Tessier's Cleft Number 6 Revisited: A Series of 26 new Cases and Literature Review of 44.

OBJECTIVE: To fix a gray zone left in Tessier's classification of rare clefts with cleft 6 and to give a more comprehensive description of cleft 6 anatomy. DESIGN: The material used for the research was a series of 26 clinical cases of patients with assessed cleft 6 and 44 cases found out of a literature review with enough data to be useful. The 70 cases were cross-examined by the authors. STUDY SETTING: The authors are senior craniofacial surgeons working in high-case load department from university centers where the patients are documented and receive primary as well as secondary treatment and follow-up. PATIENTS: The patients were selected out of the series of craniofacial deformities taken care of by the authors' department as rare clefts. MAIN OUTCOME: We describe the full spectrum of cleft 6 as an autonomous entity that could present itself in three subtypes: 6a is the most proximal and could be associated with cleft 8. The subtype 6b is medial toward the zygomatic arch and frequently associated with a bone and teeth appendage (frequently described as a "maxillary duplication"). The subtype 6C goes toward the external ear between the helix crus and the auditory meatus. CONCLUSIONS: The Tessier's opinion is that Treacher Collins syndrome was the association of clefts 6, 7, and 8 and is no longer sustainable in the light of modern genetics. Most of the cleft 6 are misdiagnosed in the literature.

Crouzon Syndrome Anatomy, Usefulness of Vestibular Orientation.

ABSTRACT: Spatial resolution of computerized tomographic scanner has reached a level to which accurate anatomic measurements could be done in. Three-dimensional accurate measurements require a reliable referential system. In craniology landmarks are usually selected in the skull base. For craniofacial malformation the classical landmarks are of no help so the authors have used the vestibular orientation to study a series of 50 Crouzon syndrome computerized tomographic scan and compare the results (shape, position, linear mensuration, volumes…) with 122 controls in unaffected patients. The authors have confirmed Crouzon description of a high level of polymorphism in phenotypes, the authors propose an organigram to understand the abnormal growth patterns in crouzon syndrome, which lead to such consequences. This polymorphism implies that the planning of surgical treatment should be tailored for each case.

Crouzon syndrome: posterior fossa volume studies in vestibular orientation.

INTRODUCTION: With the increasing possibilities of surgical treatment addressing the complex spectrum of defects in Crouzon syndrome (CS), it is of utmost importance to obtain accurate assessment of the malformation. Evaluating the volume of the posterior fossa is of great importance since many authors, considering that its volume is always decreased, favor posterior fossa enlargement as a first step in the treatment of CS. MATERIAL AND METHODS: We studied CT scans of children with CS, which were vestibular-oriented (VO) in order to conform with physiological landmarks, and we measured intracranial volume by manual segmentation; these abnormal CT scans were superposed with VO 3D-CT scanners of age-matched controls. We studied the volume index of the posterior fossa for each CS patient defined as the ratio of its volume in CS patients with the normal for age calculated from normal controls. RESULTS: We studied the imaging of 41 children with CS and 70 control. Among CS patients, the volume of the posterior fossa was increased in 10, compared with control. We found closure of the sphenoidal synchondrosis was correlated with age and with the width of the posterior fossa, but not with its length nor with the posterior fossa volume index. CONCLUSION: Segmentation on VO-CT scanner and superposition with CT scanners of normal controls is a powerful tool for the study of the impact of CS or other synostoses on volume and shape. We found that CS is more heterogeneous than previously thought, and surgical strategies should be adapted accordingly.

Mutations in endothelin 1 cause recessive auriculocondylar syndrome and dominant isolated question-mark ears.

