A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens.

Changes in gene regulatory elements play critical roles in human phenotypic divergence. However, identifying the base-pair changes responsible for the distinctive morphology of Homo sapiens remains challenging. Here, we report a noncoding single-nucleotide polymorphism (SNP), rs41298798, as a potential causal variant contributing to the morphology of the skull base and vertebral structures found in Homo sapiens. Screening for differentially regulated genes between Homo sapiens and extinct relatives revealed 13 candidate genes associated with basicranial development, with TBX1, implicated in DiGeorge syndrome, playing a pivotal role. Epigenetic markers and in silico analyses prioritized rs41298798 within a TBX1 intron for functional validation. CRISPR editing revealed that the 41-base-pair region surrounding rs41298798 modulates gene expression at 22q11.21. The derived allele of rs41298798 acts as an allele-specific enhancer mediated by E2F1, resulting in increased TBX1 expression levels compared to the ancestral allele. Tbx1-knockout mice exhibited skull base and vertebral abnormalities similar to those seen in DiGeorge syndrome. Phenotypic differences associated with TBX1 deficiency are observed between Homo sapiens and Neanderthals (Homo neanderthalensis). In conclusion, the regulatory divergence of TBX1 contributes to the formation of skull base and vertebral structures found in Homo sapiens.

Postoperative computed tomography imaging of pediatric patients with craniosynostosis: radiation dose and image quality comparison between multi-slice computed tomography and O-arm cone-beam computed tomography.

BACKGROUND: When postoperative multi-slice computed tomography (MSCT) imaging of patients with craniosynostosis is used, it is usually performed a few days after surgery in a radiology department. This requires additional anesthesia for the patient. Recently, intraoperative mobile cone-beam CT (CBCT) devices have gained popularity for orthopedic and neurosurgical procedures, which allows postoperative CT imaging in the operating room. OBJECTIVE: This single-center retrospective study compared radiation dose and image quality of postoperative imaging performed using conventional MSCT scanners and O-arm CBCT. MATERIALS AND METHODS: A total of 104 pediatric syndromic and non-syndromic patients who were operated on because of single- or multiple-suture craniosynostosis were included in this study. The mean volumetric CT dose index (CTDIvol) and dose-length product (DLP) values of optimized craniosynostosis CT examinations (58 MSCT and 46 CBCT) were compared. Two surgeons evaluated the subjective image quality. RESULTS: CBCT resulted in significantly lower CTDIvol (up to 14%) and DLP (up to 33%) compared to MSCT. Multi-slice CT image quality was considered superior to CBCT scans. However, all scans were considered to be of sufficient quality for diagnosis. CONCLUSION: The O-arm device allowed for an immediate postoperative CBCT examination in the operating theater using the same anesthesia induction. Radiation exposure was lower in CBCT compared to MSCT scans, thus further encouraging the use of O-arms. Cone-beam CT imaging with an O-arm is a feasible method for postoperative craniosynostosis imaging, yielding less anesthesia to patients, lower health costs and the possibility to immediately evaluate results of the surgical operation.

Rhinoplasty and Le Fort I Maxillary Osteotomy in Cleft Patients.

INTRODUCTION: Cleft patients often need orthognathic surgery to correct maxillary hypoplasia and rhinoplasty to correct nasal deformity. Rhinoplasty can be performed as a staged procedure after orthognathic surgery or simultaneously with maxillary osteotomy. AIM: The authors evaluated need for and complications of staged and simultaneous rhinoplasties in patients with different cleft types undergoing maxillary osteotomy. PATIENTS AND METHODS: This retrospective study examined 99 (54 females) consecutive nonsyndromic patients with cleft lip/palate [23 bilateral cleft lip and palate (BCLP), 51 unilateral cleft lip and palate (UCLP), and 25 cleft palate (CP)] with a mean age of 17.8 (range: 11.5-45.3) years who had undergone Le Fort I maxillary advancement or bimaxillary osteotomy at the Cleft Palate and Craniofacial Center, Helsinki University Hospital, Finland, between 2002 and 2016. Medical charts were accessed through the hospital's archives and database. RESULTS: Of patients who underwent maxillary osteotomy, 45% (45/99) needed rhinoplasty (14 BCLP, 27 UCLP, and 4 CP). A significant difference (P<0.01) existed in the need for rhinoplasty between different cleft types, those with BCLP and UCLP needing the most operations (60% and 53%). In 20 patients (20%), rhinoplasty was performed simultaneously with maxillary osteotomy, and in 25 patients (25%) in a second operation after osteotomy. The overall complication rate was 14%. No difference existed in complication rate in patients with or without simultaneous rhinoplasty. CONCLUSIONS: Of cleft patients who underwent maxillary osteotomy, 45% needed rhinoplasty. Patients with BCLP and UCLP needed rhinoplasty most often. Staged and simultaneous procedures were almost equally common with similar complication rates.

