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Background: Regularly discarded lip tissue obtained from corrective surgeries to close the cleft lip represents an easily accessible and rich source for the isolation of primary fibroblasts. Primary fibroblasts have been described to show compelling similarities to mesenchymal stem cells (MSCs). Hence, cleft lip and palate (CLP) lip-derived fibroblasts could be thought as an intriguing cell source for personalized regenerative therapies in CLP-affected patients., Methods: Initially, we thoroughly characterized the fibroblastic nature of the lip-derived mesenchymal outgrowths by molecular and functional assays. Next, we compared their phenotype and genotype to that of bone marrow-mesenchymal stem cells (BM-MSCs) and of human lung-derived fibroblasts WI38, by assessing their morphology, surface marker expression, trilineage differentiation potential, colony-forming (CFU) capacity, and immunomodulation property. Finally, to better decipher the heterogeneity of our CLP cultures, we performed a single cell clonal analysis and tested expanded clones for surface marker expression, as well as osteogenic and CFU potential., Results: We identified intriguingly similar phenotypic and genotypic properties between CLP lip fibroblasts and BM-MSCs, which makes them distinct from WI38. Furthermore, our own data in combination with the complex anatomy of the lip tissue indicated heterogeneity in our CLP cultures. Using a clonal analysis, we discovered single cell-derived clones with increased levels of the MSC markers CD106 and CD146 and clones with variabilities in their commitment to differentiate into bone-forming cells and in their potential to form single cell-derived colonies. However, we were not able to gain clones possessing superior MSC-like capacities when compared to the heterogeneous parental CLP population. Additionally, all clones could still generate contractile forces and retained robust levels of the fibroblast specific marker FSP1, which was not detectable in BM-MSCs., Conclusions: Our results suggest that we isolate heterogeneous populations of fibroblasts from discarded CLP lip tissue, which show a prominently multipotent character in their entirety avoiding the need for elaborate subpopulation selections in vitro. These findings suggest that CLP lip fibroblasts might be a novel potential cell source for personalized regenerative medicine of clinical benefit for CLP patients., (© 2022. The Author(s).)

Background: Cleft lip and palate is one of the most common birth defects and can cause difficulties with feeding, speech and hearing, as well as psychosocial problems. Treatment of orofacial clefts is prolonged; it typically commences after birth and lasts until the child reaches adulthood or even into adulthood. Residual deformities, functional disturbances, or both, are frequently seen in adults with a repaired cleft. Conventional orthognathic surgery, such as Le Fort I osteotomy, is often performed for the correction of maxillary hypoplasia. An alternative intervention is distraction osteogenesis, which achieves bone lengthening by gradual mechanical distraction. This review is an update of the original version that was published in 2016., Objectives: To provide evidence regarding the effects and long-term results of maxillary distraction osteogenesis compared to orthognathic surgery for the treatment of hypoplastic maxilla in people with cleft lip and palate., Search Methods: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 15 May 2018), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2018, Issue 4), MEDLINE Ovid (1946 to 15 May 2018), Embase Ovid (1980 to 15 May 2018), and LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; from 1982 to 15 May 2018). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases., Selection Criteria: We included randomised controlled trials (RCTs) comparing maxillary distraction osteogenesis to conventional Le Fort I osteotomy for the correction of cleft lip and palate maxillary hypoplasia in non-syndromic cleft patients aged 15 years or older., Data Collection and Analysis: Two review authors assessed studies for eligibility. Two review authors independently extracted data and assessed the risk of bias in the included studies. We contacted trial authors for clarification or missing information whenever possible. All standard methodological procedures expected by Cochrane were used., Main Results: We found six publications involving a total of 47 participants requiring maxillary advancement of 4 mm to 10 mm. All of them related to a single trial performed between 2002 and 2008 at the University of Hong Kong, but not all of the publications reported outcomes from all 47 participants. The study compared maxillary distraction osteogenesis with orthognathic surgery, and included participants from 13 to 45 years of age.Results and conclusions should be interpreted with caution given the fact that this was a single trial at high risk of bias, with a small sample size.The main outcomes assessed were hard and soft tissue changes, skeletal relapse, effects on speech and velopharyngeal function, psychological status, and clinical morbidities.Both interventions produced notable hard and soft tissue improvements. Nevertheless, the distraction group demonstrated a greater maxillary advancement, evaluated as the advancement of Subspinale A-point: a mean difference of 4.40 mm (95% CI 0.24 to 8.56) was recorded two years postoperatively.Horizontal relapse of the maxilla was significantly less in the distraction osteogenesis group five years after surgery. A total forward movement of A-point of 2.27 mm was noted for the distraction group, whereas a backward movement of 2.53 mm was recorded for the osteotomy group (mean difference 4.8 mm, 95% CI 0.41 to 9.19).No statistically significant differences could be detected between the groups in speech outcomes, when evaluated through resonance (hypernasality) at 17 months postoperatively (RR 0.11, 95% CI 0.01 to 1.85) and nasal emissions at 17 months postoperatively (RR 3.00, 95% CI 0.14 to 66.53), or in velopharyngeal function at the same time point (RR 1.28, 95% CI 0.65 to 2.52).Maxillary distraction initially lowered social self-esteem at least until the distractors were removed, at three months postoperatively, compared to the osteotomy group, but this improved over time and the distraction group had higher satisfaction with life in the long term (two years after surgery) (MD 2.95, 95% CI 014 to 5.76).Adverse effects, in terms of clinical morbidities, included mainly occlusal relapse and mucosal infection, with the frequency being similar between groups (3/15 participants in the distraction osteogenesis group and 3/14 participants in the osteotomy group). There was no severe harm to any participant., Authors' Conclusions: This review found only one small randomised controlled trial concerning the effectiveness of distraction osteogenesis compared to conventional orthognathic surgery. The available evidence is of very low quality, which indicates that further research is likely to change the estimate of the effect. Based on measured outcomes, distraction osteogenesis may produce more satisfactory results; however, further prospective research comprising assessment of a larger sample size with participants with different facial characteristics is required to confirm possible true differences between interventions.

