Skip to main content
Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Investigating a potential association between agenesis of the third molars and variations in dental crown dimensions

  • Gloria Guht,

    Roles Investigation, Methodology, Writing – original draft

    Affiliation Department of Orthodontics, Medical Faculty, University Hospital Bonn, Bonn, Germany

  • Christian Kirschneck,

    Roles Conceptualization, Funding acquisition, Resources, Writing – review & editing

    Affiliation Department of Orthodontics, Medical Faculty, University Hospital Bonn, Bonn, Germany

  • Nikolaos Daratsianos,

    Roles Data curation, Software, Supervision, Writing – review & editing

    Affiliation Department of Orthodontics, Medical Faculty, University Hospital Bonn, Bonn, Germany

  • Cristiano Miranda de Araujo,

    Roles Methodology, Software, Visualization, Writing – review & editing

    Affiliations School of Dentistry, Medical Faculty, University of Tuiuti of Paraná, Curitiba, Brazil, University of the Joinville Region, Joinville, Santa Catarina, Brazil

  • Natanael Henrique Ribeiro Mattos,

    Roles Software, Validation, Writing – review & editing

    Affiliation School of Dentistry, Medical Faculty, University of Tuiuti of Paraná, Curitiba, Brazil

  • Flares Baratto-Filho,

    Roles Conceptualization, Methodology, Software, Supervision, Writing – review & editing

    Affiliations School of Dentistry, Medical Faculty, University of Tuiuti of Paraná, Curitiba, Brazil, University of the Joinville Region, Joinville, Santa Catarina, Brazil

  • Peter Proff,

    Roles Data curation, Funding acquisition, Project administration, Writing – review & editing

    Affiliation Department of Orthodontics, University of Regensburg, Regensburg, Germany

  • Diulia Pereira Bubna,

    Roles Data curation, Writing – review & editing

    Affiliation School of Dentistry, Medical Faculty, University of Tuiuti of Paraná, Curitiba, Brazil

  • Svenja Beisel-Memmert,

    Roles Data curation, Project administration, Writing – review & editing, Conceptualization

    Affiliations Department of Orthodontics, Medical Faculty, University Hospital Bonn, Bonn, Germany, Department of Orthodontics, Goethe University Frankfurt, Carolinum, Frankfurt am Main, Germany

  • Erika Calvano Küchler

    Roles Conceptualization, Formal analysis, Project administration, Writing – review & editing

    erika.kuchler@ukbonn.de

    Affiliation Department of Orthodontics, Medical Faculty, University Hospital Bonn, Bonn, Germany

Abstract

The aim of this study was to investigate the association between third molar agenesis and mesiodistal crown dimensions in individuals from Germany. The sample consisted of 314 (156 males and 158 females) orthodontic patients, divided into two groups: one group with individuals presenting at least one congenitally missing third molar and a control group with individuals having a full complement of 32 teeth. The mesiodistal crown width of each fully erupted permanent tooth was measured at its maximum dimension. The t-test was used to compare mesiodistal width between groups, with additional analyses according to gender and dental arch. A chi-square test evaluated the distribution of third molar agenesis among genders, and odds ratios (OR) with 95% confidence intervals (CI95%) were calculated. Pearson correlation assessed the relationship between the number of missing third molars and mesiodistal crown size. A total of 89 patients with third molar agenesis and 225 controls were included. Forty-three males and 46 females presented agenesis; with no significant association between gender and third molar agenesis (p = 0.760; OR = 1.08; 95% CI = 0.66–1.73). Mesiodistal dimensions were significantly different between males and females (p < 0.05). Patients with third molar agenesis exhibited a significant reduction (p < 0.05) in mesiodistal size across all teeth, most notably in second molars and maxillary lateral incisors. In males, all teeth in the agenesis group showed smaller dimensions compared to controls, with differences ranging from −0.43 to −0.15, the largest observed in the second maxillary molars (−0.43). In females, 18 of 28 teeth showed significant reductions, ranging from −0.42 to 0.00, with the largest difference in the left second mandibular molar (−0.42). The correlation between the number of missing third molar and mesiodistal size showed some negative moderate correlations, especially for lower canines (left r = −0.459, and right r = −0.534). In conclusion, third molar agenesis is associated with reduced mesiodistal crown dimensions in individuals from Germany, with this effect being more pronounced in males than in females.