Speech Symptoms of Velopharyngeal Insufficiency and the Incidence of Secondary Speech Surgery in 10-Year-Old Children With Unilateral Cleft Lip and Palate: Comparison of 2 Randomized Surgical Methods for Primary Palatal Surgery.

OBJECTIVE: To compare speech symptoms of velopharyngeal insufficiency (VPI) and incidence of secondary speech surgery in 10-year-old Finnish children with unilateral cleft lip and palate (UCLP) following primary palatal surgery using 2 surgical methods. DESIGN: Single center analysis within the Scandcleft multicenter randomized controlled trial of primary surgery for UCLP. MATERIALS AND METHODS: Patients comprised 79 nonsyndromic 10-year-old children with UCLP. Two randomized surgical methods were used in the primary palatal surgery: soft palate closure at 4 months and hard palate closure at 12 months (Arm A) and closure of both the soft and hard palate at 12 months (Arm C). Speech symptoms of VPI were analyzed from standardized video recordings by 2 experienced speech pathologists. The incidences of surgery for correcting VPI, fistula closure, and speech therapy were evaluated retrospectively from patient records. RESULTS: No differences in speech symptoms of VPI, need for VPI surgery or speech therapy were found between the surgical methods. Of all 79 children, 33% had had VPI surgery and 61% had speech therapy. The number of fistulas was significantly higher in Arm A (25%) than in Arm C (2%). Moderate to severe speech symptoms of VPI (hypernasality, continuous nasal air leakage, weak pressure consonants, and/or compensatory articulation) were found in 11% of the children. CONCLUSION: No differences were present between groups in speech symptoms of VPI or need for VPI surgery or speech therapy between the 2 surgical methods. One third of the children had undergone VPI surgery. Most of the children (89%) had good or relatively good speech.

Long-term Follow-up of Bilateral Cleft Lip and Palate: Incidence of Speech-Correcting Surgeries and Fistula Formation.

While bilateral cleft lip and palate (BCLP) constitutes a clinical challenge for the whole cleft team, the ideal surgical protocol remains obscure. This study presents the long-term burden of care in terms of secondary surgeries, defined as fistula repair and speech-correcting surgeries (SCS), in a single center. Outcomes of two surgical protocols utilized over the years were also compared.A retrospective single-center analysis of 81 non-syndromic children with complete BCLP born between 1990 and 2010. Two surgical protocols comprising single-stage and two-stage (delayed hard palate closure) procedures were compared. Outcome was analyzed at the time of alveolar bone grafting (ABG) and post-ABG.Altogether 54 children (66.7%) had underwent secondary surgery by the time of bilateral ABG. At this point, 38.3% (n = 31) of patients had received SCS and 49.4% (n = 40) had undergone fistula repair. The corresponding incidences at the end of follow-up were 46.9% (n = 38) and 53.1% (n = 43). No significant difference emerged in SCS incidence between the 2 protocols; however, prior to ABG the single-stage protocol had a significantly lower need for fistula repair. Regarding the location of fistulas, some differences were observed, with the single-stage procedure more associated with anterior fistulas.BCLP has a high surgical burden of care in terms of secondary surgeries, defined as SCS and fistula repair. In our experience, the single-stage protocol, particularly the two-flap technique, offers better results in the management of BCLP than the two-stage approach with a short delay in hard palate closure.

Finnish Translation and Linguistic Validation of the CLEFT-Q Questionnaire.

