Beckwith-Widemann Macroglossia: The Role of Surgical Tongue Reduction.

Objective: This review was conducted to define the natural history of unoperated Beckwith-Wiedemann syndrome (BWS) macroglossia and the effect of tongue reduction surgery upon breathing, eating, speaking and dentoskeletal development in individuals having BWS. Design: This is a retrospective study of medical records. SETTING: All patients were evaluated and treated in one of two Children's Hospitals by an ACPA approved Craniofacial Team. PATIENTS/PARTICIPANTS: Medical records were reviewed of 526 individuals having a diagnosis of BWS and evaluated in-person by a single craniofacial surgeon between 1986 and 2014 in conjunction with a series of multi-disciplinary craniofacial team colleagues. 28 individuals were excluded having had multiple tongue reductions elsewhere. 498 individuals comprise the "pre tongue-reduction group". The "post tongue-reduction group" consists of 391 individuals who underwent surgical tongue reduction by one surgeon using one technique between 1986 and 2014. MAIN OUTCOME MEASURES: The primary outcome measure was change in anterior dental occlusion following tongue reduction surgery. Tongue reduction surgery was performed on the assumption that it would improve dentoskeletal relationships. Secondary outcome measures were: breathing, feeding/swallowing, and speech. Results: A significant difference (p<0.001) over time between the two groups was found with less anterior occlusal abnormality in the tongue reduction group. Tongue reduction surgery had no mortality and minimal morbidity for breathing, feeding/swallowing, and speech and can ameliorate obstructive sleep apnea. Conclusions: Surgical tongue reduction for BWS macroglossia is recommended for the infant or child in primary dentition with a grossly abnormal anterior tooth/jaw relationship and/or obstructive sleep apnea.

Reduction Glossectomy for Macroglossia in Beckwith-Wiedemann Syndrome: Is Post-Op Intubation Necessary?

OBJECTIVE: Macroglossia is a characteristic feature of Beckwith-Wiedemann syndrome (BWS), commonly treated with reduction glossectomy to restore form and function. There exists no consensus on the perioperative management of these patients undergoing tongue reduction surgery, including anecdotal information regarding how long postoperative intubation should be maintained. The aim of this study is to evaluate the necessity of prolonged postoperative intubation in patients receiving tongue reduction surgery via the surgical and anesthetic management methods at our center. DESIGN: Retrospective case series. SETTING: Institutional care at Level I Children's Hospital. PARTICIPANTS: All children less than 18 years old with BWS and congenital macroglossia who underwent tongue reduction surgery over 5 consecutive years at our center (N = 24). INTERVENTIONS: Tongue reduction surgery via the "W" technique. MAIN OUTCOME MEASURES: Success of immediate postoperative extubation and related surgical complications. RESULTS: Immediate, uncomplicated postoperative extubation was successfully performed in all patients who received tongue reduction surgery for congenital macroglossia. CONCLUSIONS: Prolonged postoperative intubation for tongue reduction surgery may not be necessary as immediate, uncomplicated postoperative extubation was achieved in 100% of patients who received tongue reduction surgery at our center.

Interventional management of high-flow craniofacial vascular malformations: a database analysis and review of the literature.

BACKGROUND: High-flow craniofacial vascular malformations are uncommon, locally aggressive lesions that pose a therapeutic challenge. OBJECTIVE: To report our experience with the treatment of high-flow craniofacial vascular malformations. METHODS: After institutional review board approval was obtained, the neurointerventional databases of two institutions were retrospectively reviewed for vascular malformations from October 2010 to June 2015. All patients who had been treated for a high-flow craniofacial vascular malformation were included in the analysis. Clinical presentation, location, type, agent and techniques used, procedural complications, and clinical and imaging follow-up were included in the analysis. RESULTS: Eighteen patients (12 female and 6 male) harboring 21 high-flow vascular malformations met the inclusion criteria in our study. All patients were symptomatic. One patient had two separated arteriovenous malformations (AVMs) (one nasal and the other forehead/scalp), and one patient had three separated scalp lesions. One patient with a nasal AVM had capillary malformation-AVM syndrome. Overall, 13 AVM and 8 arteriovenous fistuli were treated in 31 targeted embolization procedures (ranging from 1 procedure to 4 procedures, mean 1.7 procedures). Onyx was the predominant agent used in 25 procedures. In 31 procedures, 1 procedural complication (skin ulceration) occurred. At the end of the last treatment session 14 of the 21 lesions were cured. Symptomatic control was achieved in all cases, with resolution or significant improvement of the symptoms (mean follow-up of 10 months). CONCLUSIONS: High-flow craniofacial vascular malformations can be successfully managed with interventional techniques.

