Tooth agenesis and orofacial clefting: genetic brothers in arms?

L’Agenesia Dentaria e le Schisi Oro-facciali costituiscono comuni anomalie dello sviluppo e la loro co-occorrenza è osservata spesso in pazienti ed in modelli animali. Lo scopo della presente revisione sistematica è quello di indagare a fondo la letteratura corrente (PubMed, EMBASE) per identificare i geni e loci genomici che contribuiscono alla co-occorrenza di Agenesia Dentaria e di Schisi Oro-facciali sindromiche e non-sindromiche, al fine di conoscere i meccanismi molecolari sottostanti al duplice coinvolgimento nello sviluppo dei denti e primordi facciali. Complessivamente sono stati analizzate 84 pubblicazioni comprendenti descrizioni fenotipiche e genotipiche riconducibili a 9 loci genomici e 26 geni candidati alla base della co-occorrenza dei due difetti congeniti: MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFα, TGFβ3, TGFβR1, TGFβR2, FGF8, FGFR1, KISS1R, WNT3, Wnt5a, CDH1, CHD7, AXIN2, TWIST1, BCOR, OFD1, PTCH1, PITX2, e PVRL1. I percorsi molecolari, le funzioni cellulari, di espressione tessuto-specifica e di associazione con la patologia sono stati esaminati utilizzando database accessibili al pubblico (EntrezGene, UniProt, OMIM). I termini Gene Ontology dei processi biologici mediati da geni candidati sono stati usati per creare raggruppamenti utilizzando il GOTermMapper (Lewis-Sigler Institute, Princeton University), speculando su sei super-cluster: (a) sviluppo anatomico, (b) la divisione cellulare, crescita e motilità, (c) il metabolismo cellulare e catabolismo, (d) trasporto cellulare, (e) organizzazione struttura cellulare e (f) organo / processi specifici del sistema. Questa recensione ha lo scopo di aumentare la conoscenza sui meccanismi alla base della co-occorrenza di Agenesia Dentaria e di Schisi Oro-facciali, al fine di aprire la strada per migliorare la diagnosi molecolare mirata (prenatale) e, infine, per riflettere sullo sviluppo futuro di strategie terapeutiche o preventive per queste condizioni invalidanti.Tooth agenesis and orofacial clefts represent the most common developmental anomalies and their co-occurrence is often reported in patients as well in animal models. The aim of the present systematic review is to thoroughly investigate the current literature (PubMed, EMBASE) to identify the genes and genomic loci contributing to syndromic or non-syndromic co-occurrence of tooth agenesis and orofacial clefts, to gain insight into the molecular mechanisms underlying their dual involvement in the development of teeth and facial primordia. Altogether, 84 articles including phenotype and genotype description provided 9 genomic loci and 26 gene candidates underlying the co-occurrence of the two congenital defects: MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFα, TGFβ3, TGFβR1, TGFβR2, FGF8, FGFR1, KISS1R, WNT3, WNT5A, CDH1, CHD7, AXIN2, TWIST1, BCOR, OFD1, PTCH1, PITX2, and PVRL1. The molecular pathways, cellular functions, tissue-specific expression and disease association were investigated using publicly accessible databases (EntrezGene, UniProt, OMIM). The Gene Ontology terms of the biological processes mediated by the candidate genes were used to cluster them using the GOTermMapper (Lewis-Sigler Institute, Princeton University), speculating on six super-clusters: (a) anatomical development, (b) cell division, growth and motility, (c) cell metabolism and catabolism, (d) cell transport, (e) cell structure organization and (f) organ/system-specific processes. This review aims to increase the knowledge on the mechanisms underlying the co-occurrence of tooth agenesis and orofacial clefts, to pave the way for improving targeted (prenatal) molecular diagnosis and finally to reflect on therapeutic or ultimately preventive strategies for these disabling conditions in the future

A longitudinal three-center study of craniofacial morphology at 6 and 12 years of age in patients with complete bilateral cleft lip and palate

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 (nA = 37), Nijmegen (nB = 26), and Oslo (nC = 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. © 2011 The Author(s)

Photographs of dental casts or digital models: rating dental arch relationships in bilateral cleft lip and palate

Yardsticks have been developed to measure dental arch relations in cleft lip and palate (CLP) patients as diagnostic proxies for the underlying skeletal relationship. Travelling with plaster casts to compare results between CLP centres is inefficient so the aim of this study was to investigate the reliability of using digital models or photographs of dental casts instead of plaster casts for rating dental arch relationships in children with complete bilateral cleft lip and palate (CBCLP). Dental casts of children with CBCLP (n=20) were included. Plaster casts, digital models and photographs of the plaster casts were available for all the children at 6, 9, and 12 years of age. All three record formats were scored using the bilateral cleft lip and palate (BCLP) yardstick by four observers in random order. No significant differences were found for the BCLP yardstick scores among the three formats. The interobserver weighted kappa scores were between 0.672 and 0.934. Comparison between the formats per observer resulted in weighted kappa scores between 0.692 and 0.885. It is concluded that digital models and photographs of dental casts can be used for rating dental arch relationships in patients with CBCLP. These formats are a reliable alternative for BCLP yardstick assessments on conventional plaster casts