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.

A Clinical Report of the Complete Nasal Agenesis: Reconstruction of Congenital Arhinia and Review of the Literature.

Congenital absence of the nose or arhinia is an exceptionally rare craniofacial malformation, and the pathophysiology of the arhinia is still unknown. Most arhinia patients can have difficulties with breathing and feeding due to the absence of the nose, nasal cavities, and associated problems. A 38-day-old female patient was referred to our clinic with arhinia. Physical examination revealed the complete agenesis of nasal structures as the nasal bones and vestibulum nasi. The region of the absent nose was flat and firm at palpation. Congenital arhinia may occur with other associated malformations such as ocular, ear, palate, and gonadal. Therefore, it is recommended to evaluate computed tomography/magnetic resonance imaging in the postnatal period. Additionally, a radiological evaluation will help nasal reconstruction by documenting changes in nasal and maxillary anatomy over time. Due to the limited number of arhinia cases presented, the surgical management of this condition has not been standardized. We presented the pyramid-shaped cartilage grafts for the nasal framework and an expanded paramedian forehead flap for the skin coverage for reconstruction of arhinia.

The Relevance of Fluid and Blood Management Using Microcirculatory Parameters in Children Undergoing Craniofacial Surgery.

ABSTRACT: Perioperative management of bleeding in children can be challenging. Microvascular imaging techniques have allowed evaluating the effect of blood transfusion on the microcirculation, but little is known about these effects in children. We aimed to investigate the effects of blood management using macro- and micro-hemodynamic parameters measurement in children undergoing craniofacial surgery. This is a prospective observational repeated measurement study including fourteen children. The indications for blood transfusion were changes of hemoglobin/hematocrit (Hct) levels, the presence of signs of altered tissue perfusion and impaired microcirculation images. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, and systemic parameters (hemoglobin, Hct, lactate, mixed venous oxygen saturation, K+, heart rate, mean arterial blood pressure) were evaluated baseline (T1), at the end of the surgical bleeding (T2) and end of the operation (T3). Four patients did not need a blood transfusion. In the other 10 patients who received a blood transfusion, capillary perfusion was higher at T3 (13[9-16]) when compared with the values of at T2 (11[8-12]) (P < 0.05) but only 6 patients reached their baseline values. Although blood transfusions increased Hct values (17 ±â€Š2.4 [T2]-19 ±â€Š2.8 [T3]) (P < 0.05), there was no correlation between microvascular changes and systemic hemodynamic parameters (P > 0.05). The sublingual microcirculation could change by blood transfusion but there was not any correlation between microcirculation changes, hemodynamic, and tissue perfusion parameters even with Hct values. The indication, guidance, and timing of fluid and blood therapy may be assessed by bedside microvascular analysis in combination with standard hemodynamic and biochemical monitoring for intraoperative bleeding in children.

Presentation of Infantile Hemangiopericytoma/Solitary Fibrous Tumor as a Giant Extracranial Temporal Mass.

BACKGROUND: Infantile Hemangiopericytoma (HPC)/Solitary Fibrous Tumor (SFT), a vascular tumor of head and neck region, can be congenital or arise during the first year of the life. As the infantile form of hemangiopericytoma has a better course than the adult form, surgical excision is recommended. Case Report: A full-term neonate presented with a congenital right temporal soft tissue mass. MRI revealed a highly vascular mass with a hemorrhagic and possible necrotic core without intracranial extension. The lesion grew in 2 weeks from 4x4 cm to 9x7 cm. Histologically, a hypercellular spindle cell mesenchymal neoplasm had prominent staghorn vessels, alternating with hypocellular areas. Mitotic activity was low(1-3/HPF) and necrosis was absent. Conclusion: Infantile HPC/SFT of head and neck can grow rapidly during the infantile period. Complete excision without mutilating surgery should be curative.

A Novel Method of Neo-osseous Flap Prefabrication: Induction of Free Calvarial Periosteum with Bioactive Glass.

BACKGROUND: Reconstruction of craniofacial bone defects is a primary focus of craniofacial surgery. Although autogenous bone grafts remain as the gold standard, alloplastic materials have also gained widespread popularity due to their off-the-shelf availability, ease of use, and durability. In addition to replacing the missing bone, some of these alloplastic materials have also been found to induce new bone formation. OBJECTIVES: In this study, the phenomenon of neo-osseous induction with bioactive glass was investigated for different implant-soft tissue configurations. MATERIALS AND METHODS: Thirty-two male, Wistar albino rats were divided into four equally numbered study groups. In group 1 (FP), adipofascial groin flaps were prefabricated with free periosteal grafts. In group 2 (FPB), adipofascial groin flaps were prefabricated with free periosteal grafts and bioactive glass. In group 3 (FB), adipofascial groin flaps were prefabricated with bioactive glass. In group 4 (control), adipofascial groin flaps were not prefabricated. Morphometric analyses of the prefabricated structures were performed using micro-CT. The histologic properties of the ectopic ossification were assessed by using a modified scoring system. RESULTS: Group 1 (FP) showed the greatest rate of mature lamellar bone formation. Group 2 (FBP) showed the greatest amount of bone density and volume. However, the addition of bioactive glass in group 2 (FBP) decreased the rate of mature lamellar bone formation when compared with group 1 (FP). Ectopic ossification was not observed in the control group. CONCLUSION: Bioactive glass can be successfully used in the prefabrication of vascularized compound structures for the reconstruction of complex bone defects. However, interference with the periosteal induction of mature lamellar bone formation should be taken into consideration, especially in pediatric bone defects, which primarily rely on spontaneous osteogenesis through periosteal induction.