Non-pigmented melanoma with nodal metastases masquerading as pyogenic granuloma in a 1-year old.

Malignant melanomas are the most common skin cancer in the pediatric population. Melanoma incidence is extremely low in infants, and metastatic disease is even less common. We present the case of an 11-month-old girl who presented with a non-pigmented lesion that progressed to an ulcerated lesion. Pathology was found to be Spitzoid melanoma of 7.6-mm thickness. Micrometastases were found on examination of the sentinel lymph node. The family chose expectant observation following the excision procedure. A pediatric melanoma registry may be helpful in developing future analyses of incidence in survival in this specialized population.

Coordinated events: FGF signaling and other related pathways in palatogenesis.

Cleft palate is a common craniofacial anomaly that is costly to both patients and the health care system. Investigation of each stage of palate development enhances understanding of this anomaly. Although the exact molecular signaling mechanisms that contribute to palatogenesis remain elusive, multiple pathways, such as fibroblast growth factor (FGF) signaling, have been recognized as important contributors. Alterations in FGF signaling have previously been implicated in palatal clefting. The current review discusses FGF signaling and the major signaling mediators affecting FGF signaling during each stage of palatogenesis.

Management of lymphatic malformations.

Lymphatic malformation results from an error in the embryonic development of the lymphatic system. Clinically, lymphatic malformation is characterized by the size of the malformed channels: microcystic, macrocystic, or combined (microcystic/macrocystic).This article describes the clinical features, diagnosis, and management of lymphatic malformations.

Special considerations in vascular anomalies: operative management of craniofacial osseous lesions.

The treatment of vascular anomalies of the head and neck typically focuses on restoration of abnormal structures of the soft tissues. However, vascular anomalies can affect the craniofacial skeleton, and osseous reconstruction may be indicated. Osseous involvement occurs as either a primary or secondary phenomenon. In primary osseous involvement, the vascular anomaly expands the bone from within. Secondary osseous involvement occurs when bony hypertrophy develops because of increased flow of the surrounding soft tissue. This article focuses on the management of the osseous deformities associated with vascular anomalies.

Facelifts: a contemporary perspective.

The premium that our society has placed on youthful appearance has driven an ever increasing number of patients to seek facial rejuvenation. As the demand for these procedures has increased so has the expectation that these procedures can be performed more safely while ultimately delivering a more natural appearance than has historically been possible. More focused (and often times less invasive) procedures have been developed to better serve the needs of our patients.

Analysis of a gain-of-function FGFR2 Crouzon mutation provides evidence of loss of function activity in the etiology of cleft palate.

Cleft palate is a common birth defect in humans and is a common phenotype associated with syndromic mutations in fibroblast growth factor receptor 2 (Fgfr2). Cleft palate occurred in nearly all mice homozygous for the Crouzon syndrome mutation C342Y in the mesenchymal splice form of Fgfr2. Mutant embryos showed delayed palate elevation, stage-specific biphasic changes in palate mesenchymal proliferation, and reduced levels of mesenchymal glycosaminoglycans (GAGs). Reduced levels of feedback regulators of FGF signaling suggest that this gain-of-function mutation in FGFR2 ultimately resembles loss of FGF function in palate mesenchyme. Knowledge of how mesenchymal FGF signaling regulates palatal shelf development may ultimately lead to pharmacological approaches to reduce cleft palate incidence in genetically predisposed humans.