OBJECTIVE: Cleft lip and/or palate (CL/P) can have long-lasting effects on the appearance, function, and psychosocial wellbeing of patients. The CLEFT-Q questionnaire is a patient-reported outcomes instrument specifically designed to assess the health-related quality of life of patients with CL/P. The aim of this study was to produce and linguistically validate a Finnish version of the CLEFT-Q questionnaire. DESIGN: The CLEFT-Q questionnaire was translated into Finnish following guidelines of the International Society for Pharmacoeconomics and Outcomes Research. Pilot testing with cognitive debriefing interviews was conducted on patients of the target age range of the questionnaire, 8-29, and with various cleft types. RESULTS: The CLEFT-Q questionnaire translated readily into Finnish. A review of the backward translation led to two words being changed. Thirteen patients - ten females and three males - with a median age of 14 years, participated in the cognitive debriefing interviews. The interviews led to further nine word changes. The pilot study data suggested that the performance of the Finnish version of the instrument is in line with the original CLEFT-Q questionnaire. CONCLUSIONS: The Finnish version of CLEFT-Q produced here is linguistically valid and ready for use in the evaluation of the health-related quality of life of patients with CL/P. However, future work is needed to further assess the validity and the reliability of the CLEFT-Q in the Finnish patient population.

Le Fort I Osteotomy in Cleft Patients: Maxillary Advancement and Articulation.

BACKGROUND: Maxillary advancement may affect speech in cleft patients. AIMS: To examine whether the amount of maxillary advancement and preoperativecephalometric skeletal and dentoalveolar relationships are associated with articulation errors of the Finnish alveolar consonants /s/, /l/, and /r/ in cleft patients. MATERIALS AND METHODS: Fifty-seven nonsyndromic cleft patients who underwent Le Fort I or bimaxillary osteotomies were evaluated retrospectively. Pre- and post-operative lateral cephalometric radiographs and standardized speech video recordings were analyzed. The Aspin-Welch unequal variance t test, Student t test sign test, intraclass correlation and Kappa statistics were used in the statistical analyses. RESULTS: The mean advancement of the maxilla (point A) was 4.65 mm horizontally (range -2.80 to 11.30) and -3.82 mm vertically (range -14.20 to 3.90). The overall articulation (especially the sounds /s/ and /l/) improved significantly postoperatively, but the amount of maxillary advancement did not affect the articulation. The preoperative mean percentages of /s/, /l/, and /r/ errors were 32%, 33%, 46% and the postoperative percentages 23%, 19%, 40%, respectively. Preoperative articulation errors of /s/ were related to palatal inclination of the upper incisors. CONCLUSIONS: Orthognathic surgery may improve articulation errors. The amount of maxillary advancement is not related to the improvement.

Long-Term Follow-up of Unilateral Cleft lip and Palate: Incidence of Speech-Correcting Surgeries and Fistula Formation.

OBJECTIVE: The ideal surgical protocol and technique for primary closure of unilateral cleft lip and palate (UCLP) are unclear, and the development of velopharyngeal insufficiency and fistulae following primary repair is common. This study aimed to determine the long-term surgical burden of care in terms of secondary surgeries, defined as speech-correcting surgeries (SCSs) and fistula repair, in a UCLP population, and to compare outcomes of various surgical protocols. DESIGN: Retrospective, single-center review. PARTICIPANTS: The study comprised 290 nonsyndromic children with complete UCLP. Different surgical protocols entailing both single-stage and 2-stage approaches were compared, and the surgical outcome was analyzed at the time of alveolar bone grafting (ABG) and post ABG. RESULTS: Altogether 110 children (37.9%) underwent secondary surgery by the time of ABG. Of the total population 25.9% (n = 75) had undergone SCS and 17.2% (n = 50) had undergone fistula repair. The respective incidences at follow-up (post ABG) were 30.3% (n = 88) and 18.9% (n = 55). Median age at ABG was 9.8 years and at follow-up was 16.3 years. No significant difference emerged in terms of secondary surgeries between the techniques and protocols applied at primary repair. However, some differences occurred regarding the location of fistulae; the single-stage procedure had more anterior fistula repairs, particularly connected to a perialveolar fistula. CONCLUSIONS: Although the outcome differences between the surgical protocols were small, indicating that none of the treatment protocols was clearly superior to another, attention was drawn to the favorable outcomes of the single-stage protocol.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: comparison of dental arch relationships and dental indices at 5, 8, and 10 years.

