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Clinicopathological and molecular insights into odontogenic tumors associated with syndromes: A comprehensive review

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/> <meta name="dc.publisher" content="Baishideng Publishing Group Inc." /> <meta name="dc.date" content="Dec 20, 2024" /> <meta name="dc.identifier" content="doi:10.5493/wjem.v14.i4.98005" /> <meta name="dc.creator" content="Lauren Frenzel Schuch" /> <meta name="dc.creator" content="Felipe Martins Silveira" /> <meta name="dc.creator" content="Vanesa Pereira-Prado" /> <meta name="dc.creator" content="Estefania Sicco" /> <meta name="dc.creator" content="Deepak Pandiar" /> <meta name="dc.creator" content="Mariana Villarroel-Dorrego" /> <meta name="dc.creator" content="Ronell Bologna-Molina" /> <meta name="citation_journal_title" content="World Journal of Experimental Medicine" /> <meta name="citation_authors" content="Lauren Frenzel Schuch, Felipe Martins Silveira, Vanesa Pereira-Prado, Estefania Sicco, Deepak Pandiar, Mariana Villarroel-Dorrego, Ronell Bologna-Molina" /> <meta name="citation_title" content="Clinicopathological and molecular insights into odontogenic tumors associated with syndromes: A comprehensive review" /> <meta name="citation_publication_date" content="Dec 20, 2024" /> <meta name="citation_volume" content="14" /> <meta name="citation_issue" content="4" /> <meta name="citation_doi" content="10.5493/wjem.v14.i4.98005" /> <meta name="citation_pdf_url" content="" /> <meta name="citation_fulltext_html_url" content="https://www.wjgnet.com/2220-315x/full/v14/i4/98005.htm" /> <title>Clinicopathological and molecular insights into odontogenic tumors associated with syndromes: A comprehensive review</title> <link href="/Content/css?v=rb26yubA8f-T2hXbl5_Lk0hga4CBdoXSmzfqDaG2x281" rel="stylesheet"/> <script src="/bundles/modernizr?v=wBEWDufH_8Md-Pbioxomt90vm6tJN2Pyy9u9zHtWsPo1"></script> <link href="/Content/articlecss?v=HHrD05uoMlO8zkyk1iKufz8f2RgAceE-CPykdo9T9YU1" rel="stylesheet"/> <script src="/bundles/jquery?v=FVs3ACwOLIVInrAl5sdzR2jrCDmVOWFbZMY6g6Q0ulE1"></script> </head> <body> <input id="sitename" name="sitename" type="hidden" value="2220-315x" /> 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<span> Citation of this article </span> </div> </div> <div class="sectioncontent cl" id="cimg5div" style="display:none;"> <span id="citation_html">Schuch LF, Silveira FM, Pereira-Prado V, Sicco E, Pandiar D, Villarroel-Dorrego M, Bologna-Molina R.&nbsp;Clinicopathological and molecular insights into odontogenic tumors associated with syndromes: A comprehensive review.&nbsp;<em>World J Exp Med</em>&nbsp;2024;&nbsp;14(4): 98005 [DOI: <a href='https://dx.doi.org/10.5493/wjem.v14.i4.98005' target='_blank'>10.5493/wjem.v14.i4.98005</a>]</span> </div> </div> <div class="left-collapse cl"> <div class="sectiontitle cl" onclick="ShowDetail('cimg6');"> <div class="sectionimg fl"> <img style="border:0;" alt="" id="cimg6" src="https://www.f6publishing.com/contents/images/collapsed_yes.gif" /> </div> <div class="sectiontext fl"> <span> Corresponding Author of This Article </span> </div> </div> <div class="sectioncontent cl" id="cimg6div" style="display:none;"> <span>Ronell Bologna-Molina, DDS, MSc, PhD, Professor, Molecular Pathology Area, Faculty of Dentistry, University of the Republic, Montevideo 11600, Uruguay. <email>ronellbologna@hotmail.com</email></span> </div> </div> <div class="left-collapse cl"> <div class="sectiontitle cl" onclick="ShowDetail('cimg10');"> <div class="sectionimg fl"> <img style="border:0;" alt="" id="cimg10" src="https://www.f6publishing.com/contents/images/collapsed_yes.gif" /> </div> <div class="sectiontext fl"> <span> Research Domain of This Article </span> </div> </div> <div class="sectioncontent cl" id="cimg10div" style="display:none;"> <span>Dentistry, Oral Surgery & Medicine</span> </div> </div> <div class="left-collapse cl"> <div class="sectiontitle cl" onclick="ShowDetail('cimg11');"> <div class="sectionimg fl"> <img style="border:0;" alt="" id="cimg11" src="https://www.f6publishing.com/contents/images/collapsed_yes.gif" /> </div> <div class="sectiontext fl"> <span> Article-Type of This Article </span> </div> </div> <div class="sectioncontent cl" id="cimg11div" style="display:none;"> <span>Minireviews</span> </div> </div> <div class="left-collapse cl"> <div class="sectiontitle cl" onclick="ShowDetail('cimg12');"> <div class="sectionimg fl"> <img style="border:0;" alt="" id="cimg12" src="https://www.f6publishing.com/contents/images/collapsed_yes.gif" /> </div> <div class="sectiontext fl"> <span> Open-Access Policy of This Article </span> </div> </div> <div class="sectioncontent cl" id="cimg12div" style="display:none;"> <span>This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. 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All rights reserved.</span> </div> <div id="dpjournal"> <span>World J Exp Med.&nbsp;</span><span>Dec 20, 2024;&nbsp;</span><span>14(4): 98005</span><br /> <span>Published online Dec 20, 2024.