{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T06:02:03Z","timestamp":1784354523782,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: There is a lack of cohesion in integrating current knowledge on the genetic and environmental etiology of dental impaction. The primary aim of this article is to review the current literature to identify candidate genes involved in the pathogenesis of dental impaction. Methods: A scoping review was conducted following PRISMA-ScR guidelines to identify and organize the available body of evidence. Relevant literature was searched in MEDLINE (via PubMed), Scopus, and Web of Science, with the final search conducted on 03 January 2026. Eligibility criteria included case\u2013control, cohort, cross-sectional observational, and case report studies in humans. Selected studies focused on syndromic and non-syndromic variants, inheritance patterns, and genetic analyses. Risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists and AMSTAR 2. Results: Only 18 studies met the eligibility criteria. Most articles were case reports and retrospective observational studies, revealing a multifaceted genetic landscape underlying dental impaction, with mutations affecting transcription factors and signaling pathways critical for odontogenesis, particularly RUNX2, FGFR1, MSX1, PAX9, and AXIN2. Overall, the included studies showed moderate methodological quality. Conclusions: Current evidence does not clearly support specific genes as causal factors in dental impaction, but instead suggests a complex, likely polygenic susceptibility that modulates the anatomical threshold for tooth eruption. This review highlights RUNX2, FGFR1, MSX1, PAX9, and AXIN2, as well as emerging candidates involved in eruption and bone remodeling pathways. Future progress depends on standardized phenotyping, large replicated cohorts, and functional studies linking genetic variation to dental follicle-mediated eruptive remodeling.<\/jats:p>","DOI":"10.3390\/genes17030265","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:33:02Z","timestamp":1772101982000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Aspects of Dental Impaction: A Scoping Review"],"prefix":"10.3390","volume":"17","author":[{"given":"Elena","family":"Oliva-Ferrusola","sequence":"first","affiliation":[{"name":"Department of Dentistry, Faculty of Dentistry, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5196-1675","authenticated-orcid":false,"given":"Mar\u00eda","family":"Baus-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Dentistry, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9302-7138","authenticated-orcid":false,"given":"Daniel","family":"Torres-Lagares","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Dentistry, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Angeles","family":"Serrera-Figallo","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Dentistry, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100256","DOI":"10.1016\/j.sipas.2024.100256","article-title":"Assessment of complications in third molar surgery performed by resident surgeons: A comprehensive analysis","volume":"18","author":"Cerqueira","year":"2024","journal-title":"Surg. Pract. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e29989","DOI":"10.1097\/MD.0000000000029989","article-title":"Prevalence of and risk factors for postoperative complications after lower third molar extraction: A multicenter prospective observational study in Japan","volume":"101","author":"Yamada","year":"2022","journal-title":"Medicine"},{"key":"ref_3","first-page":"67","article-title":"Factors influencing permanent teeth eruption. Part one\u2013general factors","volume":"12","author":"Almonaitiene","year":"2010","journal-title":"Stomatologija"},{"key":"ref_4","first-page":"35","article-title":"Prevalence of impacted, retained, and impacted teeth analyzed in panoramic radiographs of the population of Bogot\u00e1, Colombia","volume":"34","year":"2015","journal-title":"Univ. Odontol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1186\/s13287-022-03140-3","article-title":"Runx2 and Nell-1 in dental follicle progenitor cells regulate bone remodeling and tooth eruption","volume":"13","author":"Zeng","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_6","first-page":"168","article-title":"A family case report: Disturbances in tooth form and eruption of the second premolar","volume":"14","author":"Symons","year":"1996","journal-title":"Aust. Orthod. J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yu, Y., Wang, K., Wang, Z., Cai, H., Liao, C., Wu, Y., Zhang, J., Tian, W., and Liao, L. (2024). Spatial and temporal gene expression patterns during the early human odontogenesis process. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1437426"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e13653","DOI":"10.1111\/cpr.13653","article-title":"Spatiotemporal cell landscape of human embryonic tooth development","volume":"57","author":"Shi","year":"2024","journal-title":"Cell Prolif."},{"key":"ref_9","first-page":"45","article-title":"Tooth eruption: Molecular basis. A literature Review","volume":"8","year":"2022","journal-title":"Rev. Odontol. Cient."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chen, J., Sun, T., You, Y., Lin, B., Wu, B., and Wu, J. (2023). Genomic identification of potential odontogenic genes involved in dental epithelial-mesenchymal interaction during early odontogenesis. BMC Genom., 24.","DOI":"10.1186\/s12864-023-09140-8"},{"key":"ref_11","first-page":"47","article-title":"Surgical orthodontic approach to dental inclusions","volume":"10","year":"2005","journal-title":"RCOE"},{"key":"ref_12","first-page":"377","article-title":"Dental anomalies and dysplasias of genetic-hereditary origin","volume":"28","year":"2012","journal-title":"Av. Odontoestomatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.14419\/ijdr.v9i1.31976","article-title":"Multiple dental retentions: Literature review","volume":"9","author":"Maftouh","year":"2022","journal-title":"Int. J. Dent. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s10038-005-0353-6","article-title":"Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis","volume":"51","author":"Mostowska","year":"2006","journal-title":"J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20220987","DOI":"10.1515\/biol-2022-0987","article-title":"Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis","volume":"20","author":"Zhong","year":"2025","journal-title":"Open Life Sci."},{"key":"ref_16","first-page":"75","article-title":"Molecular patterning of the mammalian dentition","volume":"6","author":"Lan","year":"2014","journal-title":"Int. J. Oral. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation","volume":"169","author":"Tricco","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.11124\/JBIES-20-00167","article-title":"Updated methodological guide for conducting scoping reviews","volume":"18","author":"Peters","year":"2020","journal-title":"JBI Evid. Synth."},{"key":"ref_19","unstructured":"Moola, S., Munn, Z., Tufanaru, C., Aromataris, E., Sears, K., Sfetcu, R., Currie, M., Lisy, K., Qureshi, R., and Mattis, P. (2020). Manual for Evidence Synthesis\u2013Appendix 7, 4. Critical Appraisal Checklist for Case Reports, JBI."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"j4008","DOI":"10.1136\/bmj.j4008","article-title":"AMSTAR 2, a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both","volume":"358","author":"Shea","year":"2017","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(71)90287-X","article-title":"A rapid banding technique for human chromosomes","volume":"2","author":"Seabright","year":"1971","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s12041-018-0891-2","article-title":"A novel Alu-mediated microdeletion in the RUNX2 gene in a Chinese patient with cleidocranial dysplasia","volume":"97","author":"Qian","year":"2018","journal-title":"J. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1601-0825.2011.01862.x","article-title":"Cleidocranial dysplasia: Oral features and genetic analysis of 11 patients","volume":"18","author":"Bufalino","year":"2012","journal-title":"Oral. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zou, Y., Lin, H., Chen, W., Chang, L., Cai, S., Lu, Y.G., and Xu, L. (2022). Abnormal eruption of teeth in relation to FGFR1 heterozygote mutation: A rare case of osteoglophonic dysplasia with 4-year follow-up. BMC Oral Health, 22.","DOI":"10.1186\/s12903-022-02069-6"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103729","DOI":"10.1016\/j.ejmg.2019.103729","article-title":"Heterozygous FGFR1 mutation may be responsible for an incomplete form of osteoglophonic dysplasia characterized only by radiolucent bone lesions and teeth retentions","volume":"63","author":"Marzin","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1177\/10556656231201834","article-title":"Orthodontic management of severe hypodontia and impacted maxillary second molars in a patient with Sotos syndrome","volume":"62","author":"Oka","year":"2025","journal-title":"Cleft Palate Craniofac. J."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Trybek, G., Jaro\u0144, A., and Grzywacz, A. (2021). Association of polymorphic and haplotype variants of the MSX1 gene and the impacted teeth phenomenon. Genes, 12.","DOI":"10.3390\/genes12040577"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1177\/1465312518820537","article-title":"Role of polymorphisms of MSX1 and PAX9 genes in palatal impaction of maxillary canines","volume":"46","author":"Devi","year":"2019","journal-title":"J. Orthod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"584","DOI":"10.12688\/f1000research.17147.1","article-title":"Genotyping analysis of the PAX9 gene in patients with maxillary canine impaction","volume":"8","author":"Vitria","year":"2019","journal-title":"F1000Research"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.bjoms.2020.04.006","article-title":"MSX1 is differentially expressed in the deepest impacted maxillary third molars","volume":"58","author":"Olsson","year":"2020","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"378","DOI":"10.7150\/ijms.7.378","article-title":"Non-syndromic multiple supernumerary teeth in a family unit with a normal karyotype: Case report","volume":"7","author":"Inchingolo","year":"2010","journal-title":"Int. J. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.archoralbio.2018.04.011","article-title":"Whole exome sequencing in an Italian family with isolated maxillary canine agenesis and canine eruption anomalies","volume":"91","author":"Barbato","year":"2018","journal-title":"Arch. Oral Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s10266-018-0342-9","article-title":"Gene expression profiles in dental follicles from patients with impacted canines","volume":"106","author":"Uribe","year":"2018","journal-title":"Odontology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1007\/s00784-021-04259-y","article-title":"Investigation of the expression level of long non-coding RNAs in dental follicles of impacted mandibular third molars","volume":"26","author":"Ege","year":"2022","journal-title":"Clin. Oral Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.1016\/j.jormas.2022.04.015","article-title":"Non-coding RNAs transcribed from ultra-conserved regions (T-UCRs) are differentially expressed in dental follicle tissues of impacted mandibular third molars","volume":"123","author":"Bozgeyik","year":"2022","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.2174\/0113862073256803231114095626","article-title":"Transcriptome sequencing of gingival tissues from impacted third molars patients reveals the alterations of gene expression","volume":"27","author":"Zhou","year":"2024","journal-title":"Comb. Chem. High. Throughput Screen."