BACKGROUND AND TRIAL DESIGN: The Scandcleft intercentre study evaluates the outcomes of four surgical protocols (common method Arm A, and methods B, C, and D) for treatment of children with unilateral cleft lip and palate (UCLP) in a set of three randomized trials of primary surgery (Trials 1, 2, and 3). OBJECTIVES: To evaluate and compare dental arch relationships of 5-, 8-, and 10-year-old children with UCLP after four different protocols of primary surgery and to compare three dental indices. The results are secondary outcomes of the overall trial. METHODS: Study models taken at the ages of 5 (n = 418), 8 (n = 411), and 10 years (n = 410) were analysed by a blinded panel of orthodontists using the Eurocran index, the 5-year-olds' (5YO) index, and the GOSLON Yardstick. Student's t-test, Pearson's correlation, chi-square test, and kappa statistics were used in statistical analyses. RESULTS: The reliability of the dental indices varied between moderate and very good, and those of the Eurocran palatal index varied between fair and very good. Significant correlations existed between the dental indices at all ages. No differences were found in the mean 5-, 8-, and 10-year index scores or their distributions within surgical trials. Comparisons between trials detected significantly better mean index scores in Trial 2 Arm C (at all ages) and in Trial 1 Arm B (at 5 and 10 years of age) than in Trial 3 Arm D. The mean Eurocran dental index scores of the total material at 5, 8, and 10 years of age were 2.50, 2.60, and 2.26, and those of the 5YO index and GOSLON Yardstick were 2.77, 2.90, and 2.54, respectively. At age 10 years, 75.8% of the patients had had orthodontic treatment. CONCLUSIONS: The results of these three trials do not provide evidence that one surgical method is superior to the others. The reliabilities of the dental indices were acceptable, and significant correlations existed between the indices at all ages. The reliability of the Eurocran palatal index was questionable. TRIAL REGISTRATION: ISRCTN29932826.

Prediction of orthognathic surgery need in children with unilateral cleft lip palate: Dental arch relationships and 5-year-olds' index.

OBJECTIVE: To evaluate whether dental arch relationships at 6 years of age can categorize treatment outcome and predict later need for orthognathic surgery in children with unilateral cleft lip and palate (UCLP). SETTING AND SAMPLE POPULATION: A retrospective longitudinal single-centre study. The study sample comprised 70 consecutive non-syndromic children (47 boys) with complete UCLP operated on by pushback techniques during 1981-1989 and followed until early adulthood in the same cleft centre. MATERIALS AND METHODS: Dental casts and maxillomandibular relationships were assessed before orthodontic treatment and secondary alveolar bone grafting at mean age 6.1 years (range 5.6-6.8) using the 5-year-olds' index and lateral cephalograms. The need for orthognathic surgery was retrieved from patient files. Student's t test, Pearson's correlation, and Kappa statistics were used in statistical analyses. RESULTS: Orthognathic surgery frequency was 41% (29/70). Those needing orthognathic surgery comprised all 3 patients with an index score of 5 (very poor), 14 of 17 (82%) scoring 4 (poor), 10 of 26 (38%) scoring 3 (fair), and 2 of 19 (11%) scoring 2 (good). Of the five patients with index score 1 (excellent), none needed osteotomies. The mean index score was 2.9. The score was significantly better in those without orthognathic surgery (2.4 versus 3.6). A significant negative correlation existed between the 5-year-olds' index and cephalometric angles ANB and anb. CONCLUSION: The use of 5-year-olds' index may help to predict treatment outcome and the clinical need for orthognathic surgery especially in patients with the lowest and highest index scores.

Does Coronal Suturectomies and Occipital Barrel Staves Make a Difference in Early Reconstruction for Sagittal Craniosynostosis?

