Genetic diagnosis of neurofibromatosis type 1: targeted next- generation sequencing with Multiple Ligation-Dependent Probe Amplification analysis.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a dominantly inherited tumor predisposition syndrome that targets the peripheral nervous system. It is caused by mutations of the NF1 gene which serve as a negative regulator of the cellular Ras/MAPK (mitogen-activated protein kinases) signaling pathway. Owing to the complexity in some parts of clinical diagnoses and the need for better understanding of its molecular relationships, a genetic characterization of this disorder will be helpful in the clinical setting. METHODS: In this study, we present a customized targeted gene panel of NF1/KRAS/BRAF/p53 and SPRED1 genes combined with Multiple Ligation-Dependent Probe Amplification analysis for the NF1 mutation screening in a cohort of patients clinically suspected as NF1. RESULTS: In this study, we identified 73 NF1 mutations and two BRAF novel variants from 100 NF1 patients who were suspected as having NF1. These genetic alterations are heterogeneous and distribute in a complicated way without clustering in either cysteine-serine-rich domain or within the GAP-related domain. We also detected fifteen multi-exon deletions within the NF1 gene by MLPA Analysis. CONCLUSIONS: Our results suggested that a genetic screening using a NGS panel with high coverage of Ras-signaling components combined with Multiple Ligation-Dependent Probe Amplification analysis will enable differential diagnosis of patients with overlapping clinical features.

Line Laser as an Assistance for Facial and Dental Midlines Evaluation in Single-Splint Orthognathic Surgery.

Coincidence of facial and dental midlines is one of the important goals in orthognathic-orthodontic treatment to achieve optimum facial aesthetics and good occlusal functions. Tools assisting diagnosis of facial midline are usually ruler or dental floss. These tools are usually hand held and hinder the global sight required in facial evaluation. Line laser device projects a steady narrow laser line and is commonly used in construction and carpentry to replace traditional chalk line tool. The authors take the advantages of line laser and incorporate it into facial evaluation in the authors' practice of single-splint orthognathic surgery.During June 2013 to May 2015, the authors used line laser device to evaluate facial and dental midlines in 28 patients of facial asymmetry requiring orthognathic surgery during consultation in office and intraoperative evaluation. The details of integrating this device to practice are described. All the patients showed improved facial symmetry and coincidence of facial and dental midlines after operation. Postoperative orthodontics were finished smoothly.Line laser is available from general utility stores and is safe to use according to laser safety regulation. From the authors' experiences, it is burden free to apply in facial and dental midlines evaluation and improves the practice.

Computational fluid dynamics study of the inspiratory upper airway and clinical severity of obstructive sleep apnea.

The apnea-hypopnea index (AHI) is a widely accepted measure for the severity of obstructive sleep apnea (OSA). Current methods to determine AHI fail to provide anatomic information for treatment decisions. In this report, we studied three-dimensional models of upper airways acquired by computed tomographic scanning with geometric measurements and computational fluid dynamics (CFD) analysis and evaluated the correlations with AHI.Participants had CT scans of their upper airways after standard polysomnography studies. Three-dimensional surface models of upper airways were generated for cross-sectional area measurements of the choanae (ACH) and the smallest cross-sectional area (Amin). Computational fluid dynamic analysis was then performed by using this three-dimensional model. Pressure differences required to set tidal volume during inspiration (ΔPmin-INSP) and expiration (ΔPmax-EXP) and minimum negative pressure produced in the level of ACH (Pmin-INSP at ACH) and Amin (Pmin-INSP at Amin) were calculated. Correlations of these parameters and the body mass index with AHI were analyzed. Statistical differences between groups of different AHI ranges were also compared.The pressure distribution simulated by CFD demonstrated abrupt pressure drops in Amin level, and this phenomenon was more significant in severe OSA. All parameters except ACH and Pmin-INSP at Amin significantly correlated with the AHI, and there were significant statistical differences between the OSA groups and the normal group. The results indicate that, in our study group, the geometry of pharyngeal airway and its CFD simulation correlate well with AHI. This model may be further applied for clinical evaluation.

Simultaneous fat removal with suture upper blepharoplasty.

