We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; PNSCLP = 6.51 × 10−11; homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84–3.16).

OBJECTIVES While permanent retention is today the method of choice to stabilize orthodontic treatment outcomes, recent studies have increasingly reported posttreatment changes in tooth position during permanent retention. We conducted this study to analyze changes in the anterior mandible, whether the changes follow an underlying movement pattern, and, aiming for a preventive strategy, whether any risk factors could be identified comparing findings with the pretreatment situations. METH-ODS We included 30 patients who had worn fixed Twistflex retainers (UK 3-3) extending from canine to canine in the mandible. Casts reflecting the intraoral situations before orthodontic treatment (T0), directly after completion of active therapy (T1), and 6 months later (T2) were scanned and superimposed using Imageware Surfacer software. Posttreatment changes (T2-T1) of tooth position within the retainer block were analyzed on 3D virtual models and were compared to pretreatment (T0) and treatment-related (T1-T0) findings to identify potential risk factors. RESULTS Almost all analyzed patients revealed three-dimensional changes in tooth position within the retainer block. Comparing these movements, we repeatedly found rotated retainer blocks in labio-oral direction, while the center of rotation was located at the first incisors. This pattern was associated with intercanine expansion and excessive overjet correction during orthodontic treatment. The canines underwent the most pronounced (rotational and translational) movements. CONCLUSIONS In general permanent lingual retainers are safe but in special clinical cases retainers can induce undesired tooth movement. Risk factors seem to be intercanine expansion and excessive overjet correction during orthodontic treatment. In specific cases an additional retention device might be needed. AbstractObjectives. While permanent retention is today frequently the method of choice to stabilize orthodontic treatment outcomes, recent studies have increasingly reported posttreatment changes in tooth position during permanent retention. We conducted this study to analyze such changes in the anterior mandible, whether these follow an underlying movement pattern, and, aiming for a preventive strategy, whether any risk factors could be identified by comparing findings to the pretreatment situations. Methods.We included 30 patients who had worn a fixed Twistflex retainer extending from canine to canine in the mandible. Casts reflecting the intraoral situations before orthodontic treatment (T0), directly upon completion of active therapy (T1), and 6 months into retention (T2) were scanned and superposed using Imageware Surfacer software. Posttreatment changes (T2−T1) in tooth position inside the retainer block were analyzed on 3D virtual models and were compared to pretreatment (T0) and treatment-related (T1−T0) findings to identify potential risk factors.Results. Almost all patients revealed three-dimensional changes in tooth position within the retainer block. On comparing these movements...

No abstract

No abstract

Our study did not provide support for NOG being the causal gene at 17q22. However, the observation of a significant excess of rare variants in GREM1 supports the hypothesis that this is the causal gene at chr. 15q13. Because no single causal variant was identified, future sequencing analyses of GREM1 should involve larger samples and the investigation of regulatory elements.

Nonsyndromic cleft palate only (nsCPO) is a facial malformation that has a livebirth prevalence of 1 in 2,500. Research suggests that the etiology of nsCPO is multifactorial, with a clear genetic component. To date, genome-wide association studies have identified only 1 conclusive common variant for nsCPO, that is, a missense variant in the gene grainyhead-like-3 ( GRHL3). Thus, the underlying genetic causes of nsCPO remain largely unknown. The present study aimed at identifying rare variants that might contribute to nsCPO risk, via whole-exome sequencing (WES), in multiply affected Central European nsCPO pedigrees. WES was performed in 2 affected first-degree relatives from each family. Variants shared between both individuals were analyzed for their potential deleterious nature and a low frequency in the general population. Genes carrying promising variants were annotated for 1) reported associations with facial development, 2) multiple occurrence of variants, and 3) expression in mouse embryonic palatal shelves. This strategy resulted in the identification of a set of 26 candidate genes that were resequenced in 132 independent nsCPO cases and 623 independent controls of 2 different ethnicities, using molecular inversion probes. No rare loss-of-function mutation was identified in either WES or resequencing step. However, we identified 2 or more missense variants predicted to be deleterious in each of 3 genes ( ACACB, PTPRS, MIB1) in individuals from independent families. In addition, the analyses identified a novel variant in GRHL3 in 1 patient and a variant in CREBBP in 2 siblings. Both genes underlie different syndromic forms of CPO. A plausible hypothesis is that the apparently nonsyndromic clefts in these 3 patients might represent hypomorphic forms of the respective syndromes. In summary, the present study identified rare variants that might contribute to nsCPO risk and suggests candidate genes for further investigation.

Bracket failure was more often observed with ceramic brackets and was associated with increased treatment duration.

No abstract