BACKGROUND: Various surgical methods are used for early treatment of nonsyndromic sagittal craniosynostosis. The craniofacial centers in Uppsala and Helsinki fundamentally both use the H-Craniectomy: Renier's technique. However, the Helsinki group systematically adds coronal suturectomies to prevent secondary coronal synostosis and posterior barrel staves to address posterior bulleting. The effects of these additions in early treatment of sagittal craniosynostosis are currently unknown. METHODS: Thirty-six patients from Uppsala and 27 patients from Helsinki were included in the study. Clinical data and computed tomography scans were retrieved for all patients. RESULTS: The Helsinki patients had a smaller preoperative Cranial index (CI) (65 vs 72) and a smaller preoperative width (10.1 vs 11.2). There was no difference in postoperative CI, corresponding to a difference in change in CI. Regression analysis indicated that the larger change in CI in the Helsinki group was mainly due to a lower preoperative CI allowing for a larger normalization. The Helsinki patients had less growth in length (1.5 vs 2.1 cm) and more growth in width (2.3 vs 1.9 cm). There were no differences in head circumference or surgical complications. Secondary coronal synostosis was present in 43% of the Uppsala group at 3 years of age, while calvarial defects located at sites of previous coronal suturectomies and posterior barrel staving were seen in the Helsinki group 1 year postoperatively. CONCLUSIONS: Lower preoperative CI appears to be the main factor in determining the amount of normalization in CI. Prophylactic coronal suturectomies do not seem to benefit preservation of coronal growth function since the modification correlates to less sagittal growth and more growth in width.

Alloplastic Temporomandibular Joint Reconstruction in Congenital Craniofacial Deformities.

ABSTRACT: Temporomandibular joint (TMJ) reconstruction with alloplastic prosthesis is a commonly performed procedure, which can be used as a treatment for improving pathologic conditions affecting the TMJ. Depending of the severity of the condition, the patient's ability to eat can be impaired, which in turn can affect their quality of life. Several syndromes can affect the patient's facial features, and some of those also affect TMJ's. Use of alloplastic prosthesis in TMJ's affecting syndromes, by means of correcting TMJ conditions and mandibular deformities, is still rather uncommon. Purpose of our study is to review the use TMJ total prosthesis as a treatment modality for correcting TMJ conditions and the reconstruction of mandibular deformities in congenital syndromes affecting the facial features. This study consists of a retrospective cohort of patients treated with TMJ reconstruction with alloplastic prosthesis at the Helsinki University Hospital during the past decade. All subjects with congenital syndrome who underwent TMJ reconstruction were included the study. The cohort consisted of seven patients and ten joints treated. Temporomandibular joints affecting syndromes were Goldenhar syndrome, hemifacial macrosomia, Nager syndrome, and Treacher-Collins syndrome. The majority of the patients have had several previous operative treatments on the facial skeleton during their childhood, which in turn probably affected and compromised the TMJ surgery outcome. Mouth opening was sufficiently achieved as average maximal opening was 34 mm (range 24-42 mm) postoperatively. Temporomandibular joint reconstruction with alloplastic prosthesis can offer new tools and approaches for treatment of facial deformities in syndromes with craniofacial abnormalities. Impaired jaw functions and asymmetry can be addressed with the use of alloplastic prostheses, achieving sufficient mouth opening and restoring the symmetry of the lower facial skeleton.

Dental Age, Agenesis, and Morphology in Patients With Operated Single-Suture Craniosynostoses.

OBJECTIVE: The aim of this study was to evaluate the dental age, agenesis, and morphology of children with surgically operated single-suture craniosynostoses from orthopantomographs. DESIGN: A single-centered cross-sectional observational archival study. PATIENTS: A sample of 196 Finnish patients with single-suture craniosynostosis without additional birth defects or syndromes (excluding Muenke syndrome) was included in this study. MAIN OUTCOME MEASURES: Dental age was assessed using the method developed by Demirjian et al. and modified by Nyström et al. for the Finnish population. Methods described by Tulensalo et al. and Oehlers et al. were used to study taurodontism and dens invaginatus, respectively. RESULTS: The study sample of 149 patients was divided into 3 groups: patients with sagittal synostosis (n = 103), coronal synostosis (n = 25), and metopic synostosis (n = 21). Orthopantomographs taken on average at ages 8.20 to 8.33 were used. The dental ages in different groups were on average 0.37, 0.60, and 0.66 years ahead of normative values, for sagittal, coronal, and metopic groups, respectively. Tooth agenesis, taurodontism, and invaginated teeth were found in all groups with invaginations having a high prevalence. Peg-shaped upper lateral incisors and one geminated lower lateral incisor were also found. CONCLUSIONS: These descriptive data may help improve dental care in patients with single-suture craniosynostosis.