Introduction

Tooth agenesis is defined as the congenital absence of one or multiple teeth. It may occur in the primary or in the permanent dentition. Studies have shown that considering the global population the prevalence in the permanent dentition (6.4%) is higher than in the primary dentition (0.1%−0.2%) [1,2]. These studies often exclude the third molars, also called wisdom teeth. Including third molars the average prevalence of agenesis worldwide is 22.6%, with numbers varying greatly when limited to specific population groups [3]. After the third molars the second most common tooth to not be developed in the permanent dentition is the mandibular second premolar, followed by the lateral incisor of the maxilla and the second premolar of the maxilla [1]. The absence of up to six teeth is called hypodontia, while most of those affected are only missing one or two teeth (81.6%) [1]. The absence of more than six teeth (excluding third molars) is defined as oligodontia and the absence of the entire dentition as anodontia. Such a high prevalence, especially of the third molar, makes tooth agenesis one of the most common developmental dental anomalies. A meta-analysis showed that tooth agenesis is more likely to affect the female gender [1,4,5].

Among Europeans, 20–30% are congenitally missing at least one third molar [1,6]. Third molars are the last teeth to develop [7,8], and are the only teeth that develop completely after birth [9]. Furthermore, they are frequently affected by development alterations, for instance variation in tooth position/angulation, impaction and agenesis [7,10]. In general, dental anomalies including tooth agenesis are caused by an interplay of genetic, epigenetic and environmental factors during tooth development [1,11]. Recent studies have emphasized that specifically third molar agenesis is influenced by a strong genetic background [7,8,12]. Interestingly, genes involved in tooth agenesis have been also associated with reduced dental crown dimensions [13,14] suggesting that both traits share some genetic factors.

The association between tooth agenesis and dental crown dimensions has been investigated in a wide range of studies [1517], however these studies often exclude the third molars. In the past five decades, few studies were performed and they suggested that patients with third molar agenesis had smaller teeth (mesiodistal dimension) compared to patients with a full complement of teeth [4,10,1821]. Previous studies on the question were varied in their approach, with some focused only on specific teeth dimension, such as mandibular first molars [20] or in the non-metric analysis of maxillary lateral incisor [10,18]. However, the evidence connecting third molar agenesis and dental crown reduction is still weak due to the limited number of populations that have been previously investigated. Therefore, the aim of this study is to investigate the association between third molar agenesis and the mesiodistal crown dimensions of individuals from Germany.

Materials and methods

Sample

The sample consisted of 314 German orthodontic patients undergoing treatment at two universities located in Germany: The University of Regensburg and the University of Bonn. The local Ethics committees of University of Bonn (number: 2024–100-BO) and University of Regensburg (number: 19–1549–101) approved this study.

Patient records were screened and the data were collected from 20 May 2024 until 8 September 2025. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

The patients evaluated were between 12.5 and 41 years old and comprised 156 males and 158 females. The patients were divided into two groups: one group consisting of patients congenitally missing at least one third molar, and the other group consisting of the control group. They were identified through the assessment of Orthopantomograms (OPG`s) that were taken after the age of 12.5. For the control group only patients with a full complement of teeth were chosen (32 teeth). Only individuals of European descent and patients in whom the presence or absence of agenesis was undoubtedly detectable were included. Exclusion criteria included syndromic patients or patients with illnesses that influence the tooth size or formation and patients with other congenitally missing teeth.

The sample size calculation was based on the expected mean difference in dental size between groups. The mean difference and standard deviation were derived from the results observed in a previous study in a European population from Slovenia [15]. We assumed a mean difference of 0.3 mm among groups and a standard deviation of ± 0.8 based on the average results observed [15]. The sample size was determined for independent-group design with a continuous primary endpoint using a two-sided independent samples t-test. An established alpha of 5% and power of 80% were used in the calculation and a case-to-control ratio of 1:2. Sample size was calculated using the ClinCalc online statistical tool [22], based on the standard formulas for the comparison of two independent means as described by Rosner [23]. A minimum sample of 84 patients with third molar agenesis and 168 controls would be required.

