Effects of distraction osteogenesis with Le Fort osteotomies on upper airway volumes: a systematic review and meta-analyses.

OBJECTIVE: Distraction osteogenesis is one of the treatment options in patients with severe maxillomandibular abnormalities to treat morphological and respiratory problems (obstructive sleep apnea syndrome). The study aimed to evaluate the effect of Le Fort I, II and III distraction osteogenesis (DO) on upper airway dimensions and respiratory function. METHODS: Electronic search was performed in PubMed, Scopus, Embase, Google Scholar and Cochrane databases. Studies that only involved two dimensional analyses were excluded. Besides, studies that performed DO in conjunction with orthognathic surgery were not considered. NIH quality assessment tool was used to evaluate the risk of bias. Meta-analyses were performed to assess sleep apnea indices and the mean differences in the airway dimensions before and after DO. Gradings of Recommendations, Assessment, Development and Evaluation were used to analyze the evidence level. RESULTS: Among the 114 studies that went under full-text analyses, 11 articles met the inclusion criteria. Results of the quantitative analyses showed that maxillary Le Fort III DO significantly increased the amounts of oropharyngeal, pharyngeal and upper airway volumes. However, apnea-hypopnea index (AHI) showed a non-significant improvement after this procedure. Besides, the dimensions of the airways increased with Le Fort I and II DO, according to a qualitative analysis. Considering the design of the included studies, our results had a low level of evidence. CONCLUSION: Maxillary Le Fort DO does not significantly impact AHI, while it significantly increases the airway dimensions. Meanwhile, multicentric studies with standardized evaluation are still required to confirm the effects of maxillary Le Fort DO on airway obstruction.

Hypochondroplasia gain-of-function mutation in FGFR3 causes defective bone mineralization in mice.

Hypochondroplasia (HCH) is a mild dwarfism caused by missense mutations in fibroblast growth factor receptor 3 (FGFR3), with the majority of cases resulting from a heterozygous p.Asn540Lys gain-of-function mutation. Here, we report the generation and characterization of the first mouse model (Fgfr3Asn534Lys/+) of HCH to our knowledge. Fgfr3Asn534Lys/+ mice exhibited progressive dwarfism and impairment of the synchondroses of the cranial base, resulting in defective formation of the foramen magnum. The appendicular and axial skeletons were both severely affected and we demonstrated an important role of FGFR3 in regulation of cortical and trabecular bone structure. Trabecular bone mineral density (BMD) of long bones and vertebral bodies was decreased, but cortical BMD increased with age in both tibiae and femurs. These results demonstrate that bones in Fgfr3Asn534Lys/+ mice, due to FGFR3 activation, exhibit some characteristics of osteoporosis. The present findings emphasize the detrimental effect of gain-of-function mutations in the Fgfr3 gene on long bone modeling during both developmental and aging processes, with potential implications for the management of elderly patients with hypochondroplasia and osteoporosis.

Craniofacial growth and function in achondroplasia: a multimodal 3D study on 15 patients.

BACKGROUND: Achondroplasia is the most frequent FGFR3-related chondrodysplasia, leading to rhizomelic dwarfism, craniofacial anomalies, stenosis of the foramen magnum, and sleep apnea. Craniofacial growth and its correlation with obstructive sleep apnea syndrome has not been assessed in achondroplasia. In this study, we provide a multimodal analysis of craniofacial growth and anatomo-functional correlations between craniofacial features and the severity of obstructive sleep apnea syndrome. METHODS: A multimodal study was performed based on a paediatric cohort of 15 achondroplasia patients (mean age, 7.8 ± 3.3 years), including clinical and sleep study data, 2D cephalometrics, and 3D geometric morphometry analyses, based on CT-scans (mean age at CT-scan: patients, 4.9 ± 4.9 years; controls, 3.7 ± 4.2 years). RESULTS: Craniofacial phenotype was characterized by maxillo-zygomatic retrusion, deep nasal root, and prominent forehead. 2D cephalometric studies showed constant maxillo-mandibular retrusion, with excessive vertical dimensions of the lower third of the face, and modifications of cranial base angles. All patients with available CT-scan had premature fusion of skull base synchondroses. 3D morphometric analyses showed more severe craniofacial phenotypes associated with increasing patient age, predominantly regarding the midface-with increased maxillary retrusion in older patients-and the skull base-with closure of the spheno-occipital angle. At the mandibular level, both the corpus and ramus showed shape modifications with age, with shortened anteroposterior mandibular length, as well as ramus and condylar region lengths. We report a significant correlation between the severity of maxillo-mandibular retrusion and obstructive sleep apnea syndrome (p < 0.01). CONCLUSIONS: Our study shows more severe craniofacial phenotypes at older ages, with increased maxillomandibular retrusion, and demonstrates a significant anatomo-functional correlation between the severity of midface and mandible craniofacial features and obstructive sleep apnea syndrome.

