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Joy M. Richman - One of the best experts on this subject based on the ideXlab platform.
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Identification and functional analysis of novel facial patterning genes in the duplicated beak chicken embryo.
Developmental Biology, 2015Co-Authors: Suresh Nimmagadda, Marcela Buchtová, Poongodi Geetha-loganathan, Sara Hosseini-farahabadi, Alexander J. Trachtenberg, Winston Patrick Kuo, Iva Vesela, Joy M. RichmanAbstract:Cranial neural crest cells form the majority of the facial skeleton. However exactly when the pattering information and hence jaw identity is established is not clear. We know that premigratory neural crest cells contain a limited amount of information about the lower jaw but the upper jaw and facial midline are specified later by local tissue interactions. The environmental signals leading to frontonasal identity have been explored by our group in the past. Altering the levels of two signaling pathways (Bone Morphogenetic Protein) and retinoic acid (RA) in the chicken embryo creates a duplicated midline on the side of the upper beak complete with egg tooth in place of Maxillary derivatives (Lee et al., 2001). Here we analyze the transcriptome 16 h after bead placement in order to identify potential mediators of the identity change in the Maxillary Prominence. The gene list included RA, BMP and WNT signaling pathway genes as well as transcription factors expressed in craniofacial development. There was also cross talk between Noggin and RA such that Noggin activated the RA pathway. We also observed expression changes in several poorly characterized genes including the upregulation of Peptidase Inhibitor-15 (PI15). We tested the functional effects of PI15 overexpression with a retroviral misexpression strategy. PI15 virus induced a cleft beak analogous to human cleft lip. We next asked whether PI15 effects were mediated by changes in expression of major clefting genes and genes in the retinoid signaling pathway. Expression of TP63, TBX22, BMP4 and FOXE1, all human clefting genes, were upregulated. In addition, ALDH1A2, ALDH1A3 and RA target, RARβ were increased while the degradation enzyme CYP26A1 was decreased. Together these changes were consistent with activation of the RA pathway. Furthermore, PI15 retrovirus injected into the face was able to replace RA and synergize with Noggin to induce beak transformations. We conclude that the microarrays have generated a rich dataset containing genes with important roles in facial morphogenesis. Moreover, one of these facial genes, PI15 is a putative clefting gene and is in a positive feedback loop with RA.
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Expression of Tmem26 in wild-type embryos by whole mount in situ hybridisation analysis.
2013Co-Authors: Liam Town, Joy M. Richman, Edwina Mcglinn, Tara-lynne Davidson, Catherine M. Browne, Kallayanee Chawengsaksophak, Peter Koopman, Carol WickingAbstract:(A–E) Whole embryos aged 11.0 dpc-14.5 dpc. No expression was detected before 11.0 dpc. (F–J) Forelimbs of corresponding embryos shown in A–E, dorsal view, limb anterior is to the top. (K,L) At 11.0 and 11.5 dpc Tmem26 expression in the facial Prominences is restricted primarily to mesenchyme underlying areas of facial Prominence fusion and merging. (M) At 12.5 dpc striking expression is observed in the primary palate, and expression remains at the midline of the mandible. (N) After fusion is complete at 13.5 dpc, expression is restricted to Maxillary tissue at the distal tip of the snout. (O,P) The developing secondary palate at 14.5 dpc, taken from below with the mandible removed, one showing the palatal shelves wide apart, and one as the shelves are coming together to fuse. Tmem26 is expressed in the palatal shelves prior to fusion but downregulated upon palate fusion, most obvious at 15.5 dpc (Q). (R) Ventral and (S) lateral views of a 13.5 dpc genital tubercle. Dorsal-ventral and anterior-posterior axes are indicated. 1p-primary palate, 2p-secondary palatal shelves, e-external ear, em-extraoccular musculature, fl-forelimb, lnp-lateral nasal Prominence, mes-medial epithelial seam, md-mandible, mnp-medial nasal Prominence, mx-Maxillary Prominence, n-nasal opening, vcm-ventral cephalic mesenchyme.
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Expression of Tmem26 in wild-type embryos by section in situ hybridisation.
