{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:05:22Z","timestamp":1791644722180,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"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>Primary failure of tooth eruption (PFE) is a rare genetic disorder characterized by the failure of teeth to erupt in the absence of obvious physical obstructions, often resulting in a progressive open bite that is resistant to orthodontic treatment. While PFE can be caused by genetic or systemic factors (such as cysts, tumors, and endocrine imbalances), the non-syndromic causes are primarily genetic, with an autosomal dominant inheritance pattern with variable expressivity. Several genes have been closely associated with the non-syndromic PFE form. The PTH1R (parathyroid hormone 1 receptor) is the most commonly PFE-associated gene. Additional genes associated with minor frequency are Transmembrane protein 119 (TMEM119), which reduces the glycolytic efficiency of bone cells, limiting their mineralization capacity and causing bone fragility; Periostin (POSTN), which regulates the extracellular matrix and the bone\u2019s response to mechanical stress; and Lysine (K)-specific methyltransferase 2C (KMT2C), which establishes histone methylation near the Wnt Family Member 5A (WNT5A) gene involved in dental development (odontogenesis). Syndromic forms of PFE are typically associated with complex multisystem disorders, where dental eruption failure is one of the clinical features of the spectrum. These syndromes are often linked to genetic variants that affect ectodermal development, craniofacial patterning, and skeletal growth, leading to abnormal tooth development and eruption patterns. Notable syndromes include GAPO syndrome, ectodermal dysplasia, and cleidocranial dysplasia, each contributing to PFE through distinct molecular mechanisms, such as disruptions in dental structure development, cranial abnormalities, or systemic developmental delays. The main aim of this review is to provide a comprehensive overview of the genetic basis underlying both syndromic and non-syndromic forms of PFE to facilitate precision diagnosis, foster the development of personalized therapeutic strategies, and offer new insights into managing this complex dental anomaly.<\/jats:p>","DOI":"10.3390\/genes16020147","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T10:46:07Z","timestamp":1737715567000},"page":"147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Syndromic and Non-Syndromic Primary Failure of Tooth Eruption: A Genetic Overview"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6518-1700","authenticated-orcid":false,"given":"Clarissa","family":"Modafferi","sequence":"first","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-2242","authenticated-orcid":false,"given":"Elisabetta","family":"Tabolacci","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9499-0556","authenticated-orcid":false,"given":"Cristina","family":"Grippaudo","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"UOC Clininica Odontoiatrica, Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Odontoiatria e Protesi Dentaria, Dipartimento Testa Collo ed Organi di Senso, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-1521","authenticated-orcid":false,"given":"Pietro","family":"Chiurazzi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"},{"name":"Dipartimento di Scienze della Vita e Sanit\u00e0 Pubblica, Sezione di Medicina Genomica, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0002-9416(81)90217-7","article-title":"Primary failure of eruption: A possible cause of posterior open-bite","volume":"80","author":"Proffit","year":"1981","journal-title":"Am. J. Orthod."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Xu, M., Wang, D., Li, K., Ma, T., Wang, Y., and Xia, B. (2024). TMEM119 (c.G143A, p.S48L) Mutation Is Involved in Primary Failure of Eruption by Attenuating Glycolysis-Mediated Osteogenesis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052821"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jdsr.2022.08.002","article-title":"Primary failure of tooth eruption: Etiology and management","volume":"58","author":"Yamaguchi","year":"2022","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1038\/s41431-024-01691-y","article-title":"New Insight into the genotype-phenotype correlation of PTH1R variants and primary failure of tooth eruption on an Italian Cohort","volume":"32","author":"Modafferi","year":"2024","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.ajhg.2008.11.006","article-title":"PTHR1 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_6","doi-asserted-by":"crossref","unstructured":"Davidson, M., Mayer, M., Habib, A., Rashidi, N., Filippone, R.T., Fraser, S., Prakash, M.D., Sinnayah, P., Tangalakis, K., and Mathai, M.L. (2022). Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut-Immune-Brain Axis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911224"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kanamoto, T., Mizuhashi, K., Terada, K., Minami, T., Yoshikawa, H., and Furukawa, T. (2009). Isolation and characterization of a novel plasma membrane protein, osteoblast induction factor (obif), associated with osteoblast differentiation. BMC Dev. Biol., 9.","DOI":"10.1186\/1471-213X-9-70"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9787","DOI":"10.1074\/jbc.M110.179127","article-title":"Parathyroid hormone-responsive Smad3-related factor, Tmem119, promotes osteoblast differentiation and interacts with the bone morphogenetic protein-Runx2 pathway","volume":"286","author":"Hisa","year":"2011","journal-title":"J. Bio.l Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16469","DOI":"10.1038\/s41598-019-52935-7","article-title":"KMT2C, a histone methyltransferase, is mutated in a family segregating non-syndromic primary failure of tooth eruption","volume":"9","author":"Assiry","year":"2019","journal-title":"Sci Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13005-018-0163-7","article-title":"Primary failure of eruption (PFE): A systematic review","volume":"14","author":"Hanisch","year":"2018","journal-title":"Head Face Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ajodo.2013.03.015","article-title":"Establishing the diagnostic criteria for eruption disorders based on genetic and clinical data","volume":"144","author":"Rhoads","year":"2013","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_12","first-page":"31","article-title":"Tooth formation in patients with oligodontia","volume":"63","author":"Bosman","year":"1993","journal-title":"Angle Orthod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1177\/154405910808700509","article-title":"Mechanisms of tooth eruption and orthodontic tooth movement","volume":"87","author":"Wise","year":"2008","journal-title":"J. Dent. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1086\/302622","article-title":"Mutation analysis of core binding factor A1 in patients with cleidocranial dysplasia","volume":"65","author":"Quack","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","first-page":"160","article-title":"Primary failure of eruption and PTH1R: The importance of a genetic diagnosis for orthodontic treatment planning","volume":"137","author":"Simmons","year":"2010","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_16","first-page":"1031","article-title":"Cloning and characterization of the promoter regions of the human parathyroid hormone (PTH)\/PTH-related peptide receptor gene: Analysis of deox yribonucleic acid from normal subjects and patients with pseudohypoparathyroidism type 1b","volume":"82","author":"Bettoun","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1172\/JCI3678","article-title":"Developmental upregulation of human parathyroid hormone (PTH)\/PTH-related peptide receptor gene expression from conserved and human-specific promoters","volume":"102","author":"Bettoun","year":"1998","journal-title":"J. Clin. Invest."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15557","DOI":"10.1074\/jbc.M900044200","article-title":"Structural basis for antibody discrimination between two hormones that recognize the parathyroid hormone receptor","volume":"284","author":"McKinstry","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_19","first-page":"F665","article-title":"Receptors for PTH and PTHrP: Their biological importance and functional properties","volume":"277","author":"Mannstadt","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1126\/science.7701349","article-title":"A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia","volume":"268","author":"Schipani","year":"1995","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/(SICI)1096-8628(19970822)71:3<283::AID-AJMG7>3.0.CO;2-V","article-title":"Familial Blomstrand chondrodysplasia with advanced skeletal maturation: Further delineation","volume":"71","author":"Loshkajian","year":"1997","journal-title":"Am. J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/cge.13601","article-title":"The third family with Eiken syndrome","volume":"96","author":"Jacob","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Inchingolo, F., Ferrara, I., Viapiano, F., Ciocia, A.M., Palumbo, I., Guglielmo, M., Inchingolo, A.D., Palermo, A., Bordea, I.R., and Inchingolo, A.M. (2023). Primary Failure Eruption: Genetic Investigation, Diagnosis and Treatment: A Systematic Review. Children, 10.","DOI":"10.3390\/children10111781"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e05632","DOI":"10.1002\/ccr3.5632","article-title":"Review and case report of the treatment in a young girl with primary failure of eruption","volume":"10","author":"Awad","year":"2022","journal-title":"Clin. Case Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1601-6343.2009.01440.x","article-title":"Genetic analysis of familial non-syndromic primary failure of eruption","volume":"12","author":"Simmons","year":"2009","journal-title":"Orthod. Craniofac. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s40510-021-00387-z","article-title":"Validating clinical characteristic of primary failure of eruption (PFE) associated with PTH1R variants","volume":"22","author":"Grippaudo","year":"2021","journal-title":"Prog. Orthod."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Grippaudo, C., Cafiero, C., D\u2019Apolito, I., Re, A., Genuardi, M., Chiurazzi, P., and Frazier-Bowers, S.A. (2019). A novel nonsense PTH1R variant shows incomplete penetrance of primary failure of eruption: A case report. BMC Oral. Health, 19.","DOI":"10.1186\/s12903-019-0944-9"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s12974-020-01914-1","article-title":"Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet","volume":"17","author":"Bordeleau","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mizuhashi, K., Chaya, T., Kanamoto, T., Omori, Y., and Furukawa, T. (2015). Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133704"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s00223-013-9828-1","article-title":"Involvement of the osteoinductive factors, Tmem119 and BMP-2, and the ER stress response PERK-eIF2alpha-ATF4 pathway in the commitment of myoblastic into osteoblastic cells","volume":"94","author":"Tanaka","year":"2014","journal-title":"Calcif. Tissue Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12967-021-02781-x","article-title":"TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB\/PI3K\/AKT signaling pathway","volume":"19","author":"Sun","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Gonz\u00e1lez, L., and Alonso, J. (2018). Periostin: A Matricellular Protein with Multiple Functions in Cancer Development and Progression. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00225"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00441-016-2426-6","article-title":"Periostin as a multifunctional modulator of the wound healing response","volume":"365","author":"Walker","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00428-011-1151-5","article-title":"Periostin expression and epithelial-mesenchymal transition in cancer: A review and an update","volume":"459","author":"Morra","year":"2011","journal-title":"Virchows Arch."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1186\/s12935-022-02714-8","article-title":"Periostin: Biology and function in cancer","volume":"22","author":"Dorafshan","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_36","first-page":"5358","article-title":"Periostin secreted by epithelial ovarian carcinoma is a ligand for alpha(V)beta(3) and alpha(V)beta(5) integrins and promotes cell motility","volume":"62","author":"Gillan","year":"2002","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.1128\/MCB.24.9.3992-4003.2004","article-title":"Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression","volume":"24","author":"Shao","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1182\/blood-2022-165717","article-title":"KMT2C\/MLL3 Attenuates Committed Myeloid Progenitor Self-Renewal Capacity and Balances Granulocyte and Monocyte\/Dendritic Cell Output","volume":"140","author":"Wang","year":"2022","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1128\/MCB.23.1.140-149.2003","article-title":"Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins","volume":"23","author":"Goo","year":"2003","journal-title":"Mol. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Koemans, T.S., Kleefstra, T., Chubak, M.C., Stone, M.H., Reijnders, M.R.F., de Munnik, S., Willemsen, M.H., Fenckova, M., Stumpel, C.T.R.M., and Bok, L.A. (2017). Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006864"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ajhg.2012.05.003","article-title":"Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability","volume":"91","author":"Kleefstra","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2350","DOI":"10.1002\/mgg3.2350","article-title":"A novel 11 base pair deletion in KMT2C resulting in Kleefstra syndrome 2","volume":"12","author":"Whitford","year":"2024","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"925","DOI":"10.17219\/dmp\/186086","article-title":"Most common congenital syndromes with facial asymmetry: A narrative review","volume":"61","author":"Ziomek","year":"2024","journal-title":"Dent. Med. Probl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/ajmg.c.30033","article-title":"Ectodermal dysplasias","volume":"131","author":"Itin","year":"2004","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/ng0895-409","article-title":"X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein","volume":"13","author":"Kere","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1177\/0022034508328627","article-title":"EDA gene mutations underlie non-syndromic oligodontia","volume":"88","author":"Song","year":"2009","journal-title":"J. Dent. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1111\/odi.12376","article-title":"Novel EDA mutation in X-linked hypohidrotic ectodermal dysplasia and genotype-phenotype correlation","volume":"21","author":"Zeng","year":"2015","journal-title":"Oral. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/BF00281698","article-title":"Christ-Siemens-Touraine syndrome. Investigations on two large Brazilian kindreds with a new estimate of the manifestation rate among carriers","volume":"57","author":"Pinheiro","year":"1981","journal-title":"Hum. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13023-019-1288-x","article-title":"Natural history of X-linked hypohidrotic ectodermal dysplasia: A 5-year follow-up study","volume":"15","author":"Wohlfart","year":"2020","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/ajmg.1320190202","article-title":"Growth retardation, alopecia, pseudo-anodontia, and optic atrophy--the GAPO syndrome: Report of a patient and review of the literature","volume":"19","author":"Tipton","year":"1984","journal-title":"Am. J. Med. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1158\/0008-5472.CAN-09-1086","article-title":"Host-derived tumor endothelial marker 8 promotes the growth of melanoma","volume":"69","author":"Cullen","year":"2009","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/ajmg.a.38625","article-title":"A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis","volume":"176","author":"Dinckan","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.matbio.2016.12.002","article-title":"Cell autonomous ANTXR1-mediated regulation of extracellular matrix components in primary fibroblasts","volume":"62","author":"Hu","year":"2017","journal-title":"Matrix Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.sdentj.2024.07.001","article-title":"Abnormal dental phenotypes in GAPO syndrome: A descriptive study with a new ANTXR1 variant & insights on teeth eruption","volume":"36","author":"Mostafa","year":"2024","journal-title":"Saudi Dent J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.1111\/ajd.12937","article-title":"Telogen hair loss and androgenetic-like alopecia in GAPO syndrome","volume":"60","author":"Ahmed","year":"2019","journal-title":"Australas. J. Dermatol."},{"key":"ref_56","first-page":"1057","article-title":"Novel mutation of RUNX2 gene in a patient with cleidocranial dysplasia","volume":"8","author":"Guo","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e11328","DOI":"10.1097\/MD.0000000000011328","article-title":"Identification of a novel mutation of RUNX2 in a family with supernumerary teeth and craniofacial dysplasia by whole-exome sequencing: A case report and literature review","volume":"97","author":"Ma","year":"2018","journal-title":"Medicine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1080\/15513815.2019.1710792","article-title":"Molecular Genetics of Cleidocranial Dysplasia","volume":"40","author":"Motaei","year":"2021","journal-title":"Fetal Pediatr. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"bcr2015210514","DOI":"10.1136\/bcr-2015-210514","article-title":"Cleidocranial dysplasia syndrome (CCD) with an unusual finding in a young patient","volume":"2015","author":"Singhal","year":"2015","journal-title":"BMJ Case Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"248","DOI":"10.4041\/kjod.2013.43.5.248","article-title":"Orthodontic and surgical management of cleidocranial dysplasia","volume":"43","author":"Park","year":"2013","journal-title":"Korean J. Orthod."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1093\/hmg\/5.Supplement_1.1391","article-title":"Treacher Collins syndrome","volume":"5","author":"Dixon","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4165","DOI":"10.4103\/jfmpc.jfmpc_851_24","article-title":"Treacher Collins syndrome: A comprehensive review on clinical features, diagnosis, and management","volume":"13","author":"Nassar","year":"2024","journal-title":"J. Family Med. Prim. Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/gim.2015.29","article-title":"Treacher Collins syndrome: A clinical and molecular study based on a large series of patients","volume":"18","author":"Vincent","year":"2016","journal-title":"Genet Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/ajmg.a.61147","article-title":"Autosomal recessive Treacher Collins syndrome due to POLR1C mutations: Report of a new family and review of the literature","volume":"179","author":"Ghesh","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41439-021-00168-4","article-title":"Identification of three novel TCOF1 mutations in patients with Treacher Collins Syndrome","volume":"8","year":"2021","journal-title":"Hum. Genome Var."