&nbsp;doi: <a href="http://dx.doi.org/10.5493/wjem.v14.i4.98005" target="_self">10.5493/wjem.v14.i4.98005</a></span> </div> <div id="dptitle"> Clinicopathological and molecular insights into odontogenic tumors associated with syndromes: A comprehensive review </div> <div id="dpauthors"> <a href="javascript:void(0);" id="thisauthor694079" class="author-name-link" data-f-name="Lauren Frenzel" data-l-name="Schuch" data-name="Lauren Frenzel Schuch" target="_self">Lauren Frenzel Schuch</a>, <a href="javascript:void(0);" id="thisauthor694080" class="author-name-link" data-f-name="Felipe Martins" data-l-name="Silveira" data-name="Felipe Martins Silveira" target="_self">Felipe Martins Silveira</a>, <a href="javascript:void(0);" id="thisauthor694081" class="author-name-link" data-f-name="Vanesa" data-l-name="Pereira-Prado" data-name="Vanesa Pereira-Prado" target="_self">Vanesa Pereira-Prado</a>, <a href="javascript:void(0);" id="thisauthor694082" class="author-name-link" data-f-name="Estefania" data-l-name="Sicco" data-name="Estefania Sicco" target="_self">Estefania Sicco</a>, <a href="javascript:void(0);" id="thisauthor694083" class="author-name-link" data-f-name="Deepak" data-l-name="Pandiar" data-name="Deepak Pandiar" target="_self">Deepak Pandiar</a>, <a href="javascript:void(0);" id="thisauthor694084" class="author-name-link" data-f-name="Mariana" data-l-name="Villarroel-Dorrego" data-name="Mariana Villarroel-Dorrego" target="_self">Mariana Villarroel-Dorrego</a>, <a href="javascript:void(0);" id="thisauthor694085" class="author-name-link" data-f-name="Ronell" data-l-name="Bologna-Molina" data-name="Ronell Bologna-Molina" target="_self">Ronell Bologna-Molina</a> </div> <div id="dpaff"> <div><b>Lauren Frenzel Schuch, Felipe Martins Silveira, Vanesa Pereira-Prado, Estefania Sicco, Ronell Bologna-Molina, </b>Department of Diagnosis in Pathology and Oral Medicine, Faculty of Dentistry, Universidad de la República, Montevideo 1600, Uruguay</div><div><b>Deepak Pandiar, </b>Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals Chennai, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Chennai 600077, Tamil Nādu, India</div><div><b>Mariana Villarroel-Dorrego, </b>Department of Oral Pathology, Oral Medicine, School of Dentistry, Universidad Central de Venezuela, Venezuela, Caracas 1051, Distrito Capital, Venezuela</div> </div> <div id="dporcid" style="display:;"> <b>ORCID number: </b><span>Lauren Frenzel Schuch (<a href='http://orcid.org/0000-0002-0993-936X' target='_blank'>0000-0002-0993-936X</a>); Felipe Martins Silveira (<a href='http://orcid.org/0000-0001-9834-5194' target='_blank'>0000-0001-9834-5194</a>); Vanesa Pereira-Prado (<a href='http://orcid.org/0000-0001-7747-6718' target='_blank'>0000-0001-7747-6718</a>); Estefania Sicco (<a href='http://orcid.org/0000-0003-1137-6866' target='_blank'>0000-0003-1137-6866</a>); Mariana Villarroel-Dorrego (<a href='http://orcid.org/0000-0002-0596-1527' target='_blank'>0000-0002-0596-1527</a>); Ronell Bologna-Molina (<a href='http://orcid.org/0000-0001-9755-4779' target='_blank'>0000-0001-9755-4779</a>).</span> </div> <div id="dpfn"> <div><b>Co-first authors</b>: Lauren Frenzel Schuch and Ronell Bologna-Molina.</div> <div><b>Author contributions</b>: Schuch LF and Bologna-Molina R designed and performed research, and wrote the paper; Silveira FM, Pereira-Prado V, Sicco E, and Pandiar D revised the article; Villarroel-Dorrego M contributed with the representative cases.</div> <div><b>Conflict-of-interest statement:</b> All the authors declare that they have no conflict of interest.</div><div><b>Open-Access:</b> This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: <a href="https://creativecommons.org/Licenses/by-nc/4.0/">https://creativecommons.org/Licenses/by-nc/4.0/</a></div><div><b>Corresponding author</b>: Ronell Bologna-Molina, DDS, MSc, PhD, Professor, Molecular Pathology Area, Faculty of Dentistry, University of the Republic, Montevideo 11600, Uruguay. <a href="mailto:ronellbologna@hotmail.com">ronellbologna@hotmail.com</a></div> <div><b>Received:</b> June 14, 2024<br /><b>Revised:</b> August 19, 2024<br /><b>Accepted:</b> August 26, 2024<br /><b>Published online:</b> December 20, 2024<br /><b>Processing time:</b> 138 Days and 10.6 Hours<br /></div> </div> <br /> </div> <!--Abstract--> <div id="article-abstract-container"> <div class="article-section-title-0"> <span>Abstract</span> </div> <div id="dpabstract"> <div><p>The association between genetic syndromes and odontogenic tumors encom<Hypen />passes several entities, reflecting the intricate interplay between genetic factors and the development of these lesions. The present study aimed to comprehen<Hypen />sively investigate the associations between genetic syndromes and odontogenic tumors. We delineated the diverse spectrum of syndromic connections, including key syndromes such as Gardner syndrome, Gorlin syndrome, Schimmelpenning syndrome, and others. Our findings underscore the clinical significance of re<Hypen />cognizing odontogenic tumors associated with genetic syndromes as diagnostic indicators for early intervention. We advocate for multidisciplinary collaboration among clinicians, geneticists, and researchers to deepen our understanding of the underlying mechanisms driving these syndromic associations. In light of this, our study contributes to the growing body of knowledge in dentistry and medical genetics, offering insights that may inform clinical practice and enhance patient care for individuals affected by genetic syndromes and odontogenic tumors.</p> </div> <div class="article-abstract-item" style="display:;"> <b>Key Words: </b><span><a href='https://www.f6publishing.com/ArticlesByKeywords?type=2&pageNumber=1&keyword=Genetic+syndrome' target='blank'>Genetic syndrome</a>; <a href='https://www.f6publishing.com/ArticlesByKeywords?type=2&pageNumber=1&keyword=Odontogenic+tumors' target='blank'>Odontogenic tumors</a>; <a href='https://www.f6publishing.com/ArticlesByKeywords?type=2&pageNumber=1&keyword=Head+and+neck+tumors' target='blank'>Head and neck tumors</a>; <a href='https://www.f6publishing.com/ArticlesByKeywords?type=2&pageNumber=1&keyword=Misdiagnosis' target='blank'>Misdia<Hypen />gnosis</a>; <a href='https://www.f6publishing.com/ArticlesByKeywords?type=2&pageNumber=1&keyword=Genetic+mutations' target='blank'>Genetic mutations</a></span> </div> <br /> <div class="article-abstract-item"> <span><p><b>Core Tip:</b> It is important for the health professional to know that some odontogenic tumors have a close relationship with some genetic syndromes. Knowledge of this relationship can help a correct diagnosis and comprehensive treatment of the patient. Thus, the aim of the present review was to comprehensively investigate the associations between genetic syndromes and odontogenic tumors.