The Etiology of Eruption Disorders—Further Evidence of a “Genetic Paradigm”

doi:10.1053/j.sodo.2010.05.003

Seminars in Orthodontics

Volume 16, Issue 3, September 2010, Pages 180-185

https://doi.org/10.1053/j.sodo.2010.05.003 Get rights and content

The clinical spectrum of tooth-eruption disorders includes both syndromic and nonsyndromic problems ranging from delayed eruption to a complete failure of eruption. A defect in the differential apposition/resorption mechanism in alveolar bone can cause conditions, such as tooth ankylosis, primary failure of eruption (PFE), failure of eruption caused by inadequate arch length, and canine impaction. As our knowledge of the molecular events underlying normal tooth eruption has increased, so too has our understanding of clinical eruption disorders. The recent finding that one gene, parathyroid hormone receptor 1 (PTH1R), is causative for familial cases of PFE suggests that other disturbances in tooth eruption may have a genetic etiology. In this report, we evaluated the current terminology (ie, ankylosis, PFE, secondary retention) used to describe nonsyndromic eruption disorders, in light of this genetic discovery. We observed that some patients previously diagnosed with ankylosis were subsequently found to have alterations in the PTH1R gene, indicating the initial misdiagnosis of ankylosis and the necessary reclassification of PFE. We further investigated the relationship of the PTH1R gene, by using a network pathway analysis, to determine its connectivity to previously identified genes that are critical to normal tooth eruption. We found that PTH1R acts in a pathway with genes, such as parathyroid hormone related peptide (PTHrP), that have been shown to be important in bone remodeling, hence eruption, in a rat model. Thus, recent advances in our understanding of normal and abnormal tooth eruption should allow us in the future to develop a clinical nomenclature system that is determined more by the molecular genetic cause of the eruption failures versus the clinical appearance of the various eruption disorders.

Section snippets

Diagnosis of Eruption Problems

The PTH1R gene is not likely responsible for all eruption disorders, but given recent research, it is reasonable to suspect a genetic etiology for eruption disturbances that do not involve a physical obstruction, such as mechanical failure of eruption or lateral tongue pressure. Viewing eruption disorders from a genetic perspective not only shifts the focus to the biological basis of eruption but also provides the foundation for a standardized clinical diagnosis and unified terminology. Instead

Phenotypic Variation of Eruption Failure

Previous findings in our laboratory have noted the high degree of variability in the clinical presentation of PFE.9, 19 Specifically, our phenotypic evaluation of eruption failure in a large cohort revealed that there are two distinguishable types of PFE that may be related to the timing of onset. The first (type I) is marked by a progressive open bite from the anterior to the posterior of the dental arches. For type I, we speculate that the eruption defect, which we now know is genetically

The Biological Basis of Tooth Eruption

The identification of a causative gene in human eruption failure warrants that we consider the biological basis of normal tooth eruption carefully. Much of our understanding of the cellular and molecular events surrounding tooth eruption has improved tremendously during the past two decades.² Specifically, the role of the dental follicle has emerged as a central mediator of tooth eruption20, 21, 22 and has since been shown to provide the environment and chemoattractants for monocytes to

Network Pathway Analysis of PTH1R

To further investigate the link between the PTH1R gene and the molecular basis of tooth eruption, we generated a simple network (Fig 2) using Ingenuity Pathways Analysis (Ingenuity Systems; http://www.ingenuity.com). This network recapitulates the expected link between PTH1R and PTHrP (also parathyroid-like hormone), which is secreted in the stellate reticulum and responsible for the induction of CSF1 and RANKL. We reason that this provides significant evidence of the link between PTH1R, PFE,

Conclusions

The diagnostic distinction among isolated ankylosis, secondary retention, and PFE is important in the context of whether teeth distal to the more commonly unerupted first molar are normal or abnormal. If the determination is made that PFE is the culprit, determined by a familial inheritance or positive identification of a mutation in PTH1R (and likely additional genes in the not-so-distant future), then affected teeth would be abnormal and unresponsive to orthodontic treatment. However, if it

Acknowledgments

All work originated from the University of North Carolina at Chapel Hill and the Southwest Foundation for Biomedical Research. We gratefully acknowledge the support of the families and dentists whose participation and or contribution supported this manuscript. We also acknowledge the assistance of Drs William Proffit and James Ackerman in the preparation and Richard Youngblood in the editing of the manuscript.