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder with mandibular hypoplasia and question-mark ears (QMEs) as major features. QMEs, consisting of a specific defect at the lobe-helix junction, can also occur as an isolated anomaly. Studies in animal models have indicated the essential role of endothelin 1 (EDN1) signaling through the endothelin receptor type A (EDNRA) in patterning the mandibular portion of the first pharyngeal arch. Mutations in the genes coding for phospholipase C, beta 4 (PLCB4) and guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 (GNAI3), predicted to function as signal transducers downstream of EDNRA, have recently been reported in ACS. By whole-exome sequencing (WES), we identified a homozygous substitution in a furin cleavage site of the EDN1 proprotein in ACS-affected siblings born to consanguineous parents. WES of two cases with vertical transmission of isolated QMEs revealed a stop mutation in EDN1 in one family and a missense substitution of a highly conserved residue in the mature EDN1 peptide in the other. Targeted sequencing of EDN1 in an ACS individual with related parents identified a fourth, homozygous mutation falling close to the site of cleavage by endothelin-converting enzyme. The different modes of inheritance suggest that the degree of residual EDN1 activity differs depending on the mutation. These findings provide further support for the hypothesis that ACS and QMEs are uniquely caused by disruption of the EDN1-EDNRA signaling pathway.

Internal and external spheno-orbital meningioma varieties: different outcomes and prognoses.

BACKGROUND: Internal variation among spheno-orbital meningiomas (SOM) is surgically challenging. Optic canal invasion management is discussed. METHOD: This retrospective study includes 70 patients with SOM who underwent surgery between 1995 and 2012. Preoperative ophthalmological, neurological and aesthetic clinical signs were collected. All patients benefitted from repeated tomography and magnetic resonance imaging (MRI). The surgical team consisted of a neurosurgeon and a plastic surgeon. In the majority of cases, resection was followed by bone reconstruction using an autologous iliac crest graft. The extent of resection was evaluated on the dural and osseous sides. Early clinical outcomes, long-term follow-up, recurrence and adjuvant therapies were reported. RESULTS: The mean age was 52 years old, and 91 % of the patients were women. Initial symptoms primarily included proptosis (65 %), decreased visual acuity (39 %) and soft tissue tumefaction (16 %). We classified 40 cases as the internal variety when considering the inner third of the greater wing of the sphenoid, optic canal, anterior clinoid process or cavernous sinus. The remaining cases were described as the external variety. The complete resection rates for the internal and external varieties were 12 % and 61 %, respectively (P < 0.001). In total, 90 % of cases were grade I meningiomas. For grade I, we reported 30 % recurrence, and 50 % of these cases recurred in the first 2 years. Grade II cases without early adjuvant radiotherapy increased at 2 years. We did not observe any difference in recurrence rate among grade I tumours with or without tumour remnants. At the end of follow-up, visual acuity was stabilised or increased in 88 % of patients. In addition, 14 % of patients experienced persistent pain at the location of the iliac harvesting site. CONCLUSIONS: The internal SOM variety exhibited a reduced total resection rate and a shorter progression-free survival (PFS). Unroofing of the optic canal extended PFS. Among grade I cases, the persistence of a negligible tumour remnant did not alter the probability of recurrence. For superior grades, radiotherapy must be administered in addition to surgery as soon as possible. SOMs require prolonged follow-up. Autologous iliac reconstruction is related to substantial morbidity and could be replaced by prosthetic bone three-dimensional reconstruction.

FAF1, a gene that is disrupted in cleft palate and has conserved function in zebrafish.

Cranial neural crest (CNC) is a multipotent migratory cell population that gives rise to most of the craniofacial bones. An intricate network mediates CNC formation, epithelial-mesenchymal transition, migration along distinct paths, and differentiation. Errors in these processes lead to craniofacial abnormalities, including cleft lip and palate. Clefts are the most common congenital craniofacial defects. Patients have complications with feeding, speech, hearing, and dental and psychological development. Affected by both genetic predisposition and environmental factors, the complex etiology of clefts remains largely unknown. Here we show that Fas-associated factor-1 (FAF1) is disrupted and that its expression is decreased in a Pierre Robin family with an inherited translocation. Furthermore, the locus is strongly associated with cleft palate and shows an increased relative risk. Expression studies show that faf1 is highly expressed in zebrafish cartilages during embryogenesis. Knockdown of zebrafish faf1 leads to pharyngeal cartilage defects and jaw abnormality as a result of a failure of CNC to differentiate into and express cartilage-specific markers, such as sox9a and col2a1. Administration of faf1 mRNA rescues this phenotype. Our findings therefore identify FAF1 as a regulator of CNC differentiation and show that it predisposes humans to cleft palate and is necessary for lower jaw development in zebrafish.

Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome.

BACKGROUND: Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, ß 4 (PLCB4) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. RESULTS: We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. CONCLUSIONS: These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.

Fifteen years of experience with the midfacial distraction without maxillary osteotomy protocol.

PURPOSE: Midfacial distraction for facial stenosis is minimizing the communication between cranial fossa and nasal fossa caused by the Le Fort III osteotomy during frontofacial advancement procedures. There are different types of distractors, such as internal and external devices. The aim of our study is to present a series of 22 consecutive distraction cases operated without any Le Fort osteotomy with external distraction frames. We completely avoid the gap between the skull and nose, thus avoiding related complications. PATIENTS AND METHODS: Between 1997 and 2012, we operated on 22 patients presenting syndromes associating midfacial retrusion, maxillomandibular class III malocclusion and upper airway obstruction. METHODS: We perform a fronto-orbital advancement. We do not perform any maxillary osteotomy. A vertical cut in the lateral orbital wall is done towards the inferior orbital fissure and another cut on the zygomatic arch. We realise the fixation of the frame posteriorly with a folded K-wire and anteriorly with a transmaxillary pin. Aiming overcorrection, we distract on average 1 mm a day for a mean period of 26 days and with a horizontal distraction vector. RESULTS: No deaths or life-threatening complications were reported. All midfacial retrusions were corrected without relapse. The advancement ranged between 6 and 20 mm. Several complications were notified: one sphenopetrous dislocation, one ethmoidonasal dislocation, two device disassemblages and two cases of maxillary sinusitis. Some of these complications caused an incomplete distraction result. CONCLUSIONS: Compared to other techniques, this method is safe, simple and efficient. By sparing major osteotomies, it avoids severe complications.

Trigonocephaly: Lille's surgical technique.

From the early beginning, in 1977, of our experience in the treatment of trigonocephaly and with the follow-up of 263 patients, we have been convinced that it was a condition related to the skull base. It is now proved thank to the comparison between patient's CT scan and normal template (normal skull of the same age) in vestibular orientation. We used to correct this condition by a frontal reshaping and a rotation of the superior and lateral orbital rim along an oblique axis. We call that movement: "valgisation."

Relational development in children with cleft lip and palate: influence of the waiting period prior to the first surgical intervention and parental psychological perceptions of the abnormality.

BACKGROUND: The birth of a child with a cleft lip, whether or not in association with a cleft palate, is a traumatic event for parents. This prospective, multidisciplinary and multi-centre study aims to explore the perceptions and feelings of parents in the year following the birth of their child, and to analyse parent-child relationships. Four inclusion centres have been selected, differing as to the date of the first surgical intervention, between birth and six months. The aim is to compare results, also distinguishing the subgroups of parents who were given the diagnosis in utero and those who were not. METHODS/DESIGN: The main hypothesis is that the longer the time-lapse before the first surgical intervention, the more likely are the psychological perceptions of the parents to affect the harmonious development of their child. Parents and children are seen twice, when the child is 4 months (T0) and when the child is one year old (T1). At these two times, the psychological state of the child and his/her relational abilities are assessed by a specially trained professional, and self-administered questionnaires measuring factors liable to affect child-parent relationships are issued to the parents. The Alarme Détresse BéBé score for the child and the Parenting Stress Index score for the parents, measured when the child reaches one year, will be used as the main criteria to compare children with early surgery to children with late surgery, and those where the diagnosis was obtained prior to birth with those receiving it at birth. DISCUSSION: The mental and psychological dimensions relating to the abnormality and its correction will be analysed for the parents (the importance of prenatal diagnosis, relational development with the child, self-image, quality of life) and also, for the first time, for the child (distress, withdrawal). In an ethical perspective, the different time lapses until surgery in the different protocols and their effects will be analysed, so as to serve as a reference for improving the quality of information during the waiting period, and the quality of support provided for parents and children by the healthcare team before the first surgical intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00993993.