</p></span> </div> <div id="dpcitation" class="article-abstract-item rs_skip"> <hr /> <ul> <li> <b>Citation: </b>Schuch LF, Silveira FM, Pereira-Prado V, Sicco E, Pandiar D, Villarroel-Dorrego M, Bologna-Molina R.&nbsp;Clinicopathological and molecular insights into odontogenic tumors associated with syndromes: A comprehensive review.&nbsp;<i>World J Exp Med</i>&nbsp;2024;&nbsp;14(4): 98005 </li> <li> <b>URL: </b><a href="https://www.wjgnet.com/2220-315x/full/v14/i4/98005.htm" target="_self">https://www.wjgnet.com/2220-315x/full/v14/i4/98005.htm</a> </li> <li> <b>DOI: </b><a href="https://dx.doi.org/10.5493/wjem.v14.i4.98005" target="_self">https://dx.doi.org/10.5493/wjem.v14.i4.98005</a> </li> </ul> <hr/> </div> </div> </div> <!--Main article text--> <div id="article-main-container"> <div> <div id="sec11"><div id="sec11title" class="article-section-title-0">INTRODUCTION</div><p class="article-section-content" id="p11">Odontogenic tumors (OT) represent a heterogeneous group of lesions, ranging from non-neoplastic tissue malformations (<i>i.e</i>., hamartomas) to tumors with varying degrees of malignancy and clinical implications. Although considered uncom<Hypen />mon, they account for approximately 1% of all oral diagnoses[<a class="refcontent" href="#B1" data-jats-ref-type="bibr" data-jats-rid="B1">1</a>,<a class="refcontent" href="#B2" data-jats-ref-type="bibr" data-jats-rid="B2">2</a>]. This prevalence can vary according to geographic region, with higher incidence rates reported in countries located in Asia and Africa[<a class="refcontent" href="#B3" data-jats-ref-type="bibr" data-jats-rid="B3">3</a>,<a class="refcontent" href="#B4" data-jats-ref-type="bibr" data-jats-rid="B4">4</a>]. The origin of OTs is attributed to the proliferation of remnants of the soft and hard tissues that give rise to teeth; however, the exact pathogenesis of these tumors remains unknown[<a class="refcontent" href="#B5" data-jats-ref-type="bibr" data-jats-rid="B5">5</a>].</p><p class="article-section-content" id="p12">Some cases of OTs associated with syndromes have been observed[<a class="refcontent" href="#B6" data-jats-ref-type="bibr" data-jats-rid="B6">6</a>]. Although syndromes often do not directly relate to neoplastic development, their occurrence may indicate a relationship between genetic factors and the pathogenesis of OTs, thereby contributing to a more comprehensive understanding of these entities in the realm of oral pathology. Accordingly, the aim of the present review was to provide insights into the association or concurrent lesions of OT and genetic syndromes based on clinicopathological and molecular aspects.</p></div><div id="sec12"><div id="sec12title" class="article-section-title-0">GENETIC SYNDROMES AND ODONTOGENIC TUMORS</div><p class="article-section-content" id="p11">Hereditary aspects are associated with some head and neck tumors[<a class="refcontent" href="#B7" data-jats-ref-type="bibr" data-jats-rid="B7">7</a>]. OTs can manifest in association with various syndromes (Table <a class="refcontent" href="#T1" data-jats-ref-type="table" data-jats-rid="T1">1</a>), predisposing individuals to the development of multiple tumors concurrently[<a class="refcontent" href="#B8" data-jats-ref-type="bibr" data-jats-rid="B8">8</a><span>-</span><a class="refcontent" href="#B10" data-jats-ref-type="bibr" data-jats-rid="B10">10</a>].</p><figure id="T1" class="figure_table"> <figcaption class="Caption"> <div class="caption_content"> <a href="http://www.wjgnet.com/2220-315x/full/v14/i4/98005-T1.htm" target="_blank"><span class="caption_number">Table 1</span></a>&nbsp;Summarize findings of syndromic conditions and odontogenic tumors. </div> </figcaption> <div class="table-container" style="width:666px;"> <table class="table-container" border="1"><thead><tr><td><b>Odontogenic tumor</b><hr /></td><td><b>Syndrome</b><hr /></td><td><b>Genetic alteration</b><hr /></td><td><b>General clinical condition</b><hr /></td></tr></thead><tbody><tr><td rowspan="2">Odontoma</td><td>Gardner syndrome</td><td>Mutations in the <i>APC</i> gene</td><td>Multiple colorectal polyps and various types of tumors, both benign and malignant</td></tr><tr><td>Otodental syndrome</td><td>Not yet established (chromosome 11q13 deletion syndrome)</td><td>Globodontia, sensorineural high-frequency hearing loss and ocular coloboma</td></tr><tr><td rowspan="2">Adenomatoid odontogenic tumor</td><td>Schimmelpenning syndrome</td><td>Postzygotic mutations in <i>RAS</i> genes</td><td>One or several nevus sebaceous with abnormalities of ocular, cardiac, skeletal, and nervous systems</td></tr><tr><td>Attenuated familial adenomatosis polyposis</td><td>Mutations in the <i>APC</i> gene, with less common occurrences linked to mutations in the MUTYH gene</td><td>Hundreds or thousands of adenomatous polyps in the large bowel</td></tr><tr><td rowspan="5">Ameloblastoma</td><td>Gardner syndrome</td><td>Mutations in the <i>APC</i> gene</td><td>Multiple colorectal polyps and various types of tumors, both benign and malignant</td></tr><tr><td>Gorlin syndrome</td><td>Mutations in the patched (PTCH) gene</td><td>Numerous basal