Primary failure of eruption: occlusal and dentoalveolar characteristics in mixed and permanent dentition. A study with cone beam computed tomography

Background The main objective of this study was to describe the dentoalveolar and occlusal characteristics of subjects with primary failure of eruption (PFE) in cone beam computed tomography (CBCT) and compare them with a control group without the anomaly. Material and Methods This retrospective and comparative study evaluated CBCT images of 80 permanent molars divided into 2 groups of 40 molars each, which had or did not have PFE characteristics. Using CBCT a calibrated orthodontist performed 23 measurements related to the distances of the cusps to the occlusal, palatal and mandibular planes and measured the buccal-palatal and mesiodistal widths of the molar crowns and their root lengths. Independent Student’s t or Mann-Whitney U tests were used to compare occlusal and dentoalevolar characteristics between groups according to the normality of the data. P<0.05. Results Molars affected by PFE were smaller in coronal dimensions in the PFE compared to the non-PFE group (Buccal-palatal crown width 11.60±0.95mm vs. 12.21±1.09 mm; p<0.001; and mesiodistal crown width 10.81± 1.07 mm vs. 11.84±1.32mm, respectively; p<0.001). The distal and mesial root lengths were approximately 2 mm smaller in the PFE group (p<0 .001). The three-dimensional bony position was more convergent with respect to the palatal plane, i.e., the crown was more inclined palatally and distally in the PFE compared to the non-PFE group. Conclusions Patients with molars affected by PFE present smaller bucco-palatal, mesio-distal coronal widths and mesial and distal root lengths than those without PFE and in these teeth the crowns are more inclined palatally and distally in upper molars. These specific characteristics may be pathognomonic of PFE and should be considered by clinicians when evaluating or treating patients with this condition. Key words:Occlusal characteristics, primary failure of eruption, cone-beam CT.


Introduction
Primary failure of eruption (PFE) was described by Proffit and Vig (1981) as the malfunction of dental eruptive mechanisms with delay and absence of these processes in a non-ankylosed tooth (1). Under occlusion of the affected tooth, vertical alveolar atrophy, posterior open bites, impaction of neighboring posterior teeth and sometimes anterior teeth, as well as agenesis and/ or ankylosis of deciduous molars are the most common characteristics of PFE (2). PFE is preferably unilateral, rarely symmetrical, but can affect any or all of the posterior quadrants (2). PFE and ankylosis are considered to be closely related and have frequently been associated with skeletal class III malocclusions (3). PFE is an inherited disorder that may affect approximately 0.6% of the population (4)(5)(6). Mutations in parathyroid hormone receptor 1 (PTH1R) have been identified and confirmed to be responsible for this eruptive phenotypic expression (4)(5)(6). These phenotypes can be found in the deciduous dentition as well as permanent dentition (7)(8)(9). The severity of PFE is variable and therefore treatment should be individualized depending generally on the age of the patient (10). It has been observed that the affected PFE tooth does not respond to orthodontic forces and that a non-ankylosed PFE tooth can become an ankylosed tooth when forces are applied (3,11). In some cases, it is difficult to distinguish PFE from other eruption disorders such as ankylosis and this is key for developing an adequate treatment plan (2). In recent years, different types of treatment have been proposed for patients with this condition, ranging from dental restorations to surgical procedures such as osteotomies (12,13). The combination of a good clinical diagnosis and genetic analysis can provide a guideline to improve the management of these cases, help in treatment planning to avoid unnecessary therapies for the patient, as well as to detect other relatives potentially affected by PFE (4). Cone beam computer tomography (CBCT) is a diagnostic tool that allows a three-dimensional (3D) analysis of different eruptive alterations in the jaw (12). On reviewing the scientific literature to date, little is known about 3D dentoalveolar and occlusal characteristics of PFE according to CBCT. For this reason, the purpose of this study was to compare the dentoalveolar and occlusal characteristics obtained by CBCT study in subjects with PFE with those of a control group without the anomaly.