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.

Microvascular Tissue Transfers for Midfacial and Anterior Cranial Base Reconstruction.

Reconstruction of a midfacial defect can represent a difficult challenge for the plastic surgeon. Although many midfacial deformities have traumatic or congenital origins, the vast majority of head and neck defects occur after resection of malignant head and neck neoplasms. Autogenous reconstruction is now routinely performed for larger, complex defects resulting from surgical resection or trauma. In this study, the authors present 27 patients with midfacial defects reconstructed with free flaps. Twenty-two of the defects were created by surgical ablation of cancer (maxillectomy) and the others were traumatic. The maxillectomy defects were classified into 4 according to the classification proposed by Cordeiro. Eighteen of the patients were male and 9 were female. Twenty-nine free flaps were performed. Six different types of flaps including radial forearm flap, vertical rectus abdominis (VRAM) flap, anterolateral thigh (ALT) flap, tensor fasciae latae (TFL) flap, fibula osteocutaneous flap, and iliac osteocutaneous flap were accomplished. Types I and II defects were reconstructed with radial forearm flap. Type III defects were reconstructed with VRAM and ALT. Type IV defects were reconstructed with VRAM and TFL. Two patients underwent a second flap reconstruction due to recurrent disease (9.1%). Average patient age was 53.1 years. Free-flap survival was 100%. Free tissue transfer is the method of choice in midfacial reconstruction. Following a reconstructive algorithm is useful in the decision-making process for patient evaluation and treatment. Every reconstructive microsurgeon might have different experiences with different flaps. Therefore, the algorithm for flap choices is not universal among surgeons.

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.

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.

Comparison of closed percutaneous screw reduction versus open reduction and internal fixation in the treatment of frontal sinus fractures: A retrospective study.

The aim of this study was to compare closed percutaneous screw reduction to traditional open reduction-internal fixation (OR-IF) for the treatment of anterior table fractures. Both groups were evaluated in terms of operative variables, complications, and treatment success. Of 32 patients included, 19 patients underwent OR-IF, while 13 underwent percutaneous screw reduction. The median operative time, length of hospital stays, and treatment cost of the OR-IF group were 100 min (range 60-130), 4 days (range 3-9), and $727 (range $642-$1291), respectively. The same variables for the closed reduction group were 30 min (range 20-40), 2 days (range 1-2), and $303 (range $252-$349), respectively. The closed reduction group exhibited a shorter operative time (p< 0.001), reduced length of hospital stays (p< 0.001), lower treatment cost (p< 0.001), and a lower complication rate (p = 0.025) compared to the OR-IF group. Late-term outcomes in both groups showed no visible contour changes or step deformities. In conclusion, the percutaneous screw reduction technique is a safe and effective option with minimal morbidity in the treatment of frontal sinus anterior table fractures. Therefore, traditional OR-IF should be reserved for fractures that are not suitable for reduction using minimally invasive techniques.

Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia.

We present an autosomal-recessive frontonasal dysplasia (FND) characterized by bilateral extreme microphthalmia, bilateral oblique facial cleft, complete cleft palate, hypertelorism, wide nasal bridge with hypoplasia of the ala nasi, and low-set, posteriorly rotated ears in two distinct families. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this clinical entity to chromosome 12q21. In one of the families, three siblings were affected, and CNV analysis of the critical region showed a homozygous 3.7 Mb deletion containing the ALX1 (CART1) gene, which encodes the aristaless-like homeobox 1 transcription factor. In the second family we identified a homozygous donor-splice-site mutation (c.531+1G > A) in the ALX1 gene, providing evidence that complete loss of function of ALX1 protein causes severe disruption of early craniofacial development. Unlike loss of its murine ortholog, loss of human ALX1 does not result in neural-tube defects; however, it does severely affect the orchestrated fusion between frontonasal, nasomedial, nasolateral, and maxillary processes during early-stage embryogenesis. This study further expands the spectrum of the recently recognized autosomal-recessive ALX-related FND phenotype in humans.

Spontaneous lateral temporal encephalocele.

A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

Spring-mediated cranioplasty in patients with multiple-suture synostosis and cloverleaf skull deformity.

The concept of using implantable springs in craniofacial surgery was developed to dynamically remodel the cranium at the postoperative period. Springs have been shown as an effective treatment modality especially for single-suture synostosis patients and had several advantages over traditional techniques. This report presents 2 patients with cloverleaf skull and 1 patient with multiple-suture synostosis, with severe lacunae, who showed signs of increased intracranial pressure. Decompression and reconstruction were performed using implantable springs after Pi craniectomy. In all patients, lacunae disappeared and calvarial bones ossified almost completely. The shape of the patients' cranium improved as well. Implantable springs could be a useful addition to the armamentarium of every craniofacial surgeon.