Objective: To determine whether judgment of nasolabial esthetics in cleft lip and palate (CLP) is influenced by overall facial attractiveness., Design: Experimental study., Setting: University of Bern, Switzerland., Subjects and Methods: Seventy-two fused images (36 of boys, 36 of girls) were constructed. Each image comprised (1) the nasolabial region of a treated child with complete unilateral CLP (UCLP) and (2) the external facial features, i.e., the face with masked nasolabial region, of a noncleft child. Photographs of the nasolabial region of six boys and six girls with UCLP representing a wide range of esthetic outcomes, i.e., from very good to very poor appearance, were randomly chosen from a sample of 60 consecutively treated patients in whom nasolabial esthetics had been rated in a previous study. Photographs of external facial features of six boys and six girls without UCLP with various esthetics were randomly selected from patients' files. Eight lay raters evaluated the fused images using a 100-mm visual analogue scale. Method reliability was assessed by reevaluation of fused images after >1 month. A regression model was used to analyze which elements of facial esthetics influenced the perception of nasolabial appearance., Results: Method reliability was good. A regression analysis demonstrated that only the appearance of the nasolabial area affected the esthetic scores of fused images (coefficient = -11.44; P < .001; R(2) = 0.464). The appearance of the external facial features did not influence perceptions of fused images., Conclusion: Cropping facial images for assessment of nasolabial appearance in CLP seems unnecessary. Instead, esthetic evaluation can be performed on images of full faces.

In a fraction of patients surgically treated for cleft lip/palate, excessive scarring disturbs maxillary growth and dento-alveolar development. Since certain genes are involved in craniofacial morphogenesis as well as tissue repair, a primary defect causing cleft lip/palate could lead to altered wound healing. We performed in vitro wound healing assays with primary lip fibroblasts from 16 cleft lip/palate patients. Nine foreskin fibroblast strains were included for comparison. Cells were grown to confluency and scratch wounds were applied; wound closure was monitored morphometrically over time. Wound closure rate showed highly significant differences between fibroblast strains. Statistically, fibroblast strains from the 25 individuals could be divided into three migratory groups, namely "fast", "intermediate", and "slow". Most cleft lip/palate fibroblasts were distributed between the "fast" (5 strains) and the "intermediate" group (10 strains). These phenotypes were stable over different cell passages from the same individual. Expression of genes involved in cleft lip/palate and wound repair was determined by quantitative PCR. Transforming growth factor-α mRNA was significantly up-regulated in the "fast" group. 5 ng/ml transforming growth factor-α added to the culture medium increased the wound closure rate of cleft lip/palate strains from the "intermediate" migratory group to the level of the "fast", but had no effect on the latter group. Conversely, antibody to transforming growth factor-α or a specific inhibitor of its receptor most effectively reduced the wound closure rate of "fast" cleft lip/palate strains. Thus, fibroblasts from a distinct subgroup of cleft lip/palate patients exhibit an increased migration rate into wounds in vitro, which is linked to higher transforming growth factor-α expression and attenuated by interfering with its signaling.

