Genetic Determinants of Primary Failure of Eruption: A Comprehensive Review of PTH1R Variants

TL;DR

This paper reviews how mutations in the PTH1R gene cause a dental disorder called Primary Failure of Eruption, highlighting the importance of early diagnosis to avoid future dental complications.

Contribution

The paper provides a comprehensive analysis of PTH1R gene variants linked to PFE, emphasizing genotype-phenotype correlations and diagnostic implications.

Findings

Over 50 PTH1R variants have been identified in individuals with PFE.

Non-syndromic PFE is closely associated with heterozygous PTH1R variants.

Early diagnosis of PFE can prevent invasive dental interventions later in life.

Abstract

Primary Failure of Eruption (PFE) is a disorder characterized by aberrant tooth eruption, in which one or more teeth fail to follow the physiological eruptive pathway and remain partially or completely embedded within the bone or soft tissues. Although the etiopathogenesis of PFE is not yet fully elucidated, several contributing factors have been identified, including genetic alterations, hormonal disturbances, and systemic conditions. An expanding body of evidence points to the centrality of genetic determinants in the etiopathogenesis of PFE, supporting its occurrence in both syndromic contexts and non-syndromic presentations. Non-syndromic forms are closely related to heterozygous variants in the Parathyroid Hormone 1 Receptor (PTH1R) gene, located on chromosome 3p21, which encodes a receptor essential for the regulation of bone and dental growth and development. In most cases, pathogenic variants result in a non-functional receptor. To date, a substantial number 50 PTH1R variants have been documented in individuals exhibiting a phenotype consistent with PFE, underscoring the central involvement of this gene in the disorder’s molecular basis. Advances in understanding the genetic contribution to PFE emphasize the need for early diagnosis, as timely identification of the condition can prevent secondary dental complications and reduce reliance in adulthood on invasive orthodontic or surgical interventions, including extractions, orthognathic surgery, and implant-supported rehabilitation. This review aims to provide a comprehensive analysis of the spectrum of PTH1R variants implicated in PFE, examining genotype–phenotype correlations and their implications for diagnostic strategies and clinical management.

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