Risk Factors for Tooth Eruption Diseases

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

Interventions

DIAGNOSTIC_TEST

PTH1R gene analysis

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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  lead OTHER

Principal Investigators

• Cristina Grippaudo · Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

5 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-08

Primary Completion

2029-06-08

Completion

2030-12-31