Atypical scaphocephaly: a review.

BACKGROUND AND PURPOSE: Sagittal craniosynostosis (SCS) is common and easily recognized and corrected surgically. However, rare cases of SCS are more complex: these associate closure of the metopic or delayed closure of the coronal suture, uni- or bilaterally. MATERIAL AND METHODS: We reviewed the available literature on atypical sagittal craniosynostosis (ASCS). We also reviewed retrospectively our series of SCS treated since 1980 and selected cases with simultaneous closure of the metopic (leptocephaly) or delayed closure of other sutures (plagiocephaly, oxycephaly, or Crouzon syndrome). RESULTS: ASCS is rare, representing <10 % of SCS. In our series, among 447 cases of SCS followed for a mean duration of 63.7 months, we identified 22 cases of ASCS: 6 with leptocephaly, 9 with non-syndromic oxycephaly, 4 with Crouzon syndrome, and 3 with plagiocephaly. Fourteen patients required a second operation, either planned initially (severe leptocephaly) or because of brain compression. The actuarial incidence of ASCS requiring reoperation was 5.3 % of SCS at 10 years. After a mean follow-up of 113 months, morphological results in ASCS were grade 1 (no defect) in 5, grade 2 (mild defect) in 2, grade 3 (minor reoperation) in 3, and grade 4 (major reoperation) in 12; one patient had visual impairment, and two had learning difficulties. CONCLUSIONS: ACSC can be detected initially or occur with a delay in apparently standard SCS. Leptocephaly is a specific entity. Because of the implications on the management and risk for the patient, preoperative evaluation of patients with SCS with CT scanner and prolonged follow-up are necessary.

Non-syndromic oxycephaly and brachycephaly: a review.

BACKGROUND: Non-syndromic coronal synostoses oxycephaly and brachycephaly (NSCSOB) are rare. Their natural history, surgical management, and outcome are debated. MATERIAL AND METHODS: We reviewed the available literature on NSCSOB. In addition, we reviewed retrospectively our experience with cases of NSCSOB, managed and operated by our joint craniofacial team since 1984. Newborns underwent perifrontal craniectomy, while infants and older children underwent fronto-orbital advancement with frontoparietal remodeling. Cases with delayed onset of faciosynostosis were excluded. RESULTS: Some cases of NSCSOB present at birth or even prenatally with gross dysmorphism and severe brachycephaly; others present later in life with harmonious restriction of intracranial volume and are at risk for development and vision. Some NSCSOB evolve from initially unisutural synostoses. We treated 61 cases, operated aged 1.4 to 106.7 months, 30 with brachycephaly and 31 with oxycephaly. Twelve of these (19.7 %), had been treated initially for sagittal or unicoronal synostosis, and evolved into NSCSOB. Intracranial hypertension was present initially in 28 (45.9 %), with ophthalmological consequences in 13 (21.3 %) and mental retardation in 6 (9.6 %). No patient had hydrocephalus; only two had asymptomatic Chiari malformation. The mean postoperative follow-up was 113.6 months. At last control, 21 patients had developmental delay and 5 had visual impairment. CONCLUSIONS: NSCSOB are a complex entity. They have in common a high risk of severe intracranial hypertension and rare hydrodynamic complications. Genetic screening is necessary to assert their non-syndromic nature. Prolonged follow-up of all craniosynostoses is necessary because unisutural synostoses can evolve into NSCSOB, and NSCSOB can evolve into craniofaciosynostosis.

