Biallelic truncating variants in VGLL2 cause syngnathia in humans.

BACKGROUND: Syngnathia is an ultrarare craniofacial malformation characterised by an inability to open the mouth due to congenital fusion of the upper and lower jaws. The genetic causes of isolated bony syngnathia are unknown. METHODS: We used whole exome and Sanger sequencing and microsatellite analysis in six patients (from four families) presenting with syngnathia. We used CRISPR/Cas9 genome editing to generate vgll2a and vgll4l germline mutant zebrafish, and performed craniofacial cartilage analysis in homozygous mutants. RESULTS: We identified homozygous truncating variants in vestigial-like family member 2 (VGLL2) in all six patients. Two alleles were identified: one in families of Turkish origin and the other in families of Moroccan origin, suggesting a founder effect for each. A shared haplotype was confirmed for the Turkish patients. The VGLL family of genes encode cofactors of TEAD transcriptional regulators. Vgll2 is regionally expressed in the pharyngeal arches of model vertebrate embryos, and morpholino-based knockdown of vgll2a in zebrafish has been reported to cause defects in development of pharyngeal arch cartilages. However, we did not observe craniofacial anomalies in vgll2a or vgll4l homozygous mutant zebrafish nor in fish with double knockout of vgll2a and vgll4l. In Vgll2 -/- mice, which are known to present a skeletal muscle phenotype, we did not identify defects of the craniofacial skeleton. CONCLUSION: Our results suggest that although loss of VGLL2 leads to a striking jaw phenotype in humans, other vertebrates may have the capacity to compensate for its absence during craniofacial development.

Fine-Tuning of the Supratip in Rhinoplasty: An External Approach.

BACKGROUND: Supratip deformity, also known as the pollybeak deformity, accounts for one of the most common iatrogenic deformities requiring revision surgery in rhinoplasty. We aimed to present a novel technique to prevent supratip deformity and increase the tip definition, especially in patients with thick skin. METHODS: A total of eighty-three patients were included in the study. In control group, thirty-three consecutive patients with thick skin underwent structured primary rhinoplasty without any additional maneuvers. In study group, thirty-one consecutive patients with thick skin underwent the same operation with an additional "External supratip suture (ESS)." Nineteen patients with moderate skin were also operated using the ESS to accentuate the supratip break and control the soft tissue response. Patients' supratip regions were analyzed with reference to a tangent line from the tip defining point to the nasion. Two independent blinded plastic surgeons rated the supratip aesthetics on a 5-point scale. RESULTS: The ESS maneuver had better results in the supratip region according to the two parameters which were statistically significant (p < 0.05). No ischemic complications were observed. CONCLUSION: This simple and reliable external approach is a powerful maneuver which can be an effective technique not only in patients with thick skin, but also in moderate skin patients who requires better supratip definition. It enables surgeon to reduce the nasal volume efficiently in patients with noncompliant skin by controlling skin redraping by adhering to Auersvald's hemostatic net principles. We believe that this approach will find a place in the armamentarium of rhinosurgeons. 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.

Posterior Cephalic Soft Triangle of the Nose: Surgical Implications.

BACKGROUND: The posterior cephalic soft triangle is formed between the posterior cephalic border of the lower lateral cartilage, posterior caudal border of the upper lateral cartilage, and the caudal edge of the nasal bone. PCST is an important component of the external nasal valve which provides resistance against dynamic collapse. OBJECTIVES: The objective of this study was to describe the anatomy of the PCST and to demonstrate its anatomic variations, dynamic interplays, and surgical implications. METHODS: A retrospective review was conducted of 310 primary and 42 secondary cases who underwent extended open approach rhinoplasty by the first author. The structures that create the PCST of the nose were preserved unless resection/displacement of them was absolutely necessary. Whenever an external nasal valve pathology was found, it was corrected with one or combination of the following maneuvers: triangular PCST onlay graft, caudal bone outfracture, alar rim graft, lateral crural strut graft. RESULTS: Twenty-four non-consecutive cases were identified in which PCST was intraoperatively confirmed to be weak or deformed. The most common pathology in the PCST was overresection of the posterior segments of the LLC during primary surgery (54.1%), followed by en bloc medialization of the PCST (33.3%). Triangular onlay grafting of the PCST was the most common corrective surgical intervention (83.3%), followed by corrective lateralization of caudal edge of nasal bone (29.1%). External valve function has been restored in 21 (87.5%) cases. CONCLUSIONS: PCST of the nose is an important anatomic landmark which has esthetic and functional significance in rhinoplasty. 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 .