Rejuvenation of the aging neck: current principles, techniques, and newer modifications.

Aesthetic improvement of the neck and cervicomental angle remains one of the most challenging aspects of surgical facial rejuvenation. Individuals may become dissatisfied with the appearance of their neck because of changes in skin quality, submental fat, and muscle tone or anatomic position related to aging, weight gain, weight loss, sun damage, and other causes. To achieve the patient's desired result, surgeons use various techniques, either in isolation or in combination. Careful preoperative evaluation of the patient's anatomy dictates the most appropriate procedure, ranging from laser skin resurfacing to sub-superficial muscular aponeurotic system (sub-SMAS) rhytidectomy with an extended platysmaplasty. This article reviews the techniques that are available and the decision-making process in choosing the appropriate technique for the individual patient.

Mechanism of skull suture maintenance and interdigitation.

Skull sutures serve as growth centers whose function involves multiple molecular pathways. During periods of brain growth the sutures remain thin and straight, later developing complex fractal interdigitations that provide interlocking strength. The nature of the relationship between the molecular interactions and suture pattern formation is not understood. Here we show that by classifying the molecules involved into two groups, stabilizing factors and substrate molecules, complex molecular networks can be modeled by a simple two-species reaction-diffusion model that recapitulates all the known behavior of suture pattern formation. This model reproduces the maintenance of thin sutural tissue at early stages, the later modification of the straight suture to form osseous interdigitations, and the formation of fractal structures. Predictions from the model are in good agreement with experimental observations, indicating that the model captures the essential nature of the interdigitation process.

Le premier siècle: one hundred years of progress in the treatment of Apert syndrome.

The year 2006 marked the 100th anniversary of the publication of Eugene Apert's article, De l'acrocephalosyndactylie in the Bulletin de la Société des médecins des hôspitaux de Paris. During the last century, much progress has been made in the understanding and treatment of this condition. A translation of Apert's original article is provided as is an overview of what has been learned during the last 100 years and what the future treatment of this condition may be.

Craniofacial dysmorphology of Carpenter syndrome: lessons from three affected siblings.

BACKGROUND: Carpenter syndrome, or acrocephalopolysyndactyly type II, is a disorder associated with an autosomal recessive pattern of inheritance. Because of its rarity, limited insight into the anomalies associated with this syndrome exist and little long-term follow-up of affected patients is available. METHODS: This study is a retrospective review of the clinical history, medical imaging, and therapeutic interventions for three full siblings with Carpenter syndrome over an 18-year period. The medical records were abstracted for kindred analysis, gestational and delivery history, health issues related to Carpenter syndrome, and therapeutic interventions, including indications for, age at, and outcome of. RESULTS: All three children had craniosynostosis, acral deformities, and other associated anomalies. The pattern of craniosynostosis, at birth, varied among the three siblings: one had fusion of the metopic and sagittal sutures and the other two had bilateral coronal, metopic, and anterior sagittal synostoses. All three siblings demonstrated marked absence or underdevelopment of the anterior cranial fossa and bulging of the middle cranial fossa. There was no correlation between the degree of craniofacial dysmorphology and brain dysmorphology in any of the three individuals. Computed tomographic scan data of osseous and brain anatomy and clinical photographs of treatment outcomes are provided to demonstrate the long-term craniofacial development and growth in treated individuals with Carpenter syndrome. CONCLUSIONS: The diverse anatomical variation seen in these three individuals supports the notion of marked phenotypic variability within this disorder. This spectrum of information should aid members of craniofacial teams in appreciating this variability and thereby facilitating the diagnosis and management of individuals with Carpenter syndrome.

A point-wise quantification of asymmetry using deformation fields: application to the study of the Crouzon mouse model.

