Maxillary Hypoplasia and Non-Invasive Ventilation: Literature Review and Proposed New Treatment Protocol.

The impact of non-invasive ventilation (NIV) on pediatric maxillary growth is a subject of ongoing research considering its increased use in the pediatric population due to technological advancements and broader indications. This review examines the existing literature, encompassing original articles, case reports, and reviews, to evaluate the effects of NIV on maxillary development and explore potential treatment options. Although the majority of studies agree on the adverse effects of prolonged NIV on maxillary development, techniques for its correction remain understudied. Introducing a novel treatment protocol, we addressed the challenge of correcting severe midfacial hypoplasia in a child with congenital central hypoventilation syndrome (CCHS) undergoing NIV therapy, thus sidestepping the necessity for osteotomies. This proposed protocol holds promise in correcting the adverse impact of NIV on maxillary growth, emphasizing the need for further exploration into innovative treatment modalities.

Cyclic loading failed to promote growth in a pig model of midfacial hypoplasia.

Yucatan miniature pigs, often used as large animal models in clinical research, are distinguished by a breed-specific midfacial hypoplasia with anterior crossbite. Although this deformity can be corrected by distraction osteogenesis, a less invasive method is desirable. We chose a mechanical cyclic stimulation protocol that has been successful in enhancing sutural growth in small animals and in a pilot study on standard pigs. Yucatan minipigs (n = 14) were obtained in pairs, with one of each pair randomly assigned to sham or loaded groups. All animals had loading implants installed on the right nasal and frontal bones and received labels for cell proliferation and mineral apposition. After a week of healing and under anesthesia, experimental animals received cyclic tensile loads (2.5 Hz, 30 min) delivered to the right nasofrontal suture daily for 5 days. Sutural strains were recorded at the final session for experimental animals. Sham animals received the same treatment except without loading or strain gauge placement. In contrast to pilot results on standard pigs, the treatment did not produce the expected sutural widening and increased growth. Although sutures were not fused and strains were in the normal range, the targeted right nasofrontal suture was narrowed rather than widened, with no statistically significant changes in sutural cell proliferation, mineral apposition, or vascularity. In general, Yucatan minipig sutures were more vascular than those of standard pigs and also tended to have more proliferating cells. In conclusion, either because the sutures themselves are abnormal or because of growth restrictions elsewhere in the skull, this cyclic loading protocol was unable to produce the desired response of sutural widening and growth. This treatment, effective in normal animals, did not improve naturally occurring midfacial hypoplasia in Yucatan minipigs.

The nasal septum and midfacial growth.

The nasal septum is the only element of the chondrocranium which never completely ossifies. The persistence of this nonarticular cartilage has given rise to a variety of theories concerning cranial mechanics and growth of the midface. Previously, using pigs, we demonstrated that the septum is not a strut supporting the snout and that septal growth seems capable of stretching the overlying nasofrontal suture, a major contributor to snout elongation. Here we investigate whether abnormalities of the septum are implicated in cases of midfacial hypoplasia, in which growth of the midface is inadequate. Mild midfacial hypoplasia is common in domestic pig breeds and often severe in the Yucatan minipig, a popular laboratory breed. Normal-snouted and midfacial hypoplastic heads of standard (farm mixed breed) and minipigs ranging in age from perinatal to 12 months were dissected, imaged by CT, and/or prepared for histology. Even at birth, Yucatan minipigs with midfacial hypoplasia exhibited greater caudal ossification than normal; the ventral cartilaginous sphenoidal "tail" was diminished or missing. In addition, cells that morphologically appeared to have divided recently were less numerous than in newborn standard pigs. Juvenile Yucatan minipigs lacked caudal cartilaginous growth zones almost completely. In standard newborns, the ventral caudal septum was more replicative than the dorsal, but this trend was not seen in Yucatan newborns. In conclusion, accelerated maturation of the caudal septum was associated with midfacial hypoplasia, a further indication that the septum, particularly its ventral portion, is important for midfacial elongation.

Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis.