Facial Asymmetry in Nonsyndromic and Muenke Syndrome-Associated Unicoronal Synostosis: A 3-Dimensional Study Based on Facial Surfaces Extracted From CT Scans.

OBJECTIVE: To quantify soft tissue facial asymmetry (FA) in children with nonsyndromic and Muenke syndrome-associated unicoronal synostosis (NS-UCS and MS-UCS), hypothesizing that MS-UCS presents with significantly larger FA than NS-UCS. DESIGN: Retrospective cohort study. PATIENTS AND METHODS: Twenty-one children (mean age: 0.6 years; range: 0.1-1.4 years) were included in the study (NS-UCS = 14; MS-UCS = 7). From presurgical computed tomography scans, facial surfaces were constructed for analysis. A landmark guided atlas was deformed to match each patient's surface, obtaining spatially detailed left-right point correspondence. Facial asymmetry was calculated in each surface point across the face, as the length (mm) of an asymmetry vector, with its Cartesian components providing 3 directions. Mean FA was calculated for the full face, and the forehead, eye, nose, cheek, mouth, and chin regions. RESULTS: For the full face, a significant difference of 2.4 mm (P = .001) was calculated between the 2 groups, predominately in the transverse direction (1.5 mm; P < .001). The forehead and chin regions presented with the largest significant difference, 3.5 mm (P = .002) and 3.2 mm (P < .001), respectively; followed by the eye (2.4 mm; P = .004), cheek (2.2 mm; P = .004), nose (1.7 mm; P = .001), and mouth (1.4 mm; P = .009) regions. The transverse direction presented with the largest significant difference in the forehead, chin, mouth, and nose regions, the sagittal direction in the cheek region, and the vertical direction in the eye region. CONCLUSIONS: Muenke syndrome-associated unicoronal synostosis presented with significantly larger FA in all regions compared to NS-UCS. The largest significant differences were found in the forehead and chin regions, predominantly in the transverse direction.

Taurodontism in the first permanent molars in Van der Woude syndrome compared to isolated cleft palate.

OBJECTIVES: To analyse prevalence, pattern, and severity of taurodontism in individuals with Van der Woude syndrome (VWS) exhibiting cleft palate and compare with aged-matched non-syndromic cleft palate (NSCP) and non-cleft controls. MATERIALS AND METHODS: One hundred and seventy-eight dental panoramic tomographs (DPTs) (105 girls and 73 boys) consisting of 42 VWS patients (x¯=8.55±1.02 years), 42 NSCP patients (x¯=8.59±1.02 years), and 94 normative non-cleft children (x¯=8.79±1.16 years) were assessed and their first permanent molars evaluated. Measurement 3 of the taurodontism index developed by Shifman and Chanannel with the Tulensalo modification was used. Prevalence, pattern, and severity were compared between groups. Statistical differences were determined by one-way analysis of variance and Fisher test. Repeatability was calculated by Cohens Kappa test. RESULTS: The prevalence of taurodontic molars was 59.5% in VWS, 45.2% in NSCP, and 26.6% in non-cleft controls. The prevalence and severity of taurodontism in VWS and NSCP were significantly higher than in non-cleft children in all first permanent molars. There was no significant difference in prevalence and severity between VWS and NSCP. The odds for having taurodontism in the VWS group was approximately double compared to the NSCP group. Most of the taurodontic molars showed hypotaurodontism and taurodontism occurred bilaterally more frequently than unilaterally. CONCLUSION: This study shows a higher prevalence of taurodontism in VWS and NSCP. Most taurodontic molars are hypotaurodontic and most occur bilaterally.