This paper introduces a novel approach to quantify asymmetry in each point of a surface. The measure is based on analysing displacement vectors resulting from nonrigid image registration. A symmetric atlas, generated from control subjects is registered to a given subject image. A comparison of the resulting displacement vectors on the left and right side of the symmetry plane, gives a point-wise measure of asymmetry. The asymmetry measure was applied to the study of Crouzon syndrome using Micro CT scans of genetically modified mice. Crouzon syndrome is characterised by the premature fusion of cranial sutures, which gives rise to a highly asymmetric growth. Quantification and localisation of this asymmetry is of high value with respect to surgery planning and treatment evaluation. Using the proposed method, asymmetry was calculated in each point of the surface of Crouzon mice and wild-type mice (controls). Asymmetry appeared in similar regions for the two groups but the Crouzon mice were found significantly more asymmetric. The localisation ability of the method was in good agreement with ratings from a clinical expert. Validating the quantification ability is a less trivial task due to the lack of a gold standard. Nevertheless, a comparison with a different, but less accurate measure of asymmetry revealed good correlation.

Computational mouse atlases and their application to automatic assessment of craniofacial dysmorphology caused by the Crouzon mutation Fgfr2(C342Y).

Crouzon syndrome is characterized by premature fusion of sutures and synchondroses. Recently, the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of micro-computed tomography (CT) scannings of the skulls of wild-type mice and Crouzon mice were analysed with respect to the dysmorphology caused by Crouzon syndrome. A computational craniofacial atlas was built automatically from the set of wild-type mouse micro-CT volumes using (1) affine and (2) non-rigid image registration. Subsequently, the atlas was deformed to match each subject from the two groups of mice. The accuracy of these registrations was measured by a comparison of manually placed landmarks from two different observers and automatically assessed landmarks. Both of the automatic approaches were within the interobserver accuracy for normal specimens, and the non-rigid approach was within the interobserver accuracy for the Crouzon specimens. Four linear measurements, skull length, height and width and interorbital distance, were carried out automatically using the two different approaches. Both automatic approaches assessed the skull length, width and height accurately for both groups of mice. The non-rigid approach measured the interorbital distance accurately for both groups while the affine approach failed to assess this parameter for both groups. Using the full capability of the non-rigid approach, local displacements obtained when registering the non-rigid wild-type atlas to a non-rigid Crouzon mouse atlas were determined on the surface of the wild-type atlas. This revealed a 0.6-mm bending in the nasal region and a 0.8-mm shortening of the zygoma, which are similar to characteristics previously reported in humans. The most striking finding of this analysis was an angulation of approximately 0.6 mm of the cranial base, which has not been reported in humans. Comparing the two different methodologies, it is concluded that the non-rigid approach is the best way to assess linear skull parameters automatically. Furthermore, the non-rigid approach is essential when it comes to analysing local, non-linear shape differences.

RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity.

Carpenter syndrome is a pleiotropic disorder with autosomal recessive inheritance, the cardinal features of which include craniosynostosis, polysyndactyly, obesity, and cardiac defects. Using homozygosity mapping, we found linkage to chromosome 6p12.1-q12 and, in 15 independent families, identified five different mutations (four truncating and one missense) in RAB23, which encodes a member of the RAB guanosine triphosphatase (GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling. In 10 patients, the disease was caused by homozygosity for the same nonsense mutation, L145X, that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. Surprisingly, nonsense mutations of Rab23 in open brain mice cause recessive embryonic lethality with neural-tube defects, suggesting a species difference in the requirement for RAB23 during early development. The discovery of RAB23 mutations in patients with Carpenter syndrome implicates HH signaling in cranial-suture biogenesis--an unexpected finding, given that craniosynostosis is not usually associated with mutations of other HH-pathway components--and provides a new molecular target for studies of obesity.

Identifying reproducible patterns of calvarial dysmorphology in nonsyndromic sagittal craniosynostosis may affect operative intervention and outcomes assessment.