The Effects of Maxillary Movements on Nasal Aesthetics Following Orthognathic Surgery.

Improvement of the harmony between facial subunits is the ultimate goal of orthognathic surgery and surgeons must accurately make soft tissue projections for planned bony movements. Yet, few studies have examined the effects' of orthognathic surgery on aesthetic parameters of nasolabial area on a thorough basis.This retrospective study included 61 patients that underwent orthognathic surgery. Demographic data, evaluation period, and surgical details were analyzed. Superficial topographical analysis of intercanthal distance, alar width, nasal height, nasal length, nasal tip protrusion, upper lip height, nasal bone angle, supratip break angle, nasal dorsum angle, nasal tip angle, columellar-lobular angle, columellar-labial angle, upper lip angle, and tip-to-midline angle was recorded before and after surgery. Postoperative changes in these parameters and their correlation to maxillary movements were analyzed.Alar width, upper lip height, columellar-labial angle, supratip break angle, nasal dorsum angle, and upper lip angle increased postsurgery, whereas tip-to-midline angle decreased. Upper lip height and columellar-labial angle were significantly correlated with clockwise/counter-clockwise rotation and anterior re-positioning. Columellar-labial angle increased 2° for each 1 mm of anterior movement and decreased 4° for each 1 mm of counter-clockwise rotation. Novel parameters, such as columellar-lobular angle and tip-to-midline angle, were not associated with any maxillary movement postsurgery.Orthognathic surgery primarily affected the lower third of the nose and changed alar width, upper lip height, supratip break angle, nasal dorsum angle, columellar-labial angle, upper lip angle, and tip-to-midline angle in this region; however, only columellar-labial angle and upper lip height were found to be correlated solely with maxillary movements.

Scroll Reconstruction: Fine Tuning of the Interface Between Middle and Lower Thirds in Rhinoplasty.

BACKGROUND: The junction between upper and lower lateral cartilages, known as "the scroll area," is an important determinant of the spatial relationship between the middle and lower nasal thirds. OBJECTIVES: We offer a graduated and reproducible surgical technique of scroll area management that takes into consideration anatomic, functional, and aesthetic relationships. METHODS: This study was a retrospective review of the recorded intraoperative information to investigate the frequency of the use of scroll reconstruction techniques and perioperative parameters that relate to unintended component alterations in the scroll area. A total of 364 consecutive primary open approach rhinoplasty cases performed by the first author (O.B.) between July 2011 and September 2015 were included in the study. RESULTS: Of the 364 cases who underwent primary open approach rhinoplasty, 329 received some form of scroll reconstruction. Scroll reconstruction was performed in all deviated cases, and 88% of straight noses. The most common technique for scroll reconstruction was overlapping repair (88.3%). As expected, both alar rim and alar crease asymmetries were very frequent in the deviated nose group, 89.4% and 75% respectively. Alar rim and alar crease asymmetries were frequent enough in the straight nose group to deserve special attention, 14.2% and 10.4% respectively. CONCLUSIONS: With careful attention to anatomic details of the scroll area, nasal tip refinements can be performed with predictable safety and accuracy. Our approach is a graduated, reproducible, and individualized way of scroll area management that aims to create the ideal cartilage configuration while preventing unintended component alterations.

Combined Nasal Osteotomies With Caudal Transverse Osteotomy and Their Effect on Dorsal Geometry.