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Development of dentition: From initiation to occlusion and related diseases
2022, Journal of Oral Biosciences
Citation Excerpt :
Primary failure of eruption (PFE) is also represented by its infraocclusion because of the failure of supraosseous eruption and vertical growth of alveolar bone, while affected teeth still maintain the periodontal ligament [45,46]. Interestingly, the function of the dental follicle in activating osteoclasts is not affected in PFE patients; therefore, the eruption path is superior to the dentition [47]. The genetic etiology of PFE is relatively well studied, and mutations in PTHR1 are known to cause this situation in humans [48].
The development of dentition begins in the embryonic oral cavity and progresses in the branchial arches and alveolar bone. Continuous cellular and molecular crosstalk occurs during crown formation, after which the tooth germ begins to migrate apically through the alveolar process into the oral cavity. It eventually comes in contact with its antagonist in the contralateral jaw to establish functional occlusion. Any defect in either step can result in delayed tooth development, the spectrum of which varies from a congenitally missing tooth to an impacted tooth (infraocclusion) with an eruption problem, both of which can impair oral function.
Congenitally missing teeth or eruption problems may result from genetic mutations. Several different mutations have been identified, each causing a distinct phenotype. Thus, it is imperative that medical providers understand the fundamentals of these genetic principles that govern such dental diseases.
In this review, we focus on several diseases, including congenitally missing teeth and tooth eruption problems. We review these diseases with aspect to their association with a particular syndrome, as well as independently in a non-syndromic capacity. We also review previously identified genetic mutations and discuss the possible mechanisms that cause individual phenotypes by analyzing previous investigations. We also discuss future prospects of how genetic diagnosis and precision medicine could impact the clinical environment in the field of dentistry.
Present study has been carried out in accordance with The Code of Ethics of the World Medical Association and approved by Institutional Review Board of Osaka University Graduate School of Dentistry.
Idiopathic failure of eruption: Diagnosis and management dilemma
2022, Advances in Oral and Maxillofacial Surgery
Primary failure of eruption (PFE) is a rare disease defined as incomplete tooth eruption despite the presence of a clear eruption pathway with no association to any syndromic disease. Usually diagnosed by pedodontists or orthodontists in early age, this diagnosis may be a challenge in adult patients.
This condition should be proposed as a differential diagnosis in adult patients with multiple dental impactions without systemic or syndromic problems, which is suggestive of a PFE not diagnosed in an early age or any another idiopathic eruption failure.
No orthodontic management could be provided in these cases, the management dilemma should take under consideration prosthetic possibilities, associated or not to prior surgical procedures.
We present a case with multiple impactions despite a clear eruption path way. Diagnosis built up was managed by clinical, radiological and biological investigations. Management required multidisciplinary reasoning. Subsequent prosthetic planning using a removable prosthesis revealed the need for surgical intervention. This case highlights diagnosis built up and the conservative treatment options to minimize the risk of iatrogenic damage and unnecessary treatment.
Pixel gray measurement for the diagnosis of dental ankylosis in cone beam computed tomography images
2021, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
The aim of this study was to investigate dental ankylosis in unerupted or partially erupted teeth by using cone beam computed tomography (CBCT) to quantify pixel intensity.
In total, 157 CBCT images from individuals with a total of 206 unerupted or partially erupted teeth with suspected ankylosis were evaluated. CBCT images were analyzed for the presence of ankylosis by 2 oral radiologists by quantifying mean pixel intensities (analysis 1) and variations in pixel intensities (analysis 2) in normal and ankylosed regions. The association between ankylosis and demographic and tooth-related factors was also examined.
Ankylosis was diagnosed in 57 teeth (27.7%). The diagnosis was established with all 3 multiplanar reconstruction views in 22 of these teeth (38.6%). In analysis 1, a higher pixel intensity was observed in areas with ankylosis compared with normal periodontal ligament (PDL) density as a result of bone deposition in this region, which is characteristic of ankylosis (P < .001). In analysis 2, reductions in pixel intensity were greater in the PDL areas than in the ankylosed areas. Ankylosis was significantly associated with the anterior teeth, the maxillary arch, single-rooted teeth, and impacted teeth (P ≤ .026).
Our results suggest that CBCT measurement of pixel intensity may be useful for the diagnosis of ankylosis.
Prevalence and dimensions of sella turcica bridging in Japanese female orthodontic patients
2017, Orthodontic Waves
Citation Excerpt :
A high prevalence of sella turcica bridging in congenital maxillofacial and dental anomalies has been suggested to reflect a certain genetic background and to be established in the fetal and early postnatal stages [42,43]. Failure of tooth eruption is thought to be caused by local environmental factors, such as deciduous tooth retention, dental crowding, and dental cysts, but also by genetic factors [52,53]. A recent study indicated that mutations in genes involved in tooth eruption are causative factors for the failure of tooth eruption [52,53].
The purposes of this study were to examine the prevalence of sella turcica bridging; to evaluate age-related differences in sella turcica dimensions and the prevalence of sella turcica bridging; and to clarify the associations of sella turcica dimensions and bridging with maxillofacial skeletal patterns and dental anomalies, such as tooth agenesis and impaction, in Japanese female orthodontic patients.
Lateral cephalograms and panoramic radiographs of 232 Japanese female orthodontic patients, aged 7–35 years, were examined. In addition to conventional cephalometric measurements, sella turcica diameter (STD), interclinoid distance (ICD), and degree of ICL calcification [(STD ICD) to STD ratio] were evaluated.
Sella turcica bridging occurred in 5.6% of all subjects. The mean values of STD, ICD, and degree of ICL calcification were 9.8 mm, 3.9 mm, and 60.0%, respectively. STD and degree of ICL calcification were larger and ICD was smaller in the ≥19-year-old group than in the 7–12-year-old group. No significant difference in sella turcica dimension or bridging prevalence was found in the anteroposterior or vertical skeletal pattern. Subjects with tooth impaction showed shorter ICDs and greater degrees of ICL calcification than did those without tooth impaction.
The prevalence of sella turcica bridging was 5.6%, and STD, ICD and degree of ICL calcification increased with age, in Japanese female orthodontic patients. In addition, sella turcica morphology and bridging were associated with tooth impaction, but not with maxillofacial skeletal deviations.
Twenty-year follow-up of a familial case of PTH1R-associated primary failure of tooth eruption
2017, American Journal of Orthodontics and Dentofacial Orthopedics
Nonsyndromic primary failure of eruption (PFE) is a rare autosomal dominant disorder of dental eruption with no obvious dental or soft tissue interference. The purposes of this study were to genetically and clinically characterize a family with many members affected by PFE and to describe the natural evolution of the disorder.
Three generations of a family with 18 members, 10 of them clinically affected by PFE, were evaluated periodically during 20 years of clinical follow-up. PFE was observed in varying degrees of severity in both sexes. Clinical presentation became more severe in adulthood. One patient had spontaneous reeruption of 2 posterior teeth. Cervical root resorptions were observed in 3 members. Genetic analysis showed a deleterious heterozygous mutation in intron 9 of the PTH1R gene (c.639-2A>G) and diagnosed an additional affected member.
The long-term follow-up of PFE cases in this family permitted the following observations: (1) the onset occurred from the preemergence to the postemergence phases, (2) PFE appeared to be closely related to ankylosis, (3) affected teeth maintained the eruptive potential even in adulthood, (4) the earlier the onset the more severe the open bite, and (5) cervical root resorptions occurred in 3 affected members.
Infraocclusion in the Primary and Permanent Dentition—A Narrative Review
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: This research was supported by the University of North Carolina at Chapel Hill Faculty Development Funds and NIH grants 1K23RR17442 and M01RR-00046.