2013Co-Authors: Liam Town, Joy M. Richman, Edwina Mcglinn, Tara-lynne Davidson, Catherine M. Browne, Kallayanee Chawengsaksophak, Peter Koopman, Carol WickingAbstract:(A–D, E–G,J) radioisotopic; (H,I) DIG detection. (A–D) Transverse sections through the secondary palate at indicated stages. At 12.5 dpc and 13.5 dpc Tmem26 is expressed in mesenchyme of the vertical palatal shelves. At 14.5 dpc the shelves have fused but the medial epithelial seam still remains and expression within the mesenchyme is apparent. By 15.5 dpc the epithelial seam is absent and Tmem26 expression is virtually undetectable. (A′–D′) Corresponding serial sections stained with toluidine blue. (E–G) Sections through the facial Prominences and primary palate region at indicated stages. Tmem26 is not detected at 10.5 dpc but is upregulated at 11.5 dpc and 12.5 dpc. (E′–G′) Corresponding sections stained with toluidine blue. (H) Parasagittal section through the lateral hindbrain at 12.5 dpc, showing expression in the nucleus of the seventh facial nerve region within the pons. (I) Longitudinal section through the stomach at 11.5 dpc, showing expression in the anterior stomach mesenchyme. (J) Magnification of the left eyelid from D, (J′) same section counterstained with haematoxylin. 1p-primary palate, bt-mesencyme at the base of the tongue, c-cornea, el-eyelid, em-extraocular mesenchyme and developing extrinsic muscles of the eye, ep-epithelim, L-eye lens, lnp-lateral nasal Prominence, n7-nucleus of the seventh facial nerve, mn-mandible, mnp-medial nasal Prominence, mx-Maxillary Prominence, ns-nasal septum, p-palatal shelf, pd-eyelid periderm, st-stomach mesenchyme. Size bars indicate 1 mm.
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A new origin for the Maxillary jaw
Developmental Biology, 2004Co-Authors: Olivier Bédard, Katherine Fu, Marcela Buchtová, Joy M. RichmanAbstract:Abstract One conserved feature of craniofacial development is that the first pharyngeal arch has two components, the Maxillary and mandibular, which then form the upper and lower jaws, respectively. However, until now, there have been no tests of whether the Maxillary cells originate entirely within the first pharyngeal arch or whether they originate in a separate condensation, cranial to the first arch. We therefore constructed a fate map of the pharyngeal arches and environs with a series of dye injections into stage 13–17 chicken embryos. We found that from the earliest stage examined, the major contribution to the Maxillary bud is from post-optic mesenchyme with a relatively minor contribution from the maxillo-mandibular cleft. Cells labeled within the first pharyngeal arch contributed exclusively to the mandibular Prominence. Gene expression data showed that there were different molecular codes for the cranial and caudal Maxillary Prominence. Two of the genes examined, Rarβ ( retinoic acid receptor β ) and Bmp4 (bone morphogenetic protein) were expressed in the post-optic mesenchyme and epithelium prior to formation of the Maxillary Prominence and then were restricted to the cranial half of the Maxillary Prominence. In order to determine the derivatives of the Maxillary Prominence, we performed focal injections of CM-DiI into the stage 24 Maxillary Prominence. Labeled cells contributed to the Maxillary, palatine, and jugal bones, but not the other elements of the upper beak, the premaxilla and prenasal cartilage. We also determined that the cranial cells give rise to more distal parts of the upper beak, whereas caudal cells form proximal structures. Grafts of stage 24 Maxillary Prominences were also analyzed to determine skeletal derivatives and these results concurred with the DiI maps. These early and later fate maps indicate that the Maxillary Prominence and its skeletal derivatives are not derived from the first pharyngeal arch but rather from a separate Maxillary condensation that occurs between the eye and the maxillo-mandibular cleft. These data also suggest that during evolution, recession of the first pharyngeal arch-derived palatoquadrate cartilage to a more proximal position gave way to the bony upper jaw of amniotes.
Gunvor Semb - One of the best experts on this subject based on the ideXlab platform.
