Auricles Anomalies in Patients With a TCF12 Gene Mutation.

Craniostenosis is a morphological anomaly affecting about 0.5 of 1000 births and one third of the cases are of genetic origin. Among the syndromes responsible for craniostenosis, there is the Saethre-Chotzen syndrome due to a mutation of the TWIST 1 gene located on chromosome 7. This polymalformative syndrome classically includes a particular morphology of the auricles. The penetrance is variable and results in a phenotypic variability at the origin of "Saethre-Chotzen like" clinical pictures for which the TWIST 1 gene mutation is sometimes not found. Recently, the TCF 12 gene has been implicated in some of these cases. Among the multiple facial malformations, we have carefully examined the particular morphology of the auricle of these patients. The authors found several abnormalities in patients with a TCF 12 gene mutation, namely a thickened and hammered upper pole of the helix, a narrow concha without crux cymbae and a thickened lobe. These morphological features may guide the diagnosis and allow an earlier search for a TCF 12 gene mutation.

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.

Synostosis of the lambdoid suture: a spectrum.

PURPOSE: Lambdoid synostosis (LS) is a rare condition, which is either isolated; associated with sagittal synostosis, the "Mercedes-Benz" syndrome (MBS); or with synostosis of the coronal sutures (oxycephalic form). In addition, LS is part of the phenotype of a growing number of genetic diseases. The nosology, pathophysiology, and management are controversial. We decided to review our experience with LS. METHODS: We reviewed retrospectively pediatric cases of LS proved on CT-scanner, isolated or associated with other conditions, followed in our craniofacial center during the last 15 years, regarding clinical presentation, anatomical lesions, syndromic associations, surgical management, and outcome. RESULTS: We reviewed 48 cases: 6 isolated LS, 22 MBS, and 20 oxycephalic. A syndromic context was present in 72% (up to 80% of oxycephalic cases), and faciostenosis was present in 23%, mostly oxycephalic cases (40%). Transverse sinus agenesis was found in 61% of documented patients. A total of 31% of children had a dystocic birth, up to 45% of MBS. Decompressive craniectomy or cranioplasty was needed in a majority of patients, often young infants, while posterior fossa decompression was mostly performed in older children. CONCLUSION: LS is rarely isolated and non syndromic; most cases are found in a wide spectrum of diseases, and LS is often associated with sagittal or coronal synostosis. Genetic evaluation is mandatory for LS; conversely, geneticists may require neurosurgical advice for LS in an increasing number of very rare diseases. The surgical management of LS should be tailored according to clinical presentation, age, and syndromic context.

Morphological and surgical results in sagittal synostosis: early craniectomy versus later cranioplasty.

BACKGROUND AND PURPOSE: Morphological correction is one of the main aims of surgery for sagittal synostosis (SSO). Different surgical techniques have been developed; however, few studies have compared the different surgical protocols. The morphological outcome is poorly documented, because a consensual evaluation tool is lacking. MATERIAL AND METHODS: We performed a prospective study of children operated for SSO in our institution. Children were operated whenever possible at 4 months for craniectomy; by default, children underwent cranioplasty at or after 9 months. The morphological outcome of all children was evaluated using traditional craniometry with head circumference (HC) and the cephalic index (CI), and with the Rotterdam scaphocephaly morphology score (RSMS), a total of semi-quantitative assessments of morphological hallmarks. RESULTS: Craniectomy was significantly associated with a shorter operation time and hospital stay, and a better impact on HC and CI measurements, compared with cranioplasty. The RSMS was markedly improved after surgery in both groups; however, we found no significant difference in improvement between the two groups. Although the transfusion rate and the prevalence of developmental delay were lower in the craniectomy group, and reoperations for calvarial lacunae or complex craniosynostosis occurred only this group, these differences were not significant. CONCLUSIONS: Our results support early surgery with craniectomy whenever possible; however, cranioplasty at a later age is a very acceptable by-default indication. In addition to classical craniometry, morphological evaluation using the RSMS or a similar quantitative scale appears highly desirable for future studies.