Mesiodistal crown measurment

The software OnxyCeph3TM LAB (Image Instruments, Chemnitz, Germany) was used to measure the mesiodistal crown width of each permanent tooth using 3D virtual models. If more than one dental scan was available, a dental scan from the beginning of the treatment was chosen. The measurements and the analysis of the OPG’s were made by one calibrated and trained dentist to limit variability. To determine the initial training and calibration, the examiner measured ten randomly selected digital scans from patients undergoing treatment in Bonn. Each scan was measured twice, with a two-week interval between the measurements. Intra-examiner reliability was calculated using the intraclass correlation coefficient (ICC), yielding 0.9993 (95% CI).

The mesiodistal tooth width was measured at the maximum width of every fully erupted permanent tooth, represented by the distance between the mesial and distal interproximal contact points of each tooth. The followed procedure was based on a protocol from previous publications [13]. In case of a rotated tooth or when the adjacent tooth was missing the point where the contact point would normally be chosen. Teeth with class I, II or III restorations, shape anomalies, interproximal caries, enamel reduction, fractured teeth and teeth with prosthetic restorations were excluded from the measurements.

Statistical analysis

For the analysis of the data, GraphPad Prism software (Version 10.4.1) was used. The t-test was applied to determine whether the mesiodistal width differed significantly between the third molar agenesis group and the control group. Comparisons were also performed according to gender and dental arch (maxilla and mandible). The chi-square test was used to compare the distribution of third molar agenesis among groups, and odds ratios (OR) with 95% confidence intervals (CI 95%) were calculated. A Pearson correlation test was used to evaluate the strength and direction of the correlation between mesiodistal size and the number of missing third molars. For all statistical comparisons, an alpha level of 5% (p < 0.05) was adopted.

Results

A total of 314 (156 males and 158 females) patients were analyzed, 89 patients with agenesis of at least one third molar and 225 controls. Forty-three males and 46 females presented third molar agenesis. Gender was not associated with third molar agenesis (p = 0.760; OR = 1.08, CI95% = 0.66–1.73). The sample description is presented in the Table 1.

thumbnail
Table 1. Sample characteristics according to the groups.

https://doi.org/10.1371/journal.pone.0348605.t001

Mesiodistal dimensions were statistically significantly different between males and females (p < 0.05, data not shown).

Table 2 presents the results of the mesiodistal size comparison among the control group and the third molar agenesis group. Patients with at least one congenitally absent third molar have a statistically significant reduction (p < 0.05) in mesiodistal size for each tooth in comparison to the patients in the control group. The teeth with the greatest reduction are in descending order the left second mandibular molar (−0.37), the left second maxillary molar (−0.35), the right second mandibular molar (−0.34) followed by the right maxillary second molar as well as the right and left maxillary lateral incisors (−0.32).

thumbnail
Table 2. Mesiodistal size comparison between control and third molar agenesis groups.

https://doi.org/10.1371/journal.pone.0348605.t002

Once dental size presents sexual dimorphism, the analysis was also performed according to the gender, Table 2 presents the size comparison in males, and Table 3 represents the size comparison in females.

thumbnail
Table 3. Mesiodistal size comparison between control and third molar agenesis groups in males.

https://doi.org/10.1371/journal.pone.0348605.t003

In males, all teeth in the third molar agenesis group exhibited statistically significant smaller dimensions compared to the male control group, with differences ranging between −0.43 and −0.15. The biggest difference was observed in the right and left second maxillary molars (−0.43) (Table 2).

In the female third molar agenesis group only 18 out of the 28 measured teeth displayed statistically significantly different dimensions compared to the female control group with differences ranging between −0.42 and 0.00. The biggest difference was observed for the left second mandibular molar (−0.42).

The comparison of the tooth reduction in the case of an agenesis of at least one maxillary third molar is represented in the S1 Table and the comparison of the tooth reduction in the case of an agenesis of at least one mandibular third molar is represented in the S2 Table.