In complete unilateral cleft lip and palate (CLP), a vomerplasty is assumed to improve midfacial growth because of the reduction in scarring in the growth-sensitive areas of the palate. Our aim, therefore, was to evaluate maxillofacial morphology after a modified Langenbeck technique or a vomerplasty in children with complete unilateral CLP who were operated on by a single surgeon. As part of a one-stage closure of complete unilateral CLP done during the first year of life, the technique for repair of the hard palate repair differed between the two groups. In the modified group (n=37, mean age 11 years) a modified von Langenbeck technique was used that resulted in denudation of the bony surface on the non-cleft side only. In the vomerplasty group (n=37, mean age 11 years) a vomerplasty was used to cover the palatal bone. Lateral cephalograms from both groups were compared using the Eurocleft protocol. Fourteen angular variables were measured and 2 ratios calculated. Skeletal morphology in the groups was comparable. Maxillary incisor inclination (ILs/NL angle) and interincisal angle (ILs/ILi) were better after vomerplasty (p=0.001 and 0.04, respectively) but soft tissue facial convexity (gs-prn-pgs) was less good after vomerplasty (p=0.009). However, there was no difference between the groups in the other variable that reflected facial convexity (gs-sn-pgs) (p=0.22). Modification of the palatoplasty had a limited effect on skeletal morphology in preadolescent children, but it resulted in better inclination of the maxillary incisors., (Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Palatogenesis is a complex process implying growth, elevation and fusion of the two lateral palatal shelves during embryogenesis. This process is tightly controlled by genetic and mechanistic cues that also coordinate the growth of other orofacial structures. Failure at any of these steps can result in cleft palate, which is a frequent craniofacial malformation in humans. To understand the etiology of cleft palate linked to the BMP signaling pathway, we studied palatogenesis in Bmp7-deficient mouse embryos. Bmp7 expression was found in several orofacial structures including the edges of the palatal shelves prior and during their fusion. Bmp7 deletion resulted in a general alteration of oral cavity morphology, unpaired palatal shelf elevation, delayed shelf approximation, and subsequent lack of fusion. Cell proliferation and expression of specific genes involved in palatogenesis were not altered in Bmp7-deficient embryos. Conditional ablation of Bmp7 with Keratin14-Cre or Wnt1-Cre revealed that neither epithelial nor neural crest-specific loss of Bmp7 alone could recapitulate the cleft palate phenotype. Palatal shelves from mutant embryos were able to fuse when cultured in vitro as isolated shelves in proximity, but not when cultured as whole upper jaw explants. Thus, deformations in the oral cavity of Bmp7-deficient embryos such as the shorter and wider mandible were not solely responsible for cleft palate formation. These findings indicate a requirement for Bmp7 for the coordination of both developmental and mechanistic aspects of palatogenesis.

Objective: To evaluate the correlation between symmetry of the craniofacial skeleton and aesthetics of the nose and upper lip in children with complete unilateral cleft lip and palate (CUCLP)., Material and Methods: Craniofacial symmetry was evaluated on postero-anterior (PA) cephalograms of 54 children (37 boys and 17 girls; mean age = 11.0 years, SD 1.6) with CUCLP repaired with a one-stage closure (Cleft group). Treated subjects were age- and gender-matched with 54 untreated subjects taken from the University of Michigan Growth Study (Control group). Fourteen coefficients of asymmetry (CAs) were calculated and four angles were measured. Four raters assessed the nasolabial appearance on cropped facial and profile photographs with the 5-grade aesthetic index of Asher-McDade (grade 1 means the most aesthetic and grade 5 the least aesthetical outcome) in the Cleft group only. Independent t-tests were used to evaluate the inter-group differences for CAs. Pearson's correlation coefficients were calculated to examine a relationship between particular components of the aesthetical index and CAs. Multiple regression analyses were carried out to explain the nasolabial aesthetics on the basis of craniofacial symmetry., Results: In the Cleft group, most cephalometric variables demonstrated asymmetry not exceeding 10%. The Cleft and Control groups differed regarding three angular measurements (Se, Ism, and ANS) and 1 CA (Mo-V). Three of the four nasolabial components demonstrated correlation with some cephalometric variables. However, the correlation coefficients were low (range: -0.309 to 0.305)., Conclusions: There is a weak correlation between craniofacial skeletal symmetry and aesthetics of the nose and upper lip in children with CUCLP., (Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The objective of this study was to evaluate the association between nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate (CUCLP). Frontal and basal photographs of 60 consecutively treated children with CUCLP (cleft group: 41 boys and 19 girls, mean (SD) age 11 (2) years) and 44 children without clefts (control group: 16 boys and 28 girls, mean (SD) age 11(2) years), were used for evaluation of nasolabial symmetry and aesthetics. Nasal and labial measurements were made to calculate the coefficient of asymmetry (CA). The 5-grade aesthetic index described by Asher-McDade et al. was used to evaluate nasolabial appearance. Correlation and regression analysis were used to identify an association between aesthetics and CA, sex, and the presence of CUCLP. Ten measurements in the cleft, and 2 in the control, group differed significantly between the cleft and non-cleft (or right and left) sides, respectively. The significantly higher values of 9 of 11 CA in the children with CUCLP indicated that they had more asymmetrical nasolabial areas than children without clefts. However, the regression analyses showed that only a few CA were associated with nasolabial aesthetics. In conclusion, nasolabial aesthetics and nasolabial symmetry seem to be only weakly associated in patients with CUCLP., (Copyright © 2011 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