Linear craniectomy for early posterior decompression in craniosynostoses: technique and results.

INTRODUCTION: Early decompressive posterior linear craniectomy (PLC) can be indicated in very young infants with complex multisuture synostosis, which often involve the lambdoid suture (LS). The literature data on the surgical technique and its results are scarce. MATERIAL AND METHODS: Based on our experience with PLC during the last 10 years, we detail our surgical technique for PLC, the possible pitfalls, and complication avoidance. RESULTS: We review seven observations, 5 girls and 2 boys, 6 of these with identified mutations, operated for PLC at a mean age of 3.19 months (6 days to 6.1 months). One patient died of unexplained cardiac arrest on postoperative day two, the others had a favorable outcome with good development and no visual loss. Three of these required additional cranioplasty at a later age, one of these with craniofacial distraction. DISCUSSION: PLC can be a salvage operation in very young patients with complex synostosis involving the LS, and with proper preparation and careful technique, allows favorable outcome. The approach must be versatile in order to anticipate further surgeries in these complex, most often syndromic cases.

Benefits of cryopreserved human amniotic membranes in association with conventional treatments in the management of full-thickness burns.

The use of split-thickness skin autografts (STSA) with dermal substitutes is the gold standard treatment for third-degree burn patients. In this article, we tested whether cryopreserved amniotic membranes could be beneficial to the current treatments for full-thickness burns. Swines were subjected to standardised full-thickness burn injuries, and then were randomly assigned to treatments: (a) STSA alone; (b) STSA associated with the dermal substitute, Matriderm; (c) STSA plus human amniotic membrane (HAM); and (d) STSA associated with Matriderm plus HAM. Clinical and histological assessments were performed over time. We also reported the clinical use of HAM in one patient. The addition of HAM to classic treatments reduced scar contraction. In the presence of HAM, skin wound healing displayed high elasticity and histological examination showed a dense network of long elastic fibres. The presence of HAM increased dermal neovascularization, but no effect was observed on the recruitment of inflammatory cells to the wound. Moreover, the use of HAM with classical treatments in one human patient revealed a clear benefit in terms of elasticity. These results give initial evidence to consider the clinical application of HAM to avoid post-burn contractures and therefore facilitate functional recovery after deep burn injury.

Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1.

PURPOSE: Blepharocheilodontic (BCD) syndrome is a rare autosomal dominant condition characterized by eyelid malformations, cleft lip/palate, and ectodermal dysplasia. The molecular basis of BCD syndrome remains unknown. METHODS: We recruited 11 patients from 8 families and performed exome sequencing for 5 families with de novo BCD syndrome cases and targeted Sanger sequencing in the 3 remaining families. RESULTS: We identified five CDH1 heterozygous missense mutations and three CTNND1 heterozygous truncating mutations leading to loss-of-function or haploinsufficiency. Establishment of detailed genotype-phenotype correlations was not possible because of the size of the cohort; however, the phenotype seems to appear more severe in case of CDH1 mutations. Functional analysis of CDH1 mutations confirmed their deleterious impact and suggested accelerated E-cadherin degradation. CONCLUSION: Mutations in CDH1 encoding the E-cadherin were previously reported in hereditary diffuse gastric cancer as well as in nonsyndromic cleft lip/palate. Mutations in CTNND1 have never been reported before. The encoded protein, p120ctn, prevents E-cadherin endocytosis and stabilizes its localization at the cell surface. Conditional deletion of Cdh1 and Ctnnd1 in various animal models induces features reminiscent of BCD syndrome and underlines critical role of the E-cadherin-p120ctn interaction in eyelid, craniofacial, and tooth development. Our data assert BCD syndrome as a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1 and widen the phenotypic spectrum of E-cadherin anomalies.Genet Med advance online publication 09 March 2017.

Case update on cranial osteopetrosis: which is the role of the neurosurgeon?