Syndromic craniosynostosis (CS) patients exhibit early, bony fusion of calvarial sutures and cranial synchondroses, resulting in craniofacial dysmorphology. In this study, we chronologically evaluated skull morphology change after abnormal fusion of the sutures and synchondroses in mouse models of syndromic CS for further understanding of the disease. We found fusion of the inter-sphenoid synchondrosis (ISS) in Apert syndrome model mice (Fgfr2S252W/+ ) around 3 weeks old as seen in Crouzon syndrome model mice (Fgfr2cC342Y/+ ). We then examined ontogenic trajectories of CS mouse models after 3 weeks of age using geometric morphometrics analyses. Antero-ventral growth of the face was affected in Fgfr2S252W/+ and Fgfr2cC342Y/+ mice, while Saethre-Chotzen syndrome model mice (Twist1+/- ) did not show the ISS fusion and exhibited a similar growth pattern to that of control littermates. Further analysis revealed that the coronal suture synostosis in the CS mouse models induces only the brachycephalic phenotype as a shared morphological feature. Although previous studies suggest that the fusion of the facial sutures during neonatal period is associated with midface hypoplasia, the present study suggests that the progressive postnatal fusion of the cranial synchondrosis also contributes to craniofacial dysmorphology in mouse models of syndromic CS. These morphological trajectories increase our understanding of the progression of syndromic CS skull growth.

Three-dimensional orthodontic imaging in children across the age spectrum and correlations with obstructive sleep apnea.

STUDY OBJECTIVES: To determine baseline facial convexity measurements in children with obstructive sleep apnea (OSA) across the age spectrum. METHODS: Polysomnogram, stereophotogrammetry, and biometric data were collected from children aged 0-18 years who were being investigated for OSA. Analyses evaluated differences in facial convexity according to OSA severity and other sleep parameters, while adjusting for age, ethnicity, and sex. RESULTS: Ninety-one children, aged 0.05-16.02 years, met the inclusion criteria for this study. Initial analysis showed that the logarithm of age had a significant effect on facial convexity (P = 8.3·10-7) with significant effects of sex (P = 1.3·10-2), while excluding OSA. Ordinal logistic regression taking into consideration age, sex, weight, height, and ethnicity with OSA severity categorized as obstructive apnea-hypopnea index negative, mild, moderate, or severe showed that facial convexity was associated with OSA severity (P = 2.2·10-3); an increasing obtuse angle of convexity increased the tendency to be classified as having severe OSA. CONCLUSIONS: Using three-dimensional imaging, we found an added impact of infancy on changes of facial convexity with age. While modeling could describe facial convexity without any OSA-associated sleep parameters, differences in facial convexity were present among groups with different levels of OSA severity adjusted for growth (age, weight, and height), sex, and ethnicity. The method provides a safer and cheaper alternative to other medical imaging techniques in children and holds potential for future use in studies of craniofacial structure. CITATION: Tyler G, Machaalani R, Waters KA. Three-dimensional orthodontic imaging in children across the age spectrum and correlations with obstructive sleep apnea. J Clin Sleep Med. 2023;19(2):275-282.

Does the Timing of 1-Stage Palatoplasty With Radical Muscle Dissection Effect Long-Term Midface Growth? A Single-Center Retrospective Analysis.