The number of missing third molars ranged from 1 to 4 and the mean was 2.04 ± 1.19. The correlation between the number of missing third molars (in the third molar agenesis group) and mesiodistal size are presented in the Table 4. Negative moderate correlations were observed, especially for lower canines (left r = −0.459, and right r = −0.534). The correlation data is presented in the Table 4.

thumbnail
Table 4. Mesiodistal size comparison between control and third molar agenesis groups in females.

https://doi.org/10.1371/journal.pone.0348605.t004

Discussion

Tooth agenesis is often associated with other developmental conditions, including craniofacial anomalies such as oral cleft, and other developmental dental anomalies such as microdontia/ peg shaped lateral incisors [24,25], and taurodontism [24] suggesting a shared underlying genetic basis. Other interesting relationship observed in cross-sectional studies are the association between tooth agenesis and mesiodistal tooth width reduction [11,1517]. However, these studies often excluded the third molars [11,15]. A study from Keene in 1964 [20] investigated 195 male naval recruits and evaluated mandibular first molars. The author observed a crown reduction in the mandibular right first molar. A study from Lavelle et al. in 1970 [21] evaluated 301 casts from British subjects and observed an association between third molar agenesis and crown‌‌ dimension reduction (Table 5).

thumbnail
Table 5. Correlation between number of missing third molars and dental size.

https://doi.org/10.1371/journal.pone.0348605.t005

Celikoglu et al. in 2011 [18] and Sujon in 2011 [10] investigated developmental dental anomalies associated with third molar agenesis in Turkish and Bangladesh patients (respectively). Both studies observed that these patients had higher prevalence of maxillary lateral incisor microdontia. Although microdontia was evaluated as a non-metric dental trait, these results support the hypothesis that third molar agenesis is associated with the reduction of crown size of the remaining teeth.

Thus, although some evidence suggests an association between third molar agenesis and dental crown size exist, this topic has been poorly explored in the literature and only few studies had focused in this type of teeth in the past 5 decades [10,1821]. Therefore, the current study aimed to investigate if third molar agenesis is associated with crown width reduction in a German population in order to add new evidence in the literature. Our study confirmed previous findings and raises some new interesting concepts.

Besides the association between third molar agenesis and dental crown reduction, another interesting result observed here was the differences between males and females. Dental crown size exhibits sexual dimorphism, with males having larger crown dimensions than females. This difference is most pronounced in canines and molars [26]. In our study, we observed that the mesiodistal reduction occurred in all teeth of males with third molar agenesis, but this trend was not observed in females, in which only 18 teeth presented statistically significant reduction in the third molar agenesis group. Similar results were previously reported, Brook et al. [11] compared the amount of difference between the female and male patients, discovering that the reduction in female patients was less than the reduction in the male patients with hypodontia (excluding third molars) [11]. They stated that the higher reduction for the males could be explained by the fact that men have larger teeth in general and therefore have a higher reduction as well [11]. However, in our sample, some teeth did not show any or only a small morphometric change in females with third molar agenesis, suggesting that, in females, the factors involved concomitantly in agenesis and dental size do not play a role in some teeth, such as maxillary central incisor.

In our study, different types of teeth presented different levels of reduction. Brook et al. (2009) [11] observed that the teeth with the greatest reduction were the mandibular central incisor and maxillary lateral incisor. Furthermore, Fekonja (2013) [15] discovered in her study, that the teeth with the highest reduction are maxillary lateral incisors, lower central incisor and the lower second molar. Although Brook et al. (2009) [11] and Fekonja (2013) [15] included the general agenesis of permanent teeth and excluded the third molars, their results present some similarities to ours, and we observed bigger difference in molars and maxillary lateral incisors. Both of them concluded, that this result could suggest, that these teeth are the most vulnerable to disturbances throughout their development [11,15]. Interestingly, maxillary lateral incisors are frequently affected by agenesis and morphological alterations such as peg-shaped, dens invaginatus, talon cusp, and root alteration such as root angulation [27].

Other interesting observation that is important to highlight is the correlation observed between the number of missing third molars and crown dimensions of each permanent tooth. Although the correlation strength ranged from low to moderate, we were able to note that in some tooth types this moderate negative correlation exists, suggesting that patients with multiple third molar agenesis have smaller crown dimension. A similar result was also reported by Keene (1964) [20], which described a reduction more pronounced in subjects with four missing teeth. Garn and Lewis (1970) [4] concluded in their study on the American population with hypodontia, that this reduction is higher in multiple agenesis than in single agenesis. These suggest that the number of congenitally missing teeth are correlated with the crown size.

