Risk Factors for Tooth Eruption Diseases

NCT07587567 | Not Yet Recruiting

• 1 other identifier: 27111-1
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

Failure of eruption of primary and/or permanent teeth is a rare condition caused by four possible causes. The first is ankylosis of the tooth roots, which, in the absence, even partial, of the alveolar ligament, join the surrounding bone. The second possible cause is failure of eruption due to mechanical impediment, in the presence of a cyst or lack of resorption of the bone overlying the developing tooth, or due to severe lack of space or an abnormal inclination of the tooth's eruption path. The third cause, called Primary Failure of Eruption (PFE), is genetic in nature due to insufficient production of the factors that determine tooth eruption. In this case, molars are the most affected teeth, and pathogenic variants of the PTH1R gene are often observed. The fourth possibility is delayed tooth eruption. In cases of ankylosis and PFE, orthodontic treatments to help recover the teeth in the arch may fail. This interventional study, comprising a retrospective cohort, aims to evaluate the clinical signs of dental eruption disorders to identify criteria to facilitate clinical diagnosis. Furthermore, in cases where PFE is suspected, diagnostic testing for the PTH1R gene will be performed. The study will be conducted at the Fondazione Policlinico Universitario "A. Gemelli" IRCCS in Rome and will enroll 50 consecutive patients with dental eruption disorders of deciduous and/or permanent molars. The primary outcome will be to strengthen the differential diagnostic hypothesis. The study will also examine the phenotype/genotype correlation in patients tested for PTH1R gene variants. The characteristics of the sample will be compared with those of the sample enrolled in the previous study (C.E. UCSC ID 565-11/2015), which will be examined retrospectively. Extending the analysis to the patient cohort enrolled since 2015 is particularly valuable given the rarity of the diseases under study and the resulting small number of cases available for research. The study results will provide new data on pathogenic variants of PTH1R and on the phenotype/genotype correlation of the various diseases characterized by tooth eruption disorder. They will also help identify more sustainable and effective clinical strategies.

Conditions

Tooth Eruption Disorder

Keywords

primary failure of dental eruption; Dental ankylosis; mechanical failure of dental eruption; PTH1R gene

Outcome Measures

Primary Outcomes (1)

• Evaluation of delayed tooth eruption

  Differential diagnosis between ankylosis, MFE, PFE and delayed tooth eruption based on the presence and frequency of clinical signs and PTH1R gene variants.

  60 months

Study Arms (1)

Patients with eruption disorders

OTHER

Patients with eruption disorders of deciduous and/or permanent molars

Diagnostic Test: PTH1R gene analysis

Interventions

PTH1R gene analysis DIAGNOSTIC_TEST

Diagnostic records will be reviewed and clinical signs related to the eruption defect will be identified and classified. DNA samples will be collected using three cytobrushes (Cooper Surgical, Trumbull, CT, USA) and extracted with the QIAamp DNA mini kit (part number 51304, Qiagen). Amplification and nucleotide sequencing of the intronic/exonic regions of the PTH1R gene (NM\_000316.3) will be performed as described in Grippaudo et al. (2021). All sequences will be aligned to the reference genome (GRCh38/hg38), and the frequency of variants in the general population will be verified against the Genome Aggregation Database (GnomAD) (https://gnomad.broadinstitute.org/) and the Single Nucleotide Polymorphism Database (dbSNP) (https://www.ncbi.nlm.nih.gov/snp/). The potential pathogenicity of the identified variants will be searched in the NCBI ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/). The data will be collected using a password-protected Excel file.

Patients with eruption disorders

Eligibility Criteria

• Age: 5 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Partial or complete failure of one or more deciduous and/or permanent molar teeth to erupt
• Diagnostic records (medical history, orthopantomography, clinical photographs)
• Age between 5 and 80 years
• Ability to understand and sign consent forms from patients, if adults, or their parents/guardians

You may not qualify if:

• Malformative syndromes and/or systemic diseases
• Lack of diagnostic records
• Failure of eruption due to traumatic causes

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Related Publications (19)

• Roulias P, Kalantzis N, Doukaki D, Pachiou A, Karamesinis K, Damanakis G, Gizani S, Tsolakis AI. Teeth Eruption Disorders: A Critical Review. Children (Basel). 2022 May 24;9(6):771. doi: 10.3390/children9060771.

  PMID: 35740708 BACKGROUND

• Suri L, Gagari E, Vastardis H. Delayed tooth eruption: pathogenesis, diagnosis, and treatment. A literature review. Am J Orthod Dentofacial Orthop. 2004 Oct;126(4):432-45. doi: 10.1016/j.ajodo.2003.10.031.

  PMID: 15470346 BACKGROUND

• Raghoebar GM, Jansen HW, Jongebloed WL, Boering G, Vissink A. Secondary retention of permanent molars: an assessment of ankylosis by scanning electron and light microscopy. Br J Oral Maxillofac Surg. 1992 Feb;30(1):50-5. doi: 10.1016/0266-4356(92)90137-8.

  PMID: 1550806 BACKGROUND

• Raghoebar GM, Boering G, Jansen HW, Vissink A. Secondary retention of permanent molars: a histologic study. J Oral Pathol Med. 1989 Sep;18(8):427-31. doi: 10.1111/j.1600-0714.1989.tb01338.x.

  PMID: 2691646 BACKGROUND

• Bertl MH, Weinberger T, Schwarz K, Gruber R, Crismani AG. Resonance frequency analysis: a new diagnostic tool for dental ankylosis. Eur J Oral Sci. 2012 Jun;120(3):255-8. doi: 10.1111/j.1600-0722.2012.00959.x. Epub 2012 Apr 21.