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.ajodo.2015.06.013","article-title":"Etiology of maxillary canine impaction: A review","volume":"148","author":"Becker","year":"2015","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e375","DOI":"10.1016\/j.jcms.2012.02.004","article-title":"The sequential hypothesis of impaction of maxillary canine: A hypothesis based on clinical and radiographic findings","volume":"40","author":"Sajnani","year":"2012","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Papadopoulos, S., Ziakas, Y., Panteris, E., and Chatzigianni, U. (2025). The genetic basis of tooth impaction: A systematic review. Clin. Oral Investig.","DOI":"10.1007\/s00784-025-06520-0"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.ajhg.2008.11.006","article-title":"PTH1R loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption","volume":"83","author":"Decker","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Trybek, G., Jaro\u0144, A., Gabrysz-Trybek, E., Rutkowska, M., Markowska, A., Chmielowiec, K., Chmielowiec, J., and Grzywacz, A. (2023). Genetic factors of teeth impaction: Polymorphic and haplotype variants of PAX9, MSX1, AXIN2, and IRF6 genes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813889"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Inchingolo, A.D., Patano, A., Coloccia, G., Ceci, S., Inchingolo, A.M., Marinelli, G., Malcangi, G., Montenegro, V., Laudadio, C., and Palmieri, G. (2021). Genetic Pattern, Orthodontic and Surgical Management of Multiple Supplementary Impacted Teeth in a Rare, Cleidocranial Dysplasia Patient: A Case Report. Medicina, 57.","DOI":"10.3390\/medicina57121350"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"24225","DOI":"10.1038\/srep24225","article-title":"RUNX2 mutation alters 1\u03b1,25-dihydroxyvitamin D3-mediated osteoclastogenesis in dental follicle cells","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1601-6343.2009.01439.x","article-title":"Cellular and molecular basis of tooth eruption","volume":"12","author":"Wise","year":"2009","journal-title":"Orthod. Craniofac. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e13005","DOI":"10.1111\/eos.13005","article-title":"Epigenetic markers of tooth eruption-DNA methylation and histone acetylation","volume":"132","author":"Westerlund","year":"2024","journal-title":"Eur. J. Oral Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e236395","DOI":"10.1136\/bcr-2020-236395","article-title":"Non-syndromal multiple supernumerary and permanent impacted teeth in mother and her one child","volume":"13","author":"Rai","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1179\/1465312513Z.00000000081","article-title":"Triplets with bilateral palatally displaced canines in association with third molar agenesis: An example of biologically related dental anomaly patterns?","volume":"40","author":"Harte","year":"2013","journal-title":"J. Orthod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/cge.14400","article-title":"Genotype-phenotype analysis of selective failure of tooth eruption\u2014A systematic review","volume":"104","author":"Guo","year":"2023","journal-title":"Clin. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1177\/0022034517750109","article-title":"Rare and Common Variants Conferring Risk of Tooth Agenesis","volume":"97","author":"Jonsson","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/cge.14225","article-title":"Expanding the genetic spectrum of tooth agenesis using whole-exome sequencing","volume":"102","author":"Yu","year":"2022","journal-title":"Clin. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1093\/hmg\/ddac037","article-title":"Polygenic risk impacts PDGFRA mutation penetrance in non-syndromic cleft lip and palate","volume":"31","author":"Yu","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Antal, G., Zsigmond, A., Till, \u00c1., Orsi, E., Szanto, I., B\u00fcki, G., Kereskai, L., Herbert, Z., Hadzsiev, K., and Bene, J. (2024). Case report: Initial atypical skeletal symptoms and dental anomalies as first signs of Gardner syndrome: The importance of genetic analysis in the early diagnosis. Pathol. Oncol. Res., 30.","DOI":"10.3389\/pore.2024.1611768"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"341","DOI":"10.37358\/MP.19.2.5183","article-title":"Comparative Study on the Efficiency of Intermaxillary Elastic Polymers Used in the Treatment of Skeletal Class II Malocclusions in Growing Patients","volume":"56","author":"Vaida","year":"2019","journal-title":"Mater. Plast."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Joy-Thomas, A., Lalwani, Z., Guajardo, L., Valenza, J., and Fakhouri, W.D. (2025). The role of genetics in human oral health: A systematic-narrative review. Dent. J., 13.","DOI":"10.3390\/dj13030133"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bruner, W.S., and Grant, S.F.A. (2024). Translation of genome-wide association study: From genomic signals to biological insights. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1375481"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/3\/265\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:44:24Z","timestamp":1772102664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/3\/265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["genes17030265"],"URL":"https:\/\/doi.org\/10.3390\/genes17030265","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]}}}