One of the strengths of the current study design is that only patients older than 12.5 years old were included. Third molars are the last teeth to develop and to erupt with eruption times ranging between 17 and 24 years [7,8]. Therefore, the agenesis of third molars cannot be reliably detected on panoramic radiographs before the patient has reached the age of 12.5 years [2]. This is because in some patients, before the age of 12 the tooth has often not started to mineralize [2]. For this reason, all cases of third molar agenesis were confirmed in radiographs in which the patients were 12.5 or older; to avoid the inclusion of individuals with delayed third molar development.

To understand the factors involved in mesiodistal crown dimensions of permanent teeth of patients with third molar agenesis is important for the planning of an orthodontic treatment, because it determines the spatial requirements. This knowledge regarding crown dimension in patients with third molar agenesis is also important for forensic estimation of gender based on dental size. Recognizing the association between third molar agenesis and reduced crown dimensions is critical in forensic odontometrics because this systemic reduction in tooth size can mimic female dental patterns, potentially leading to the misclassification of male remains if sexually dimorphic standards are applied without adjusting for known dental developmental anomalies.

While the current findings establish an interesting association between third molar agenesis and reduced mesiodistal crown dimensions, further cross-sectional research involving diverse ethnic cohorts is necessary to determine if these odontometric reductions are universal or to‌‌ population-specific.

Conclusions

Third molar agenesis is associated with mesiodistal crown dimensions of individuals from Germany and this difference is more pronounced in males than in females. The number of missing third molars might also be correlated with the degree of reduction in mesiodistal crown width of the remaining permanent teeth.

Supporting information

S1 Table. Mesiodistal size comparison between control and third molar agenesis groups in the agenesis of maxillary third molars.

https://doi.org/10.1371/journal.pone.0348605.s001

(DOCX)

S2 Table. Mesiodistal size comparison between control and third molar agenesis groups in the agenesis of mandibular third molars.

https://doi.org/10.1371/journal.pone.0348605.s002

(DOCX)

Acknowledgments

This work was supported by the Open Access Publication Fund of the University of Bonn