Background: Congenital, traumatic, or developmental bony vault deformities may require additional interventions rather than classical osteotomies to correct the surface structure or angulations of the nasal bones in rhinoplasty. Objectives: The aim of the study was to determine the effects of the additional osteotomies applied for the correction of the nasal vault asymmetries retrospectively. Methods: Twenty-one patients among 512 primary rhinoplasty cases between 2011 and 2016 with bony vault asymmetries were included in the study. Three patients had bilateral convex, 6 patients had unilateral convex, and 7 patients had unilateral concave surface deformities. Five patients had concave deformity on one side and convex deformity on the other side. Double-layer lateral osteotomies and caudal transverse osteotomies were conducted for the correction of the severe surface anatomy deformities of the nasal bones. The caudal transverse osteotomy was delicately performed with a special osteotome, which was designed to protect inner periosteum and mucosa of the nasal bone, and to prevent uncontrolled fracture formation with thinned edge. Results: Twenty patients (95.2%) had favorable results with restoration of a symmetric bony and cartilaginous nasal vault configuration. None of the bone fragments showed any rotation or malposition. One (4.8%) patient with a crooked nose had suboptimal dorsal geometry without requiring revisional surgery at the level of the cartilaginous nasal vault. Conclusions: The author described the morphology, clinical relevance, and correction methods of the nasal vault and the changes that occur in this area during rhinoplasty in patients with concave, convex, or combined three-dimensional nasal bone deformities. Level of Evidence: 4.

Distraction of Fronto-Orbital Segment as a Nonvascularized Bone Graft in Craniosynostotic Patients.

Fronto-orbital advancement using distraction techniques involves the dura left attached to the osteotomized bone segment to avoid dead space formation and dural injury, whereas it is impossible to reshape the supraorbital bar and the frontal bone complex, when necessary. Our approach combines advantageous parts of conventional and distraction osteogenesis techniques as remodel and distract the supraorbital bar and frontal bone complex as a free bone graft. Twenty-seven patients either being syndromic and nonsyndromic craniosynostosis, with at least 3 years of follow-up were reviewed in this study. Mean age of the patients at the time of the operation was 23.44 ±â€Š18.42 months and mean operative time was 4.96 ±â€Š0.97 hours. Blood transfusion was required in all patients, with an average of 112.04 ±â€Š44.60 mL. Amount of the distraction ranged 10 to 30 mm, a mean of 17.26 ±â€Š4.71 mm for the right side and 18.15 ±â€Š4.69 mm for the left side. Mean duration of consolidation was 98.26 ±â€Š12.98 days and mean follow-up was 41.33 ±â€Š22.92 months. In this study, result of internal distraction of fronto-orbital segment as a nonvascularized bone graft in craniosynostotic patients is reviewed to emphasize the efficacy of the nonvascularized bone graft distraction in management of craniosynostosis. Graft distraction after fronto-orbital and cranial vault remodeling appears to be safe and effective approach in correcting severe craniosynostosis deformities especially necessitating asymmetrical advancement.

An extremely rare complication following frontoorbital advancement: infarction of the recurrent artery of Heubner.

Many intracranial as well as extracranial complications can be seen following craniosynostosis surgeries. In this article, we would like to share an extremely rare complication of the infarction of the recurrent artery of Heubner, occurred following frontoorbital advancement. In this case, an 18-month-old male patient underwent supraorbital bar and frontal bone remodeling surgery for nonsyndromic metopic suture synostosis. The preoperative neurosurgical evaluation revealed no signs of increased intracranial pressure. On the 3rd postoperative day, the patient developed asymmetric smile and weakness on the left extremities. Computerized tomography showed a hypodense infarction region around the right basal ganglia and internal capsule, concordant with the region supplied by the recurrent artery of Heubner. The patient's symptoms started to regress on the 2nd day of enoxaparine treatment and he was discharged on 12th postoperative day with almost no signs of the event. In this paper, we presented an unlikely complication after frontoorbital advancement. Keeping in mind the long operating time and the proximity of the procedure to the central nervous system, assessment of the neurological function of the patients both before and after the operation and rapid intervention in case of development of neurologic symptoms are of great importance.

Functional outcomes of mandibular distraction for the relief of severe airway obstruction and feeding difficulties in neonates with Pierre Robin sequence.