BACKGROUND: Suture blepharoplasty for double eyelids is one of the most common aesthetic plastic surgery procedures in Asia. Because the technique of celebrity arcade suture blepharoplasty is effective and reliable, it has gained in popularity over the past 10 years. During this period, a significant group of patients has requested double-eyelid suture blepharoplasty combined with correction of upper eyelid puffiness. In the past, upper eyelid fat removal was performed primarily by an open excision technique, which could result in a visible scar and a prolonged recovery period. Fat removal performed simultaneously with suture blepharoplasty was a technique not considered. The reported technique is introduced to achieve simultaneous fat removal and suture blepharoplasty for double eyelids. METHODS: The operative design is almost the same as that of the celebrity arcade suture blepharoplasty technique. The difference is that the lateral incision should be longer (3-4 mm) and placed 5-mm medially to the vertical line of the lateral canthus. From this lateral incision, a bulky fat pad can be removed with cauterization. RESULTS: From June 2001 to December 2011, 79 of 807 patients who received celebrity arcade suture blepharoplasty also had simultaneous fat removal. No complications of hematoma, granuloma, or transient dry-eye symptoms occurred. CONCLUSIONS: The results show that fat removal simultaneous with celebrity arcade suture blepharoplasty is a reliable and easily duplicated technique for patients who request correction of puffy eyelids and suture blepharoplasty for double eyelids. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Surgery-first accelerated orthognathic surgery: orthodontic guidelines and setup for model surgery.

The surgery-first approach indicates that the orthognathic surgery precedes the orthodontic treatment, whereas the orthodontics-first approach indicates that the orthodontic treatment precedes the orthognathic surgery. The conventional approach is an orthodontics-first approach. The purposes of this article are to introduce the concept of the surgery-first approach and to report the guidelines for orthodontic management and model surgery without presurgical orthodontic decompensation. The surgery-first approach treats facial esthetics first and then occlusion, whereas the conventional approach treats occlusion first and then facial esthetics. The surgery-first approach uses osteotomy to solve both skeletal problems and dental compensation, and a "transitional" occlusion is set up postoperatively. Orthodontics in the surgery-first approach is a postoperatively adjunctive treatment to transfigure the transitional occlusion into the solid final occlusion. The advantages of the surgery-first approach are that 1) the patient's chief complaint, dental function, and facial esthetics are achieved and improved in the beginning of the treatment; 2) the entire treatment period is shortened to 1 to 1.5 years or fewer depending on the complexity of orthodontic treatment; and 3) the phenomenon of postoperatively accelerated orthodontic tooth movement reduces the difficulty and treatment time of orthodontic management in the surgery-first approach.

Surgery-first accelerated orthognathic surgery: postoperative rapid orthodontic tooth movement.

PURPOSE: Clinically, we have observed the phenomenon of postoperatively accelerated orthodontic tooth movement in patients who had orthognathic surgery. This phenomenon lasts for a period of 3 to 4 months. However, the underlying mechanisms of this phenomenon have not been well studied yet. The purpose of this prospective clinical pilot study was to study the postoperative changes in bone physiology and metabolism and the corresponding responses in the dentoalveolus, such as the changes in tooth mobility. MATERIALS AND METHODS: Twenty-two consecutive adult patients who had 2-jaw orthognathic surgery were included in this study. The levels of serum alkaline phosphatase and C-terminal telopeptide of type I collagen (ICTP), as well as the tooth mobility of the maxillary and mandibular incisors based on the Periotest method (Siemens AG, Bensheim, Germany), were examined preoperatively and 1 week, 1 month, 2 months, 3 months, and 4 months postoperatively. The data were analyzed statistically. RESULTS: Both tooth mobility of the maxillary and mandibular incisors and ICTP significantly increased from 1 week to 3 months postoperatively and then decreased to their preoperative levels in the fourth month postoperatively. The changes in tooth mobility were significantly in correspondence with the changes in ICTP. The alkaline phosphatase level significantly increased from the first to fourth month postoperatively, but it was not significantly correlated to the changes in tooth mobility. CONCLUSION: The orthognathic surgery triggers a 3- to 4-month period of higher osteoclastic activities and metabolic changes in the dentoalveolus postoperatively, which possibly accelerates postoperative orthodontic tooth movement.

Surgical repair for macrostomia: significance of Z-plasty limb directions.

The objective of this study was to determine whether the direction of Z-plasty limbs incorporated into the surgical repair for macrostomia had a significant influence on the quality of the resultant scar. A total of 41 patients who underwent macrostomia repair by means of the same technique, and who had a follow up period of at least 2 years, were retrospectively reviewed through postoperative photographs and medical records. Quality of scar, lip symmetry, and commissure shape and thickness were recorded. Our results showed that a more favorable scar would be achieved in the medial limb of the Z-plasty if it was planned parallel to relaxed skin tension lines (P < 0.05). An unfavorable scar would be more likely if the medial limb of the Z-plasty was made in a horizontal direction or perpendicular to relaxed skin tension lines (P < 0.05). The quality of scar in both the central and lateral limbs of the Z-plasty was not significantly influenced by their direction.