Dental age, agenesis, and morphological anomalies in individuals with Van der Woude syndrome and isolated cleft palate.

OBJECTIVES: To analyse the differences between dental age and chronological age and dental anomalies in individuals with Van der Woude syndrome (VWS) and compare with non-syndromic cleft palate (NSCP) and non-cleft controls. MATERIALS AND METHODS: In total, 204 oral panoramic radiographs (118 girls and 86 boys) consisting of 51 VWS patients (age x̅ = 8.17 ± 1.34 years), 51 NSCP patients (age x̅ = 8.09 ± 1.41 years), and 102 normative non-cleft children (age x̅ = 8.62 ± 1.24 years) were collected. Dental stages were assessed by the Demirjian method, with the local dental maturity index as reference. Dental anomalies including agenesis were investigated. Statistical differences were determined by One-way ANOVA and regression. Repeatability was calculated by an intra-class correlation test and 95% confidence interval. RESULTS: The difference between dental age and chronological age of the VWS group (0.12 years) and the NSCP group (0.09 years) was significantly lower than the non-cleft group (0.40 years) (P = 0.002). There was no significant difference between the VWS and NSCP groups (P = 0.885). Hypodontia was more prevalent in both the VWS group (37.25%, P = 0.0001) and the NSCP group (19.60%, P = 0.035) compared with the non-cleft group (5.88%). The odds for hypodontia in the VWS group were approximately double compared with the NSCP group. In VWS patients, the most commonly missing teeth were the permanent second premolars and the maxillary permanent laterals incisors. Peg-shaped teeth had a prevalence of 13.70% in VWS patients. CONCLUSIONS: In VWS and NSCP patients compared with non-cleft children, the difference in dental age compared with chronological age decreased. Hypodontia occurs at a high prevalence in VWS and NSCP patients compared with non-cleft children.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: impact of maxillary dental agenesis on craniofacial growth and dental arch relationship in 8 year olds.

BACKGROUND: It is suggested that dental agenesis affects maxillary protrusion and dental arch relationship in children with unilateral cleft lip and palate (UCLP). In addition, an association between the need for orthognathic surgery and dental agenesis is reported. AIM: The aim was to study the impact of maxillary dental agenesis on craniofacial growth and dental arch relationship in 8-year-old children with UCLP. SUBJECTS AND METHODS: The sample consisted of individuals with UCLP from Scandcleft randomized trials. The participants had available data from diagnosis of maxillary dental agenesis as well as cephalometric measurements (n = 399) and GOSLON assessment (n = 408) at 8 years of age. RESULTS: A statistically significant difference was found for ANB between individuals with agenesis of two or more maxillary teeth (mean 1.52°) in comparison with those with no or only one missing maxillary tooth (mean 3.30° and 2.70°, respectively). Mean NSL/NL was lower among individuals with agenesis of two or more maxillary teeth (mean 9.90°), in comparison with individuals with no or one missing maxillary tooth (mean 11.46° and 11.45°, respectively). The number of individuals with GOSLON score 4-5 was 47.2% in the group with two or more missing maxillary teeth and 26.1% respectively 26.3% in the groups with no or one missing maxillary tooth. No statistically significant difference was found in the comparison between individuals with no agenesis or with agenesis solely of the cleft-side lateral. CONCLUSION: Maxillary dental agenesis impacts on craniofacial growth as well as dental arch relationship and should be considered in orthodontic treatment planning.

Scandcleft trial of primary surgery for unilateral cleft lip and palate: Craniofacial cephalometrics at 8 years.