PURPOSE: Osteopetrosis (OP) is a rare skeletal disease, which can affect the skull base and calvaria. A multidisciplinary approach is mandatory and patient may need neurosurgical care. Few observations have been published, and optimal management of OP is not established yet. METHOD: We report a case of an infant with OP diagnosed at 5 months, who presented signs of intracranial hypertension associated with unilateral blindness. Bone marrow allograft was performed at 6 months of age. At neurosurgical first examination at 11 months, the child was hypotonic, with severe amblyopia; features of bicoronal synostosis were appreciated, with tense anterior fontanel bulging indicating synostotic oxycephaly. Head circumference had decreased from +3 SD to +1SD. Cerebral CT scan showed reduction of intracranial volume, inward thickening of the calvaria, bilateral stenosis of optic canal, ventricular dilatation, enlarged arachnoid spaces, and tonsillar herniation. We performed cranial vault expansion with frontal advancement and bi parietal decompression, thinning of the inner table, unroofing of the left orbit and optic canal in order to obtain optic nerve decompression. RESULTS: Postoperative course was uneventful, and the patient was discharged on day 8. Vision was unchanged but rapid improvement of axial tonus was noted. The CT scan showed satisfactory calvarial expansion with regression of tonsillar herniation. CONCLUSIONS: Neurosurgical evaluation and care are necessary in the context of a multidisciplinary approach to the patient affected by osteopetrosis. Cranial vault remodeling and expansion should be considered in patients with sign of intracranial hypertension. Timing of optic canal decompression is to be defined.

Lengthening temporalis myoplasty: a surgical tool for dynamic labial commissure reanimation.

Lengthening temporalis myoplasty (LTM), first described by Labbé in 1997, ensures the transfers of the entire temporal muscle from the coronoid process to the upper half of the lip without interposition of aponeurotic tissue. The temporal muscle changes function because it is entirely mobilized toward another effector: the labial commissure. Thanks to brain plasticity, the muscle loses its chewing function, and after 6 months of speech rehabilitation it acquires its new smiling function. We describe technical points especially the coronoid process approaches both through an upper temporal fossa approach and a lower nasolabial fold approach. Rehabilitation starts 3 weeks after the surgery following a standardized protocol to move from a mandibular smile to a voluntary, then spontaneous, smile in three steps. The LTM is the main part of a one-stage global treatment of the paralyzed face. It constitutes a dynamic palliative treatment usually started at the sequelae stage, 18 month after the outcome of a peripheral facial paralysis. This one-stage procedure is a reproducible and relevant surgical technique in the difficult treatment of peripheral facial paralysis. It allows implementing an active muscle transfer to reanimate the labial commissure and re-create a mobile nasolabial fold.

Orbital exenteration and periorbital skin cancers.

PURPOSE: Orbital exenteration is a disfiguring surgical procedure that requires thoughtful reconstruction. PATIENTS AND METHODS: We analyzed all cases of orbital exenteration done in our department since 1998. RESULTS: A total of 26 patients had undergone surgery during our study period, and 27 exenterations have been conducted since 1998. The reconstruction was performed in 20 patients using an ipsilateral temporal muscle flap. One patient underwent reconstruction using a temporalis fascia flap and 6 using free flaps. A total of 11 patients received postoperative radiotherapy. Data collection revealed 6 patients with an ocular prosthesis. The prosthesis had either been glued or mounted onto glasses. CONCLUSIONS: Analyzing our results and the published data, we found that the reconstruction mode influences prosthetic rehabilitation. Thus, we have identified 2 categories. In the first category, postoperative radiotherapy will be required and coverage with a flap will be needed. In the second category, postoperative radiotherapy is not indicated and thus the healing time might be extended in favor of more space for better retention of the prosthetic rehabilitation.

Perception of aesthetic impairment in patients with systemic sclerosis determined using a semi-quantitative scale and its association with disease characteristics.