FGFR3 overactivation in the brain is responsible for memory impairments in Crouzon syndrome mouse model.

Crouzon syndrome with acanthosis nigricans (CAN, a rare type of craniosynostosis characterized by premature suture fusion and neurological impairments) has been linked to a gain-of-function mutation (p.Ala391Glu) in fibroblast growth factor receptor 3 (FGFR3). To characterize the CAN mutation's impact on the skull and on brain functions, we developed the first mouse model (Fgfr3A385E/+) of this syndrome. Surprisingly, Fgfr3A385E/+ mice did not exhibit craniosynostosis but did show severe memory impairments, a structurally abnormal hippocampus, low activity-dependent synaptic plasticity, and overactivation of MAPK/ERK and Akt signaling pathways in the hippocampus. Systemic or brain-specific pharmacological inhibition of FGFR3 overactivation by BGJ398 injections rescued the memory impairments observed in Fgfr3A385E/+ mice. The present study is the first to have demonstrated cognitive impairments associated with brain FGFR3 overactivation, independently of skull abnormalities. Our results provide a better understanding of FGFR3's functional role and the impact of its gain-of-function mutation on brain functions. The modulation of FGFR3 signaling might be of value for treating the neurological disorders associated with craniosynostosis.

Surgery-first orthognathic approach vs conventional orthognathic approach: A systematic review of systematic reviews.

Surgery-first approach (SFA) has been introduced as an alternative for conventional orthognathic approach (COA) in the treatment of patients with dentoskeletal deformities. This review aimed to evaluate skeletal stability, treatment time, surgical complications, and quality of life in SFA and COA. Six databases were accessed up to May 2020 to obtain all systematic reviews (SRs). After title and abstract reading, data extraction was performed from eligible SRs. The methodological quality was calculated for the included SRs using the last version of A Measurement Tool to Assess Systematic Review (AMSTAR-2). Ten SRs were included in this review. A good stability of the jaws was assessed both with SFA and COA by most of low- or critically low-quality SRs. Less treatment time was reported for SFA than COA with a moderate quality level. Slightly higher complications rate was recorded with SFA than COA by SRs with low or moderate quality. A better quality of life with SFA than COA was reported by moderate- or low-quality SRs. SFA may represent a reasonable alternative to COA. However, for the heterogeneity of the included SRs, well-designed studies with a long term follow-up are needed to clarify the findings of this analysis.

Cherubism as a systemic skeletal disease: evidence from an aggressive case.

BACKGROUND: Cherubism is a rare autosomal dominant genetic condition caused by mutations in the SH3BP2 gene. This disease is characterized by osteolysis of the jaws, with the bone replaced by soft tissue rich in fibroblasts and multinuclear giant cells. SH3BP2 is a ubiquitous adaptor protein yet the consequences of SH3BP2 mutation have so far been described as impacting only face. Cherubism mouse models have been generated and unlike human patients, the knock-in mice exhibit systemic bone loss together with a systemic inflammation. CASE PRESENTATION: In light of these observations, we decided to search for a systemic cherubism phenotype in a 6-year-old girl with an aggressive cherubism. We report here the first case of cherubism with systemic manifestations. Bone densitometry showed low overall bone density (total body Z-score = - 4.6 SD). Several markers of bone remodelling (CTx, BALP, P1NP) as well as inflammation (TNFα and IL-1) were elevated. A causative second-site mutation in other genes known to influence bone density was ruled out by sequencing a panel of such genes. CONCLUSIONS: If this systemic skeletal cherubism phenotype should be confirmed, it would simplify the treatment of severe cherubism patients and allay reservations about applying a systemic treatment such as those recently published (tacrolimus or imatinib) to a disease heretofore believed to be localised to the jaws.