Material and Methods
This retrospective comparative study was approved by the Research Ethics Committee of the Universidad Científica del Sur, Lima, Peru (registration number 247-2021-POS8). Written informed consent was obtained from all participants and the parents of minors, and all data were fully anonymized prior to access by the investigators. For this study, CBCT images of 80 molars divided into 2 groups were evaluated: Group 1 was composed of 40 molars from 20 patients (8 females and 12 males aged 7 to 20 years) who presented PFE characteristics; and Group 2, or the control group, was composed of CBCT images of 40 molars belonging to 7 patients (3 females and 4 males aged 7 to 20 years) who did not present characteristics related to any eruptive anomaly. This sample selection and distribution was performed by 2 calibrated orthodontists with 10 years of experience. In case of discrepancy, the final concept was defined by consensus. The sample size for the study group was obtained using a formula to compare two means (root length of teeth with and without PFE), with the following parameters, 95% confidence interval, test power 80%, mean difference of 1.87 mm and ± of 2.11 (data obtained from a previous pilot test). The required sample size was 22 teeth for each group; however, 40 teeth with and without PFE per group were obtained and the sample was similar to previous studies. (14,15) Furthermore, since the prevalence of this condition is low, it was decided to obtain a multicenter sample and the CBCT images were obtained from imaging centers in Honduras, Colombia, Dominican Republic, Peru and Mexico. The characteristics of the sample are described in Table 1 and 2. The inclusion criteria consisted of: complete unimaxillary or bimaxillary CBCT of healthy, asymptomatic subjects of both sexes; no systemic disease; authorization and consent for the use of images in research; in permanent dentition; older than 12 years; under occlusion of at least one permanent molar or premolar; arrested intraosseous or supraosseous evolution associated with posterior open bite; absence of signs of eruptive potential; and having exceeded the average eruptive period of the population and teeth without signs of ankylosis. Exclusion criteria were: CBCT of syndromic individuals, or total or partial edentulism, with the presence of congenital and dental anomalies, obstruction of the eruptive pathway by the third molar, teeth with a history of dentoalveolar trauma, or CBCT of poor quality.   DICOM files were analyzed with Dolphin Imaging software version 11.9 (Dolphin Imaging and Management Solutions, Chatsworth, California 2017). 3D evaluation and description of the dentoalveolar and occlusal characteristics of patients with PFE in the upper and lower jaw were measured using 3D and multiplanar reconstructions. For the measurements of each tomography, the axial and sagittal planes were aligned with the anterior (ANS) and posterior (PNS) nasal spine. In this way, the palatal plane and the mid-sagittal plane were constructed. The occlusal plane was constructed by means of a line drawn along the occlusal edges of the posterior teeth on the volumetric reconstruction. In some cases, only the cusps of the first or second molar and the cusp of the canine were taken as reference. The lengths and angles evaluated are described in Table 3

Results
The comparisons of the variables evaluated are summarized in Table 4

Variables
-Distance in millimeters from the tip of the mesial and distal cusps of the tooth with PFE to the occlusal plane and to the palatal and mandibular planes, according to their location on the sagittal plane.
-Distance from the apices of the distal and mesial root of the PFE tooth to the occlusal, palatal, or mandibular plane on the sagittal plane.
-Presence or not of root dilaceration in the affected tooth with PFE, evaluated in the sagittal plane.
-Maximum mesodistal coronal width on axial slices, and palatal vestibule on coronal slices of the affected tooth with FPE, as described in the study by Tokavanich et al. (15) -Root length of the molar with FPE, taking the distance from the tip of the cusp to the mesial and distal root apices, on sagittal slices, as described in the article by Tokavanich et al. (15) -Angle between the longitudinal axis of the palatal root of the molar with PFE and the palatal plane on coronal slices, which classified its position as buccal, medial, or palatal. A point was marked at the apex of the palatal root and another at the palatal cusp, in this way a line was drawn and the external angle of the intersection of this line with the palatal plane was measured.
-Angle between the longitudinal axis of the palatal root of the molar with PFE and the palatal plane on sagittal slices. One point was located at the apex of the palatal root of the molar and another at the palatal cusp. A line was drawn through both points and the angle of intersection between this line and the palatal plane was measured.
-Angle between the longitudinal axis of the distal root of the molar with PFE and the mandibular plane. on sagittal slices.
-Angle between the longitudinal axis of the distal root of the lower molar with PFE and the mandibular plane on coronal slices to evaluate the vestibular or lingual inclination of these teeth compared to the control group. A point was taken at the apex of the distal root of the molar and another at the distal cusp and a line was drawn that intersected the mandibular plane on a coronal cut and the angle formed was measured.
-Length of the upper jaw, taking as reference points for this measurement the distance between a point on the anterior nasal spine and a point on the posterior nasal spine.   group compared to the PFE group with 12.21± 1.09mm vs. 11.60 ± 0.95 mm, respectively (P<0.001) and the mesiodistal crown width was 11.84 ± 1.32 mm vs. 10.81± of 1.07 mm, respectively (p<0.001). Moreover, the distal and mesial root lengths were approximately 2 mm smaller in the PFE group than the non-PFE group (p<0.001).
On the other hand, significant association was found between root dilaceration and the absence of PFE (62.50%) versus the presence of roots without dilaceration and the presence of PFE (79.20%) (P<0.001). These findings are summarized in Table 5. Finally, the binary logistic regression analysis to detect the occurrence of PFE according to the study covariates showed that the presence of root dilaceration could be a protective factor for presenting PFE (p=0.016) ( Table 6).