OBJECTIVE: To evaluate the long-term effect of timing of 1-stage palatoplasty on midfacial growth in patients with cleft lip and palate (CLP). DESIGN: Retrospective observational cohort study. STUDY SETTING: Institutional hospital. PATIENTS: One hundred twelve patients with CLP who underwent palatoplasty and were divided into 3 groups: group I: operated between 9 and 11 months; group II: operated between 18 and 20 months; and group III: operated between 21 and 24 months. INTERVENTIONS: All patients underwent von Langenbeck palatoplasty technique, which was converted to a Bardach 2-flap technique in case of any technical difficulties. The patients were followed up between 8 and 9 years when they reported for secondary alveolar bone grafting. Postsurgical cephalometric and dental casts measurements were taken for midfacial growth analysis. MAIN OUTCOME MEASURES: The cephalometric measures were analyzed for midfacial growth and compared within the groups. RESULTS: Statistically significant difference (P < .01) was found on comparing the cephalometric parameters such as sella-nasion-A point angle (SNA), A point-nasion-B point angle (ANB), n toperpendicular to point A (N-perpA), condylon to point A (Co-A), anterior nasal spine to posterior nasal spine (ANS-PNS), nasion to Anterior nasal spine (N-ANS), nasion to menton (N Me), and witts appraisal (Witt (AO-BO)) in group I when compared to both group II and group III patients, implying deficient midfacial growth in group I. No statistical difference was found in the cephalometric values between group II and group III. Group II had better cephalometric measurements than group III, showing better growth in group II than group III. Overall, there was less incidence of midfacial hypoplasia in patients treated between 18 and 20 months (group II). CONCLUSION: We conclude that palatal closure carried out at 18 to 20 months and 21 to 24 months is associated with better midfacial growth when compared to closure at 9 to 11 months. The best time to operate would be between 18 and 20 months to avoid speech disturbances. Midfacial growth can be greatly influenced by the timing of 1-stage palatoplasty.

Osteotomía Le Fort III modificada en un paciente no sindrómico / Modified Le Fort III osteotomy in a non-syndromic patient

Las discrepancias dento-esqueletales severas presentan un reto para el cirujano maxilofacial, existe una versatilidad de osteotomías para las diferentes anomalías del crecimiento y desarrollo, sin embargo, son pocas las que permiten mejorar la proyección malar. La osteotomía Le Fort III modificada fue utilizada en un principio en pacientes con algún síndrome craneofacial, pero actualmente es una alternativa útil para discrepancias severas en pacientes no sindrómicos, ya que permite un avance cigomático-maxilar, favorece la proyección malar y disminuye la exposición escleral con un número limitado de complicaciones. Se presenta el caso de un paciente masculino de 33 años con antecedente de fractura orbitocigomática y piso orbitario izquierda con una discrepancia dento-esqueletal severa, la que fue tratada mediante osteotomía Le Fort III modificada, osteotomías sagitales mandibulares para un avance máxilo-malar y retroceso mandibular respectivamente y una genioplastia de avance; logrando un resultado funcional y estético adecuado.

The dento-skeletal severe discrepancies present a challenge for the maxillofacial surgeon, there is a versatility of osteotomies for the different growth and development anomalies, however, a few of them make possible to improve malar projection. The modified Le Fort III osteotomy was originally used in patients with some craniofacial syndrome, but now it is a useful alternative for severe discrepancies in non-syndromic patients, since it allows a zygomatic-maxillary advance, favors malar projection and reduces scleral exposure with a limited number of complications. The case of a 33-year-old male patient with a history of orbitozygomatic fracture and left orbital floor with a severe dento-skeletal discrepancy is presented, who was treated by modified Le Fort III osteotomy, mandibular sagittal osteotomies for maxillo-malar advancement and retrogression mandibular respectively and geniplasty for advance; achieving a suitable functional and aesthetic result.

Neural crest-specific deletion of Bmp7 leads to midfacial hypoplasia, nasal airway obstruction, and disordered breathing modelling Obstructive Sleep Apnea.

Pediatric obstructive sleep apnea (OSA), a relatively common sleep-related breathing disorder (SRBD) affecting approximately 1-5% of children, is often caused by anatomical obstruction and/or collapse of the nasal and/or pharyngeal airways. The resulting sleep disruption and intermittent hypoxia lead to various systemic morbidities. Predicting the development of OSA from craniofacial features alone is currently not possible and a controversy remains if upper airway obstruction facilitates reduced midfacial growth or vice-versa. Currently, there is no rodent model that recapitulates both the development of craniofacial abnormalities and upper airway obstruction to address these questions. Here, we describe that mice with a neural crest-specific deletion of Bmp7 (Bmp7ncko) present with shorter, more acute angled cranial base, midfacial hypoplasia, nasal septum deviation, turbinate swelling and branching defects, and nasal airway obstruction. Interestingly, several of these craniofacial features develop after birth during periods of rapid midfacial growth and precede the development of an upper airway obstruction. We identified that in this rodent model, no single feature appeared to predict upper airway obstruction, but the sum of those features resulted in a reduced breathing frequency, apneas and overall reduced oxygen consumption. Metabolomics analysis of serum from peripheral blood identified increased levels of hydroxyproline, a metabolite upregulated under hypoxic conditions. As this model recapitulates many features observed in OSA, it offers unique opportunities for studying how upper airway obstruction affects breathing physiology and leads to systemic morbidities.