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one stage warsaw and two stage oslo repair of unilateral cleft lip and palate craniofacial outcomes
Journal of Cranio-maxillofacial Surgery, 2015Co-Authors: Piotr Fudalej, Gunvor Semb, Ewa Wegrodzka, Maria HortisdzierzbickaAbstract:The aim of this study was to compare facial development in subjects with complete unilateral cleft lip and palate (CUCLP) treated with two different surgical protocols. Lateral cephalometric radiographs of 61 patients (42 boys, 19 girls; mean age, 10.9 years; SD, 1) treated consecutively in Warsaw with one-stage repair and 61 age-matched and sex-matched patients treated in Oslo with two-stage surgery were selected to evaluate craniofacial morphology. On each radiograph 13 angular and two ratio variables were measured in order to describe hard and soft tissues of the facial region. The analysis showed that differences between the groups were limited to hard tissues – the Maxillary Prominence in subjects from the Warsaw group was decreased by almost 4° in comparison with the Oslo group (sella-nasion-A-point (SNA) = 75.3° and 79.1°, respectively) and maxillo-mandibular morphology was less favorable in the Warsaw group than the Oslo group (ANB angle = 0.8° and 2.8°, respectively). The soft tissue contour was comparable in both groups. In conclusion, inter-group differences suggest a more favorable outcome in the Oslo group. However, the distinctiveness of facial morphology in background populations (ie, in Poles and Norwegians) could have contributed to the observed results.
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the americleft study an inter center study of treatment outcomes for patients with unilateral cleft lip and palate part 5 general discussion and conclusions
The Cleft Palate-Craniofacial Journal, 2011Co-Authors: Kathleen Russell, Ana Mercado, Ronald R. Hathaway, Marilyn Cohen, John Daskalogiannakis, Ross E. Long, Gunvor Semb, William C. ShawAbstract:Objective: To summarize the Americleft study regarding treatment outcomes for patients with complete unilateral cleft lip and palate (CUCLP). Setting: Five cleft palate centers in North America. Subjects: One hundred sixty‐nine subjects, between the ages of 6 years and 12 years, with repaired CUCLP who were consecutively treated at the five centers. Methods: Study consisted of model comparisons assessing maxillomandibular relationship using the GOSLON Yardstick (169 patients from all 5 centers), soft and hard tissue craniofacial morphologic comparisons using lateral cephalometric analyses (148 patients from four of the centers), and nasolabial esthetics assessments (125 patients from four of the centers). Results: Significant differences were found between the center with the best GOSLON scores and the remaining centers. These differences also corresponded to those found in the craniofacial morphologic cephalometric assessment. Sagittal Maxillary Prominence was found to be significantly better for the cen...
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The Americleft Study: An Inter-Center Study of Treatment Outcomes for Patients with Unilateral Cleft Lip and Palate Part 3. Analysis of Craniofacial Form:
The Cleft Palate-Craniofacial Journal, 2011Co-Authors: John Daskalogiannakis, Ana Mercado, Ronald R. Hathaway, Gregory Dugas, Kathleen Russell, Marilyn Cohen, Ross E. Long, Gunvor Semb, William C. ShawAbstract:OBJECTIVE: To compare craniofacial morphology for individuals with nonsyndromic complete unilateral cleft lip and palate between the ages of 6 and 12 years. DESIGN: Retrospective cohort study. SETTING: Four North American cleft palate centers. SUBJECTS: A total of 148 subjects with repaired complete unilateral cleft lip and palate who were consecutively treated at the four centers. METHODS: The 148 preorthodontic lateral cephalometric radiographs were scanned, scaled, digitized, and coded to blind the examiners to radiograph origin. On each radiograph, 18 (angular and ratio) cephalometric measurements were performed. Measurement means, by center, were compared using analysis of variance and Tukey-Kramer analysis. RESULTS: Significant differences were found for sagittal Maxillary Prominence among the four centers. The most significant difference was seen between Center B (lowest SNA) and Center C (highest SNA). Similar differences were seen at the soft tissue level, with Center C showing a significantly larger ANB angle compared with Centers B and D. Center C was also shown to have statistically greater mean soft tissue convexity than Centers B, D, and E. The mean nasolabial angle in Center B was significantly more acute than in Centers C, D, and E. No statistically significant differences were seen for mandibular Prominence, vertical dimensions, or dental inclinations. CONCLUSION: Significant differences were seen among the centers for hard and soft tissue Maxillary Prominence, but not for mandibular Prominence, vertical dimensions, or dental inclinations. A modest but statistically significant (p < .001) negative correlation was found between Goslon scores and ANB angle (r = -.607).