cell carcinomas and accompanying skeletal, ophthalmological, and neurological abnormalities</td></tr><tr><td>Schimmelpenning syndrome</td><td>Postzygotic mutations in <i>RAS</i> genes</td><td>One or several nevus sebaceous with abnormalities of ocular, cardiac, skeletal, and nervous systems</td></tr><tr><td>Simpson-Golabi-Behmel syndrome</td><td>Mutations in a semi-dominant X-linked gene encoding Glypican 3 </td><td>Pre- and postnatal overgrowth, distinctive facial anomalies, and abnormalities affecting internal organs, the skeleton, and occasionally, varying degrees of intellectual disability</td></tr><tr><td>Williams syndrome</td><td>Deletion of genes on chromosome 7q11.23</td><td>Developmental delay, intellectual disability, a specific cognitive profile, unique personality characteristics, cardiovascular disease, connective tissue abnormalities, growth deficiency, endocrine abnormalities, and distinctive facies</td></tr><tr><td>Odontogenic myxoma</td><td>Gardner syndrome</td><td>Mutations in the <i>APC</i> gene</td><td>Multiple colorectal polyps and various types of tumors, both benign and malignant</td></tr></tbody></table> </div> <div class="table_footer"> <div> <div id=''>APC: <i>Adenomatous polyposis coli</i>.</div> </div> </div> </figure> <div id="sec23"><div id="sec23title" class="article-section-title-1">Gardner Syndrome (Familial Adenomatous Polyposis)</div><p class="article-section-content" id="p21">Gardner syndrome, a distinct subtype of familial adenomatous polyposis, is characterized by mutations in the <i>Adeno<Hypen />matous polyposis coli</i> (<i>APC</i>) gene[<a class="refcontent" href="#B11" data-jats-ref-type="bibr" data-jats-rid="B11">11</a>]. The genetic link between Gardner syndrome and the <i>APC</i> gene, located on chromo<Hypen />some 5, specifically within band 5q21, was identified in research studies[<a class="refcontent" href="#B12" data-jats-ref-type="bibr" data-jats-rid="B12">12</a><span>-</span><a class="refcontent" href="#B14" data-jats-ref-type="bibr" data-jats-rid="B14">14</a>]. The <i>APC</i> gene functions as a tumor suppressor, producing a protein that regulates cell growth and ensures proper cell cycle timing[<a class="refcontent" href="#B15" data-jats-ref-type="bibr" data-jats-rid="B15">15</a>]. In Gardner syndrome, mutations in the <i>APC</i> gene result in uncontrolled cell growth. Additionally, Gardner syndrome involves other genetic anomalies, including loss of DNA methylation, mutations in the <i>RAS</i> gene on chromosome 12, deletion of the <i>DCC</i> gene on chromosome 18, and mutations in the TP53 gene on chromosome 17.</p><p class="article-section-content" id="p22">Due to the genetic heterogeneity of Gardner syndrome, there can be diverse phenotypic expressions; however, the three primary features are multiple gastrointestinal polyps, osteomas, and soft tissue tumors[<a class="refcontent" href="#B16" data-jats-ref-type="bibr" data-jats-rid="B16">16</a>]. This syndrome holds more historical than clinical significance today, as these extraintestinal growths are more closely associated with specific mutation locations in the <i>APC</i> gene rather than with familial patterns.</p><p class="article-section-content" id="p23">In terms of oral manifestations, individuals may present with osteomas, supernumerary teeth, impacted teeth, odon<Hypen />tomas, and osteomyelitis[<a class="refcontent" href="#B7" data-jats-ref-type="bibr" data-jats-rid="B7">7</a>,<a class="refcontent" href="#B17" data-jats-ref-type="bibr" data-jats-rid="B17">17</a>]. Concerning OTs, several cases of compound odontomas located in the anterior maxilla or complex odontomas in the posterior mandible or anterior maxilla have been described in the literature[<a class="refcontent" href="#B18" data-jats-ref-type="bibr" data-jats-rid="B18">18</a><span>-</span><a class="refcontent" href="#B21" data-jats-ref-type="bibr" data-jats-rid="B21">21</a>]. Addi<Hypen />tionally, in 2018, Salti and coauthors[<a class="refcontent" href="#B22" data-jats-ref-type="bibr" data-jats-rid="B22">22</a>] published a case involving a large odontogenic myxoma in a patient with Gardner syndrome, who also presented with multiple osteomas and a compound odontoma. Figure <a class="refcontent" href="#F1" data-jats-ref-type="fig" data-jats-rid="F1">1</a> illustrates a case of Gardner syndrome in a patient with multiple osteomas and an odontoma.</p><div class="article-item-container article-item-fig" id="F1"> <div class="article-item-image-container"> <a href="http://www.wjgnet.com/2220-315x/full/v14/i4/98005-g001.htm" target="_blank"> <picture> <source srcset="https://f6publishing.blob.core.windows.net/bce7c8fa-ffdc-420f-9733-7aedfd2ff5fa/98005-g001.webp" alt="Figure 1" loading="lazy" class="graphic" type="image/webp" /> <img src="https://f6publishing.blob.core.windows.net/bce7c8fa-ffdc-420f-9733-7aedfd2ff5fa/98005-g001.png" class="graphic" alt="Figure 1" loading="lazy" border="0" title="Figure 1" /> </picture> </a> <div class="image-btn-container"> <a href="http://www.wjgnet.com/2220-315x/full/v14/i4/98005-g001.htm" class="image-btn" target="_blank">Open in New Tab</a>&nbsp;&nbsp; <a href="https://f6publishing.blob.core.windows.net/bce7c8fa-ffdc-420f-9733-7aedfd2ff5fa/98005-g001.png" class="image-btn" target="_blank">Full Size Figure</a>&nbsp;&nbsp; <a href="https://www.f6publishing.com/forms/main/downloadfile.aspx?download=true&FilePath=CB003B19887926FEAC999C717AA9D0489843606D1A5BE87445E22985C8D7097BD8900EC505ADB4CD780FE980C3393E64F8FB26B9101F2D84" class="image-btn" target="_blank">Download Figure</a> </div> </div> <div> <b>Figure 1&nbsp;<b>Gardner syndrome in a 22-years-female patient.