},{"key":"ref_66","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2024). Treacher Collins Syndrome. GeneReviews [Internet], University of Washington. 2004 Jul 20 [updated 2024 Jun 20]."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.tripleo.2005.07.016","article-title":"Prevalence of dental anomalies, ectopic eruption and associated oral malformations in subjects with Treacher Collins syndrome","volume":"101","author":"Costa","year":"2006","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/cge.14243","article-title":"A systematic review on Treacher Collins syndrome: Correlation between molecular genetic findings and clinical severity","volume":"103","author":"Ulhaq","year":"2023","journal-title":"Clin. Genet."},{"key":"ref_69","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2005). COL1A1\/2 Osteogenesis Imperfecta. GeneReviews\u00ae [Internet], University of Washington. 2005 Jan 28 [updated 2024 Mar 14]."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/humu.9430","article-title":"Mutation analysis of COL1A1 and COL1A2 in patients diagnosed with osteogenesis imperfecta type I\u2013IV","volume":"27","author":"Pollitt","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zhytnik, L., Maasalu, K., Pashenko, A., Khmyzov, S., Reimann, E., Prans, E., K\u00f5ks, S., and M\u00e4rtson, A. (2019). COL1A1\/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00722"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1007\/s00198-018-4663-x","article-title":"Osteogenesis imperfecta and the teeth, eyes, and ears-a study of non-skeletal phenotypes in adults","volume":"29","author":"Hald","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/S0140-6736(04)16051-0","article-title":"Osteogenesis imperfecta","volume":"363","author":"Rauch","year":"2004","journal-title":"Lancet"},{"key":"ref_74","first-page":"489","article-title":"Dentinogenesis imperfecta associated with osteogenesis imperfecta","volume":"9","author":"Biria","year":"2012","journal-title":"Dent. Res. J."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Futagawa, N., Hasegawa, K., Miyahara, H., Tanaka, H., and Tsukahara, H. (2024). Trabecular bone scores in children with osteogenesis imperfecta respond differently to bisphosphonate treatment depending on disease severity. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1500023"},{"key":"ref_76","first-page":"42","article-title":"Syndromes associated with dental agenesis","volume":"68","author":"Sinigaglia","year":"2019","journal-title":"Minerva Stomatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jds.2018.04.003","article-title":"Symmetry of dental agenesis in Down Syndrome children","volume":"14","author":"Gallo","year":"2019","journal-title":"J. Dent. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/eos.12282","article-title":"Prevalence and patterns of permanent tooth agenesis in individuals with Down syndrome: A meta-analysis","volume":"124","author":"Palaska","year":"2016","journal-title":"Eur. J. Oral. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1111\/scd.13042","article-title":"Patterns of tooth agenesis in individuals with Down syndrome: A secondary analysis using the Tooth Agenesis Code","volume":"44","author":"Wijk","year":"2024","journal-title":"Spec. Care Dent."},{"key":"ref_80","unstructured":"Micheelis, W., and Schiffner, U. (2006). Vierte Deutsche Mundgesundheitsstudie (DMS IV), Deutscher \u00c4rzte-Verlag."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s00784-024-05846-5","article-title":"Orthodontic findings in adults with Trisomy 21","volume":"28","author":"Wriedt","year":"2024","journal-title":"Clin. Oral. Investig."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1590\/S0103-64402007000400014","article-title":"Dental anomalies in patients with Down syndrome","volume":"18","author":"Dotto","year":"2007","journal-title":"Braz. Dent. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00056-023-00479-x","article-title":"Prevalence and local causes for retention of primary teeth and the associated delayed permanent tooth eruption","volume":"85","author":"Henklein","year":"2024","journal-title":"J. Orofac. Orthop."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/2\/147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:35:44Z","timestamp":1759919744000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/2\/147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,24]]},"references-count":83,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["genes16020147"],"URL":"https:\/\/doi.org\/10.3390\/genes16020147","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,24]]}}}