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a cephalometric intercenter comparison of patients with unilateral cleft lip and palate analysis at 5 and 10 years of age and long term
The Cleft Palate-Craniofacial Journal, 2008Co-Authors: Maria Costanza Meazzini, Gunvor Semb, Greta Giussani, Alberto Morabito, G Garattini, Roberto BrusatiAbstract:OBJECTIVE: To compare the short- and long-term craniofacial growth of patients operated with the Milan protocol to those operated with the Oslo protocol. DESIGN: The Milan sample included 88 patients with unilateral cleft lip and palate (UCLP) at 5 years, 26 at 10 years, and 23 at the end of growth. The Oslo samples included 48 UCLP patients at 5 years, 29 at 10, and 23 at growth completion. Lateral cephalograms were used for comparison. An unpaired t test was run for the 5- and 10-year-old samples. The samples long term were matched for age and sex, and a paired t test was run. RESULTS: There was no significant cephalometric difference in the Maxillary Prominence at 5 years, a mild but significant difference at 10 years, and again no difference at the end of growth. Nevertheless, at an older age, the need for orthognathic surgery was larger in the Milan sample (26%) than in the Oslo sample (13%). CONCLUSION: Although no statistically significant differences in the cephalometric measurements were found long term, the need for orthognathic surgery was clinically judged to be larger in the Milan sample. On the other hand, although the Milan protocol seemed to require more final jaw surgery, only the cases that needed an additional orthognathic procedure in the Milan group will undertake a third surgical step, while the Oslo protocol included three surgical steps for all the patients.
Maria Hortisdzierzbicka - One of the best experts on this subject based on the ideXlab platform.
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one stage warsaw and two stage oslo repair of unilateral cleft lip and palate craniofacial outcomes
Journal of Cranio-maxillofacial Surgery, 2015Co-Authors: Piotr Fudalej, Gunvor Semb, Ewa Wegrodzka, Maria HortisdzierzbickaAbstract:The aim of this study was to compare facial development in subjects with complete unilateral cleft lip and palate (CUCLP) treated with two different surgical protocols. Lateral cephalometric radiographs of 61 patients (42 boys, 19 girls; mean age, 10.9 years; SD, 1) treated consecutively in Warsaw with one-stage repair and 61 age-matched and sex-matched patients treated in Oslo with two-stage surgery were selected to evaluate craniofacial morphology. On each radiograph 13 angular and two ratio variables were measured in order to describe hard and soft tissues of the facial region. The analysis showed that differences between the groups were limited to hard tissues – the Maxillary Prominence in subjects from the Warsaw group was decreased by almost 4° in comparison with the Oslo group (sella-nasion-A-point (SNA) = 75.3° and 79.1°, respectively) and maxillo-mandibular morphology was less favorable in the Warsaw group than the Oslo group (ANB angle = 0.8° and 2.8°, respectively). The soft tissue contour was comparable in both groups. In conclusion, inter-group differences suggest a more favorable outcome in the Oslo group. However, the distinctiveness of facial morphology in background populations (ie, in Poles and Norwegians) could have contributed to the observed results.
Paul A. Trainor - One of the best experts on this subject based on the ideXlab platform.