In this longitudinal study, the craniofacial morphology and evaluated soft tissue profile changes, at 6 and 12 years of age in patients with complete bilateral cleft lip and palate (CBCLP) were compared. Lateral cephalograms from 148 patients with CBCLP, treated consecutively at three European cleft centers, Gothenburg (n (A) = 37), Nijmegen (n (B) = 26), and Oslo (n (C) = 85), were evaluated. Eighteen hard tissue and ten soft tissue landmarks were digitized. Paired t test, Pearson's correlation coefficients, and multiple regression models were applied for statistical analysis. ANOVA and Tukey-B, as a post hoc test, were used to evaluate the increments and compare centers. Hard and soft tissue data were superimposed using the generalized Procrustes analysis. For Nijmegen, the increments of the variables SNA, ANB, SN-NL, SN-ML, NL-ML, Snss, and Snpg were significantly different than the two other centers (p = 0.041 to <0.001). SNPg increments were significantly different between Nijmegen and Oslo (p = 0.002). The three cleft centers followed different treatment protocols, but the main differences in craniofacial morphology until 12 years of age were the growth pattern and the maxillary and upper incisor variables. Follow-up of these patients until facial growth has ceased, which may elucidate components for improving treatment outcome.

The objective of this study is to compare dental arch relationship following one-stage and three-stage surgical protocols of unilateral cleft lip and palate. Dental casts of 61 children (mean age, 11.2 years; SD, 1.7), consecutively treated in one center with one-stage closure of the complete cleft at 9.2 months (SD, 2.0), were compared with a sample of 97 patients (mean age, 8.7 years; SD, 0.9), consecutively treated with a three-stage protocol including delayed hard palate closure in another center. The dental casts were assigned random numbers to blind their origin. Four raters graded dental arch relationship and palatal morphology using the EUROCRAN index. The strength of agreement of rating was assessed with kappa statistics. Independent t tests were run to compare the EUROCRAN scores between one-stage and three-stage samples, and Fisher's exact tests were performed to evaluate differences of distribution of the EUROCRAN grades. The intra- and inter-rater agreement was moderate to very good. Dental arch relationship in the one-stage sample was less favorable than in three-stage group (mean scores, 2.58 and 1.97 for one-stage and three-stage samples, respectively; p < 0.000). Palatal morphology in the one-stage sample was more favorable than in the three-stage group (mean scores, 1.79 and 1.96 for one-stage and three-stage samples, respectively; p = 0.047). The dental arch relationship following one-stage repair was less favorable than the outcome of three-stage repair. The palatal morphology following one-stage repair, however, was more favorable than the outcome of three-stage repair.

Objective: To compare two scoring systems: the Huddart/Bodenham system (HB system) and the Bauru-BCLP yardstick (BCLP yardstick), which classify treatment outcome in terms of dental arch relationships in patients with complete bilateral cleft lip and palate (CBCLP). The predictive value of these scoring systems for treatment outcome was also evaluated., Design: Retrospective longitudinal study., Patients: Dental arch relationships of 43 CBCLP patients were evaluated at 6, 9, and 12 years. Setting : Treatment outcome in BCLP patients using two scoring systems., Main Outcome Measures: For each age group, the HB scores were correlated with the BCLP yardstick scores using Spearman's correlation coefficient. The predictive value of the two scoring systems was evaluated by backward regression analysis., Results: Intraobserver Kappa values for the BCLP yardstick scoring for the two observers were .506 and .627, respectively, and the interobserver reliability ranged from .427 and .581. The intraobserver reliability for the HB system ranged from .92 to .97 and the interobserver reliability from .88 to .96. The BCLP yardstick scores of 6 and 9 years together were predictors for the outcome at 12 years (explained variance 41.3%). Adding the incisor and lateral HB scores in the regression model increased the explained variance to 67%., Conclusions: The BCLP yardstick and the HB system are reliable scoring systems for evaluation of dental arch relationships of CBCLP patients. The HB system categorizes treatment outcome into similar categories as the BCLP yardstick. In case a more sensitive measure of treatment outcome is needed, selectively both scoring systems should be used.

