Abstract
Abstract
Introduction
Dental agenesis refers to the developmental absence of at least one permanent tooth and falls under the category of dental anomalies related to tooth number. While this condition is commonly observed in permanent dentition, it is relatively rare in primary dentition. Previous meta-analyses, conducted over a decade ago, have investigated its frequency and highlighted significant variability particularly when assessing different populations. This systematic review aims to answer the research question: “What is the worldwide frequency of agenesis of permanent teeth?”
Methods and analysis
A literature search was conducted on 15 April 2026, using the following databases will be searched for relevant publications: MEDLINE (via PubMed), Embase, Latin American and Caribbean Health Sciences Literature, Scopus and Web of Science. Cross-sectional studies that present data on the frequency of permanent tooth agenesis, as assessed through imaging exams, in individuals without known congenital abnormalities or syndromes will be included. There will be no restrictions on language or publication date. After defining the search strategy, two independent authors will conduct the study selection process in two phases, adhering to predefined eligibility criteria. The risk of bias will be assessed using the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data. The results will be summarised narratively, and a meta-analysis will be performed if feasible.
Ethics and dissemination
This systematic review does not require ethical approval. On completion, it will be published in a peer-reviewed academic journal and presented at a conference.
PROSPERO registration number
CRD42024617722.
Keywords: Systematic Review, Prevalence, Dentistry
STRENGTHS AND LIMITATIONS OF THIS STUDY.
This study was conducted based on a protocol developed in accordance with the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocol) guidelines and registered in PROSPERO.
No restrictions regarding language or publication period were applied to the search and eligibility criteria.
All stages of the review will be carried out by two independent reviewers.
Limitations include the absence of population-based studies, with only convenience samples included due to the outcome investigated.
Introduction
Dental agenesis is the developmental absence of at least one permanent tooth and is categorised as a dental anomaly related to tooth number.1 2 Different terms are used to describe this condition based on the number of teeth that are missing. Anodontia refers to the complete absence of teeth, hypodontia is the absence of up to six teeth, and oligodontia refers to the absence of six or more teeth, excluding the third molars.3
The aetiology of dental agenesis is linked to a complex interplay of genetic and environmental factors.4 Advances in genetic research have enabled the sequencing of genes involved in tooth morphogenesis, contributing to a clearer understanding of the mechanisms associated with agenesis.5 Currently, fifteen genes associated with this condition have been identified, accounting for 198 distinct mutations. Among them, the PAX9 gene expressed in the dental mesenchyme is responsible for initiating and activating tooth development, being involved in the early stages of odontogenesis.6 Studies have shown that in PAX9 related agenesis, individuals often present with severe oligodontia, with maxillary teeth being more frequently absent than mandibular teeth.7 Notably, tooth agenesis and cancer development share some molecular pathways. A previous study found that nearly all types of tumours were more prevalent in families with a history of tooth agenesis, highlighting the importance of early diagnosis and clinical investigation by dental professionals.8 9 Additionally, environmental factors can contribute to the occurrence of this condition, depending on their timing and the stage of dental formation during which the teeth are exposed to these factors.2
Dental agenesis is considered common in permanent dentition but rare in deciduous dentition.2 Previous meta-analyses have explored its prevalence and revealed significant variability, particularly when comparing different populations.2 3 The review by Polder et al3 reported a prevalence range from 0.3% to 36.5%, although it included only 33 studies published in English, which may have limited the scope of its findings. Another systematic review found a range between 0.1% and 17.8%, suggesting that discrepancies may stem from sample heterogeneity.2 The author also noted increased prevalence in European studies but emphasised the need for further research using more robust statistical methods to improve reliability. A recent cross-sectional study by Meistere et al8 among Latvian adolescents provides additional evidence. This study assessed 2692 patients aged 11 to 14 at the Institute of Stomatology of Riga Stradins University using panoramic radiographs. The reported prevalence of non-syndromic tooth agenesis was 9.3%. Furthermore, a statistically significant association was found between tooth agenesis and other dental anomalies.8
