Abstract
BackgroundPrimary failure of eruption (PFE) is a hereditary condition, and linkage with variants in the PTH1R gene has been demonstrated in many cases. The clinical severity and expression of PFE is variable, and the genotype–phenotype correlation remains elusive. Further, the similarity between some eruption disorders that are not associated with PTH1R alterations is striking. To better understand the genotype–phenotype correlation, we examined the relationship between the eruption phenotype and PTH1R genotype in 44 patients with suspected PFE and 27 unaffected relatives. Sanger sequencing was employed to analyze carefully selected PFE patients. Potential pathogenicity of variants was evaluated against multiple genetic databases for function prediction and frequency information.ResultsMutational analysis of the PTH1R coding sequence revealed 14 different variants in 38 individuals (30 patients and 8 first-degree relatives), 9 exonic and 5 intronic. Their pathogenicity has been reported and compared with the number and severity of clinical signs. In 72.7% of patients with pathogenic variants, five clinical and radiographic criteria have been found: involvement of posterior teeth, involvement of the distal teeth to the most mesial affected, supracrestal presentation, altered vertical growth of the alveolar process and posterior open-bite. In cases with mixed dentition (3), the deciduous molars of the affected quadrant were infraoccluded.DiscussionThe probability of an affected patient having a PTH1R variant is greater when five specific clinical characteristics are present. The likelihood of an eruption defect in the absence of specific clinical characteristics is rarely associated with a PTH1R mutation.ConclusionsWe report here that systematic clinical and radiographic observation using a diagnostic rubric is highly valuable in confirming PFE and offers a reliable alternative for accurate diagnosis.
Highlights
Primary failure of eruption (PFE) is a hereditary condition, and linkage with variants in the parathyroid hormone 1 receptor gene (PTH1R) gene has been demonstrated in many cases
We report here that systematic clinical and radiographic observation using a diagnostic rubric is highly valuable in confirming PFE and offers a reliable alternative for accurate diagnosis
Eruption disorders are ideally classified based on their etiology; those secondary to obstruction, or those with genetic underpinnings (e.g., primary failure of eruption (PFE); cleidocranial dysplasia, Hunter’s disease and osteopetrosis) should be considered [6]
Summary
Primary failure of eruption (PFE) is a hereditary condition, and linkage with variants in the PTH1R gene has been demonstrated in many cases. To better understand the genotype–phenotype correlation, we examined the rela‐ tionship between the eruption phenotype and PTH1R genotype in 44 patients with suspected PFE and 27 unaffected relatives. Eruption disorders are ideally classified based on their etiology; those secondary to obstruction (cysts, ankyloses, lateral tongue pressure, impaction, etc.), or those with genetic underpinnings (e.g., primary failure of eruption (PFE); cleidocranial dysplasia, Hunter’s disease and osteopetrosis) should be considered [6]. Among the more common diagnostic distinctions, mechanical failure of eruption (MFE), ankylosis and primary failure of eruption (PFE) are examples of nonsyndromic eruption disorders, but with vastly different clinical implications. In case of an early diagnosis of a first molar’s ankylosis, the therapy consists in the extraction of the ankylosed tooth and probably the second molar will drift mesially and will erupt [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