BACKGROUND: The Scandcleft trial is a randomized controlled trial that includes children with unilateral cleft lip and palate where registrations are standardized and therefore provides the opportunity to describe craniofacial characteristics in a very large sample of patients. OBJECTIVES: The aim of this study was to describe craniofacial growth and morphology in a large study sample of 8-year-old children with unilateral cleft lip and palate (UCLP); before orthodontic treatment and before secondary alveolar bone grafting; and to compare the cephalometric values with age-matched non-cleft children from previous growth studies to identify the differences between untreated cleft- and non-cleft children. MATERIALS: There are 429 eight-year-old UCLP patients in the Scandcleft study group. A total of 408 lateral cephalograms with a mean age of 8.1 years were analysed. Cephalometric analyses were performed digitally. The results from three previously published growth studies on non-cleft children were used for comparison. RESULTS: Cephalometric analyses showed a large variation in craniofacial morphology among the UCLP group. In general, they present with significant maxillary retrusion and reduced intermaxillary relationships compared to the age-matched non-cleft children. In addition, the vertical jaw relationship was decreased, mainly due to decreased maxillary inclination. The upper and lower incisors were retroclined. It can be expected that these differences will increase in significance as the children age. CONCLUSION: Results from this study provide proposed norms for the young UCLP before any orthodontic treatment and can be valuable for the clinician in future treatment planning. TRIAL REGISTRATION: ISRCTN29932826.

Pierre Robin Sequence: Incidence of Speech-Correcting Surgeries and Fistula Formation.

OBJECTIVE: Children with Pierre Robin sequence (PRS) and cleft palate have a high rate of velopharyngeal insufficiency (VPI) following primary palatoplasty. Our purpose was to determine the long-term incidence of speech-correcting surgeries (SCSs) and fistula rates in PRS after primary palatoplasty and the influence of possible causal factors. DESIGN: A retrospective single-center, observational chart review study. PARTICIPANTS: After exclusion, the study cohort comprised 78 nonsyndromic PRS children (48 females) born between 1990 and 2009 and treated at the Cleft Palate and Craniofacial Center of Helsinki University Hospital, Finland. Causal factors included gender, surgeon, age at primary palatoplasty, surgical technique, airway obstruction in infancy, and cleft severity. We analyzed the outcome at age 8 years and at data retrieval, with a median follow-up of 14 years (range: 8-27 years). RESULTS: Thirty-four (43.6%) children received SCS by age 8 years, and of the 19 (24.4%) postoperative fistulas, 6 (7.7%) underwent closure. At data retrieval, 37 (47.4%) children had undergone SCS and 8 (10.3%) had a fistula closure. Median age at SCS was 6 years. The results showed no significant association for gender, surgeon, age at primary palatoplasty, surgical technique, cleft severity, or airway obstruction in infancy regarding incidence of SCS, fistulas, or repaired fistulas. CONCLUSION: Pierre Robin sequence in children is associated with a high incidence of SCS and fistula formation, which necessitates accurate clinical follow-up and observation of speech development. The development of VPI in PRS is complex and most likely involving multiple factors.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate. Dental arch relationships in 8 year-olds.

BACKGROUND AND TRIAL DESIGN: The Scandcleft intercentre study evaluates the outcomes of four surgical protocols for treatment of children with unilateral cleft lip and palate (UCLP). Originally 10 cleft centres in Denmark, Finland, Norway, Sweden, and the UK participated in a set of three randomized trials of primary surgery. Three groups of centres (Trials 1, 2, and 3) tested their traditional local surgical protocols (Arms B, C, and D) against a common protocol (Arm A). OBJECTIVES: To evaluate dental arch relationships at age 8 years after four different protocols of primary surgery for UCLP. These results are secondary outcomes of the overall trial. METHODS: Study models of 411 children (270 boys, 141 girls) with non-syndromic UCLP at a mean age of 8.1 (range 7.0-10.0) years were available. Dental arch relationships were analysed using the GOSLON Yardstick by a blinded panel of 11 orthodontists. To assess reliability, Kappa statistics were calculated. The trials were tested statistically with t-tests. RESULTS: Comparisons within each trial showed no statistically significant differences in the mean 8-year index scores or their distributions between the common protocol and the local team protocol. The mean index scores were Trial 1: Arm A 3.03, Arm B 2.82, Trial 2: Arm A 2.78, Arm C 2.64, and Trial 3: Arm A 3.06, Arm D 3.08. Comparisons between the trials detected a significantly (P < 0.005) better mean index score Trial 2 Arm C than in Trial 3 Arm D. The intra- and inter-rater reliabilities were acceptable. CONCLUSION: The results of these three trials do not provide evidence that one surgical protocol is better than the others. TRIAL REGISTRATION: ISRCTN29932826.