: Statements and opinions expressed in the articles and communications herein are those of the author(s) and not necessarily those of the Editor(s) or Publisher, and the Editor(s) and Publisher disclaim any responsibility or liability for such material.

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The Etiology of Eruption Disorders—Further Evidence of a “Genetic Paradigm”

Section snippets

Diagnosis of Eruption Problems

Phenotypic Variation of Eruption Failure

The Biological Basis of Tooth Eruption

Network Pathway Analysis of PTH1R

Conclusions

Acknowledgments

Am J Orthod Dentofac Orthop

Am J Orthod

Am J Orthod Dentofac Orthop

Am J Orthod Dentofac Orthop

Am J Hum Genet

Am J Orthod Dentofac Orthop

Int J Oral Surg

J Dent

Am J Orthod

Oral Surg Oral Med Oral Pathol

Arch Oral Biol

Physiologic tooth movement: Eruption and shedding

Mechanisms of tooth eruption and orthodontic tooth movement

J Dent Res

Mechanism and control of tooth eruption: Overview and clinical implications

Orthod Craniofac Res

The palatally displaced canine as a dental anomaly of genetic origin

Angle Orthod

Palatal displacement of canine is genetic and related to congenital absence of teeth

J Dent Res

A controlled study of associated dental anomalies

Angle Orthod

Familial trends in palatal canines, anomalous lateral incisors, and related phenomena

Eur J Orthod