</b></b> <span> A and B: Three-dimensional reconstruction images show multiple variable sized osteomas in craniofacial bones; C: Panoramic radiograph shows radiopacity in the right posterior region of the mandible diagnostic as odontoma; D: Haematoxylin and eosin staining section of the odontoma characterized by the presence of dentinal tubules, odontoblasts, and dental pulp. </span> </div> </div> <p class="article-section-content" id="p25">Interestingly, Preuss <i>et al</i>[<a class="refcontent" href="#B23" data-jats-ref-type="bibr" data-jats-rid="B23">23</a>] conducted a systematic review addressing the prevalence of oral lesions associated with Gardner syndrome. Their investigation revealed that the syndrome could present with lesions localized in the proximity of the jawbones. Notably, unicystic ameloblastoma emerged as the most frequently reported lesion, documented in three cases.</p></div><div id="sec24"><div id="sec24title" class="article-section-title-1">Gorlin syndrome</div><p class="article-section-content" id="p21">Gorlin syndrome is a hereditary cancer syndrome inherited in an autosomal dominant manner[<a class="refcontent" href="#B7" data-jats-ref-type="bibr" data-jats-rid="B7">7</a>]. This condition is caused by mutations in the patched gene, which encodes a transmembrane receptor responsible for recognizing sonic hedgehog signaling proteins[<a class="refcontent" href="#B24" data-jats-ref-type="bibr" data-jats-rid="B24">24</a>,<a class="refcontent" href="#B25" data-jats-ref-type="bibr" data-jats-rid="B25">25</a>]. The syndrome is characterized by the presence of numerous basal cell carcinomas, along with accompanying skeletal, ophthalmological, and neurological abnormalities[<a class="refcontent" href="#B26" data-jats-ref-type="bibr" data-jats-rid="B26">26</a>]. A small proportion of patients may present with additional features such as hypertelorism, macrocephaly, and cleft lip and/or palate during childhood, along with desmoplastic medulloblastoma. Furthermore, ovarian neoplasms, cardiac fibromas, mesenteric keratocysts, rhabdomyosarcomas, and meningiomas may also be observed in some cases[<a class="refcontent" href="#B7" data-jats-ref-type="bibr" data-jats-rid="B7">7</a>].</p><p class="article-section-content" id="p22">The diagnostic criteria for Gorlin syndrome have evolved over time. Initially proposed by Evans <i>et al</i>[<a class="refcontent" href="#B24" data-jats-ref-type="bibr" data-jats-rid="B24">24</a>] in 1993, the criteria were modified by Kimonis <i>et al</i>[<a class="refcontent" href="#B27" data-jats-ref-type="bibr" data-jats-rid="B27">27</a>] in 1997 and later revised by Bree <i>et al</i>[<a class="refcontent" href="#B28" data-jats-ref-type="bibr" data-jats-rid="B28">28</a>] in 2011. A diagnosis can be established based on one of the following: (1) One major criterion and genetic confirmation; (2) Two major criteria, or (3) One major criterion and two minor criteria. Specific criteria typically include the presence of multiple basal cell carcinomas, jaw keratocysts, and various skeletal, ophthalmological, and neurological abnormalities. It is important to highlight that a thorough medical and family history, along with a physical examination - including an assessment for dysmorphic features, skeletal abnormalities, and skin abnormalities - is essential in suspected cases of the syndrome[<a class="refcontent" href="#B29" data-jats-ref-type="bibr" data-jats-rid="B29">29</a>].</p><p class="article-section-content" id="p23">In the gnathic bones, Gorlin syndrome is strongly associated with odontogenic keratocysts (OKCs)[<a class="refcontent" href="#B30" data-jats-ref-type="bibr" data-jats-rid="B30">30</a>]. However, cases reporting individuals with Gorlin syndrome and ameloblastomas have been published in the literature, underscoring the diverse spectrum of syndromic associations, including those with OTs, and the potential for multifocal manifestations in affected individuals[<a class="refcontent" href="#B31" data-jats-ref-type="bibr" data-jats-rid="B31">31</a><span>-</span><a class="refcontent" href="#B33" data-jats-ref-type="bibr" data-jats-rid="B33">33</a>]. A systematic review by Atarbashi-Moghadam <i>et al</i>[<a class="refcontent" href="#B6" data-jats-ref-type="bibr" data-jats-rid="B6">6</a>] summarizing syndromic conditions and ameloblastomas identified six cases of ameloblastoma associated with Gorlin syndrome. Interestingly, these cases demonstrated a female predilection and a tendency for maxillary involvement.</p><p class="article-section-content" id="p24">Careful clinical evaluation and genetic testing are essential to confirm the diagnosis and guide management strategies. Early intervention is crucial in preventing complications and improving patient outcomes. Comprehensive patient care often requires a multidisciplinary approach, involving dermatologists, geneticists, dentists, and other specialists to monitor and treat the diverse manifestations of this syndrome[<a class="refcontent" href="#B34" data-jats-ref-type="bibr" data-jats-rid="B34">34</a>,<a class="refcontent" href="#B35" data-jats-ref-type="bibr" data-jats-rid="B35">35</a>].</p></div><div id="sec25"><div id="sec25title" class="article-section-title-1">Schimmelpenning syndrome (Epidermal nevus syndrome)</div><p class="article-section-content" id="p21">Schimmelpenning syndrome, also known as epidermal nevus syndrome, is a rare congenital disorder characterized by the presence of epidermal nevi-patches of abnormal skin that typically appear as raised, warty, or thickened areas. These are often associated with cerebral, ocular, or skeletal defects[<a class="refcontent" href="#B36" data-jats-ref-type="bibr" data-jats-rid="B36">36</a>,<a class="refcontent" href="#B37" data-jats-ref-type="bibr" data-jats-rid="B37">37</a>]. Postzygotic mutations in <i>RAS</i> genes have been linked to the development and progression of this disorder[<a class="refcontent" href="#B38" data-jats-ref-type="bibr" data-jats-rid="B38">38</a>].