Computational fluid dynamic study on obstructive sleep apnea syndrome treated with maxillomandibular advancement.

Maxillomandibular advancement is one of the treatments available for obstructive sleep apnea. The influence of this surgery on the upper airway and its mechanism are not fully understood. The present research simulates the flow fields of narrowed upper airways of 2 patients with obstructive sleep apnea treated with maxillomandibular advancement. The geometry of the upper airway was reconstructed from computed tomographic images taken before and after surgery. The consequent three-dimensional surface model was rendered for measurement and computational fluid dynamics simulation. Patients showed clinical improvement 6 months after surgery. The cross-sectional area of the narrowest part of the upper airway was increased in all dimensions. The simulated results showed a less constricted upper airway, with less velocity change and a decreased pressure gradient across the whole conduit during passage of air. Less breathing effort is therefore expected to achieve equivalent ventilation with the postoperative airway. This study demonstrates the possibility of computational fluid dynamics in providing information for understanding the pathogenesis of OSA and the effects of its treatment.

Delayed obturator artery rupture: a complication of high-voltage electrical injury.

Electrical burns cause damage to the cardiovascular system through different mechanisms. Immediate cardiac arrhythmia is one of the common consequences. A large vessel blow out due to an electrical burn is rarely documented. It is often undetected due to its "silent" symptoms. This article reports a delayed obturator artery rupture in a 32-year-old male patient 6 weeks after he sustained severe high-voltage electrical burns. The vessel injury was treated with computed tomography (CT)-aided embolization. The patient recovered to an ambulatory status 10 weeks after the injury.

Craniofacial deformity in patients with uncorrected congenital muscular torticollis: an assessment from three-dimensional computed tomography imaging.

Congenital muscular torticollis is caused by idiopathic fibrosis of the sternocleidomastoid muscle that restricts movement and pulls the head toward the involved side. Deformation of the craniofacial skeleton will develop if the restriction is not released and result in aesthetic and functional problems. The purpose of this study was to use three-dimensional computed tomography imaging for qualitative and quantitative evaluation of the craniofacial deformity in a series of patients with uncorrected congenital muscular torticollis, and to assess age as a precipitating factor for severity of the deformity. A total of 14 patients from 1 month to 24 years of age were included. The skull images were rotated into standard orientation and reconfigured for evaluation of the cranium, endocranial base, and facial skeletal structures. The midlines of cranial base and facial bone, angle of midline deviation, width of each hemicranium and hemiface, and the orbital index were defined and measured. The results showed that the cranium and cranial base deformation took place as early as in infant stage, with the most prominent change occurring in the posterior cranial fossa. Facial bone asymmetry started to appear after 5 years of age, at which time the mandibular and occlusal abnormalities were observed. The deformity of the orbits and maxilla occurred at an older age, characterized by the deviation and decreased vertical height on the affected side. The severity of the observed deformities increased with age. The angle of midline deviation was 2.48 +/- 1.68 degrees in the cranial base and 3.26 +/- 3.28 degrees on the facial bone. Both of the midline deviations were significantly correlated with age. Compared with the contralateral side, the width of the ipsilateral posterior hemicranium was longer (54.36 +/- 6.72 mm versus 50.81 +/- 6.55 mm), and the width of the ipsilateral lower hemiface was shorter (35.30 +/- 7.27 mm versus 43.49 +/- 11.34 mm). Both differences were statistically significant. Measurement of the orbital index demonstrated a significantly flatter orbit on the ipsilateral side (89.48 +/- 0.11 versus 92.74 +/- 0.08). This study showed that the cranium and cranial base deformity occurred early in patients with uncorrected torticollis, while the facial bone deformity occurred in childhood stage. The cranial and facial deformity became more severe with age. Early release of the muscle restriction is advised to prevent craniofacial deformation.

Craniofacial neurofibromatosis: treatment of the midface deformity.

Craniofacial Neurofibromatosis is a benign but devastating disease. While the most common location of facial involvement is the orbito-temporal region, patients often present with significant mid-face deformities. We reviewed our experience with Craniofacial Neurofibromatosis from June 1981 to June 2011 and included patients with midface soft tissue deformities defined as gross alteration of nasal or upper lip symmetry. Data reviewed included the medical records and photobank. Over 30 years, 52 patients presented to and underwent surgical management for Craniofacial Neurofibromatosis at the Chang Gung Craniofacial Center. 23 patients (43%) demonstrated gross mid-facial deformities at initial evaluation. 55% of patients with lip deformities and 28% of patients with nasal deformities demonstrated no direct tumour involvement. The respective deformity was solely due to secondary gravitational effects from neurofibromas of the cheek subunit. Primary tumour infiltration of the nasal and/or labial subunits was treated with excision followed by various methods of reconstruction including lower lateral cartilage repositioning, forehead flaps, free flaps, and/or oral commissure suspension. Soft tissue deformities of the midface are very common in patients with Craniofacial Neurofibromatosis and profoundly affect overall aesthetic outcomes. Distinguishing primary from secondary involvement of the midface assists in surgical decision making.