Modified high-level Le Fort I advancement without malar augmentation: assessment of effect on midfacial aesthetics.

The 'beauty arch', an aesthetic feature of the midface, is a double-S-shaped curve that extends downward from the lateral canthus. This retrospective study evaluated whether modified high Le Fort I advancement (combined with impaction or down-grafting) without malar augmentation can approximate a patient's 'ideal' beauty arch (IBA). Pre- and postoperative profile (natural head position) photographs for 36 patients with midfacial hypoplasia were aligned digitally. For each individual, standardized methods were used to identify landmarks and draw the preoperative real beauty arch (RBA), postoperative RBA, and IBA. Distances from a defined landmark to each arch were measured and means were compared. The mean advancement range was 4.2 ± 2.2 mm, and the mean pre- and postoperative RBA distances were significantly different (138.7 ± 24.1 vs 145.0 ± 25.8 pixels, respectively; P = 0.0001). In the impaction and down-grafting subgroups, there was no significant correlation between amount of maxillary movement and the difference between pre- and postoperative RBA distances (P > 0.05 for both). The postoperative RBA was satisfactorily close to the IBA in 35 cases (97.2%); one patient required later augmentation. The findings suggest that modified high Le Fort I advancement surgery without malar augmentation provides satisfactory malar projection for most patients with maxillary hypoplasia.

Morphological changes in the midface of Beagle dogs treated by trans-sutural distraction / Cambios morfológicos en la cara media de perros Beagle tratados por distracción trans-sutural

Trans-sutural distraction is a biological process that induces the formation of new bone and changes the position of bone by pulling on growing suture under the action of external forces. Currently, therapy to midfacial hypoplasia treated by trans-sutural distraction has been applied. In this study, Beagle dogs were selected as experimental animals, and a traction device designed by ourselves was applied to Beagle dogs to simulate the treatment process of trans-sutural distraction in human face, so as to provide a basis for the subsequent research on the related mechanism of trans-sutural distraction. The objective is that the animal model can provide the basis for the follow-up study of transsutural distraction. 45 month beagle dogs were randomly divided into two groups 3 in experiment group and 3 in control group. Implant nails were implanted as the bone marker in the bilateral zygomatic temporal suture, zygomandibular maxillary suture and palatine transverse suture in experimental group. The traction of the maxilla was carried out by the external cranial traction frame with canine fossa as bearing point, 800g force each side, elastic traction for 15 days. The control group only implanted the implant nail as the bone marker on both sides of the bone suture. The distance between two implant nails was measured by vernier calipers and X-ray examination, compared with preoperative and postoperative changes. X-ray and cephalometric measurements were used to measure change in the cranial basal angle. HE staining was used to observe the width of the bone seams, the morphology and structure of the cells and the tissue of the new bone under the phase contrast microscope. Then descriptive statistical analysis and t-test between two independent samples are carried out for the measurement data. The experimental group had a good retention of the beagle traction frame. In the experimental group, the maxillaries of dogs were protrudent in the process of traction gradually and the occlusal relationship changed to type II malocclusion. When the traction is 15 days, the coverage distance is about 8~9 mm. Before and after the traction, the distance between landmark points indicated that the spacing between the transverse palatine suture was the largest (experimental group: 5.52±0.19 mm control group 1.31±0.06 mm P<0.05), and zygomaticotemporal suture was the second (experimental group: 3.12±0.15 mm, control group 0.73±0.04 mm, P<0.05), and zygomaticomaxillary suture was less (experimental group: 2.60±0.34 mm, control group 0.53±0.05 mm, P<0.05). The cranial basal angle was no change before and after operation (controlgroup: 32.3±1.3°, experimental group: 33.2±1.1° P>0.05. Histology showed that the collagenous fibers in the suture of the control group were denser and the osteoblasts were visible on the edge of the suture, showing osteogenic activity. The experimental group significantly widened suture (experimental group: 1209.388±42.714 µm, control group 248.276±22.864 µm, P<0.05), the number of fibroblasts increased significantly with loose collagen fiber. The direction of cell and fiber arrangement were parallel to the traction force. There were many small blood vessels and marrow cavities, and the bone trabecula around the bone suture was thin (experimental group: 23.684±3.774 mm, control group: 86.810±9.219 mm, P < 0.05), showing active osteogenic activity. The growing beagle dog can be used to establish a suture traction animal model for experimental study. In the experiment, Kirschner wire was used to penetrate the bottom plane of the piriform hole of the maxilla (about the position of the canine fossa at the back) and the traction direction was basically the same as the growth direction, and the maxilla was basically parallel and moved forward.