As in Meister et al8 recent studies have explored the association between tooth agenesis and other dental anomalies. Early diagnosis of this condition has proven essential for appropriate planning and screening for related anomalies, such as microdontia, altered crown morphology, impacted maxillary canines, enamel defects, taurodontism and distoangulation of the second premolar.2 10 11 These findings reinforce the importance of clinical surveillance in patients with tooth agenesis, enabling the early detection of developmental dental changes.10
The presence of dental agenesis requires specialised treatment focused on both functional and aesthetic rehabilitation. From a functional perspective, individuals with hypodontia often present with deep overbites and interdental spacing. Moreover, these patients tend to experience greater masticatory difficulties due to the reduced available occlusal area.5 12 Treatment typically involves a combination of orthodontic procedures for space management, dental implants, prostheses and restorative interventions. This process tends to be long, spanning from childhood into adulthood, and often entails high costs. Diagnosis is confirmed through imaging exams that detect the absence of the dental germ in the permanent dentition.5 This condition can negatively impact oral health-related quality of life and is a significant factor contributing to increased rates of bullying among children and adolescents.8 13 Therefore, raising awareness about the prevalence of tooth agenesis is essential for dental professionals and public health services. Given that treatment is typically lengthy and multidisciplinary, it requires continuous support for the patient and their family. Dentists must be well prepared to identify and manage these cases effectively.
As the most recent systematic reviews on the prevalence of tooth agenesis were conducted over ten years ago,2 3 14 and new studies have since been published that may offer less heterogeneous data, there is a clear rationale for updating the literature with findings collected during this period. Given the relevance of this anomaly in terms of diagnosis, treatment and the general knowledge required by dental professionals, such an update is justified. This will allow for a critical assessment of any changes—or lack thereof—in prevalence trends. Therefore, the aim of this study is to determine the overall frequency of tooth agenesis in permanent teeth, as well as to analyse the data by continent, sex and ethnicity.
Methods
Protocol and registration
This systematic review protocol was developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P), presented in online supplemental appendix 1.15 It has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number (CRD42024617722).
Patient and public involvement
This study does not involve patients. The data to be obtained are from published primary studies.
Research question
This systematic review addresses the question: “What is the worldwide frequency of agenesis of permanent teeth?” The research question is based on the CoCoPop (Concept, Context, Population) acronym (figure 1).16
Figure 1. Research question based on CoCoPop acronym.
Eligibility criteria
Inclusion criteria
The inclusion criteria for this study are cross-sectional studies that evaluated tooth agenesis in individuals with permanent teeth through imaging exams, including panoramic radiographs, periapical radiographs and tomography. Permanent tooth agenesis will be defined according to the diagnostic criteria adopted in each included study and confirmed by radiographic examination. Because the radiographic diagnosis of permanent tooth agenesis depends on the stage of dental development, the age of participants will be extracted from all included studies and considered during data synthesis. Third molars will be excluded from all analyses because their high prevalence of agenesis may substantially influence prevalence estimates and reduce comparability across studies. The sample may come from any context, such as hospitals, universities or private and public clinics. No restrictions will be applied based on language or publication period.
Exclusion criteria
The following studies will be excluded from this review:
Studies that do not specify the method used to identify agenesis.
Studies where the sample consists solely of specific groups, such as individuals with congenital abnormalities or syndromes.
Reviews, case-control studies, cohort studies, randomised clinical trials, non-randomised clinical trials, letters, editorials, books, conference abstracts, case reports, opinion articles, technical articles and guidelines.
Studies for which the full text is unavailable, even after three attempts to contact the corresponding authors over 3 weeks.
Outcomes
The primary outcome of this systematic review will be the frequency of permanent tooth agenesis at the individual level (ie, the proportion of affected individuals). Secondary outcomes will include the distribution of agenesis according to tooth type, dental arch and laterality (unilateral or bilateral involvement).