Conservative management is effective in unicystic ameloblastoma occurring from the neonatal period: A case report and a literature review.

Unicystic ameloblastoma (UA), a benign odontogenic tumor of the jaw, represents less than a third of all ameloblastomas and seems less aggressive than other types of ameloblastoma. We present here the first case of UA that developed prenatally and was successfully managed in the early neonatal period with marsupialization and curettage performed carefully to avoid injury to the tooth germ. BRAF and SMO mutations were not detected. After 2 years of follow-up, complete reossification and normal eruption of deciduous teeth were noted, and there was no recurrence of UA. We recommend conservative treatment of UA in the pediatric population to avoid loss of and/or injury to the tooth germ, provided close follow-up is carried out all through the individual's growth for early detection of potential recurrences, growth impairments, or tooth eruption disorders. The intratumoral somatic mutational status of BRAF, SMO, RAS family, and FGFR2 may help determine personalized targeted treatment, particularly in case of recurrence.

Pediatric Nasal Reconstruction by Washio Procedure.

The use of the Washio retroauricular flap for nasal reconstruction has been infrequently covered in recent literature, particularly concerning the pediatric population. A retrospective study was conducted between 2014 and 2018 and included all pediatric patients who underwent a Washio retroauricular flap procedure for nasal reconstruction operated on by the same surgeon at a referral center for pediatric plastic and maxillofacial surgery. The mean age at the time of the first stage of the Washio procedure was just under 8 years of age (range: 6 years 3 months-8 years 10 months). The Washio retroauricular flap procedure was successfully employed in three patients with three different anatomical defects, including the nasal alae, nasal tip, and columella, without postoperative healing complications. Arguably, the Washio method is sufficiently versatile to be used in various defect types, allows space and planning for subsequent surgical corrections, avoids additional visible scarring of the face, and spares flaps that may be required at the end of the growth, such as the pedicled forehead flap. It is a safe procedure, provided that at least a two-stage procedure is performed, and a progressive postoperative verticalization is prescribed to limit venous drainage complications.

Severity of Retrognathia and Glossoptosis Does Not Predict Respiratory and Feeding Disorders in Pierre Robin Sequence.

Pierre Robin sequence (PRS) may lead to life-threatening respiratory and feeding disorders. With the aim to analyse the association of the severities of retrognathia and glossoptosis with those of respiratory and feeding disorders, we retrospectively studied a series of 50 infants with retrognathia, glossoptosis, cleft palate, and airway obstruction. The patients were managed from birth to at least 6 years of age by a single pediatric team at the Armand Trousseau Hospital in Paris within a 12 years period (2000-2012). Retrognathia and glossoptosis were graded in the neonatal period according to a specific clinical examination. Ventilation assistance was required for 32/50 (64%) patients, and enteral feeding for 41/50 (82%). The grades of retrognathia and glossoptosis and the severity of respiratory disorders did not differ between patients with isolated PRS and syndromic PRS. Severe respiratory disorders were more common and long-lasting feeding (>12 months) was more frequently required in patients with syndromic PRS compared with isolated PRS (42 vs. 13%, p = 0.04 and 42 vs. 4%, p < 0.01 respectively). Using univariate analysis, neurological impairments and laryngomalacia were associated with severe respiratory disorders [Odds ratio (OR) 5.0, 95% CI 1.3-19.6; and OR 14.6, 95% CI 1.3-161.4; p < 0.05] as well as with long-lasting feeding (>12 months) disorders (OR 18.6, 95% CI 3.9-89.2 and OR 20.4, 95% CI 3,4-122.8; p < 10-2). Syndromic SPR status was also associated with severe respiratory disorders (OR 4.9, 95% CI 1-32.5; p < 0.05). Using multivariate analysis, only syndromic PRS status was predictive for severe respiratory disorders (adjusted OR 8, 95% CI 1.47-44.57; p < 0.05); and only neurological impairments remained a significant risk for long lasting feeding disorders (>12 months) (adjusted OR 21.72, 95% CI 3.4-138.63; p < 10-2). The grades of retrognathia and glossoptosis were not predictive factors for the severity of respiratory and feeding disorders. Conclusion: In children with PRS, the severity of clinical conditions may not correlate with anatomic variables but rather with laryngeal abnormalities, neurological impairement and syndromic PRS status.