La distracción trans-sutural es un proceso biológico que induce la formación de hueso nuevo y cambia la posición del éste al tirar de la sutura en crecimiento bajo la acción de fuerzas externas. Actualmente, se ha aplicado la terapia para la hipoplasia de la cara media tratada por distracción trans-sutural. En este estudio, fueron seleccionados perros Beagle como animales experimentales, y un dispositivo de tracción fue instalado a los perros para simular el proceso de tratamiento de la distracción trans-sutural en el rostro humano. El objetivo fue proporcionar una base para la investigación posterior sobre mecanismos relacionados con la distracción trans-sutural. El modelo animal puede proporcionar la base para este tipo de estudio de seguimiento de la distracción trans-sutural. Perros Beagle de 45 meses de edad se dividieron aleatoriamente en dos grupos: 3 en el grupo experimental y 3 en el grupo control. Los clavos de implante se usaron como marcadores óseos en la sutura temporal cigomática bilateral, la sutura maxilar cigomandibular y en la sutura transversal palatina en el grupo experimental. La tracción del maxilar se realizó mediante el marco de tracción craneal externo con fosa canina como punto de apoyo, 800 g de fuerza a cada lado, tracción elástica durante 15 días. En el grupo control solo se implantó el clavo del implante como marcador óseo en ambos lados de la sutura. La distancia entre dos clavos de implante se midió mediante calibradores de vernier y examen de rayos X, en comparación con los cambios preoperatorios y postoperatorios. Se utilizaron mediciones cefalométricas y de rayos X para medir el cambio en el ángulo basal craneal. La tinción con HE se usó para observar el ancho de las suturas óseas, la morfología y la estructura de las células y el tejido del hueso nuevo bajo el microscopio de contraste de fase. Luego se realizó un análisis estadístico descriptivo y una prueba t entre dos muestras independientes para los datos de medición. El grupo experimental tuvo una buena retención del cuadro de tracción del Beagle. En el grupo experimental, los maxilares de los perros sobresalieron gradualmente en el proceso de tracción y la relación oclusal cambió a maloclusión tipo II. Cuando la tracción era de 15 días, la distancia de cobertura fue de aproximadamente 8 ~ 9 mm. Antes y después de la tracción, la distancia entre los puntos de referencia indicaba que el espacio entre la sutura palatina transversal era más grande (grupo experimental: 5,52 ± 0,19 mm, grupo de control 1,31 ± 0,06 mm, P <0,05), y la sutura cigomáticotemporal fue la segunda. (Grupo experimental: 3,12 ± 0,15 mm, grupo control 0,73 ± 0,04 mm, P <0,05), y la sutura cigomaticomaxilar fue menor (grupo experimental, 2,60 ± 0,34 mm, grupo control 0,53 ± 0,05 mm, P <0,05). El ángulo basal craneal no cambió antes ni después de la operación (grupo control 32,3 ± 1,3, grupo experimental, 33,2 ± 1,1 ° , P> 0,05). La histología mostró que las fibras colágenas en la sutura del grupo control eran más densas y los osteoblastos se observaron en el margen de la sutura, mostrando actividad osteogénica. En el grupo experimental se amplió significativamente la sutura (1209,388 ± 42,714 µm, grupo control 248,276 ± 22,864 µm, P <0,05), el número de fibroblastos aumentó significativamente con fibras colágenas dispersas. La dirección de la disposición de la celda y las fibras era paralela a la fuerza de tracción. Se observó gran cantidad de vasos sanguíneos pequeños, cavidades medulares, y trabéculas óseas alrededor de la sutura ósea (grupo experimental: 23,684 ± 3,774 mm, grupo control: 86,810 ± 9,219 mm, P <0,05), que mostró actividad osteogénica activa. El perro Beagle en crecimiento se puede utilizar para estudios experimentales y así establecer un modelo animal de tracción de sutura. En el proceso, se usó alambre de Kirschner para penetrar en el plano inferior del foramen piriforme del maxilar (aproximadamente en la posición de la fosa canina en la parte posterior) y la dirección de tracción fue básicamente la misma que en el crecimiento.