Discussion
PFE is a disorder that has also been investigated under a genetic approach. In the present study, we evaluated   some of the dentoalveolar and occlusal characteristics of a group of 40 teeth with PFE and compared these characteristics with a group of 40 teeth without PFE by CBCT imaging. Compared to normal teeth, teeth affected by PFE present special characteristics. While the significant differences found between groups in the distances to the occlusal plane and palatal or mandibular plane were predictable, the remaining measurements make the findings of the present study of clinical and imaging significant. Using the mesial and distal roots as references, the coronal dimensions (bucco-palatal and meso-distal width) and root length were smaller in the molars affected by PFE. Regarding their 3D osseous position, they were more convergent with respect to the palatal plane, that is, the crowns were more inclined towards the palatine and distal than those without PFE. However, this crown behavior is apparently exclusive of maxillary PFE molars, because it was not found in mandibular molars. This was confirmed by the angle formed between the axis and the mandibular plane, in which no significant differences were found with the control group. All the above characteristics could be defined as pathognomonic of PFE. These differences are important to achieve early diagnosis, and especially in the development of a differential diagnosis with ankylosed teeth. The differentiation between these two entities is difficult, but our imaging findings can shed light on correct identification. Although not comparable, these findings are consistent with the morphological abnormalities of the root and crown of molars with PFE observed in studies in mice by Tokavanich et al. (16), Cohen-Lévy and Cohen (17), Deffrennes and Cohen-Lévy (10), Pilz et al. (18), in which PFE was associated with tooth root anomalies and normal crown morphology. Likewise, Vedtofte et al. (19) reported that arrested eruption of molars was related to root and crown morphological abnormalities of the affected molar.    (17) and Standerwick (24) stated that root dilaceration is a consequence of decreased tooth movement. However, our study as well as others by Grippaudo et al. (14) and Pilz et al. (18) show that the percentage of molars with PFE without root dilaceration was higher than that of molars with PFE with root dilaceration. Therefore, our findings could contribute to clarifying the imaging diagnosis of PFE. Finally, this article concluded that the molars affected with PFE present smaller coronal dimensions (bucco-palatal and meso-distal width) and mesial and distal root lengths than those without PFE. Likewise, the crowns of teeth with PFE are more palatally and distally inclined in upper molars but this is not observed in lower molars. These features may be pathognomonic of PFE. Nonetheless, our study has some limitations such as the heterogeneity of the study group sample, which was composed of maxillary and mandibular first and second molars with PFE. Thus, the sample for each subdivision and location of PFE was small. More studies are needed to further clarify and elucidate these results.

Conclusions
Molars affected by PFE have smaller coronal dimensions (bucco-palatal and meso-distal width) and smaller mesial and distal root lengths than those without PFE. Likewise, in these teeth the crowns are more inclined palatally and distally in upper molars. These specific features may be pathognomonic of PFE and should be considered by clinicians when evaluating or treating patients with possible PFE.