References

  1. 1. Khalaf K, Miskelly J, Voge E, Macfarlane TV. Prevalence of hypodontia and associated factors: a systematic review and meta-analysis. J Orthod. 2014;41(4):299–316. pmid:25404667
  2. 2. Scheiwiller M, Oeschger ES, Gkantidis N. Third molar agenesis in modern humans with and without agenesis of other teeth. PeerJ. 2020;8:e10367. pmid:33240669
  3. 3. Carter K, Worthington S. Morphologic and Demographic Predictors of Third Molar Agenesis: A Systematic Review and Meta-analysis. J Dent Res. 2015;94(7):886–94. pmid:25883107
  4. 4. Garn SM, Lewis AB. The gradient and the pattern of crown-size reduction in simple hypodontia. Angle Orthod. 1970;40(1):51–8. pmid:5262688
  5. 5. Mattheeuws N, Dermaut L, Martens G. Has hypodontia increased in Caucasians during the 20th century? A meta-analysis. Eur J Orthod. 2004;26(1):99–103. pmid:14994889
  6. 6. Paddenberg E, Silva-Souza AC, Blancato AB, Lepri CP, Proff P, Küchler EC, et al. Association between craniofacial patterns and third molar agenesis in orthodontic patients. J Orofac Orthop. 2024;85(Suppl 2):120–6. pmid:37378838
  7. 7. Herrmann S, Küchler EC, Reis CLB, Paddenberg E, Zbidat N, Mattos NHR, et al. Association of third molar agenesis and microdontia with genetic polymorphisms in vitamin-D-related genes. Ann Anat. 2022;244:151972. pmid:35738313
  8. 8. Trakinienė G, Andriuškevičiūtė I, Šalomskienė L, Vasiliauskas A, Trakinis T, Šidlauskas A. Genetic and environmental influences on third molar root mineralization. Arch Oral Biol. 2019;98:220–5. pmid:30508675
  9. 9. John J, Nambiar P, Mani SA, Mohamed NH, Ahmad NF, Murad NA. Third molar agenesis among children and youths from three major races of Malaysians. J Dent Sci. 2012;7(3):211–7.
  10. 10. Sujon MK, Alam MK, Rahman SA. Prevalence of Third Molar Agenesis: Associated Dental Anomalies in Non-Syndromic 5923 Patients. PLoS One. 2016;11(8):e0162070. pmid:27580050
  11. 11. Brook AH, Griffin RC, Smith RN, Townsend GC, Kaur G, Davis GR, et al. Tooth size patterns in patients with hypodontia and supernumerary teeth. Arch Oral Biol. 2009;54 Suppl 1:S63-70. pmid:18675390
  12. 12. Vukelic A, Cohen JA, Sullivan AP, Perry GH. Extending Genome-Wide Association Study Results to Test Classic Anthropological Hypotheses: Human Third Molar Agenesis and the “Probable Mutation Effect”. Hum Biol. 2017;89(2):157–69. pmid:29299963
  13. 13. Cunha AS, Dos Santos LV, Marañón-Vásquez GA, Kirschneck C, Gerber JT, Stuani MB, et al. Genetic variants in tooth agenesis-related genes might be also involved in tooth size variations. Clin Oral Investig. 2021;25(3):1307–18. pmid:32648061
  14. 14. Kirac D, Eraydin F, Avcilar T, Ulucan K, Özdemir F, Guney AI, et al. Effects of PAX9 and MSX1 gene variants to hypodontia, tooth size and the type of congenitally missing teeth. Cell Mol Biol (Noisy-le-grand). 2016;62(13):78–84. pmid:28040065
  15. 15. Fekonja A. Comparison of mesiodistal crown dimension and arch width in subjects with and without hypodontia. J Esthet Restor Dent. 2013;25(3):203–10. pmid:23773516
  16. 16. Higashihori N, Takada J-I, Katayanagi M, Takahashi Y, Moriyama K. Frequency of missing teeth and reduction of mesiodistal tooth width in Japanese patients with tooth agenesis. Prog Orthod. 2018;19(1):30. pmid:30123921
  17. 17. Kuabara MR, Madalena IR, Soares TB, Dos Anjos ID, Marañón-Vásquez GA, Brancher JA, et al. Dental agenesis is associated with mesiodistal dental dimensions: a study in a Brazilian population. CONJ. 2022;22(5):119–30.
  18. 18. Celikoglu M, Bayram M, Nur M. Patterns of third-molar agenesis and associated dental anomalies in an orthodontic population. Am J Orthod Dentofacial Orthop. 2011;140(6):856–60. pmid:22133951
  19. 19. Garn Sm, Lewis Ab, Kerewsky Rs. Third Molar Agenesis And Size Reduction Of The Remaining Teeth. Nature. 1963;200:488–9. pmid:14076752
  20. 20. Harris JK. Third molar agenesis, spacing and crowding of teeth, and tooth size in caries-resistant naval recruits. Am J Orthod. 1964;50(6):445–51.
  21. 21. Lavelle CL, Ashton EH, Flinn RM. Cusp pattern, tooth size and third molar agenesis in the human mandibular dentition. Arch Oral Biol. 1970;15(3):227–37. pmid:5268156
  22. 22. Kane SP. Sample Size Calculator. ClinCalc. https://clincalc.com/stats/samplesize.aspx 2024. 2026 March 31.
  23. 23. Rosner B. Fundamentals of biostatistics. 8th ed. Boston (MA): Cengage Learning. 2016.
  24. 24. de Aguiar PCS, Mesquita CM, Lerner FE, Borges LB, Rodrigues R, Vieira WA, et al. Association between agenesis of permanent teeth and other dental anomalies in nonsyndromic patients: Systematic review. Arch Oral Biol. 2025;173:106223. pmid:40086039
  25. 25. Küchler EC, Risso PA, Costa M de C, Modesto A, Vieira AR. Studies of dental anomalies in a large group of school children. Arch Oral Biol. 2008;53(10):941–6. pmid:18490001
  26. 26. Küchler EC, Kirschneck C, Marañón-Vásquez GA, Schroder ÂGD, Baratto-Filho F, Romano FL, et al. Mandibular and dental measurements for sex determination using machine learning. Sci Rep. 2024;14(1):9587. pmid:38671054
  27. 27. Küchler EC, de Oliveira Stroparo JL, Bitencourt Reis CL, Ullrich N, Olsson B, Scariot R, et al. Oral Cleft Related-Genes may be Involved in Root Curvature of Maxillary Lateral Incisors. Cleft Palate Craniofac J. 2024;61(2):177–83. pmid:35979589