Objective: To develop yardsticks for assessment of dental arch relationship in young individuals with repaired complete bilateral cleft lip and palate appropriate to different stages of dental development., Participants: Eleven cleft team orthodontists from five countries worked on the projects for 4 days. A total of 776 sets of standardized plaster models from 411 patients with operated complete bilateral cleft lip and palate were available for the exercise., Statistics: The interexaminer reliability was calculated using weighted kappa statistics., Results: The interrater weighted kappa scores were between .74 and .92, which is in the "good" to "very good" categories., Conclusions: Three bilateral cleft lip and palate yardsticks for different developmental stages of the dentition were made: one for the deciduous dentition (6-year-olds' yardstick), one for early mixed dentition (9-year-olds' yardstick), and one for early permanent dentition (12-year-olds' yardstick).

The embryonic head development, including the formation of dental structures, is a complex and delicate process guided by specific genetic programs. Genetic changes and environmental factors can disturb the execution of these programs and result in abnormalities in orofacial and dental structures. Orofacial clefts and hypodontia/ oligodontia are examples of such abnormalities frequently seen in dental clinics. An insight into the mechanisms and genes involved in the formation of orofacial and dental structures has been gradually gained by genetic analysis of families and by the use of experimental vertebrate models such as the mouse and chick models. The development of novel clinical therapies for orofacial and dental pathological conditions depends very much on a detailed knowledge of the molecular and cellular processes that are involved in head formation.

Objective: To retrospectively evaluate the craniofacial morphology of children with a complete unilateral cleft lip and palate treated with a 1-stage simultaneous cleft repair performed in the first year of life., Methods: Cephalograms and extraoral profile photographs of 61 consecutively treated patients (42 boys, 19 girls) who had been operated on at 9.2 (SD, 2.0) months by a single experienced surgeon were analyzed at 11.4 (SD, 1.5) years. The noncleft control group comprised 81 children (43 boys and 38 girls) of the same ethnicity at the age of 10.4 (SD, 0.5) years., Results: In children with cleft, the maxilla and mandible were retrusive; the palatal and mandibular planes were more open, and sagittal maxillomandibular relationship was less favorable in comparison to noncleft control subjects. Soft tissues in patients with cleft reflected retrusive morphology of hard tissues--subnasal and supramental regions were less convex, profile was flatter, and nasolabial angle was more acute relative to those of the control subjects., Conclusions: Craniofacial morphology after 1-stage repair was deviated in comparison with noncleft control subjects. However, the degree of deviation was comparable with that found after treatment with alternative surgical protocols.

Objective: To compare and evaluate longitudinally the dental arch relationships from 4.5 to 13.5 years of age with the Bauru-BCLP Yardstick in a large sample of patients with bilateral cleft lip and palate (BCLP)., Design: Retrospective longitudinal intercenter outcome study., Patients: Dental casts of 204 consecutive patients with complete BCLP were evaluated at 6, 9, and 12 years of age. All models were identified only by random identification numbers., Setting: Three cleft palate centers with different treatment protocols., Main Outcome Measures: Dental arch relationships were categorized with the Bauru-BCLP yardstick. Increments for each interval (from 6 to 9 years, 6 to 12 years, and 9 to 12 years) were analyzed by logistic and linear regression models., Results: There were no significant differences in outcome measures between the centers at age 12 or at age 9. At age 6, center B showed significantly better results (p=.027), but this difference diminished as the yardstick score for this group increased over time (linear regression analysis), the difference with the reference category (center C, boys) for the intervals 6 to 12 and 9 to 12 years being 10.4% (p=.041) and 12.9% (p=.009), respectively., Conclusions: Despite different treatment protocols, dental arch relationships in the three centers were comparable in final scores at age 9 and 12 years. Delaying hard palate closure and employing infant orthopedics did not appear to be advantageous in the long run. Premaxillary osteotomy employed in center B appeared to be associated with less favorable development of the dental arch relationship between 9 and 12 years.

A popular method for nasolabial rating in unilateral cleft lip and palate (UCLP) is the Asher-McDade system consisting of a 5-point ordinal scale assessing nasal form, nasal symmetry, nasal profile, and vermilion border. The aim of the current study was to identify reference photographs illustrating this scale to facilitate its use.Four observers assessed nasolabial appearance on frontal and profile photographs of the nasolabial area of 42 children of Caucasian origin with a repaired UCLP at age 9 years. Cronbachs alpha, based on the individual scores of the 4 observers, ranged from 0.73 to 0.82 for the 4 nasolabial ratings, indicating a good reliability. The reliability of the overall score (mean of the 4 component scores) was also high (Cronbachs alpha, 0.83). Both for the nasolabial component ratings and for the overall score, duplicate measurement errors were small. The reliability for the mean of the 4 observers' scores was good, Spearman rank correlation coefficients ranging from 0.56 to 0.96.Subsequently, photographs were selected that showed the highest agreement among observers. For each of the 4 components (eg, nasal form, nasal deviation, nasal profile, and shape of the vermilion border), 5 photographs were selected to illustrate the whole range of the scale (score, 1-5), resulting in the selection of 20 pictures.It was concluded that nasolabial appearance rating can be performed reliably using a panel of judges and averaging the scores of all observers. Reference photographs, as developed from this study, may facilitate the rating task.