A Surgery-first approach in surgical-orthodontic treatment of mandibular prognathism--a case report.

The conventional approach in orthodontic surgery treatment of dentofacial anomalies requires a varied period of pre-surgical orthodontic treatment. This presurgical period is considered to be important for adequate surgical treatment and stable results. This period is usually long bothersome for patients because dental decompensation is required and there is consequent deterioration of aesthetics and function, especially in cases of skeletal Class III occlusion. At Chang Gung Craniofacial Center, a surgery-first approach (SFA), i.e. minimal pre-surgical orthodontics, is one of the treatment choices for Class III patients. In this report, we present a 19-year-old man with mandibular prognathism, an anterior open bite and severe dental crowding treated with SFA. The patient received orthognathic surgery a week after bracing of the teeth. The operation and recovery were uneventful as well as the following orthodontic treatment. The total treatment time was only four months, much shorter than with the conventional approach. The patient benefitted from immediate improvement of the facial profile after surgery, and a much shorter total treatment, and the results were not compromised. We believe in selected cases, SFA is a good and effective treatment alternative.

Single-splint technique in orthognathic surgery: intraoperative checkpoints to control facial symmetry.

BACKGROUND: Despite the most meticulous preoperative planning and execution, intraoperative soft-tissue response to dentoskeletal changes is often different from those statistically predicted, especially when midline asymmetry is present. A "single-splint" technique for bimaxillary surgery, with intraoperative adjustments and checkpoints, was developed in an attempt to overcome these limitations. The purpose of this study was therefore to determine whether this technique can improve the midline symmetry of facial soft tissues. METHODS: Forty-five patients who underwent at least a Le Fort I and a bilateral sagittal split osteotomy of the mandible were identified in the authors' patient database. Standardized frontal photographs were used to measure the change in midfacial, intercommissural, chin to midface, and chin to ideal facial midline angles. The facial midline symmetry index, an overall score of facial symmetry, was also calculated. RESULTS: This study demonstrates that there is a statistically significant improvement of the four angles measured and of the facial midline symmetry index. CONCLUSIONS: These findings demonstrate that the single-splint technique with its intraoperative checkpoints can successfully maintain or improve facial midline symmetry. Thus, the single-splint technique is a useful alternative to the classic two-splint technique for bimaxillary surgery.

Single-splint technique for correction of severe facial asymmetry: correlation between intraoperative maxillomandibular complex roll and restoration of mouth symmetry.

BACKGROUND: One of the most difficult problems to treat is the patient presenting with severe facial asymmetry and malocclusion whose chief complaint is the need for facial improvement. A canted intercommissural plane appears to be a major contributor to the patient's perception of facial asymmetry, but little is known about its correction. The authors adjust the intercommissural plane intraoperatively by modifying the maxillomandibular roll. However, a correlation between maxillomandibular roll and intercommissural plane change has not been demonstrated. The purpose of this study was therefore to determine whether such a correlation exists. METHODS: A retrospective series of 18 patients with severe maxillomandibular asymmetry requiring differential maxillary impaction/extrusion (>2 mm difference in posterior maxillary vertical movement between the right and left sides) was studied. Preoperative and postoperative frontal photographs and lateral cephalometrics were studied to determine the effect of maxillomandibular complex roll on the intercommissural plane. Linear regression and statistical analysis were performed to determine the strength of the association between the two movements. RESULTS: A linear regression could be derived from the scatterplot tracing. A Pearson correlation demonstrated a significant positive relationship between vertical maxillomandibular complex change in roll and intercommissural plane changes (r = 0.8; p = 0.000, one-tailed). CONCLUSIONS: A correlation between maxillomandibular complex roll and intercommissural plane change has been demonstrated. This supports the usefulness of intraoperative change in maxillary roll to restore mouth symmetry in patients with severe facial asymmetry. It also identifies a major factor that can be modified to change mouth symmetry in the vertical plane during presurgical planning.

Botulinum toxin a for lower facial contouring: a prospective study.