BACKGROUND: The authors tested the premise that there are four distinctive patterns of calvarial dysmorphology in nonsyndromic sagittal craniosynostosis that can be reproducibly recognized. METHODS: Twenty-nine computed tomographic scan data sets of infants met the following criteria: nonsyndromic sagittal craniosynostosis, age younger than 12 months, and satisfactory computed tomographic data. Osseous reformations were constructed in the anteroposterior, right lateral, and vertex projections for each patient. From these images, four templates--coronal constriction, occipital protuberance, bifrontal bossing, and bitemporal protrusion--were selected as prototypes of the specific dysmorphologies the authors observed in patients with sagittal craniosynostosis. Four residents assigned the 29 calvarial image sets to one of the four templates or, if they were unable to do so, to the group "other." The sortings were then assessed for clustering. The same patient computed tomographic data were reformatted with osseous color images, which were then sorted according to template group by eight senior craniofacial surgeons, who repeated the task approximately 3 months later. The repeatability and assessment of clustering of image sets using the templates was evaluated. RESULTS: In the residents' pilot study, 41 percent (12 of 29) of patients had 100 percent concordance rates, 31 percent (nine of 29) had 75 percent concordance, 24 percent (seven of 29) had 50 percent, and 3 percent (one of 29) had 25 percent concordance. In summary, greater than 70 percent of the patient image sets could be sorted with at least 75 percent concordance by residents. In the senior surgeons' study, 90 percent of patients could be identified as falling into two of five possible groups. Senior raters demonstrated nearly 70 percent repeatability between sortings. CONCLUSION: These findings support the hypothesis that there are identifiable and reproducible patterns of varying calvarial dysmorphology in patients with sagittal craniosynostosis.

The craniofacial phenotype of the Crouzon mouse: analysis of a model for syndromic craniosynostosis using three-dimensional MicroCT.

OBJECTIVE: To characterize the craniofacial phenotype of a mouse model for Crouzon syndrome by a quantitative analysis of skull morphology in mutant and wild-type mice and to compare the findings with skull features observed in humans with Crouzon syndrome. METHODS: MicroCT scans and skeletal preparations were obtained on previously described Fgfr2(C342Y/+) Crouzon mutant mice and wild-type mice at 6 weeks of age. Three-dimensional coordinate data from biologically relevant landmarks on the skulls were collected. Euclidean Distance Matrix Analysis was used to quantify and compare skull shapes using these landmark data. RESULTS: Obliteration of bilateral coronal sutures was observed in 80% of skulls, and complete synostosis of the sagittal suture was observed in 70%. In contrast, fewer than 40% of lambdoid sutures were found to be fully fused. In each of the 10 Fgfr2(C342Y/+) mutant mice analyzed, the presphenoid-basisphenoid synchondrosis was fused. Skull height and width were increased in mutant mice, whereas skull length was decreased. Interorbital distance was also increased in Fgfr2(C342Y/+) mice as compared with wild-type littermates. Upper-jaw length was shorter in the Fgfr2(C342Y/+) mutant skulls, as was mandibular length. CONCLUSION: Skulls of Fgfr2(C342Y/+) mice differ from normal littermates in a comparable manner with differences between the skulls of humans with Crouzon syndrome and those of unaffected individuals. These findings were consistent across several regions of anatomic interest. Further investigation into the molecular mechanisms underlying the anomalies seen in the Crouzon mouse model is currently under way.

The S.O.F.T. Cheek method: an approach to lower eyelid and midface rejuvenation.

Procedures to rejuvenate the lower eyelids and cheek are amongst the most common aesthetic surgeries performed today. Rejuvenation should be individualized based on the patients concerns, anatomic deformity, and medical condition. A balanced and natural clinical result often requires a combination of techniques designed to address each patient's individual pattern of aging, while maximizing patient safety. We present the S.O.F.T. Cheek method of analysis and treatment, which utilizes well-developed principles and techniques, to consistently maximize clinical results and patient satisfaction.