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Interaction between Foxc1 and Fgf8 during Mammalian Jaw Patterning and in the Pathogenesis of Syngnathia
2015Co-Authors: Kimberly E. Inman, Patricia Purcell, Tsutomu Kume, Paul A. TrainorAbstract:Syngnathia (bony fusion of the upper and lower jaw) is a rare human congenital condition, with fewer than sixty cases reported in the literature. Syngnathia typically presents as part of a complex syndrome comprising widespread oral and maxillofacial anomalies, but it can also occur in isolation. Most cartilage, bone, and connective tissue of the head and face is derived from neural crest cells. Hence, congenital craniofacial anomalies are often attributed to defects in neural crest cell formation, survival, migration, or differentiation. The etiology and pathogenesis of syngnathia however remains unknown. Here, we report that Foxc1 null embryos display bony syngnathia together with defects in Maxillary and mandibular structures, and agenesis of the temporomandibular joint (TMJ). In the absence of Foxc1, neural crest cell derived osteogenic patterning is affected, as osteoblasts develop ectopically in the Maxillary Prominence and fuse with the dentary bone. Furthermore, we observed that the craniofacial musculature is also perturbed in Foxc1 null mice, which highlights the complex tissue interactions required for proper jaw development. We present evidence that Foxc1 and Fgf8 genetically interact and that Fgf8 dosage is associated with variation in the syngnathic phenotype. Together our data demonstrates that Foxc1 – Fgf8 signaling regulates mammalian jaw patterning and provides a mechanistic basis for the pathogenesis of syngnathia. Furthermore, our work provides a framework for understanding jaw patterning and the etiology of othe
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interaction between foxc1 and fgf8 during mammalian jaw patterning and in the pathogenesis of syngnathia
PLOS Genetics, 2013Co-Authors: Kimberly E. Inman, Patricia Purcell, Tsutomu Kume, Paul A. TrainorAbstract:Syngnathia (bony fusion of the upper and lower jaw) is a rare human congenital condition, with fewer than sixty cases reported in the literature. Syngnathia typically presents as part of a complex syndrome comprising widespread oral and maxillofacial anomalies, but it can also occur in isolation. Most cartilage, bone, and connective tissue of the head and face is derived from neural crest cells. Hence, congenital craniofacial anomalies are often attributed to defects in neural crest cell formation, survival, migration, or differentiation. The etiology and pathogenesis of syngnathia however remains unknown. Here, we report that Foxc1 null embryos display bony syngnathia together with defects in Maxillary and mandibular structures, and agenesis of the temporomandibular joint (TMJ). In the absence of Foxc1, neural crest cell derived osteogenic patterning is affected, as osteoblasts develop ectopically in the Maxillary Prominence and fuse with the dentary bone. Furthermore, we observed that the craniofacial musculature is also perturbed in Foxc1 null mice, which highlights the complex tissue interactions required for proper jaw development. We present evidence that Foxc1 and Fgf8 genetically interact and that Fgf8 dosage is associated with variation in the syngnathic phenotype. Together our data demonstrates that Foxc1 – Fgf8 signaling regulates mammalian jaw patterning and provides a mechanistic basis for the pathogenesis of syngnathia. Furthermore, our work provides a framework for understanding jaw patterning and the etiology of other congenital craniofacial anomalies, including temporomandibular joint agenesis.
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Early morphologic abnormalities of Foxc1−/− PA1 detected despite no significant alteration of cell cycle dynamics or apoptosis.
2013Co-Authors: Kimberly E. Inman, Patricia Purcell, Tsutomu Kume, Paul A. TrainorAbstract:(A) Confocal z-stack projections of DAPI stained, whole mount Foxc1+/+ and Foxc1−/− embryos showing gross PA1 morphology. A red asterisk marks the Maxillary Prominence in all panels. A white arrowhead indicates the maxilla-mandibular junction (Mx-Md). At E9.0-9.5, the mutant Maxillary Prominence is smaller than wild-type, and the Mx-Md is shallower than in controls. By E10.5, the lambdoidal junction (λ) and nasal Prominence epithelium has formed in Foxc1+/+ and Foxc1−/− embryos. The Foxc1−/− Maxillary Prominence continues to develop between E10.5-11.5, but remains smaller compared to wild-type embryos. The distance from the λ to Mx-Md junction is reduced in Foxc1−/− embryos. (B) Representative sections of IdU and BrdU immunostained embryos. (C) Average S-phase and cell cycle lengths were determined based upon incorporation of IdU and BrdU. A trend toward longer S-phase and cell cycle length was noted in the cranial mesenchyme at 5–7-s. (D) Projections of confocal Z-stacks showing whole mount TUNEL staining to detect apoptotic cells in Foxc1+/+ and Foxc1−/− embryos at E8.75 and E9.0. Although change in morphology of PA1 is evident, no abnormal level or localization of apoptosis is detected in the mutants. Scale bars: 100 µm.