Unicoronal synostotic plagiocephaly: surgical correction: Lille's technique.

INTRODUCTION: For 35 years, we have a tight neuro-plastic surgical cooperation for the surgical correction and long-term systematic follow-up of 125 cases of unicoronal synostotic plagiocephaly. METHODS: We have tried to understand why some patients had kept an asymmetrical facial growth pattern in spite of a good fronto orbital correction. Analysis in vestibular orientation which was available from 1993 has demonstrated a discrepancy between the ocular and the vestibular verticality referential system. So we have designed a surgical procedure to try to fix that problem. RESULTS AND CONCLUSION: Preliminary results in 27 cases operated according to this procedure, for which we have pre- and post-CT scan demonstrate significative improvements of our results.

Midfacial distraction without osteotomy using a transfacial pin and external devices.

INTRODUCTION: During the 1970s, frontofacial advancement revolutionized the treatment of severe facial stenosis. Unfortunately, this method was associated with significant morbidity due to the Le Fort III osteotomy, which creates a major communication between the frontocranial dead space and the nasal fossae. Midfacial distraction improves the complication rate by diminishing the size of this gap. The aim of our study was to present an original technique that uses external distraction frames and eliminates the need for Le Fort osteotomies. This innovative technique eliminates the gap between the skull and nose, thus avoiding related complications. PATIENTS AND METHODS: Between 1997 and 2008, we operated on 17 patients presenting midfacial retrusion and maxillomandibular class III malocclusion. We performed classic fronto-orbital advancement. The only facial osteotomies are vertical cuts of both the lateral orbital wall and the zygomatic arch. The distraction device is then anchored posteriorly with a K-wire and anteriorly with a transfacial pin through the maxilla. Finally, the distraction is performed horizontally until a class II overcorrection is obtained. RESULTS: No life-threatening complications or mortalities occurred. In all cases, the midfacial retrusion was corrected without relapse. All patients with complications fully recovered. It was observed that most complications were a result of either an overly rapid activation (>1 mm/d). DISCUSSION: Midface distraction using the external transfacial pin is a simple and safe procedure that allows an efficient correction of major facial retrusion. The external transfacial pin acts directly onto the maxilla and allows distraction without Le Fort osteotomy. By eliminating major osteotomies, it reduces the number of severe complications encountered in craniofacial surgery.

Management of Hypertelorism.

Aim: To summarize the experience of the author with the treatment of hypertelorism. Settings and Design: The author has been heading a high-caseload department of craniofacial surgery for 38 years; the research is based on his experience with this pathology by this time. Materials and Methods: The charts of 38 patients were used for this research. Statistical Analysis Used: No statistic was used; the author has just given his personal insights as the result of a professional life devoted to the problem. Results: Most of the hypertelorism cases requiring surgical correction are rare interorbital clefts (Tessier's 14-12). Among the syndromic ones, cranio-fronto orbital dysplasia is the most demanding for surgery because it is associated with craniosynostosis, which has to be addressed at the same time. Among the technics published for hypertelorism correction, craniofacial bipartition has our preference for several reasons: easily done and redone when necessary, safer to the vascularization, and trophicity of displaced parts of the skeleton. Conclusions: Complex craniofacial conditions such as hypertelorism have to be treated only in specialized craniofacial centers by a multidisciplinary team. The caseload has to be high, and the follow-up is very strict to get the benefits of experience to improve the results.

Maxillonasal osteochondral complex repair in maxillonasal dysplasia.