Background: Systemic sclerosis is a fibrotic disease. Body image assessments could be key in optimizing care; however, data are scarce. The main objective was to assess the perception of aesthetic impairment using a visual aesthetic evaluation scale in patients with systemic sclerosis compared with healthy subjects. The secondary objectives were to assess associations between the perception of aesthetic impairment and scores on standardized questionnaires for aesthetic impairment as well as clinical, psychological/quality of life, and functional parameters of patients with systemic sclerosis. Methods: This study evaluated and compared the perception of aesthetic impairment in two populations: patients with systemic sclerosis from a referral center at Lille Hospital, France, and healthy controls. Results: This study included 88 patients (69 (78.4%) women) with a median age of 52 years and 88 controls (49 (55.7%) women) with a median age of 45 years. The perception of aesthetic impairment assessed using the aesthetic evaluation scale was poorer in systemic sclerosis patients than in controls (3.7 ± 0.3 vs 2.8 ± 0.3, p = 0.028) and was statistically correlated with assessments using the adapted satisfaction with appearance, a specific aesthetic impact assessment questionnaire for patients with systemic sclerosis. Patients with anxiety or depressive symptoms had significantly higher aesthetic evaluation scale scores. Systemic sclerosis patients with facial involvement and pitting scars had a worse perception of aesthetic impairment. Compared with healthy controls, systemic sclerosis patients had a worse perception of aesthetic impairment, especially systemic sclerosis patients with anxiety or depression and those with facial and hand involvement. Conclusion: The aesthetic evaluation scale appears to be an easy-to-use tool to evaluate body image. Correlations of the aesthetic evaluation scale score with psychological and quality of life parameters reflect the importance of these parameters for body image evaluation and its complex assessment. Trial registration: Clinical Trial NCT03271320 (Registered 9 January 2017, https://www.clinicaltrials.gov/ct2/show/NCT03271320?term=NCT03271320&cntry=FR&draw=2&rank=1).

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."

Engineering 3D-Printed Bioresorbable Scaffold to Improve Non-Vascularized Fat Grafting: A Proof-of-Concept Study.

Autologous fat grafting is the gold standard for treatment in patients with soft-tissue defects. However, the technique has a major limitation of unpredictable fat resorption due to insufficient blood supply in the initial phase after transplantation. To overcome this problem, we investigated the capability of a medical-grade poly L-lactide-co-poly ε-caprolactone (PLCL) scaffold to support adipose tissue and vascular regeneration. Deploying FDM 3D-printing, we produced a bioresorbable porous scaffold with interconnected pore networks to facilitate nutrient and oxygen diffusion. The compressive modulus of printed scaffold mimicked the mechanical properties of native adipose tissue. In vitro assays demonstrated that PLCL scaffolds or their degradation products supported differentiation of preadipocytes into viable mature adipocytes under appropriate induction. Interestingly, the chorioallantoic membrane assay revealed vascular invasion inside the porous scaffold, which represented a guiding structure for ingrowing blood vessels. Then, lipoaspirate-seeded scaffolds were transplanted subcutaneously into the dorsal region of immunocompetent rats (n = 16) for 1 or 2 months. The volume of adipose tissue was maintained inside the scaffold over time. Histomorphometric evaluation discovered small- and normal-sized perilipin+ adipocytes (no hypertrophy) classically organized into lobular structures inside the scaffold. Adipose tissue was surrounded by discrete layers of fibrous connective tissue associated with CD68+ macrophage patches around the scaffold filaments. Adipocyte viability, assessed via TUNEL staining, was sustained by the presence of a high number of CD31-positive vessels inside the scaffold, confirming the CAM results. Overall, our study provides proof that 3D-printed PLCL scaffolds can be used to improve fat graft volume preservation and vascularization, paving the way for new therapeutic options for soft-tissue defects.

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.

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.

Preclinical Study of Radiation on Fat Flap Regeneration under Tissue-engineering Chamber: Potential Consequences for Breast Reconstruction.

