 had a 'beaten copper' appearance on skull radiographs, and 4 underwent lumbar puncture, which in each case demonstrated an opening pressure above 20 cm H2O. Only 3 children exhibited symptoms from the ICP elevation. Six children with a head size < or = the 25th percentile underwent a repeat cranial expansion; after the cranial vault expansion, one child who initially had slit-like ventricles developed ventriculomegaly and, because of persistent papilledema, underwent insertion of ventriculoperitoneal (VP) shunt. Two other patients with a head circumference above the 50th percentile and the development of moderate ventriculomegaly underwent VP shunt insertion alone. All children have had complete resolution of papilledema as well as other symptoms and signs of increased ICP without evidence of optic atrophy or neurological sequelae. This study indicates that the incidence of delayed, asymptomatic increases in ICP among children with complex craniosynostosis is higher than previously estimated. The pathophysiologic bases for this process are discussed. Because the detection of this problem at a presymptomatic stage should optimize the likelihood of a good functional outcome, we strongly recommend close ophthalmological and clinical follow-up as a part of the comprehensive care of all young children with complex craniosynostosis, even after a cosmetically successful cranial expansion.

Craniosynostoses↗
PubMed1980

The foot and ankle in multiple hereditary exostoses.

Twenty-two cases of multiple hereditary exostoses revealed pathological changes in two areas: the first group caused by epiphyseal disturbances, and the second group due to mechanical problems created by the exostoses. The epiphyseal disturbances resulted in ankle valgus, shortened metatarsals, and angular deformities of the necks of the metatarsals. The exostoses produced local tenderness, synostosis of the medical subtalar facet resulting is loss of subtalar motion, and asymptomatic synostosis of the lower tibial fibular syndesmosis.

Adolescent↗
PubMed1999

Unilateral tibial hemimelia with leg length inequality and varus foot: external fixator treatment.

A 15-year-old girl with type II unilateral hemimelia presented with a 13.5-cm shortening of her right leg, absence of the distal half of the tibia, tibiofibular synostosis, and medial dislocation of a cavus and varus foot. She was treated by means of an external fixator. The shortening was significantly corrected, and realignment of the foot with the limb was achieved. An arthrodesis of the talus and lower end of the fibula was carried out operatively and stabilized with an external fixator. In the same surgical procedure, we performed an osteotomy of the tibiofibular synostosis, and progressive distraction was done with another external fixator. We emphasize the advantages of progressive distraction for the correction of congenital deformities of the limbs.

Adolescent↗
PubMed2004

Computed tomography assessment of Apert syndrome.

Apert syndrome, or acrocephalosyndactyly type I, is a craniofacial dysostosis, an autosomal dominant condition characterized by severe developmental disturbances of the craniofacial region including bilateral coronal synostosis associated with midface hypoplasia, exophthalmia, hypertelorism, and symmetric syndactyly of the hands and feet. The aim of this study is to assess the clinical and computed tomography imaging patterns of non-operated patients with Apert syndrome, correlating the bone abnormalities of the cranium, face and the skull base. The study population consisted of 5 patients with Apert syndrome. As part of the craniofacial assessment of the imaging center's routine, all patients underwent clinical evaluation and CT (computed tomograph) exam. Three-dimensional images were generated from helical CT scans, using an independent workstation, to evaluate the craniofacial abnormalities of the syndrome. Clinical exam determined that syndactyly of the hands and feet, pseudocleft in the midline palate and midface hypoplasia were features observed in all of the Apert patients. 3D-CT showed that some abnormalities such as bilateral coronal synostosis, calvarial midline defect and reduction in the antero-posterior dimension of the anterior, medial and posterior cranial fossae were present in all cases. In conclusion, the correlation of clinical and CT imaging findings can be useful to assess the main features observed in Apert patients, improving the criteria for examining the patient and diagnosing this condition, and contributing to the therapeutic planning and surgical follow-up.

Acrocephalosyndactylia↗
PubMed2006

Three-dimensional computed tomography cephalometry of plagiocephaly: asymmetry and shape analysis.

OBJECTIVE: To investigate facial asymmetry associated with both deformational and synostotic plagiocephaly and to identify variables based on skeletal landmarks that distinguish the conditions and quantify severity. DESIGN: Retrospective, cross sectional. SETTING: Australian Craniofacial Unit, Adelaide. MAIN OUTCOME MEASURES: Proportional differences between bilateral distances and principal component (PC) analysis of the skeletal landmarks. PATIENTS: The three-dimensional positions of 78 osseous landmarks were determined from computed tomography (CT) scans of 21 patients with deformational plagiocephaly (DP), 20 patients with unilateral coronal synostosis (UCS), and 2 patients with unilateral lambdoid synostosis (ULS). RESULTS: For both DP and UCS, significant asymmetry was found for the orbital depths, mandibular lengths, maxillary depths, zygomatic arch lengths, lateral base of the parietal bone, and the angle between the anterior and the posterior cranial base projected onto the axial plane. The small sample size for ULS precluded definitive statistical statements but allowed some useful comparisons with the other conditions. The first three PC scores were able to distinguish among the three conditions and which side was affected. CONCLUSIONS: The asymmetry of the cranial base and facial structures, arising from localized abnormality or deformational forces in either the frontal or the occipital regions, can be quantified by a plethora of bilateral features or summarized by PC analysis.

Cephalometry↗
PubMed2006

Mutational screening of FGFR1, CER1, and CDON in a large cohort of trigonocephalic patients.

OBJECTIVE: Screen the known craniosynostotic related gene, FGFR1 (exon 7), and two new identified potential candidates, CER1 and CDON, in patients with syndromic and nonsyndromic metopic craniosynostosis to determine if they might be causative genes. DESIGN: Using single-strand conformational polymorphisms (SSCPs), denaturing high-performance liquid chromatography, and/or direct sequencing, we analyzed a total of 81 patients for FGFR1 (exon 7), 70 for CER1, and 44 for CDON. PATIENTS: Patients were ascertained in the Centro de Estudos do Genoma Humano in São Paulo, Brazil (n = 39), the Craniofacial Unit, Oxford, U.K. (n = 23), and the Johns Hopkins University, Baltimore, Maryland (n = 31). Clinical inclusion criteria included a triangular head and/or forehead, with or without a metopic ridge, and a radiographic documentation of metopic synostosis. Both syndromic and nonsyndromic patients were studied. RESULTS: No sequence alterations were found for FGFR1 (exon 7). Different patterns of SSCP migration for CER1 compatible with the segregation of single nucleotide polymorphisms reported in the region were identified. Seventeen sequence alterations were detected in the coding region of CDON, seven of which are new, but segregation analysis in parents and homology studies did not indicate a pathological role. CONCLUSIONS: FGFR1 (exon 7), CER1, and CDON are not related to trigonocephaly in our sample and should not be considered as causative genes for metopic synostosis. Screening of FGFR1 (exon 7) for diagnostic purposes should not be performed in trigonocephalic patients.

Cell Adhesion Molecules↗