</p><p class="article-section-content" id="p22">In individuals with Schimmelpenning syndrome, abnormalities in the development of the jaws may occur, primarily presenting as multiple adenomatoid odontogenic tumors (AOT)[<a class="refcontent" href="#B10" data-jats-ref-type="bibr" data-jats-rid="B10">10</a>]. A systematic review conducted by Neumann <i>et al</i>[<a class="refcontent" href="#B39" data-jats-ref-type="bibr" data-jats-rid="B39">39</a>] identified synchronous OTs in two cases diagnosed with Schimmelpenning syndrome[<a class="refcontent" href="#B40" data-jats-ref-type="bibr" data-jats-rid="B40">40</a>,<a class="refcontent" href="#B41" data-jats-ref-type="bibr" data-jats-rid="B41">41</a>]. These cases presented with multiple odontomas and an AOT[<a class="refcontent" href="#B40" data-jats-ref-type="bibr" data-jats-rid="B40">40</a>], with one case also exhibiting synchronous squamous OT[<a class="refcontent" href="#B41" data-jats-ref-type="bibr" data-jats-rid="B41">41</a>].</p></div><div id="sec26"><div id="sec26title" class="article-section-title-1">Otodental syndrome</div><p class="article-section-content" id="p21">Otodental syndrome, also known as otodental dysplasia, features a distinctive dental condition called globodontia, often accompanied by sensorineural high-frequency hearing loss and ocular coloboma[<a class="refcontent" href="#B42" data-jats-ref-type="bibr" data-jats-rid="B42">42</a>]. Although the specific gene associated with this syndrome remains incompletely elucidated, studies have indicated a deletion on chromosome 11q13[<a class="refcontent" href="#B43" data-jats-ref-type="bibr" data-jats-rid="B43">43</a>].</p><p class="article-section-content" id="p22">Interestingly, the dental characteristics alone can be definitive for diagnosis. The most consistent anatomical feature is the abnormal morphology of certain teeth[<a class="refcontent" href="#B44" data-jats-ref-type="bibr" data-jats-rid="B44">44</a>]. This condition is marked by distinctive tooth fusion features, including abnormal bulbous enlargement of the crown, which appears spherical with poorly defined grooves[<a class="refcontent" href="#B45" data-jats-ref-type="bibr" data-jats-rid="B45">45</a>]. Additionally, molars often exhibit taurodontism, characterized by an inverted crown-to-body ratio. There are also frequent alterations in the roots and pulp canals, making endodontic treatment unpredictable[<a class="refcontent" href="#B45" data-jats-ref-type="bibr" data-jats-rid="B45">45</a>,<a class="refcontent" href="#B46" data-jats-ref-type="bibr" data-jats-rid="B46">46</a>]. Other dental abnormalities associated with otodental syndrome include congenitally missing teeth and enamel hypoplasia[<a class="refcontent" href="#B46" data-jats-ref-type="bibr" data-jats-rid="B46">46</a>]. Although few cases have been described, individuals with this syndrome may also exhibit a propensity for multiple odontomas[<a class="refcontent" href="#B44" data-jats-ref-type="bibr" data-jats-rid="B44">44</a>,<a class="refcontent" href="#B45" data-jats-ref-type="bibr" data-jats-rid="B45">45</a>,<a class="refcontent" href="#B47" data-jats-ref-type="bibr" data-jats-rid="B47">47</a>].</p><p class="article-section-content" id="p23">Differential diagnoses for otodental syndrome include autosomal recessive sensorineural hearing impairment with dizziness and hypodontia, bilateral sensorineural hearing loss with multiple anterior dens invaginatus, and double dens invaginatus with developmental delay, progressive sensorineural hearing loss, and multituberculated mandibular incisors. For accurate diagnosis and management of the syndrome, a thorough medical, dental, and family history is crucial. An interdisciplinary approach is recommended.</p></div><div id="sec27"><div id="sec27title" class="article-section-title-1">Simpson-Golabi-Behmel syndrome</div><p class="article-section-content" id="p21">Simpson-Golabi-Behmel syndrome (SGBS) is a rare condition characterized by overgrowth and multiple congenital anomalies[<a class="refcontent" href="#B48" data-jats-ref-type="bibr" data-jats-rid="B48">48</a>,<a class="refcontent" href="#B49" data-jats-ref-type="bibr" data-jats-rid="B49">49</a>]. It results from mutations in a semi-dominant X-linked gene responsible for encoding Glypican 3 (GPC3). Information regarding the clinical and oral presentations of SGBS is limited in the literature. To the best of our knowledge, only one case of this syndrome associated with an OT has been reported[<a class="refcontent" href="#B49" data-jats-ref-type="bibr" data-jats-rid="B49">49</a>]. The case involved a 16-year-old male who presented with multiple jaw lesions, including an OKC, ameloblastoma, lateral periodontal cyst, dentigerous cyst, and mucous retention cyst, affecting both the mandible and maxilla.</p></div><div id="sec28"><div id="sec28title" class="article-section-title-1">Williams syndrome</div><p class="article-section-content" id="p21">Williams syndrome results from the deletion of genes on chromosome 7q11.23, specifically involving the elastin gene. Since the initial description of the syndrome, understanding of the phenotype's complexity and its evolving characteristics has significantly advanced[<a class="refcontent" href="#B50" data-jats-ref-type="bibr" data-jats-rid="B50">50</a>]. This includes insights into the genetic underpinnings, mechanisms driving specific phenotypes, and the benefits of various interventions. However, many questions remain unresolved, which limits the capacity to optimize care and enhance patient outcomes.