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.

Algorithms for the management of frontal sinus fractures: A retrospective study.

The aim of this study was to evaluate the long-term results and to evaluate the validity of the treatment algorithm that can be safely applied in dfrontal sinus fractures. All patients were evaluated in terms of late-term contour deformity and further craniometric analysis for measurement of maximum amount of displacement, fracture surface area (mm2) and the maximum angulation of the fracture (degree) were done. 125 patients (101 male, 24 female) with frontal sinus fractures with an average age of 22.4 years (range,17-66 years) were reviewed. All patients with isolated anterior table fractures without displacement were followed up on conservative basis. 33 patients with anterior table fractures with displacement and 39 patients with anterior and posterior table fractures were also followed on conservative basis without surgical intervention. The cut-off value of the maximum amount of displacement was confirmed to be 4.5 mm in prediction of late-term contour deformities (p < 0.001). The maximum amount of displacement was decreased by an average of 1.8 mm at late-term. Apart from the standard protocols, within the limitations of the study it seems that isolated anterior table fractures with a maximum amount of displacement of less than 4.5 mm can be treated conservatively without leading to contour deformities. CSF leakage in the acute setting might not always require cranialization and this may spontaneously resolve within 10 days. Cranialization should be considered whenever CSF leakage lasts longer than 10 days.

ALX4 dysfunction disrupts craniofacial and epidermal development.

Genetic control of craniofacial morphogenesis requires a complex interaction of numerous genes encoding factors essential for patterning and differentiation. We present two Turkish families with a new autosomal recessive frontofacial dysostosis syndrome characterized by total alopecia, a large skull defect, coronal craniosynostosis, hypertelorism, severely depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, callosal body agenesis and mental retardation. Using homozygosity mapping, we mapped the entity to chromosome 11p11.2-q12.3 and subsequently identified a homozygous c.793C-->T nonsense mutation in the human ortholog of the mouse aristaless-like homeobox 4 (ALX4) gene. This mutation is predicted to result in a premature stop codon (p.R265X) of ALX4 truncating 146 amino acids of the protein including a part of the highly conserved homeodomain and the C-terminal paired tail domain. Although the RNA is stable and not degraded by nonsense-mediated RNA decay, the mutant protein is likely to be non-functional. In a skin biopsy of an affected individual, we observed a hypomorphic interfollicular epidermis with reduced suprabasal layers associated with impaired interfollicular epidermal differentiation. Hair follicle-like structures were present but showed altered differentiation. Our data indicate that ALX4 plays a critical role both in craniofacial development as in skin and hair follicle development in human.

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.

Skeletal and dental stability after maxillary distraction with a rigid external device in adult cleft lip and palate patients.

PURPOSE: To evaluate skeletal and dental stability in adult cleft lip and palate patients treated with a rigid external distraction system at the end of distraction and during the postdistraction period. PATIENTS AND METHODS: Lateral cephalograms of 7 patients were obtained before distraction, at the end of distraction, and during the postdistraction period. The mean age before distraction was 21.56 +/- 4.73 years. The mean follow-up was 37.3 +/- 12.4 months. RESULTS: The assessment of findings showed that skeletal maxillary sagittal movement was achieved in a superoanterior direction. The maxillary depth angle and effective maxillary length increased significantly (2 degrees and 9 mm, respectively) after distraction, whereas the palatal plane angle increased by 8 degrees , resulting in an anterior movement of the maxilla with a counterclockwise rotation. The lower facial height showed no significant changes after distraction. The sagittal movement of the upper incisors and the angulation of the upper first molars increased significantly (4.5 mm and 5.5 degrees , respectively). During the postdistraction period, the maxilla showed a slight relapse (22%). The effective maxillary length decreased by 2 mm. The palatal plane angle almost returned to its original position, showing 7 degrees of clockwise rotation. The lower facial height remained stable. The upper incisors moved anteriorly and the upper first molars showed a significant mesioangular change during follow-up. CONCLUSIONS: After distraction, significant maxillary advancement was achieved with a counterclockwise rotation. The upper incisors moved labially, and the upper first molars angulated mesially. After 3 years, a 22% relapse rate was seen in the maxilla. The counterclockwise rotation of the maxilla was returned to its original position. The upper incisors moved more anteriorly.

Congenital bony syngnathia with unilateral palatal shelf and soft palate agenesis.

Congenital fusion of upper and lower jaw is rare. Only 35 bony syngnathia have been reported up to date, and 9 of them revealed posterior topography. A 10-day-old female infant with facial asymmetry, limited mouth opening, and cardiac murmurs is presented. The radiological findings revealed congenital bony fusion of right coronoid process of the mandible to posterior maxillary region and right palatal shelf agenesis of palatal bone, which seems to be the first case in the literature. Classification systems of bony syngnathia and applied treatment procedures for palatal closure and release of the bony fusion are discussed.