Information sources and search strategy
A preliminary search strategy was developed for MEDLINE (via PubMed) with an experienced health sciences librarian (figure 2). Another librarian will further complete the Peer Review of Electronic Search Strategies (PRESS checklist) to strengthen the search strategy.17 Later, this final MEDLINE (via PubMed) strategy will be adapted for other databases as follows: Embase, Latin American and Caribbean Health Sciences Literature (LILACS), via BVS (in Portuguese Biblioteca Virtual em Saúde), Scopus and Web of Science. Grey literature will be consulted through Google Scholar and ProQuest Dissertation & Thesis Global. As an additional search approach, the snowballing technique was applied: the reference lists of all included studies and relevant reviews were screened, and the lists of articles citing the included studies were also examined using the CitationChaser tool (Haddaway NR, Grainger MJ, Grey CT. CitationChaser (Internet), 2021). Google Scholar was also consulted to identify these citations as an additional tool. Experts in the field were consulted to identify any unpublished or ongoing studies; these experts were identified based on the first five authors listed in the Scopus database. The first author performed the search on 15 April 2026.
Figure 2. Preliminary search strategy for MEDLINE (via PubMed).
Study records
Data management
The files for each database will be imported into a reference management software (EndNote X9, Thompson Reuters, Philadelphia, PA) to organise the references and remove duplicate articles. Then, the selected studies will be imported into a reading platform Rayyan (Qatar Computing Research Institute, Data Analytics, Doha, Qatar) for screening.
Study selection
First of all, two authors (NS; SABP) will do a pilot test by screening references according to the eligibility criteria. After that, these two independent reviewer authors will select the articles in two phases. In Phase 1, they will evaluate the titles and abstracts based on the eligibility criteria. At the end of phase 1, the different reports for the same study will be grouped. In Phase 2, they will assess the full texts and select articles using the same criteria as in Phase 1, followed by cross-checking all the information. If disagreements arise at any stage, a third reviewer author (JMDO) will be consulted to resolve the issue before a final decision is made in both phases. If it is necessary to translate any abstract or full article into another language in order to verify eligibility, Google Translate will be used.
Data collection
Data extraction will be conducted using a combined researcher–artificial intelligence (AI) approach. The first author (N.S.) will perform manual data extraction. The second reviewer (S.A.B.P.) will perform AI-assisted extraction using ChatGPT (OpenAI, GPT-5.5). AI will be used only to identify and organise relevant information. It will not replace human assessment or decision-making. The prompts will be pilot-tested and refined before formal data extraction. The second reviewer will manually verify all AI-assisted results against the original full-text article before entering the validated data into a Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, Washington, USA). Disagreements will be resolved by discussion between the reviewers or, if necessary, by a third reviewer. The prompts used for AI-assisted extraction will be provided as Supplementary Material.
The following variables will be collected from the selected studies: author, year of publication, country, continent, study design, patient characteristics (sample size, age, sex and ethnicity) and clinical characteristics (number of missing teeth, affected jaws, type of malocclusion, pattern of missing teeth (unilateral or bilateral), frequency of dental agenesis, measurement method, and site of data collection). If relevant information is missing or unclear, the corresponding author of the respective study will be contacted up to three times over three consecutive weeks to obtain clarification or additional data.
Risk of bias in individual studies
Two independent reviewers (NS and SABP) will assess the risk of bias of the included studies using the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data.18 Prior to the formal assessment, a calibration exercise will be conducted to ensure consistency and agreement between reviewers regarding the interpretation of each checklist question. Any disagreements will be resolved through discussion and, when necessary, consultation with a third reviewer (JMDO).
The risk of bias assessment will be conducted at the question level, considering each of the nine items included in the JBI checklist individually. Specifically, the following questions will be evaluated: appropriateness of participant sampling methods; adequacy of the sample size; detailed description of study subjects and study setting; sufficient coverage of the identified sample in the data analysis; validity of the methods used for identification of the condition; standardisation and reliability of condition measurement across participants; appropriateness of the statistical analysis performed; and adequacy of the response rate and appropriate management of low response rates.