Mechanobiology of bone and suture - Results from a pig model.

OBJECTIVE: To compare the morphology and mechanical function of sutures in normal pigs and minipigs to those of Yucatan minipigs, a natural model for midfacial hypoplasia. SETTING AND SAMPLE POPULATION: Research took place at the Department of Orthodontics at the University of Washington and used varying sample sizes of normal-snouted pigs and Yucatan minipigs. MATERIAL AND METHODS: Skulls and heads were examined for morphology of the nasofrontal suture using computed tomography and histology. Strain gauge recordings were made of sutural strain during mastication and during cyclic tensile loading of the nasofrontal suture. RESULTS: Sutures in Yucatans had narrower gaps than same-age normal pigs. The nasofrontal suture was simpler in construction and had more active osteoblasts on the bone fronts in Yucatans. The sutural ligament was less well organized, and based on a small sample, masticatory strain appeared to be lower than in normal minipigs. However, sutures were not fused and showed similar strains in response to the cyclic loading procedure. CONCLUSION: Midfacial hypoplasia in Yucatan pigs has the likely proximate cause of hyperossification. Yet prior to fusion, the sutures appear to be amenable to treatment that would promote their growth rate.

The use of Medpor implants for midface contouring in cleft patients.

Three-dimensional midfacial deficiency in cleft patients is common and is frequently connected to impairment of the aesthetic facial appearance. Different approaches to augment relevant facial regions are available. Alloplastic facial implants have been established as a viable alternative to autologous tissue augmentation in various circumstances. However, in cleft patients, the application of facial implants has rarely been reported. This retrospective study aimed to evaluate the use of Medpor implants for midfacial contouring in cleft patients. Fifty-one patients with orofacial clefts were assessed with regard to defined parameters. A range of Paranasal, Malar and Nasal Dorsum Medpor implants had been used. Unilateral cleft lip and palate (UCLP) represented the most common indication, followed by bilateral cleft lip and palate (BCLP). Bilateral implant insertion was performed as a general rule with few exceptions. Insertion of implants was frequently combined with other cleft-related surgical procedures. Even after orthognathic surgery, midfacial augmentation was implemented to specifically address residual volume deficiency, particularly in the malar region. The complication rate amounted to 4.9% (6/122 implants). Based on our findings, Medpor implants are reliable and long-term stable materials to successfully augment paranasal, subnasal and malar areas as well as a solid nasal dorsum material with few complications in cleft patients.

Critical Growth Processes for the Midfacial Morphogenesis in the Early Prenatal Period.

