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.Peer reviewe

Dominant Mutations in GRHL3 Cause Van der Woude Syndrome and Disrupt Oral Periderm Development

Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6+/−;Grhl3+/−) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS

Dominant Mutations in GRHL3 Cause Van der Woude Syndrome and Disrupt Oral Periderm Development

Peer reviewe

Effects of adenoidectomy and changed mode of breathing on incisor and molar dentoalveolar heights and anterior face heights

Background: Mouth breathing may affect facial form and the positions of the teeth

Validation of reported dentoalveolar relationships in the Swedish Quality Registry for Cleft Lip and Palate

Objectives: The present study validated data that had been reported to the Swedish Quality Registry for Cleft Lip and Palate (CLP) under new requirements from 2016, when use of the 5-year-old (5YO) and the Modified Huddart and Bodenham (MHB) indices for rating occlusion in children born with unilateral CLP (UCLP) was introduced. Materials and methods: The sample included blinded study casts (n = 97) and photos (n = 4) of 5-year-old children who had been born with UCLP in 2009−2011 and were enrolled at one of six cleft centres in Sweden. Fourteen orthodontists from the centres assessed the patients (n = 101) using the 5YO and the MHB indices. Median 5YO and MHB scores of the 14 assessments were compared with original registry data (n = 61). Each centre devised code keys to protect the identities of their patients in the registry. Results: Interrater agreement among the 14 orthodontists was good for the 5YO index (quadratic-weighted kappa: 0.72−0.92) and the MHB index (intraclass correlation coefficient: 0.991−0.994). Comparisons of median 5YOs for each identifiable child with their registry data (n = 61) found total agreement for 70.5 per cent. Comparisons between median MHBs and registry data showed very good or good agreement in 93.4 per cent of the cases. Limitations: Two teams lost their code keys, which reduced the sample to 61 patients. Conclusions: The dentoalveolar outcome data in the CLP registry was trustworthy. There was good agreement among the Swedish cleft teams assessing the 5YO and MHB indices in children born with UCLP at age 5 years