</p><p class="article-section-content" id="p22">The syndrome is characterized as a multisystemic disorder, with diagnosis typically guided by the presence of indicative signs and/or symptoms[<a class="refcontent" href="#B50" data-jats-ref-type="bibr" data-jats-rid="B50">50</a>]. Notable signs include supravalvular aortic stenosis, facial dysmorphisms, dental anomalies, neurodevelopmental delays, learning disabilities, and an excessively sociable demeanor[<a class="refcontent" href="#B51" data-jats-ref-type="bibr" data-jats-rid="B51">51</a>]. The occurrence of OTs is exceedingly rare, with only one case of ameloblastoma reported thus far[<a class="refcontent" href="#B52" data-jats-ref-type="bibr" data-jats-rid="B52">52</a>]. In this case, the authors suggest that further molecular and clinical studies are necessary to establish a definitive association between the syndrome and tumor development.</p></div><div id="sec29"><div id="sec29title" class="article-section-title-1">Attenuated familial adenomatous polyposis</div><p class="article-section-content" id="p21">Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of at least 100 adenomas in the large bowel and various associated manifestations. It is inherited in an autosomal dominant manner and primarily arises from mutations in the <i>APC</i> gene, with less common occurrences linked to mutations in the <i>MUTYH</i> gene. A milder form, known as attenuated FAP, is characterized by the presence of fewer than 100 adenomas in the large bowel, distinguishing it from classical FAP. To date, only one case of an OT (specifically, an AOT) has been described in the literature in association with this syndrome[<a class="refcontent" href="#B53" data-jats-ref-type="bibr" data-jats-rid="B53">53</a>].</p></div></div><div id="sec13"><div id="sec13title" class="article-section-title-0">CONCLUSION</div><p class="article-section-content" id="p11">This manuscript provides a comprehensive exploration of the intricate relationship between genetic syndromes and OTs. Our findings underscore the importance of recognizing the oral and maxillofacial manifestations associated with genetic syndromes, as these can serve as diagnostic clues for early detection and intervention. In this context, a thorough clinical examination is crucial. This should include a detailed patient history, consideration of underlying conditions, and relevant imaging tests. Additionally, understanding the associations between OTs and genetic syndromes helps clinicians identify patterns of presentation and anticipate potential complications or comorbidities. This knowledge can guide diagnostic workup, treatment planning, and long-term management strategies for affected individuals. Furthermore, it is important to note that while cases in the literature report OTs occurring in syndromic patients, the syndrome may not necessarily be associated with the etiopathogenesis of the neoplasm.</p><p class="article-section-content" id="p12">A significant aspect highlighted is the impact of missed diagnoses of genetic syndromes. Delayed or inaccurate identification can lead to suboptimal management and potentially worsen patient outcomes. For example, in Gardner syndrome, a delayed diagnosis may result in the progression of colorectal polyps to cancer and the development of jawbone lesions, which can lead to facial asymmetry, discomfort, and an increased risk of cancer. In the case of Gorlin syndrome, delays can lead to the progression of jawbone lesions and skin cancers, resulting in severe deformities, chronic pain, and more complex surgical needs.</p><p class="article-section-content" id="p13">We also emphasize the importance of incorporating genetic testing into clinical practice when a syndromic condition is suspected. Comprehensive genetic evaluations can not only confirm diagnoses but also provide valuable insights into the hereditary nature of these syndromes. Finally, managing OTs in syndromic patients requires a collaborative approach, involving researchers with expertise across the diverse conditions and genetic factors associated with each syndrome. This approach should consider both the specific characteristics of the tumor and the syndromic condition, aiming to provide optimal care, minimize complications, and enhance the overall quality of life for the patient.</p><p class="article-section-content" id="p14">Due to the nature of the study design employed, several limitations are evident. Firstly, the lack of a systematic search method meant that some relevant studies could not be included. Secondly, some case reports lacked the comprehensive details necessary to fully understand the syndrome and its association with OTs. Finally, the findings may not be universally applicable across all healthcare settings or populations due to variations in clinical practices and patient demographics.</p></div> </div> <div class="article-section-title-0" style="display:block"> <span>Footnotes</span> </div> <div style="display:block;" class="article-section-content"> <p><bold>Provenance and peer review:</bold> Invited article; Externally peer reviewed.