Craniofacial measurements in children with sella turcica shape’s anomalies

Objectives: The objective of the study is to evaluate the cephalometric measurements of Tunisian children who presented sella turcica’s (ST) shape anomalies. Materials and Methods: This cross-sectional study was conducted between January and June 2019 in the Department of Pediatric Dentistry of Monastir and Faculty of Dentistry of Tunisia. Radiographs were gathered from patients aged between 7 and 12 years old (n = 104) who had consulted for a malocclusion. The inclusion criteria were considered as follows: Good visibility of anatomic structures and absence of congenital craniofacial deformities. We excluded bad radiographs with errors and discrepancies: Double limits, deformities as well as children having hereditary craniofacial anomalies and underlying diseases. The cephalometric analysis was conducted according to Segner and Hassund’s method. ST’s shape was identified according to Axelsson’s classification modified by Becktor. The sample size was divided into groups: Group 1 with normal ST’s shape and Group 2 with sella’s anomaly. Statistics were performed using IBM SPSS STATISTICS 22. Data normality has been tested using Shapiro–Wilk test. The normality of variance was investigated too with Levene’s test, and comparison of means between groups was performed with t-test. Results: The prevalence of aberrations of ST’s form in Tunisian children is about 59.6%. The inclination of upper incisors to the maxilla differed in children with ST’s anomaly compared to normal kids. Children with sella aberration are characterized by retroclination of upper incisors to the maxilla. The variables which showed a statistically significant relationship between abnormalities of ST and cephalometric measurements were 1+NA with P = 0.03 and NL-NSL with P = 0.04. Conclusion: The prevalence of ST’s shape anomalies in Tunisian children is about two-thirds. It seems that the anomaly of ST influences the position of the maxilla to the cranial base and the position of upper incisors to the maxilla.

An in vitro and computational validation of a novel loss-of-functional mutation in PAX9 associated with non-syndromic tooth agenesis

Congenital tooth agenesis (CTA) is one of the most common craniofacial anomalies. Its frequency varies among different population depending upon the genetic heterogeneity. CTA could be of familial or sporadic and syndromic or non-syndromic. Five major genes are found to be associated with non-syndromic CTA namely, PAX9, MSX1, EDA1, AXIN2 and WNT10A. In this study, an India family with CTA was investigated and a novel c.336C>G variation was identified in the exon 3 of PAX9, leading to substitution of evolutionary conserved Cys with Trp at 112 amino acid position located at the functionally significant DNA binding paired domain region. Functional analysis revealed that p.Cys112Trp mutation did not prevent the nuclear localization although mutant protein had higher cytoplasmic retention. EMSA using e5 probe revealed that mutant protein was unable to bind with the paired-domain binding site. Subsequently, GST pull-down assay revealed lower binding activity of the mutant protein with its known interactor MSX1. Further RNA-sequencing of PAX9 over-expressed HEK293, identified two potential novel targets, WNT4 and WNT7b those are up-regulated by wild-type PAX9 but not by mutant. These in vitro results were consistent with the computational results. The in vitro and computational observations altogether suggest that c.336C>G (p.Cys112Trp) variation leads to loss-of-function of PAX9 leading to CTA in this family.

Evidence against the “anomalous-is-bad” stereotype in Hadza hunter gatherers

People have an “anomalous-is-bad” stereotype whereby they make negative inferences about the moral character of people with craniofacial anomalies like scars. This stereotype is hypothesized to be a byproduct of adaptations for avoiding pathogens. However, evidence for the anomalous-is-bad stereotype comes from studies of European and North American populations; the byproduct hypothesis would predict universality of the stereotype. We presented 123 Hadza across ten camps pairs of morphed Hadza faces—each with one face altered to include a scar—and asked who they expected to be more moral and a better forager. Hadza with minimal exposure to other cultures chose at chance for both questions. Hadza with greater exposure to other cultures, however, expected the scarred face to be less moral and a better forager. These results suggest the anomalous-is-bad stereotype is culturally shared, providing evidence against a universal pathogen avoidance byproduct hypothesis.