Each domain will be rated as ‘yes’, ‘no’, ‘unclear’, or ‘not applicable’, according to JBI guidance. For transparency and visual presentation, domain-level ‘traffic light’ plots and summary figures will be generated using the robvis (Risk-Of-Bias VISualization) application. As recommended by JBI guidance, no overall numerical score or summary classification will be assigned to the included studies. Instead, the results of the critical appraisal will be interpreted narratively and descriptively at the question level. The frequency and distribution of responses across the included studies will be summarised to identify the most common methodological strengths and limitations within the body of evidence. Particular attention will be given to domains considered more relevant to prevalence studies, such as sampling strategy, adequacy of sample size, validity of condition measurement, and appropriateness of statistical analyses.
Data synthesis
The findings of the included studies will be described narratively and summarised in tables presenting their main methodological and clinical characteristics. If feasible, a global distribution map will also be developed to illustrate the prevalence of dental agenesis according to countries or continents.
Where appropriate, quantitative synthesis will be carried out through meta-analysis of prevalence estimates and subgroup analyses using R Statistics software (R Foundation for Statistical Computing, Vienna, Austria). Considering the anticipated methodological and clinical variability among studies, random-effects models will be adopted. To improve the statistical handling of proportion data and reduce the impact of extreme prevalence values, prevalence estimates will be transformed using the Freeman–Tukey double arcsine approach prior to pooling. The pooled estimates and their respective 95% CIs will then be back-transformed to facilitate interpretation.
When a sufficient number of studies is available, meta-regression analyses will be conducted to investigate the potential influence of study-level characteristics on prevalence estimates. Potential moderators may include geographic region, sex distribution, ethnic background, diagnostic methods, sample source, sampling strategy, sample size and other methodological aspects reported in the included studies.
Heterogeneity assessment
Statistical heterogeneity will be evaluated through visual inspection of CI overlap in forest plots, in addition to the χ², Cochran’s Q statistic and the I² statistic.19 The I² statistic will be used to estimate the proportion of variability attributable to between-study differences rather than random error. Due to the expected heterogeneity across populations and study designs, random-effects models will be applied in all meta-analyses.
Subgroup analyses
Provided that sufficient data are available, predefined subgroup analyses will be performed according to continent, sex, ethnicities, different types of dental agenesis, diagnostic methods, sample source and sampling strategies. Separate pooled analyses will be conducted for these subgroups in order to explore possible sources of heterogeneity and variations in prevalence estimates.
Different forms of dental agenesis will be categorised according to the criteria adopted in the original studies, including hypodontia, oligodontia and anodontia, whenever applicable. Additional subgroup analyses based on methodological characteristics may also be considered if relevant.
Sensitivity analyses
Sensitivity analyses will be performed by excluding studies considered to have a high risk of bias to evaluate the stability and robustness of the pooled prevalence estimates.
Assessment of reporting bias
To minimise the possibility of publication bias, a comprehensive search strategy including grey literature sources will be performed. In addition, information regarding funding sources and potential conflicts of interest reported by the authors of the included studies will be examined. If at least ten studies are included in a meta-analysis, reporting bias will be investigated through visual inspection of funnel plots and, where appropriate, by applying Egger’s regression test.
Unit of analysis issues
Studies reporting outcomes at the patient level and those reporting outcomes at the tooth level will be analysed separately to avoid conceptual and statistical inconsistency. In studies where the tooth is considered the unit of analysis, each tooth will be evaluated individually, and these data will be synthesised in distinct meta-analyses according to the specific unit of analysis adopted in each study.
Confidence in cumulative evidence
As there is currently no specific guidance from the GRADE Working Group for systematic reviews of prevalence studies, and because the “Requirements for claiming the use of GRADE” discourage adaptations of the framework, the certainty of evidence will not be formally assessed.