Purpose: Facial esthetics play an important role in social interactions. However, children with a repaired complete unilateral cleft lip and palate usually show some disfigurement of the nasolabial area. To date, few studies have assessed the nasolabial appearance after different treatment protocols. The aim of the present study was to compare the nasolabial esthetics after 1- and 3-stage treatment protocols., Materials and Methods: Four components of the nasolabial appearance (nasal form, nasal deviation, mucocutaneous junction, and profile view) were assessed by 4 raters in 108 consecutively treated children who had undergone either 1-stage closure (Warsaw group, 41 boys and 19 girls, mean age 10.8 years, SD 2.0) or 3-stage (Nijmegen group, 30 boys and 18 girls, mean age 8.9 years, SD 0.7). A 5-grade esthetic index of Asher-McDade was used, in which grade 1 indicates the most esthetic and grade 5 the least esthetic outcome., Results: The nasal form was judged the least esthetic in both groups and graded 3.1 (SD 1.1) and 3.2 (SD 1.1). The nasal deviation, mucocutaneous junction, and profile view were scored from 2.1 (SD 0.8) to 2.3 (SD 1.0) in both groups. The treatment outcome after the Warsaw and Nijmegen protocols was comparable. Neither overall nor any of the 4 components of the nasolabial appearance showed intercenter differences (P > .1)., Conclusions: The nasolabial appearance after the Warsaw (1-stage) and Nijmegen (3-stage) protocols was comparable. The technique of lip repair (triangular flap in Warsaw and Millard rotation advancement in Nijmegen) gave comparable results for the esthetics of the nasolabial area.

Objective: To evaluate nasolabial appearance of patients with UCLAP treated in Nijmegen and to compare them with those from six other individual centers from the Eurocleft study. Relationships between nasolabial aesthetics, dental arch relationships and cleft width at birth were also investigated., Patients: Children of Caucasian origin with complete UCLAP (n=42 consecutive cases) from the Nijmegen Cleft Palate Unit, The Netherlands., Methods: Nasolabial appearance was assessed by applying an aesthetic index and subsequently compared with the six-centre Eurocleft study. Cleft width at birth was measured on maxillary plaster casts., Results: The 90% central range for the overall aesthetic rating of the 42 Nijmegen patients is 2.0-3.7 on a scale from 1 to 5 (1=very good nasolabial appearance, 5=very poor nasolabial appearance). With regard to the overall aesthetic rating, Nijmegen showed similar treatment outcomes with Eurocleft centres A, D, E and F. Nijmegen scored significantly better than Eurocleft centre C and significantly worse than Eurocleft centre B (p

Objective: To assess dental age in children with a complete unilateral cleft lip and palate and to compare this with a noncleft control group., Design: Two-group, mixed-longitudinal cohort study., Setting: Cleft group from an academic center for cleft lip and palate treatment. Noncleft control group from the same population., Patients: Participants included 70 Caucasian children with a full complement of teeth and a complete unilateral cleft lip and palate (45 boys and 25 girls) from the Cleft Palate Craniofacial Center at the Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands. The control group (90 boys and 91 girls) was taken from the Nijmegen Growth Study., Main Outcome Measure: Dental age was assessed on orthopantomograms. In the unilateral cleft lip and palate group, linear interpolation in individual age curves was applied to obtain the dental age at 5, 9.5, and 14 years of age. For these ages, a comparison was made with the noncleft control group., Results: Boys and girls with a unilateral cleft lip and palate showed a significant delay in dental age, as compared with their noncleft peers at all three ages. This delay was more pronounced in boys than in girls. The gender effect was significant at chronological ages 5 and 14 years., Conclusions: Children with a complete unilateral cleft lip and palate have a delay in dental age, compared with noncleft children.