BACKGROUND: A prominent mandibular angle is a common reason for aesthetic treatment among Asian women. Such women usually present with hypertrophic masseteric muscles, and one treatment for this uses botulinum toxin A (BoNTA). Detailed effectiveness and physiologic influences of this therapy are still under investigation. METHODS: The authors report a prospective study of 10 female volunteers with hypertrophic masseteric muscles who received a single treatment comprising intramuscular injection of BoNTA. The facial change and the discomfort of the injection were self-rated using a visual analog scale, and the patients were regularly inspected up to 1 year. Bite forces also were measured for chronological documentation. Volume changes of masticating muscles were evaluated by three-dimensional computed tomography (CT) scans before and 3 months after injection of BoNTA. RESULTS: The serial photographs and patient subjective evaluation showed an obvious facial change 3 to 6 months after injection. Bite forces decreased from the first day after injection, but started to recover during week 3 and were normal 3 months after injection. Three-dimensional CT evaluation showed a statistically significant mean masseter reduction of about 30%, but no change in the volume of other masticating muscles. There were no serious complications during this study. CONCLUSIONS: Injection of BoNTA is an effective alternative for contouring of the lower facial profile by reducing the bulkiness of masseteric muscles. Its effectiveness was noticed as early as 2 weeks after injection and reached a peak effect in month 3. The facial contour gradually returned 6 months after injection. The reduction in bite force was temporary and caused no daily life interference.

Optic nerve compression in craniofacial fibrous dysplasia: the role and indications for decompression.

BACKGROUND: Fibrous dysplasia is a benign bone disorder in which craniofacial bones are involved in approximately one-fifth of cases. Optic nerve compression is one of its most potentially devastating complications. The approach to visual disturbance caused by disease involvement of the optic canal has been varied and controversial. This is especially the case with regard to surgical decompression, particularly prophylactic decompression. METHODS: The authors performed a retrospective review of fibrous dysplasia patients who showed clinical or radiographic evidence of optic canal involvement over a 27-year period. RESULTS: Twenty-two optic canals in 18 patients were affected by disease. Of these, 14 optic canals had symptoms (i.e., affected visual acuity or visual field). Twelve therapeutic and six prophylactic optic nerve decompressions were performed in total. At long-term follow-up (of at least 1 year), there was deterioration of vision in one-third of the patients who had undergone prophylactic decompression. Therapeutic decompression seemed to prevent visual deterioration in slightly more than half of the patients, with the majority having improvement in vision. There was visual deterioration in the remaining patients within this group, with most ultimately ending up with blindness. CONCLUSIONS: Therapeutic optic nerve decompression is advocated in patients with continuous deterioration of vision. Prophylactic decompression, in contrast, is not advised to be performed as a primary surgical procedure but as a procedure secondary to excision of lesion in the anterior skull base during the same operation.

Stigma, body image, and quality of life in women seeking orthognathic surgery.

BACKGROUND: Orthognathic surgery has been increasingly performed in the authors' country. To ascertain the increased satisfaction that comes with surgery, it is necessary to evaluate the patient's motivation for surgery. METHODS: Seventy-four female patients were evaluated before surgery. The control group consisted of 124 female patients. All participants completed the measures of perception of appearance, body image, stigma, and quality of life on an individual basis. These measures were tested, with satisfactory reliability and validity. RESULTS: Patients scored significantly lower than the control group on the measures for perception of appearance, stigma of surgery, and quality of life, but higher on appearance orientation and stigma of deformity. Correlation analyses revealed various patterns of intercorrelations of subscales of stigma and body image in both groups. Regression analysis yielded three significant predictors for surgery motivation (i.e., satisfaction of facial areas, stigma of surgery, and appearance orientation), altogether accounting for 46.2 percent of the total variance. CONCLUSIONS: Given the broadly known importance of body image in seeking surgery, it may be equally important to take stigma into consideration of the patient's motivation. Further investigations are needed.

The medial surface of the mandible as an alternative source of bone grafts in orthognathic surgery.

A technique of harvesting bone grafts from the medial surface of the angle of the mandible during a bilateral sagittal split osteotomy procedure is described. In 20 patients who underwent mandibular setback for the correction of class III dentofacial deformities, bone grafts were harvested from the medial mandibular angle and used for simultaneous augmentation of the midface or for interpositioning and stabilization of the maxilla after LeFort I maxillary anterior or inferior repositioning. The mean postoperative follow-up was 6 months (range, 3-12 months). No complications occurred, and postoperative morbidity was similar to that encountered by patients who undergo sagittal split osteotomy without bone harvest. The technique described shows that the medial mandibular angle is a suitable donor site for membranous bone grafts in patients who undergo sagittal split osteotomy.