Use of a tissue-engineering chamber (TEC) for growth of fat flap is a promising approach for breast reconstruction. Here, we evaluated in a preclinical model the effects of radiation on adipose tissue growth either before or after 3D-printed bioresorbable TEC implantation. Methods: Twenty-eight female Wistar rats were distributed into three groups: TEC implantation as nonirradiated controls (G1), TEC insertion followed by irradiation 3 weeks later (G2), and irradiation 6 weeks before TEC insertion (G3). G2 and G3 received 33.3 Gy in nine sessions of 3.7 Gy. Growth of the fat flap was monitored via magnetic resonance imaging. At 6 months after implantation, fat flaps and TECs were harvested for analysis. Results: Irradiation did not alter the physicochemical features of poly(lactic-co-glycolic acid)-based TECs. Compared with G1, fat flap growth was significantly reduced by 1.6 times in irradiated G2 and G3 conditions. In G2 and G3, fat flaps consisted of mature viable adipocytes sustained by CD31+ vascular cells. However, 37% (3 of 8) of the G2 irradiated adipose tissues presented a disorganized architecture invaded by connective tissues with inflammatory CD68 + cells, and the presence of fibrosis was observed. Conclusions: Overall, this preclinical study does not reveal any major obstacle to the use of TEC in a radiotherapy context. Although irradiation reduces the growth of fat flap under the TEC by reducing adipogenesis and inducing inconsistent fibrosis, it does not impact flap survival and vascularization. These elements must be taken into account if radiotherapy is proposed before or after TEC-based breast reconstruction.

Radiotherapy alone for Merkel cell carcinoma: a comparative and retrospective study of 25 patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare skin cancer. Cumulative data from retrospective series support the notion that benefits are obtained by both wide excision and adjuvant radiation therapy. However, surgery may be difficult to perform with tumors located in the head and neck region and/or in elderly patients with comorbidities incompatible with general anesthesia. OBJECTIVE: We assessed the benefit of treating MCC exclusively with radiation when conventional treatment (surgery followed by radiotherapy) is not possible. METHODS: A total of 25 patients with primary MCC were treated at our institution exclusively with radiotherapy. Because there is no consensus about this specific approach, we compared the recurrence rate of the 25 patients receiving radiotherapy alone with that of 25 patients who received conventional treatment at our institution. RESULTS: The median follow-up periods were 3 years (range: 5 months-11 years) for the group receiving only radiotherapy (group 1) and 9 years (range: 12 months-16 years) for the conventional therapy group (group 2). No local relapses were observed, but two locoregional relapses were observed in group 1, and 4 in group 2. No statistical differences were found in overall and disease-free survival between the two groups of patients. LIMITATIONS: The limitation of this study is its retrospective nature. CONCLUSIONS: This study confirms the results of our previous research demonstrating that it is possible to treat inoperable MCC exclusively with radiotherapy to obtain an outcome similar to that which is achievable with conventional treatment.

Masseter muscle termination over the deep surface of the temporal fascia: look out the wrong path.

PURPOSE: The masticatory muscles have a common embryological origin. Despite numerous anatomical studies their close anatomical relationships are not always accurately described in anatomical treatises. An expansion of the masseter muscle inserted into the deep surface of the superficial temporal aponeurosis has been described. Despite the classical description of two transition bundles (Yoshikawa et al. in Kaibogaku Zasshi 37:206-217, 1962), the literature concerning these fibres has remained difficult to interpret. Given the clinical applications of the lengthening of the temporal muscle in myoplasty, it is important that we have accurate anatomical knowledge of it. METHODS: We dissected 14 embalmed or untreated anatomical cadaver heads with a sex ratio of 1 in order to analyse the aforementioned fibres and their variations. A radiologic study allowed us to understand the entanglement of the fibres. 10 craniofacial MRI were processed by 3D MPR reconstruction. RESULTS: The fibres were identified as an expansion of the posterior head of the masseter muscle and distinct from the two classically described transition bundles. These were present in all subjects of both sexes. We can systematically describe their origin, trajectory and termination. CONCLUSION: Fibres belonging to masseter muscle pass up to the zygomatic arch and terminate on the deep surface of the temporal fascia. Awareness of the nature and trajectory of these muscular fibres allows us to avoid taking "wrong path" when approaching the temporal muscle tendon on the coronoid process via the temporal fossa.