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Interaction betweenFoxc1 and Fgf8 during Mammalian Jaw Patterning and in the Pathogenesis of Syngnathia
2013Co-Authors: Kimberly E. Inman, Patricia Purcell, Tsutomu Kume, Paul A. TrainorAbstract:Syngnathia (bony fusion of the upper and lower jaw) is a rare human congenital condition, with fewer than sixty cases reported in the literature. Syngnathia typically presents as part of a complex syndrome comprising widespread oral and maxillofacial anomalies, but it can also occur in isolation. Most cartilage, bone, and connective tissue of the head and face is derived from neural crest cells. Hence, congenital craniofacial anomalies are often attributed to defects in neural crest cell formation, survival, migration, or differentiation. The etiology and pathogenesis of syngnathia however remains unknown. Here, we report that Foxc1 null embryos display bony syngnathia together with defects in Maxillary and mandibular structures, and agenesis of the temporomandibular joint (TMJ). In the absence of Foxc1, neural crest cell derived osteogenic patterning is affected, as osteoblasts develop ectopically in the Maxillary Prominence and fuse with the dentary bone. Furthermore, we observed that the craniofacial musculature is also perturbed in Foxc1 null mice, which highlights the complex tissue interactions required for proper jaw development. We present evidence that Foxc1 and Fgf8 genetically interact and that Fgf8 dosage is associated with variation in the syngnathic phenotype. Together our data demonstrates that Foxc1 – Fgf8 signaling regulates mammalian jaw patterning and provides a mechanistic basis for the pathogenesis of syngnathia. Furthermore, our work provides a framework for understanding jaw patterning and the etiology of other congenital craniofacial anomalies, including temporomandibular joint agenesis.
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CrefaceT/T embryos exhibit general facial Prominence hypoplasia.
2012Co-Authors: Jennifer F. Dennis, Hiroshi Kurosaka, Angelo Iulianella, Jennifer Pace, Nancy Thomas, Sharon Beckham, Trevor Williams, Paul A. TrainorAbstract:Fluorescent images of whole DAPI stained E10.5 control (A, C, E) and CrefaceT/T (B, D, F) embryos highlighting the pharyngeal (asterisk) and midfacial hypoplasia evident in the form of a single nasal slit (double arrows) in mutant embryos. Bright field images of E14.5 control (G) and CrefaceT/T (H) embryos illustrating the severe frontonasal defects in mutant embryos (asterisk). Abbreviations: LNP, lateral nasal Prominence; MN, mandibular Prominence; MNP, medial nasal Prominence; MX, Maxillary Prominence. Scale bars: 200 uM.
Piotr Fudalej - One of the best experts on this subject based on the ideXlab platform.
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one stage warsaw and two stage oslo repair of unilateral cleft lip and palate craniofacial outcomes
Journal of Cranio-maxillofacial Surgery, 2015Co-Authors: Piotr Fudalej, Gunvor Semb, Ewa Wegrodzka, Maria HortisdzierzbickaAbstract:The aim of this study was to compare facial development in subjects with complete unilateral cleft lip and palate (CUCLP) treated with two different surgical protocols. Lateral cephalometric radiographs of 61 patients (42 boys, 19 girls; mean age, 10.9 years; SD, 1) treated consecutively in Warsaw with one-stage repair and 61 age-matched and sex-matched patients treated in Oslo with two-stage surgery were selected to evaluate craniofacial morphology. On each radiograph 13 angular and two ratio variables were measured in order to describe hard and soft tissues of the facial region. The analysis showed that differences between the groups were limited to hard tissues – the Maxillary Prominence in subjects from the Warsaw group was decreased by almost 4° in comparison with the Oslo group (sella-nasion-A-point (SNA) = 75.3° and 79.1°, respectively) and maxillo-mandibular morphology was less favorable in the Warsaw group than the Oslo group (ANB angle = 0.8° and 2.8°, respectively). The soft tissue contour was comparable in both groups. In conclusion, inter-group differences suggest a more favorable outcome in the Oslo group. However, the distinctiveness of facial morphology in background populations (ie, in Poles and Norwegians) could have contributed to the observed results.