The purpose of this study was to review the application of mandibular distraction to relieve severe airway obstruction or feeding problems of neonates. Thirteen neonates with Pierre Robin sequence who underwent bilateral mandibular distraction between 2010 and 2013 for relief of their severe airway obstruction or feeding problems were retrospectively reviewed. The mean preoperative and postoperative airway diameters were 3.89±1.64 and 9.03±1.98 mm. respectively and significant difference was observed with distraction (p < 0.001). The rate of severe airway infection also significantly decreased from 69.2% to 23.1% (p=0.016). 84.6% of the patients were able to be fed orally at discharge whereas 6 patients (46.2%) required support via orogastric tube before distraction (p=0.125). No growth disturbance, dental complications or malocclusion was observed in the long-term follow up. Mandibular distraction appears to be a promising and effective surgical option for relieving airway obstruction and feeding problems in severe Pierre Robin Sequence patients.

Orthognathic Treatment of Skeletal Class III Malocclusion with Severe Facial Asymmetry.

A 26-year, 9-month-old woman had chief complaints of mandibular protrusion and facial asymmetry. Extraoral examination indicated mandibular deviation to the left side, severe facial asymmetry, and a concave profile. Because the patient had a vertical maxillary height difference and an occlusal plane cant together with maxillary retrusion, a differential downgraft and advancement surgery with Lefort I osteotomy was planned. To correct the facial asymmetry and mandibular protrusion, concurrent bilateral sagittal split osteotomy was performed. Double-jaw surgical procedures, including maxillary and mandibular movements, are effective in correcting severe facial asymmetry and skeletal Class III malocclusion.

Congenital maxillomandibular syngnathia: a new management technique using distraction techniques.

Complex zygomaticomandibular syngnathia is an extremely rare condition with an unknown etiology. The main goal of the surgery is to release the ankylosis, establish good functioning mandible, and prevent reankylosis, if possible. In our case, we offer a new solution to have an adequate oral opening and to prevent reankylosis. After the release of bony syngnathia, we placed a distractor between mandibular segment and maxillozygomatic complex. To our best knowledge, this is the only syngnathia case in the literature treated using distraction techniques. There is a major improvement in the patient's status. Distraction may broaden our horizons in this rare and difficult-to-treat deformity.

Aggressive giant cystic lymphatic malformation in a newborn.

Lymphatic malformations are uncommon, benign and congenital malformations of the lymphatic system exhibiting lack of development of communication between the lymphatic and venous circulation. We report the unusual case of rapidly expanding giant lymphatic malformation of the torso, bilateral axillae and left upper extremity of a newborn. As the first-line treatment, aspiration and sclerotherapy with bleomycin were performed. The sclerotherapy failed to cause regression of the mass, and rapid expansion of the malformation necessitated surgery. Partial resection of the mass was performed. Clinical symptoms of respiratory distress resolved in the early postoperative period, and the patient became hemodynamically stable. However, intrathoracic invasion of the mass developed, leading to restriction of thoracic expansion, ending in death. In conclusion, surgical treatment of giant lymphatic malformations remains challenging.

Mutations in the interleukin receptor IL11RA cause autosomal recessive Crouzon-like craniosynostosis.

We have characterized a novel autosomal recessive Crouzon-like craniosynostosis syndrome in a 12-affected member family from Antakya, Turkey, the presenting features of which include: multiple suture synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next-generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice-site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon-like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11-mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon-like craniosynostosis.

Three-layer oronasal fistula repair with sandwiched mastoid fascia graft.

Oronasal fistula can cause speech problems, hearing loss, velopharyngeal insufficiency, and social problems related with fetor oris and oronasal fluid leakage. The purpose of this study was to achieve 3-layer closure with autogenous mastoid fascia graft in a group of patients with recalcitrant oronasal fistulas.Sixteen patients, aged between 2 and 56 years (mean, 13.9 y), with recalcitrant palatal fistula were operated on and included into the study in a tertiary clinic. Nine patients had previous fistula repairs. The patients' mean follow-up period was 6.8 months.Fistula closure was obtained in 14 of 16 patients. All 2 failures had type IV + V fistulas according to Pittsburgh Classification. A 3-layer technique for the closure of fistulas with autogenous mastoid fascia graft allows three-dimensional repair of the defect without tension. Using mastoid fascia via postauricular sulcus incision is a good alternative regarding hiding incision scars and not requiring intraoperative repositioning.