Discussion
This study aims to determine the worldwide frequency of dental agenesis in permanent teeth through a systematic review, using a rigorous methodology that is widely considered the gold standard for scientific evidence. While previous studies have explored this topic, they were conducted over a decade ago and had notable methodological limitations, such as temporal restrictions in their search strategies,2 3 14 underscoring the need for an updated review.
To ensure comprehensive and reliable results, searches will be conducted across five databases, supplemented by grey literature and manual searches of reference lists from the included articles, with no restrictions on time or language. This approach will help ensure the retrieval of all relevant data on the topic. Pairs of blinded reviewers will carry out the study selection and data extraction processes to maintain the quality and reliability of the data for analysis.
A notable limitation of this review is that it will include only studies with convenience samples, as data on this condition is not typically collected from population-based samples.
The expected results are of significant importance for both private clinical practice and public health. By providing detailed epidemiological data, this study will help dentists better understand the prevalence of dental agenesis in the population and identify the most affected groups.
Dental agenesis negatively impacts patients’ quality of life due to aesthetic concerns,13 prolonged treatments, and the need for an interdisciplinary approach involving multiple dental specialties. Therefore, it is crucial for healthcare professionals and systems to be aware of its prevalence. This awareness will enable them to provide appropriate support and treatment, ultimately improving the management of the condition.
Ethics and dissemination
This systematic review does not require ethical approval. On completion, it will be published in a peer-reviewed academic journal and presented at a conference. This review protocol was registered on the PROSPERO platform.
Strengths and limitations of this study
This study aims to determine the worldwide frequency of dental agenesis in permanent teeth through a systematic review, using a rigorous methodology that is widely considered the gold standard for scientific evidence. While previous studies have explored this topic, they were conducted over a decade ago and had notable methodological limitations, such as temporal restrictions in their search strategies,2 3 14 underscoring the need for an updated review. The expected results are of significant importance for both private clinical practice and public health. By providing detailed epidemiological data, this study will help dentists better understand the prevalence of dental agenesis in the population and identify the most affected groups. Limitation: A notable limitation of this review is that it will include only studies with convenience samples, as data on this condition is not typically collected from population-based samples.
Supplementary material
Acknowledgements
The authors thank the librarians, MSc. Karyn Munyk Lehmkuhl (Federal University of Santa Catarina, Brazil, E-mail: karyn.lehmkuhl@ufsc.br) and Camilla Belo Tavares Ferreira (Brazilian National Cancer Institute, INCA, Brazil, E-mail: camila.ferreira@inca.gov.br) for their support in developing the search strategy.
Footnotes
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Prepublication history for this paper is available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2026-120244).
Data availability free text: Data will be analysed during the systematic review and meta-analysis, including extracted data and statistical code, will be available from the corresponding author on reasonable request.
Patient consent for publication: Not applicable.
Ethics approval: Not applicable.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Data availability statement
Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.