Predictors of speech outcomes in children with Pierre Robin sequence.

BACKGOUND: Pierre Robin sequence (PRS) has worse speech outcomes than isolated cleft palate. We aimed to search for possible associations of phonological outcomes with PRS status (isolated vs syndromic), clinical severity, soft palate muscles deficiency, or surgical procedure. METHODS: We designed a retrospective study of 130 children (male/female ratio: 0.4) with isolated (96) or syndromic (34) PRS with cleft palate. Grading systems were used to classify retrognathia, glossoptosis, and respiratory and feeding disorders. Electromyography was used to investigate levator veli palatini muscles. Hard cleft palate was measured using maxillary casts. Intravelar veloplasty was performed using the Sommerlad's technique. Phonological outcomes were assessed using the Borel-Maisonny classification. RESULTS: Cleft palate was repaired in one stage (65.5%) or hard palate closure was postponed (34.5%). Velopharyngeal insufficiency was more frequent in syndromic PRS (53%) vs. isolated PRS (30.5%) (p = 0.01), but was not statistically associated with clinical grade, hard cleft palate width, soft palate electromyography, and surgical procedure. CONCLUSIONS: In children with PRS, anatomic variables, initial clinical severity, and soft palate muscle deficiency are not predictors of speech prognosis.

Preoperative Detailed Coagulation Tests Are Required in Patients With Noonan Syndrome.

PURPOSE: Patients with Noonan syndrome often require surgery at young ages. They are at high risk of perioperative bleeding from coagulation defects that might not have been detected by routine screening. These risks are rarely described in the oral and maxillofacial surgery (OMS) literature. The aim of this study was to evaluate the perioperative bleeding risks associated with Noonan syndrome and to propose preoperative guidelines. MATERIALS AND METHODS: This report describes a retrospective case series of patients with Noonan syndrome who underwent OMS procedures during a continuous observational period (2013 through 2016) in the authors' center. Clinical data, blood screening test results, and perioperative bleeding were analyzed. RESULTS: Five patients (age, 4 to 20 yr) with Noonan syndrome who underwent OMS procedures were included in this study. One patient presented a spontaneous bleeding tendency (epistaxis requiring cauterization). Blood screening showed clotting defects in 3 patients. One patient presented abnormal perioperative bleeding owing to a mild defect in factor XI. CONCLUSION: Patients with Noonan syndrome must be referred to a hematologist for specific preoperative investigations and for adapted perioperative management.

Anterior Skull Base and Pericranial Flap Ossification after Frontofacial Monobloc Advancement.

BACKGROUND: Frontofacial monobloc advancement creates a communication between the anterior cranial fossa and nasal cavities. To tackle this issue, transorbital pericranial pedicled flaps are routinely performed in the authors' center. This study aimed to assess the postoperative ossification of the anterior skull base and pedicled flaps following frontofacial monobloc advancement, and to identify factors influencing this ossification. METHODS: Measurements of the skull base only and of the ossified pedicled flaps together with the skull base were performed on computed tomographic scans at the nasofrontal and the nasoethmoid frontal junctions. The total thickness of the skull vault was measured and a qualitative defect score for the anterior skull base was computed. RESULTS: Twenty-two patients who underwent frontofacial monobloc advancement at a median age of 3.1 years (range, 1.9 to 3.6 years) were included: 14 with Crouzon, five with Pfeiffer, and three with Apert syndrome. One year and 5 years after surgery, the distraction gap was completely ossified in the anterior skull base midline in all patients. Ossified pedicled flaps together with the skull base were thicker in patients than in controls at these two time points (p < 0.005 and p < 0.02). Patients with Pfeiffer syndrome had a significantly thicker skull base only and ossified pedicled flaps together with the skull base thicknesses (p = 0.01 and p = 0.03) and lower defect scores than patients with Crouzon or Apert syndrome (p = 0.03) 1 year postoperatively. CONCLUSION: As ossification of the pedicled flaps and total reossification of the anterior skull base midline were observed in all patients, the authors indicate that performing pedicled flaps in frontofacial monobloc advancement surgery could promote the reossification of the anterior skull base. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Systemic juvenile xanthogranuloma: a case of spontaneous regression of intramedullary spinal cord, cerebral, and cutaneous lesions.