Surgical treatment of maxillonasal dysplasia or Binder syndrome is a challenge for surgeons. Its aim is to replace or substitute the missing or malformed anatomic structures. The authors report a comprehensive analysis for the understanding of the mechanisms resulting in the lack of maxillonasal development observed in Binder syndrome. The evolution of the surgical treatment due to facial function analysis is explained, and the surgical treatment of 20 consecutive cases over the last 20 years is reviewed, illustrated by three-dimensional reconstruction to emphasize the choice made and the results obtained. Bone grafts were always performed, and an arrow-shaped graft for the neospine reconstruction is described. This analysis allowed the authors to ameliorate patient self-image subsequently to facial contour improvement.

Clinical and experimental study of autologous fat grafting after processing by centrifugation and serum lavage.

BACKGROUND: This clinical and experimental study compared adipose tissue transplant behavior after two different techniques of purifying: centrifugation at 3400 rpm for 3 min and serum lavage without centrifugation. METHODS: Clinical evaluation was performed under standardized conditions for lipofilling on a series of 51 female patients, intentionally selected to have similar characteristics and assigned to two groups based on the method of processing. Experimentally, a culture system in diffusion chambers with vitaline membranes was designed to mimic the behavior and to study the morphology of the adipose tissue used for autografting. Survival, structure, and proliferation of the adipose cells in vitro were examined by classical histologic H&E staining and immunohistochemistry for leptin and cyclin D1. RESULTS: The main differences encountered experimentally were the presence of a greater amount of preadipocytes in the noncentrifuged adipose tissue cultures and more distinctly expressed cell proliferation. The postoperative clinical results favored of the serum lavage purifying technique. CONCLUSION: Our data suggest that with transplantation of noncentrifuged adipose tissue more active preadipocytes are applied which could possibly lead to better potential chances of survival and even de novo development of fat.

Three-dimensional study of 31 cases of synostotic anterior plagiocephaly before and after surgical management the Lille protocol.

Synostotic anterior plagiocephaly is a rare pathological cranial malformation. Therapeutic options are rarely studied due to the rarity of the malformation and difficulties in diagnosis and care management. The objective of this study was to analyze the results obtained with the Lille protocol based on 62 CT-scans done before and after surgery in 31 patients. A specific analysis was designed for this work. Nine cephalometric measures enabled to evidence on each CT-Scan the corrections made on the fronto-orbital bandeau and the potential impact of surgery on the craniofacial structures. Results show that surgical symmetry of the fronto-orbital bandeau in the transversal plane, according to the symmetrical axis of the semicircular canals, allows a normalization of the skull's growth and morphogenesis for the surgically affected structures but also adjacent ones.

Facial diplegia revealing ventriculoperitoneal shunt failure in a patient with Crouzon syndrome. Case report.

The authors report on the case of a 15-year-old boy with Crouzon syndrome (CS) who presented with headache and facial diplegia. He had undergone several craniofacial interventions and a posterior fossa decompression for tonsillar herniation caused by the CS. A ventriculoperitoneal (VP) shunt had been inserted for hydrocephalus. Emergency computed tomography (CT) disclosed slight dilation of the ventricular cavities compared with their appearance on a baseline CT scan. Magnetic resonance imaging showed a deformed brainstem but no compression at the occipital foramen; there was no apparent explanation for the facial diplegia. The neuroophthalmological examination revealed neither papilledema nor oculomotor palsy. Electromyography confirmed incomplete peripheral facial diplegia. The patient underwent emergency shunt revision, during which complete obstruction of the ventricular catheter and severe cerebrospinal fluid hypertension were found. After surgery, cranial hypertension symptoms completely resolved and the facial diplegia improved slowly with a persistent and incomplete right superior facial palsy. Cranial 3D CT scanning reconstructions and brain magnetic resonance imaging demonstrated severe petrous bone distortion that could have been responsible for direct stretching injuries on the facial nerves at the level of the internal acoustic meatus. The present case represents the first reported occurrence of VP shunt failure as revealed by a facial palsy; the authors discuss the pathophysiology of facial palsy in intracranial hypertension.