BACKGROUND: Congenital midfacial hypoplasia often requires intensive treatments and is a typical condition for the Binder phenotype and syndromic craniosynostosis. The growth trait of the midfacial skeleton during the early fetal period has been assumed to be critical for such an anomaly. However, previous embryological studies using 2-dimensional analyses and specimens during the late fetal period have not been sufficient to reveal it. OBJECTIVE: To understand the morphogenesis of the midfacial skeleton in the early fetal period via 3-dimensional quantification of the growth trait and investigation of the developmental association between the growth centers and midface. METHODS: Magnetic resonance images were obtained from 60 human fetuses during the early fetal period. Three-dimensional shape changes in the craniofacial skeleton along growth were quantified and visualized using geometric morphometrics. Subsequently, the degree of development was computed. Furthermore, the developmental association between the growth centers and the midfacial skeleton was statistically investigated and visualized. RESULTS: The zygoma expanded drastically in the anterolateral dimension, and the lateral part of the maxilla developed forward until approximately 13 weeks of gestation. The growth centers such as the nasal septum and anterior portion of the sphenoid were highly associated with the forward growth of the midfacial skeleton (RV = 0.589; P < .001). CONCLUSIONS: The development of the midface, especially of the zygoma, before 13 weeks of gestation played an essential role in the midfacial development. Moreover, the growth centers had a strong association with midfacial forward growth before birth.

Modified Le Fort III osteotomy: A simple solution to severe midfacial hypoplasia.

PURPOSE: There are multiple conditions that may affect the development of the middle third of the face and with varying degrees of severity. The surgical treatment alternatives for major midfacial sagittal deficiencies consist in Le Fort I, II, or III with conventional osteotomies or with distraction osteogenesis (DO). Both techniques have advantages and disadvantages that should be evaluated specifically in each case. The aim of this report is to present a group of patients with severe hypoplasia of the middle third of the face, with different origins, and their treatment with a Modified Le Fort III osteotomy and distraction osteogenesis, using a minimally invasive surgical approach. MATERIALS AND METHODS: The surgical technique was performed in a group of patients with severe hypoplasia of the middle third of the face, through a transconjunctival approach with lateral canthotomy and a trans-oral approach. The osteotomy consisted of a Le Fort III without the nasofrontal component. A rigid external distractor (RED) type II or internal distractor was installed. The amount of distraction, surgical time, blood loss, and complications were evaluated. RESULTS: A total of 7 patients underwent operation, 5 men and 2 women with an average age of 20.8 (range 11-41) years; 3 patients with Crouzon syndrome, 2 with Pfeiffer syndrome, 1 patient with cleft lip and palate sequel, and 1 with a severe non-syndromic class III. The average follow-up was 3.14 years. All patients achieved stable occlusion without postoperative changes, positive overbite and overjet, without relapse in the skeletal position. The average advancement was 14.7 (±4.07) mm, in 1.1 incisors, and 15.2 (±3.19) in point A. The average time of surgery was 2.78 (±0.64) hours, with an average blood loss of 240 (±48.6) ml. Four patients required a rhinoplasty in a secondary surgery. CONCLUSION: This technique shows a surgical approach with low morbidity, short surgery time, and low blood loss. It allows optimal resolution of severe hypoplasia of the middle third of the face with long-term stability. It avoids the use of grafts and osteosynthesis material. By not including the nasal pyramid in the osteotomy design, the size, position, and nasofrontal angle in patients with adequate facial balance is maintained. If nasal correction is necessary, a second surgery may be done. In cases of asymmetrical hypoplasia of the middle third, this osteotomy shows great versatility and can be done unilaterally and/or simultaneously combined with other distractions.

Developmental and Evolutionary Significance of the Zygomatic Bone.

The zygomatic bone is derived evolutionarily from the orbital series. In most modern mammals the zygomatic bone forms a large part of the face and usually serves as a bridge that connects the facial skeleton to the neurocranium. Our aim is to provide information on the contribution of the zygomatic bone to variation in midfacial protrusion using three samples; humans, domesticated dogs, and monkeys. In each case, variation in midface protrusion is a heritable trait produced by one of three classes of transmission: localized dysmorphology associated with single gene dysfunction, selective breeding, or long-term evolution from a common ancestor. We hypothesize that the shape of the zygomatic bone reflects its role in stabilizing the connection between facial skeleton and neurocranium and consequently, changes in facial protrusion are more strongly reflected by the maxilla and premaxilla. Our geometric morphometric analyses support our hypothesis suggesting that the shape of the zygomatic bone has less to do with facial protrusion. By morphometrically dissecting the zygomatic bone we have determined a degree of modularity among parts of the midfacial skeleton suggesting that these components have the ability to vary independently and thus can evolve differentially. From these purely morphometric data, we propose that the neural crest cells that are fated to contribute to the zygomatic bone experience developmental cues that distinguish them from the maxilla and premaxilla. The spatiotemporal and molecular identity of the cues that impart zygoma progenitors with their identity remains an open question that will require alternative data sets. Anat Rec, 299:1616-1630, 2016. © 2016 The Authors The Anatomical Record Published by Wiley Periodicals, Inc.