General principles governing record taking in patients with cleft lip and palate

(WHO meetings on International Collaborative Research on Craniofacial Anomalies).One of the most common congenital anomaly we come across is the Cleft Lip and palate where affected children suffer from range of functional as well as aesthetic problems. Cleft lip and palate is a multifunctional disease associated with environmental factors. Management of cleft is a complex procedure and demands co-operation among experts from different fields. Clinical treatment procedure extends from beginning of birth, to achieving skeletal maturity effectively.

Evidence against the "anomalous-is-bad" stereotype in Hadza hunter gatherers

People have an “anomalous-is-bad” stereotype whereby they make negative inferences about the moral character of people with craniofacial anomalies like scars. This stereotype is hypothesized to be a byproduct of adaptations for avoiding pathogens. However, evidence for the anomalous-is-bad stereotype comes from studies of European and North American populations; the byproduct hypothesis would predict universality of the stereotype. We presented 123 Hadza across ten camps pairs of morphed Hadza faces—each with one face altered to include a scar—and asked who they expected to be more moral and a better forager. Hadza with minimal exposure to other cultures chose at chance for both questions. Hadza with greater exposure to other cultures, however, expected the scarred face to be less moral and a better forager. These results suggest the anomalous-is-bad stereotype is culturally shared, providing evidence against a universal pathogen avoidance byproduct hypothesis.

Case Report and Review of the Literature: Congenital Diaphragmatic Hernia and Craniosynostosis, a Coincidence or Common Cause?

Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect that presents as either an isolated diaphragm defect or as part of a complex disorder with a wide array of anomalies (complex CDH). Some patients with complex CDH display distinct craniofacial anomalies such as craniofrontonasal dysplasia or craniosynostosis, defined by the premature closure of cranial sutures. Using clinical whole exome sequencing (WES), we found a BCL11B missense variant in a patient with a left-sided congenital diaphragmatic hernia as well as sagittal suture craniosynostosis. We applied targeted sequencing of BCL11B in patients with craniosynostosis or with a combination of craniosynostosis and CDH. This resulted in three additional BCL11B missense mutations in patients with craniosynostosis. The phenotype of the patient with both CDH as well as craniosynostosis was similar to the phenotype of previously reported patients with BCL11B missense mutations. Although these findings imply that both craniosynostosis as well as CDH may be associated with BCL11B mutations, further studies are required to establish whether BCL11B variants are causative mutations for both conditions or if our finding was coincidental.

Synergistic Mutations of LRP6 and WNT10A in Familial Tooth Agenesis

Familial tooth agenesis (FTA), distinguished by developmental failure of selected teeth, is one of the most prevalent craniofacial anomalies in humans. Mutations in genes involved in WNT/β-catenin signaling, including AXIN2 WNT10A, WNT10B, LRP6, and KREMEN1, are known to cause FTA. However, mutational interactions among these genes have not been fully explored. In this study, we characterized four FTA kindreds with LRP6 pathogenic mutations: p.(Gln1252*), p.(Met168Arg), p.(Ala754Pro), and p.(Asn1075Ser). The three missense mutations were predicted to cause structural destabilization of the LRP6 protein. Two probands carrying both an LRP6 mutant allele and a WNT10A variant exhibited more severe phenotypes, suggesting mutational synergism or digenic inheritance. Biallelic LRP6 mutations in a patient with many missing teeth further supported the dose-dependence of LRP6-associated FTA. Analysis of 21 FTA cases with 15 different LRP6 loss-of-function mutations revealed high heterogeneity of disease severity and a distinctive pattern of missing teeth, with maxillary canines being frequently affected. We hypothesized that various combinations of sequence variants in WNT-related genes can modulate WNT signaling activities during tooth development and cause a wide spectrum of tooth agenesis severity, which highlights the importance of exome/genome analysis for the genetic diagnosis of FTA in this era of precision medicine.