References
- 1.Gomes RR, da Fonseca JAC, Paula LM, et al. Prevalence of hypodontia in orthodontic patients in Brasilia, Brazil. Eur J Orthod. 2010;32:302–6. doi: 10.1093/ejo/cjp107. [DOI] [PubMed] [Google Scholar]
- 2.Khalaf K, Miskelly J, Voge E, et al. Prevalence of hypodontia and associated factors: a systematic review and meta-analysis. J Orthod. 2014;41:299–316. doi: 10.1179/1465313314Y.0000000116. [DOI] [PubMed] [Google Scholar]
- 3.Polder BJ, Van’t Hof MA, Van der Linden FPGM, et al. A meta-analysis of the prevalence of dental agenesis of permanent teeth. Community Dent Oral Epidemiol. 2004;32:217–26. doi: 10.1111/j.1600-0528.2004.00158.x. [DOI] [PubMed] [Google Scholar]
- 4.Intarak N, Tongchairati K, Termteerapornpimol K, et al. Tooth agenesis patterns and variants in PAX9: A systematic review. Jpn Dent Sci Rev. 2023;59:129–37. doi: 10.1016/j.jdsr.2023.04.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Al-Ani AH, Antoun JS, Thomson WM, et al. Hypodontia: An Update on Its Etiology, Classification, and Clinical Management. Biomed Res Int. 2017;2017:9378325. doi: 10.1155/2017/9378325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lei R, Qiu X, Han Y, et al. Identification and functional study of a novel variant of PAX9 causing tooth agenesis. Oral Dis. 2024;30:5175–82. doi: 10.1111/odi.14937. [DOI] [PubMed] [Google Scholar]
- 7.Chu K-Y, Wang Y-L, Chen J-T, et al. PAX9 mutations and genetic synergism in familial tooth agenesis. Ann N Y Acad Sci. 2023;1524:87–96. doi: 10.1111/nyas.14988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Meistere D, Kronina L, Karkle A, et al. Non-syndromic tooth agenesis in Latvian adolescent dental patients: a retrospective study with relevant literature review. Eur Arch Paediatr Dent. 2024;25:427–32. doi: 10.1007/s40368-024-00901-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Gu M, Yu X, Fan L, et al. Genetic Variants in miRNAs Are Associated With Risk of Non-syndromic Tooth Agenesis. Front Physiol. 2020;11:1052. doi: 10.3389/fphys.2020.01052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.de Aguiar PCS, Mesquita CM, Lerner FE, et al. Association between agenesis of permanent teeth and other dental anomalies in nonsyndromic patients: Systematic review. Arch Oral Biol. 2025;173:106223. doi: 10.1016/j.archoralbio.2025.106223. [DOI] [PubMed] [Google Scholar]
- 11.Fernandes EC, Santos PB. Association between molar-incisor hypomineralisation and dental anomalies. Int J Paediatr Dent. 2025;35:414–21. doi: 10.1111/ipd.13252. [DOI] [PubMed] [Google Scholar]
- 12.Silva Rodrigues A, Santos Freire J, Inácio Melandes da Silva G, et al. Does dental agenesis have an impact on OHRQoL of children, adolescents and young adults? A systematic review. Acta Odontol Scand. 2018;76:621–7. doi: 10.1080/00016357.2018.1482421. [DOI] [PubMed] [Google Scholar]
- 13.Elsherif N, Rodriguez J, Ahmed F. Prevalence and management of patients with hypodontia: A cross-sectional study. J Orthod. 2022;49:332–7. doi: 10.1177/14653125211065457. [DOI] [PubMed] [Google Scholar]
- 14.Rakhshan V, Rakhshan H. Meta-analysis of congenitally missing teeth in the permanent dentition: Prevalence, variations across ethnicities, regions and time. Int Orthod. 2015;13:261–73. doi: 10.1016/j.ortho.2015.06.008. [DOI] [PubMed] [Google Scholar]
- 15.Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Luca Canto G, Porporatti A, Souza BD M, et al. Revisões Sistemáticas Da Literatura: Guia Prático. Brazil Publishing; 2020. [Google Scholar]
- 17.McGowan J, Sampson M, Salzwedel DM, et al. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol. 2016;75:40–6. doi: 10.1016/j.jclinepi.2016.01.021. [DOI] [PubMed] [Google Scholar]
- 18.Moola S, Munn Z, Sears K, et al. Conducting systematic reviews of association (etiology): The Joanna Briggs Institute’s approach. Int J Evid Based Healthc. 2015;13:163–9. doi: 10.1097/XEB.0000000000000064. [DOI] [PubMed] [Google Scholar]
- 19.Deeks JJ, Higgins JP, Altman DG, et al. In: Cochrane Handbook for Systematic Reviews of Interventions version 6.4. Higgins JPT, Thomas J, Chandler J, et al., editors. 2023. Chapter 10: analysing data and undertaking meta‐analyses.www.training.cochrane.org/handbook Available. [Google Scholar]