  PMID: 22607343 BACKGROUND

• Mubeen S, Seehra J. Failure of eruption of first permanent molar teeth: a diagnostic challenge. J Orthod. 2018 Jun;45(2):129-134. doi: 10.1080/14653125.2018.1462902. Epub 2018 Apr 16.

  PMID: 29659339 BACKGROUND

• Raghoebar GM, Boering G, Vissink A. Clinical, radiographic and histological characteristics of secondary retention of permanent molars. J Dent. 1991 Jun;19(3):164-70. doi: 10.1016/0300-5712(91)90007-l.

  PMID: 1939817 BACKGROUND

• Wu Y, Yuan X, Perez KC, Hyman S, Wang L, Pellegrini G, Salmon B, Bellido T, Helms JA. Aberrantly elevated Wnt signaling is responsible for cementum overgrowth and dental ankylosis. Bone. 2019 May;122:176-183. doi: 10.1016/j.bone.2018.10.023. Epub 2018 Oct 25.

  PMID: 30408613 BACKGROUND

• Islam ST, Kurashige Y, Minowa E, Yoshida K, Paudel D, Uehara O, Okada Y, Bolortsetseg D, Sakakibara S, Abiko Y, Saitoh M. Analysis of the cells isolated from epithelial cell rests of Malassez through single-cell limiting dilution. Sci Rep. 2022 Jan 10;12(1):382. doi: 10.1038/s41598-021-04091-0.

  PMID: 35013397 BACKGROUND

• Dogramaci E, Rossi-Fedele G. Infraposition or infraocclusion- Is it time to rename? Dent Traumatol. 2021 Dec;37(6):813-814. doi: 10.1111/edt.12711. Epub 2021 Sep 19.

  PMID: 34538004 BACKGROUND

• Grippaudo C, D'Apolito I, Cafiero C, Re A, Chiurazzi P, Frazier-Bowers SA. Validating clinical characteristic of primary failure of eruption (PFE) associated with PTH1R variants. Prog Orthod. 2021 Dec 13;22(1):43. doi: 10.1186/s40510-021-00387-z.

  PMID: 34897565 BACKGROUND

• Frazier-Bowers SA, Koehler KE, Ackerman JL, Proffit WR. Primary failure of eruption: further characterization of a rare eruption disorder. Am J Orthod Dentofacial Orthop. 2007 May;131(5):578.e1-11. doi: 10.1016/j.ajodo.2006.09.038.

  PMID: 17482073 BACKGROUND

• Ahmad S, Bister D, Cobourne MT. The clinical features and aetiological basis of primary eruption failure. Eur J Orthod. 2006 Dec;28(6):535-40. doi: 10.1093/ejo/cjl033. Epub 2006 Oct 13.

  PMID: 17041084 BACKGROUND

• Frazier-Bowers SA, Simmons D, Wright JT, Proffit WR, Ackerman JL. Primary failure of eruption and PTH1R: the importance of a genetic diagnosis for orthodontic treatment planning. Am J Orthod Dentofacial Orthop. 2010 Feb;137(2):160.e1-7; discussion 160-1. doi: 10.1016/j.ajodo.2009.10.019.

  PMID: 20152661 BACKGROUND

• Stellzig-Eisenhauer A, Decker E, Meyer-Marcotty P, Rau C, Fiebig BS, Kress W, Saar K, Ruschendorf F, Hubner N, Grimm T, Witt E, Weber BH. Primary failure of eruption (PFE)--clinical and molecular genetics analysis. J Orofac Orthop. 2010 Jan;71(1):6-16. doi: 10.1007/s00056-010-0908-9. Epub 2010 Feb 5. English, German.

  PMID: 20135246 BACKGROUND

• Nagata M, Ono N, Ono W. Mesenchymal Progenitor Regulation of Tooth Eruption: A View from PTHrP. J Dent Res. 2020 Feb;99(2):133-142. doi: 10.1177/0022034519882692. Epub 2019 Oct 17.

  PMID: 31623502 BACKGROUND

• Richman JM. Shedding new light on the mysteries of tooth eruption. Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):353-355. doi: 10.1073/pnas.1819412116. Epub 2019 Jan 2. No abstract available.

  PMID: 30602459 BACKGROUND

• Siotou K, Kouskouki MP, Christopoulou I, Tsolakis AI, Tsolakis IA. Frequency and Local Etiological Factors of Impaction of Permanent Teeth among 1400 Patients in a Greek Population. Dent J (Basel). 2022 Aug 11;10(8):150. doi: 10.3390/dj10080150.

  PMID: 36005248 BACKGROUND

• Wise GE, King GJ. Mechanisms of tooth eruption and orthodontic tooth movement. J Dent Res. 2008 May;87(5):414-34. doi: 10.1177/154405910808700509.

  PMID: 18434571 BACKGROUND

MeSH Terms

Conditions

Tooth Ankylosis

Condition Hierarchy (Ancestors)

Tooth Diseases; Stomatognathic Diseases

Study Officials

• Cristina Grippaudo

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cristina Grippaudo, Prof

CONTACT

+393334121137; cristina.grippaudo@unicatt.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2026
• First Posted: May 14, 2026
• Study Start (Estimated): June 8, 2026
• Primary Completion (Estimated): June 8, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 14, 2026

Record last verified: 2026-05