</p><p><bold>Peer-review model:</bold> Single blind</p><p><bold>Specialty type:</bold> Dentistry, oral surgery and medicine</p><p><bold>Country of origin:</bold> Uruguay</p><p><bold>Peer-review report’s classification</bold></p><p><bold>Scientific Quality:</bold> Grade C</p><p><bold>Novelty:</bold> Grade C</p><p><bold>Creativity or Innovation:</bold> Grade B</p><p><bold>Scientific Significance:</bold> Grade C</p><p><bold><b>P-Reviewer:</b></bold> Sharma G <bold><b>S-Editor:</b></bold> Liu JH <bold><b>L-Editor:</b></bold> A <bold><b>P-Editor:</b></bold> Wang WB</p> </div> <div class="article-section-title-0" style="display:block"> <span>References</span> </div> <div style="margin-top:10px;display:block"> <div class="article-ref" id="B1"> <table> <tr> <td style="vertical-align:top;width:30px;"><a class="article-ref-vol" title="View reference 1 in text" ref-list-rid="B1" target="_self">1.&nbsp;</a></td> <td> <span></span> <span> &nbsp;World Health Organization classification of head and neck tumours. 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href='/2220-315x/CitedArticlesInF6?id=10.1186%2fs13023-014-0138-0' target='_blank'>Cited by in F6Publishing: 61</a><span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class='ref-count-sep'>[</span><a href='javascript:void(0);' onclick="ShowInflu('10.1186%2fs13023-014-0138-0','2220-315x')">Article Influence: 6.1</a><span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class='ref-count-sep'>[</span><a href='javascript:void(0);' onclick="ShowRefArticle('10.1186/s13023-014-0138-0','25238977','2220-315x')">Reference Citation Analysis (0)</a><span class='ref-count-sep'>]</span></span> </td> </tr> </table> </div> <div class="article-ref" id="B49"> <table> <tr> <td style="vertical-align:top;width:30px;"><a class="article-ref-vol" title="View reference 49 in text" ref-list-rid="B49" target="_self">49.&nbsp;</a></td> <td> <span><b>Kaya GŞ</b>,&nbsp;Özalp Ö,&nbsp;Özbudak İH.&nbsp;Synchronous occurrence of multiple distinct jaw lesions in 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target="_blank">DOI</a>]</span> <span>&nbsp;<span class="ref-count-sep">[</span>Cited in This Article: <span id="B50thiscited"></span><span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class="ref-count-sep">[</span>Cited by in Crossref: 49<span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class='ref-count-sep'>[</span><a href='/2220-315x/CitedArticlesInF6?id=10.1038%2fs41572-021-00276-z' target='_blank'>Cited by in F6Publishing: 107</a><span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class='ref-count-sep'>[</span><a href='javascript:void(0);' onclick="ShowInflu('10.1038%2fs41572-021-00276-z','2220-315x')">Article Influence: 35.7</a><span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class='ref-count-sep'>[</span><a href='javascript:void(0);' onclick="ShowRefArticle('10.1038/s41572-021-00276-z','34140529','2220-315x')">Reference Citation Analysis (0)</a><span 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target="_self">52.&nbsp;</a></td> <td> <span><b>Tuncer FB</b>,&nbsp;Sacak B,&nbsp;Akdeniz ZD,&nbsp;Celebiler O.&nbsp;Ameloblastoma in a Patient With Williams Syndrome and Use of Fibular Flap.</span> <span> <em><a href='javascript:void(0);' name='refsource' data-id='69219'>J Craniofac Surg</a></em>.&nbsp;2017;<b>28</b>:e241-e242. </span> <span style="display:inline">&nbsp;[<a href="http://www.ncbi.nlm.nih.gov/pubmed/28468204" pub-id-type="pubmed" pub-id="28468204" target="_blank">PubMed</a>]</span> <span style="display:inline">&nbsp;[<a href="https://dx.doi.org/10.1097/scs.0000000000003449" pub-id-type="doi" pub-id="10.1097/scs.0000000000003449" target="_blank">DOI</a>]</span> <span>&nbsp;<span class="ref-count-sep">[</span>Cited in This Article: <span id="B52thiscited"></span><span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class="ref-count-sep">[</span>Cited by in Crossref: 1<span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class='ref-count-sep'>[</span><a href='/2220-315x/CitedArticlesInF6?id=10.1097%2fscs.0000000000003449' target='_blank'>Cited by in F6Publishing: 1</a><span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class='ref-count-sep'>[</span><a href='javascript:void(0);' onclick="ShowInflu('10.1097%2fscs.0000000000003449','2220-315x')">Article Influence: 0.1</a><span class='ref-count-sep'>]</span></span> <span class="ref-count">&nbsp;<span class='ref-count-sep'>[</span><a href='javascript:void(0);' onclick="ShowRefArticle('10.1097/scs.0000000000003449','28468204','2220-315x')">Reference Citation Analysis (0)</a><span class='ref-count-sep'>]</span></span> </td> </tr> </table> </div> <div class="article-ref" id="B53"> <table> <tr> <td style="vertical-align:top;width:30px;"><a class="article-ref-vol" title="View reference 53 in text" ref-list-rid="B53" target="_self">53.&nbsp;</a></td> <td> <span><b>Marrelli M</b>,&nbsp;Pacifici A,&nbsp;Di Giorgio G,&nbsp;Cassetta M,&nbsp;Stefanelli LV,&nbsp;Gargari M,&nbsp;Promenzio L,&nbsp;Annibali S,&nbsp;Cristalli MP,&nbsp;Chiaravalloti E,&nbsp;Pacifici L,&nbsp;Tatullo M.&nbsp;Diagnosis and treatment of a rare case of adenomatoid odontogenic tumor in a young patient affected by attenuated familial adenomatosis polyposis (aFAP): case report and 5 year follow-up.</span> <span> <em><a href='javascript:void(0);' name='refsource'>Eur Rev Med Pharmacol Sci</a></em>.&nbsp;2014;<b>18</b>:265-269. </span> <span style="display:inline">&nbsp;[<a href="http://www.ncbi.nlm.nih.gov/pubmed/24488918" pub-id-type="pubmed" pub-id="24488918" target="_blank">PubMed</a>]</span> <span style="display:none">&nbsp;[<a href="https://dx.doi.org/$[DOI]" pub-id-type="doi" pub-id="$[DOI]" target="_blank">DOI</a>]</span> <span>&nbsp;<span class="ref-count-sep">[</span>Cited in This Article: <span id="B53thiscited"></span><span class='ref-count-sep'>]</span></span> </td> </tr> </table> </div> </div> </div> </div> <div id="videoPopup_PW-1" 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