Assessment of Midfacial Hypoplasia in Down Syndrome Fetuses - Validity of a Two-Line Approach and Introduction of a Novel Angle (Maxilla-Mandible-Nasion Angle).

PURPOSE: To scrutinize the validity of a novel angle (maxilla-mandible-nasion angle, MMN) as objective proof of midfacial hypoplasia in trisomy 21 fetuses. MATERIALS AND METHODS: Volume data sets of 2(nd) trimester fetuses were reviewed in this retrospective study. After achievement of the correct midsagittal position, the fetal profile line (FP line) and the mandibulo-maxillary line (MML) were applied and the resulting angle was calculated. Additionally, the prefrontal space ratio (PFSR) was assessed. Both measurements were obtained from 401 euploid fetuses and 42 fetuses with trisomy 21. Values for MMN and PFSR<5(th) percentile were considered abnormal. RESULTS: The study included 443 fetuses with a mean gestational age of 21.3 weeks (range: 14.0-26.3). The MMN angle sufficiently identified hypoplasia of the midface in trisomy 21 fetuses (mean: 14.6°; range: 10.1°- 22.0°) compared to controls (mean: 20.5°; range: 17.3°-23.7°; p<0.0001). Concomitantly, the PFSR of Down syndrome fetuses was significantly lower (mean: 0.53; range: 0.21-1.22) than in euploid individuals (1.38; range: 0.54-2.23; p<0.0001). CONCLUSION: Calculation of the novel MMN angle in 2(nd) trimester fetuses reliably allows rapid assessment of craniofacial anatomy in order to rule out the midfacial hypoplasia frequently found in trisomy 21.

Possible Achondroplastic Dwarf Skull from Montevideo, Uruguay.

Achondroplasia (chondrodystrophia) is an autosomal dominant inherited disorder affecting approximately 1 in 26,000 live births and is the most common cause of dwarfism in humans. Disproportionate short stature and a suite of craniofacial characteristics typify achondroplasia. The literature available for differential diagnosis of the disorder relies primarily on the postcranial skeleton. In this paper, a possible case of achondroplasia is presented. The cranium presents a unique suite of cranial and craniofacial dysmorphologies. The lack of postcranial remains does not permit their use in the analysis. To make a differential diagnosis and to quantify the observed craniofacial dysmorphologies, craniometric data are compared to modern clinical literature and to craniometric data from known achondroplastic dwarfs. Thin-plate spline analysis is integrated to quantify the differences in degree and magnitude of shape change. This manuscript demonstrates an appropriate methodology for identifying achondroplasia from the cranial skeleton alone.

BCL11B regulates sutural patency in the mouse craniofacial skeleton.

The transcription factor BCL11B plays essential roles during development of the immune, nervous, and cutaneous systems. Here we show that BCL11B is expressed in both osteogenic and sutural mesenchyme of the developing craniofacial complex. Bcl11b(-/-) mice exhibit increased proliferation of osteoprogenitors, premature osteoblast differentiation, and enhanced skull mineralization leading to synostoses of facial and calvarial sutures. Ectopic expression of Fgfr2c, a gene implicated in craniosynostosis in mice and humans, and that of Runx2 was detected within the affected sutures of Bcl11b(-/-) mice. These data suggest that ectopic expression of Fgfr2c in the sutural mesenchyme, without concomitant changes in the expression of FGF ligands, appears to induce the RUNX2-dependent osteogenic program and craniosynostosis in Bcl11b(-/-) mice.