Background: The goal of this study was to assess determinants for treatment outcome in unilateral cleft lip and palate, evaluated according to the Great Ormond Street London and Oslo (GOSLON) Yardstick and 5-year-index ratings by means of a meta-analysis., Methods: Multiple databases were searched for publications in which patient groups were evaluated by GOSLON ranking or the GOSLON-like 5-year index. From the 15 selected publications, the following background variables could be extracted and were evaluated as determinants for treatment outcome in unilateral cleft lip and palate: year of birth, average age of the patient at the time of GOSLON classification, racial background, presence of Simonart's band, infant orthopedics, palatal closure before the age of 3 versus palatal closure at a later age, bone graft, and number of surgeons., Results: The total number of patients included in the meta-analysis was 1236. Patients whose soft and hard palate were closed before the age of 3 presented significantly poorer (p = 0.003) GOSLON scores (mean score, 2.9; SD 0.4) than patients whose palate was closed at a later age (mean GOSLON score, 2.3; SD 0.2)., Conclusions: Delayed palatal closure generally results in better dental arch relationships than early palatal closure. Well-designed, randomized clinical trials are required for further investigation of the optimal timing for palatal closure.

Objective: To evaluate dental arch relationships of patients with unilateral cleft lip and palate (UCLP) treated with a two-stage palatal closure and to compare them with the six centers from the Eurocleft study that used various treatment protocols., Design: Repeated-measures study., Setting: Cleft Palate Craniofacial Unit of Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands., Patients: Records of 9-year-old children with complete unilateral cleft lip and palate (n = 43) were included., Interventions: The dental arch relationships of these patients were assessed by applying the Goslon Yardstick and subsequently compared with the Goslon outcome of the six-center Eurocleft study., Mean Outcome Measures: Statistics of intra- and interexaminer agreement., Results: For the Nijmegen UCLP group, 9% of dental arch relationships had a Goslon score of 1, 52% had a score of 2, 30% has a score of 3, 9% had a score of 4, and none had a score of 5. The mean Nijmegen Goslon score showed no significant differences with Eurocleft centers A, B, and E, which achieved the best treatment results, but did significantly differ from Goslon outcomes of Eurocleft centers D (p < .001), C, and F (p < .01), which had relatively poor treatment outcome., Conclusions: Treatment outcome of the patients in the Nijmegen UCLP group treated with two-stage palatal closure was comparable with the results of the Eurocleft centers with the best outcome. Treatment protocol could not explain differences in the quality of treatment results.

Objective: To investigate the reliability of using photographs of study casts as an alternative to casts for rating dental arch relationships., Design: Repeated-measures study., Setting: Cleft Palate Center of the University Medical Center Nijmegen, Nijmegen, The Netherlands., Patients: Records of children with complete unilateral cleft lip and palate (UCLP) (n = 49) at the age of 9 years were included., Mean Outcome Measure(s): Statistics of intra- and interexaminer agreement., Results: No significant differences were found between the rating of dental casts and photographs of dental casts, using the Goslon Yardstick., Conclusions: Photographs of dental casts provide a consistent, reproducible method for rating dental arch relationships in patients with UCLP at the age of 9 years and provide a reliable alternative to the application of the Goslon Yardstick on dental casts.

Objective: To demonstrate a method for reduction of wide alveolar clefts prior to bone grafting. This method aims to facilitate bone grafting and achieve adequate soft tissue coverage of the graft with attached gingiva., Case Report: Treatment of a patient with bilateral cleft lip and palate with a severe alveolar defect on the left side is illustrated. Distraction osteogenesis was used to mesialize the left segment so that the alveolar cleft was reduced to a minimum. After a 10-week retention period, bone grafting of the reduced alveolar defect was successfully performed. After consolidation of the bone graft, the alveolar cleft was found to have an osseous closure with adequate soft tissue coverage., Conclusion: In patients with a wide alveolar cleft, soft tissue coverage with keratinized mucosa can be more readily assured by reducing the alveolar cleft by callus distraction to mesialize the lateral segment prior to bone grafting.

Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf-β/Bmp activity. [ABSTRACT FROM AUTHOR]

Objective: To compare two scoring systems: the Huddart/Bodenham system (HB system) and the Bauru-BCLP yardstick (BCLP yardstick), which classify treatment outcome in terms of dental arch relationships in patients with complete bilateral cleft lip and palate (CBCLP). The predictive value of these scoring systems for treatment outcome was also evaluated. Design: Retrospective longitudinal study. Patients: Dental arch relationships of 43 CBCLP patients were evaluated at 6, 9, and 12 years. Setting: Treatment outcome in BCLP patients using two scoring systems. Main Outcome Measures: For each age group, the HB scores were correlated with the BCLP yardstick scores using Spearman's correlation coefficient. The predictive value of the two scoring systems was evaluated by backward regression analysis. Results: Intraobserver Kappa values for the BCLP yardstick scoring for the two observers were .506 and .627, respectively, and the interobserver reliability ranged from .427 and .581. The intraobserver reliability for the HB system ranged from .92 to .97 and the interobserver reliability from .88 to .96. The BCLP yardstick scores of 6 and 9 years together were predictors for the outcome at 12 years (explained variance 41.3%). Adding the incisor and lateral HB scores in the regression model increased the explained variance to 67%. Conclusions: The BCLP yardstick and the HB system are reliable scoring systems for evaluation of dental arch relationships of CBCLP patients. The HB system categorizes treatment outcome into similar categories as the BCLP yardstick. In case a more sensitive measure of treatment outcome is needed, selectively both scoring systems should be used. [ABSTRACT FROM AUTHOR]