Pharyngeal airway changes associated with maxillary distraction osteogenesis in adult cleft lip and palate patients.

PURPOSE: To investigate 1) the changes in pharyngeal airway sizes associated with maxillary distraction osteogenesis and 2) the correlations between maxillary skeletal variables and the pharyngeal airway in adult patients with cleft lip and palate. PATIENTS AND METHODS: The study was carried out in 14 adult subjects with cleft lip and palate. Predistraction records were taken at a mean age of 22.7 ± 4.6 years. All patients had placement of a rigid external distraction device (RED I; KLS Martin, Tuttlingen, Germany) after Le Fort I osteotomy. Lateral cephalograms were assessed before surgery and at short-term follow-up (8.0 ± 6.4 months). The cephalometric skeletal and pharyngeal airway variables were statistically evaluated by use of the Wilcoxon signed-rank test. Spearman ρ correlation was performed to check the correlations between maxillary skeletal and pharyngeal variables. RESULTS: The maxillary movement was 8.7 mm (P < .01). The maxillary depth angle (+7.9°) and effective maxillary length (9.4 mm) increased significantly (P < .01) after distraction, whereas the palatal plane angle remained unchanged. Anterior nasal spine (8.2 mm) and Posterior nasal spine (6.9 mm) moved anteriorly. The overjet increased (9.5 mm) significantly (P < .01). Posterior, superoposterior, and middle airway spaces increased significantly, with mean differences of 7.5 mm, 5.1 mm, and 3.3 mm, respectively. The soft palate moved anteriorly, with the greatest movement at its superior point. Significant positive correlations were observed for the posterior and superoposterior airway spaces and maxillary movement. PNS changes showed the highest correlation with posterior airway changes. CONCLUSIONS: The significant anterior movement of the maxilla resulted in significant increases in posterior, superoposterior, and middle airway spaces. The posterior airway space showed the highest significant positive correlation with the movement of PNS. The posterior and superoposterior airway spaces also showed significant positive correlations with the maxillary skeletal variables.

A new concept in treatment of burn injury: controlled slow-release granulocyte-monocyte colony-stimulating factor chitosan gel system.

OBJECTIVE: The aim of the study is to investigate the effectiveness of the controlled slow-release granulocyte-monocyte colony-stimulating factor (GM-CSF) system in burn wound healing. MATERIAL AND METHODS: In vivo effect of controlled slow-release GM-CSF from chitosan gel on burn wound healing was evaluated on 18 Wistar-Albino rats, weighing between 250 and 300 g. They were randomly divided into 3 groups; (1) burned only group (n = 6), (2) burned + chitosan group (n = 6), (3) burned + chitosan + GM-CSF group (n = 6). Wound area was measured macroscopically. Hematoxylin and eosin and Masson's trichrome stained sections were evaluated for wound healing and tissue response to the polymer. RESULTS: The best healing process was observed with the controlled slow-release GM-CSF-applied group (group 3) in which the wound area was significantly narrowed. CONCLUSION: The study demonstrated the positive contribution of the single-dose controlled slow-release GM-CSF from chitosan gel on burn wound healing.

Splint-assisted reduction of comminuted or complex maxillofacial fractures.

The aim of the study was to obtain anatomic bone healing and restoration of the patient's premorbid occlusion in complex facial fractures or comminuted facial fracture. Ten patients who applied to a tertiary health care clinic with complex or comminuted fractures, and mandibular fractures combined with condylar fractures which may impair the occlusal harmony were included in the study.After the preparation of premorbid occlusal splints and direct bonded orthodontic brackets, splint-assisted reduction and internal fixation have been performed. The treatment protocol was completed with 4 to 6 weeks of intermaxillary fixation over the splint. All fracture lines showed complete bone healing, without major complications requiring further treatment. Complications included a minor degree of malocclusion in one of the panfacial fracture patients and slight avascular resorption of the condyle in one of the avulsive open comminuted mandibular fracture patients.Using orthodontic splints and direct bonded brackets to obtain and maintain delicate reduction is an efficacious method for the prevention of occlusal disharmony and aesthetic impairments in comminuted lower facial unit and complicated facial fracture patients.