Juvenile xanthogranuloma (JXG) is a rare disease that belongs to the non-Langerhans cell histiocytoses. It presents a wide clinical spectrum, usually occurs before 5 years of age, and is commonly confined to the skin; however, it can affect multiple sites, including the nervous system, and can lead to severe disorders. Although JXG is a benign disease that usually regresses spontaneously, several curative treatments have been proposed in cases of organ involvement. Treatment options include corticosteroids, chemotherapy, and radiotherapy; however, these can have severe, long-term adverse effects in children. The authors here describe the first case of spontaneous resolution of an intramedullary spinal cord lesion of JXG associated with cerebral and cutaneous lesions in a young boy with 9 years of follow-up. The initial neurological symptoms resolved without any surgical or medical treatment. This case shows that extracutaneous lesions of JXG, including those with intramedullary spinal cord involvement, can regress without curative treatment-like cutaneous lesions-although both multidisciplinary care and close follow-up should be implemented.

Reconstruction of a large calvarial traumatic defect using a custom-made porous hydroxyapatite implant covered by a free latissimus dorsi muscle flap in an 11-year-old patient.

Reconstruction of complex skull defects requires collaboration between neurosurgeons and plastic surgeons to choose the most appropriate procedure, especially in growing children. The authors describe herein the reconstruction of an extensive traumatic bone and soft tissue defect of the cranial vault in an 11-year-old boy. The size of the defect, quality of the tissues, and patient's initial condition required a 2-stage approach. Ten months after an initial emergency procedure in which lacerated bone and soft tissue were excised, reconstruction was performed. The bone defect, situated on the left frontoparietal region, was 85 cm2 and was filled by a custom-made porous hydroxyapatite implant. The quality of the overlying soft tissue did not allow the use of classic local and locoregional coverage techniques. A free latissimus dorsi muscle flap branched on the contralateral superficial temporal pedicle was used and left for secondary healing to take advantage of scar retraction and to minimize alopecia. Stable well-vascularized implant coverage as well as an esthetically pleasing skull shape was achieved. Results in this case suggest that concomitant reconstruction of large calvarial defects by cranioplasty with a custom-made hydroxyapatite implant covered by a free latissimus dorsi muscle flap is a safe and efficient procedure in children, provided that there is no underlying infection of the operative site.

[Application of "tennis racket" flap with fascial pedicle on the healthy chest for the radiation ulcer after surgical treatment of breast carcinoma].

OBJECTIVE: To introduce the application of "tennis racket" flap with fascial pedicle on the healthy chest for radiation ulcer after surgical treatment of breast cancer. METHODS: The " tennis racket" flap was designed on the healthy chest along the cartilage with fascia pedicle near the sternum. 9 cases were treated. The flaps size ranged from 5.0 cm x 3.5 cm to 13 cm x 11 cm with pedicle size of 2-8 cm in length and 2.0-3.0 cm in width. RESULTS: All the 9 flaps survived completely with satisfactory appearance. The patients were followed up for 2 months to 3 years without ulcer reoccurrence. CONCLUSIONS: The "tennis racket" flap has a slender fascial pedicle without major blood vessel. It has the advantages of good flexibility for rotation and large flap size for the reconstruction of the radiation ulcer after surgical treatment of breast cancer.