Objective: To develop yardsticks for assessment of dental arch relationship in young individuals with repaired complete bilateral cleft lip and palate appropriate to different stages of dental development. Participants: Eleven cleft team orthodontists from five countries worked on the projects for 4 days. A total of 776 sets of standardized plaster models from 411 patients with operated complete bilateral cleft lip and palate were available for the exercise. Statistics: The interexaminer reliability was calculated using weighted kappa statistics. Results: The interrater weighted kappa scores were between .74 and .92, which is in the "good" to "very good" categories. Conclusions: Three bilateral cleft lip and palate yardsticks for different developmental stages of the dentition were made: one for the deciduous dentition (6-year-olds' yardstick), one for early mixed dentition (9-year-olds' yardstick), and one for early permanent dentition (12-year-olds' yardstick). [ABSTRACT FROM AUTHOR]

Objective: To compare and evaluate longitudinally the dental arch relationships from 4.5 to 13.5 years of age with the Bauru-BCLP Yardstick in a large sample of patients with bilateral cleft lip and palate (BCLP). Design: Retrospective longitudinal intercenter outcome study. Patients: Dental casts of 204 consecutive patients with complete BCLP were evaluated at 6, 9, and 12 years of age. All models were identified only by random identification numbers. Setting: Three cleft palate centers with different treatment protocols. Main Outcome Measures: Dental arch relationships were categorized with the Bauru-BCLP yardstick. Increments for each interval (from 6 to 9 years, 6 to 12 years, and 9 to 12 years) were analyzed by logistic and linear regression models. Results: There were no significant differences in outcome measures between the centers at age 12 or at age 9. At age 6, center B showed significantly better results (p = .027), but this difference diminished as the yardstick score for this group increased over time (linear regression analysis), the difference with the reference category (center C, boys) for the intervals 6 to 12 and 9 to 12 years being 10.4% (p = .041) and 12.9% (p = .009), respectively. Conclusions: Despite different treatment protocols, dental arch relationships in the three centers were comparable in final scores at age 9 and 12 years. Delaying hard palate closure and employing infant orthopedics did not appear to be advantageous in the long run. Premaxillary osteotomy employed in center B appeared to be associated with less favorable development of the dental arch relationship between 9 and 12 years. [ABSTRACT FROM AUTHOR]

Objective: To assess dental age in children with a complete unilateral cleft lip and palate and to compare this with a noncleft control group. Design: Two-group, mixed-longitudinal cohort study. Setting: Cleft group from an academic center for cleft lip and palate treatment. Noncleft control group from the same population. Patients: Participants included 70 Caucasian children with a full complement of teeth and a complete unilateral cleft lip and palate (45 boys and 25 girls) from the Cleft Palate Craniofacial Center at the Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands. The control group (90 boys and 91 girls) was taken from the Nijmegen Growth Study. Main outcome measure: Dental age was assessed on orthopantomograms. In the unilateral cleft lip and palate group, linear interpolation in individual age curves was applied to obtain the dental age at 5, 9.5, and 14 years of age. For these ages, a comparison was made with the noncleft control group. Results: Boys and girls with a unilateral cleft lip and palate showed a significant delay in dental age, as compared with their noncleft peers at all three ages. This delay was more pronounced in boys than in girls. The gender effect was significant at chronological ages 5 and 14 years. Conclusions: Children with a complete unilateral cleft lip and palate have a delay in dental age, compared with noncleft children. [ABSTRACT FROM AUTHOR]

Objective: To investigate the reliability of using photographs of study casts as an alternative to casts for rating dental arch relationships. Design: Repeated-measures study. Setting: Cleft Palate Center of the University Medical Center Nijrnegen, Nijmegen, The Netherlands. Patients: Records of children with complete unilateral cleft lip and palate (UCLP) (n = 49) at the age of 9 years were included. Mean Outcome Measure(s): Statistics of Intra- and interexaminer agreement. Results: No significant differences were found between the rating of dental casts and photographs of dental casts, using the Gosion Yardstick. Conclusions: Photographs of dental casts provide a consistent, reproducible method for rating dental arch relationships in patients with UCLP at the age of 9 years and provide a reliable alternative to the application of the Gosion Yardstick on dental casts. [ABSTRACT FROM AUTHOR]