Anomalies of the Primary Dentition in Patients with Oculo-Facio-Cardio-Dental (OFCD) Syndrome

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Hermann, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7989161/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Background Oculo-Facio-Cardio-Dental (OFCD) syndrome is a rare X-linked dominant disorder caused by pathogenic variants in BCOR gene primarily affecting structures derived from ectoderm and neural crest, including the eyes, facial region, heart, and dentition. The cardinal dental hallmark is radiculomegaly in the permanent dentition, especially affecting the canines but also observed in incisors and premolars. Since variations in the BCOR gene have been shown to promote dentinogenesis, it seems likely that the primary dentition would be affected as well. However, most of the literature on the subject so far has focused on the permanent dentition. The aim of the present study was to provide a detailed description of the phenotype of the primary dentition in OFCD syndrome. Methods Literature review including patients with genetically verified OFCD syndrome with focus on the primary dentition in combination with description of two new Danish cases. Results The most prominent phenotypic feature in the primary dentition was the presence of radiculomegaly in all cases, where relevant data were available. The tooth type most frequently affected was the canine (mandible > maxilla) followed by the incisors. Delayed eruption of primary teeth and later shedding/persistence was also noted together with fusion of the primary teeth. Conclusions Our findings indicate that radiculomegaly in OFCD syndrome may be present already in the primary dentition. Therefore, early clinical and radiographic evaluation by an experienced pediatric dentist is essential, as dental findings may provide key clues for the diagnosis, and in combination with genetic testing may lead to timely and sufficient treatment intervention resulting in improved oral quality of life for the patient and support earlier recognition and management of OFCD’s ocular, cardiac, and other systemic manifestations. Oculo-Facio-Cardio-Dental syndrome OFCD children primary dentition radiculomegaly long roots dental anomalies Figures Figure 1 Figure 2 1. Introduction Oculo-Facio-Cardio-Dental (OFCD) syndrome is a rare X-linked dominant disorder caused by pathogenic variants in the BCOR gene, which encodes the BCL6 corepressor protein. This protein remains incompletely understood; however, it has a critical function as a key transcriptional regulator during early embryogenesis [ 1 ]. The estimated prevalence of OFCD syndrome is less than 1 per million and is observed almost exclusively in females due to the presumed embryonic lethality in males [ 1 ]. The cardinal features of the syndrome were delineated by Marashi and Gorlin (1992) [ 2 ], and the causative gene was identified in 2004 by Ng et al. [ 3 ]. The syndrome primarily affects structures derived from the ectoderm and neural crest, including the eyes, facial region, heart, and dentition. Commonly reported ocular anomalies in patients with OFCD syndrome include congenital cataract, microphthalmia, and progressive loss of vision. Characteristic facial features comprise a long, narrow face, high nasal bridge, and broad nasal tip with widely spaced nasal cartilages. Cardiac abnormalities vary but may include atrial or ventricular septal defects, mild cardiomegaly, and mitral valve prolapse. In some cases, skeletal anomalies such as syndactyly of the toes and radioulnar synostosis have also been reported [ 4 ]. The cardinal dental hallmark of OFCD syndrome is radiculomegaly (abnormally elongated dental roots) in the permanent dentition, especially affecting the canines but also observed in incisors and premolars [ 4 , 5 ]. Other reported dental anomalies include tooth agenesis, fusion, malposition, and markedly delayed eruption of teeth [ 6 ]. Considering the extreme rarity of radiculomegaly in the permanent canines in the general population, this trait is considered pathognomonic of OFCD syndrome [ 7 ]. However, the value of this trait as a diagnostic marker is limited by the fact that the diagnosis cannot be made with certainty until adolescence, when the patient is 13–15 years of age and the roots of the canines fully developed. Since variations in the BCOR gene have been shown to promote dentinogenesis and increase proliferation of periodontal ligament cells [ 5 ], it would seem likely that the primary dentition would be affected as well. However, most published case reports and reviews so far have focused exclusively on the permanent dentition [ 8 ]. If the primary dentition, like the permanent dentition, shows a syndrome-specific pattern of dental anomalies, including radiculomegaly, these traits could be identified by age 3–4 years, leading to a much earlier diagnosis and possible earlier treatment intervention which would be of great value for the patient. These facts underscore a clear need for a systematic investigation of the phenotype of the primary dentition in OFCD syndrome. To our knowledge, no publications have systematically correlated early dental findings with the later diagnosis of OFCD syndrome caused by pathogenic BCOR variants. This may represent a missed opportunity for an earlier identification of the syndrome, especially given that dental anomalies may be present well before other signs become clinically evident. Although many patients present with congenital cataract and microphthalmia, these ocular features can be subtle or mild; in such cases, characteristic dental anomalies, alone or in combination with mild eye findings, may constitute the first striking feature in early childhood and should prompt consideration of OFCD syndrome. This study aims to fill that knowledge-gap by providing a structured and detailed description of the phenotype of the primary dentition in reported patients with OFCD syndrome. A literature review on the syndrome was carried out with this focus in combination with description of two new Danish cases. Our goal is to highlight the importance of identifying early dental signs that could facilitate an earlier recognition and diagnosis of OFCD syndrome; especially in cases where ocular or cardiac anomalies may not yet have prompted further genetic evaluation. 2. Materials and Methods A structured literature search was conducted in PubMed in May 2025 using the following search terms: (oculo facio cardio dental syndrome [Title/Abstract]) OR (OFCD[Title/Abstract]) OR (radiculomegaly [Title/Abstract]) The search yielded 92 articles published between December 1990 and May 2025. Filters were applied to include only case reports, clinical studies, reviews, and systematic reviews, narrowing the dataset to 60 articles. Among these, only studies describing cases with genetically confirmed OFCD syndrome with molecular verification of a pathogenic BCOR gene variant were selected, resulting in 15 eligible articles describing 27 individual patient cases. From this cohort, we further selected only the patient cases that contained documented findings related to the primary dentition. Eighteen patient cases met this criterion. However, 12 of these patient cases relied solely on general statements or anecdotal observations on the dentition provided by caregivers or authors, without radiographic or clinical documentation. These cases were deemed insufficient for detailed phenotypic analysis. The remaining six cases provided objective and verifiable data including clinical photographs, panoramic radiographs, or cone beam CT images describing anomalies in the primary dentition. Accordingly, these six cases were included in the final review. In addition, we have included two identified Danish patients with genetically confirmed diagnosis of OFCD syndrome, whose cases have not previously been published, and we present detailed descriptions of their primary dentition. In total, eight cases with genetically confirmed OFCD syndrome and documented anomalies in the primary dentition were thus extracted and analyzed. 3. Results A detailed presentation and structured assessment of the two Danish cases is first provided. As these patients have been followed longitudinally, information on the primary as well as the permanent dentition is included. Subsequently, the relevant findings are summarized in a comprehensive table (Table 1 ) for the two Danish patients and the six additional patients included in the study. Case Reports : Case 1 ● General information Case 1 is a female born by planned cesarean section at 39 + 0 weeks of gestation following an uneventful pregnancy. At 10 days of age, she was hospitalized due to neonatal jaundice. During this admission, a congenital malformation of the female genital tract was identified. At 7 weeks of age, she was diagnosed with bilateral congenital cataracts and underwent early ophthalmic surgery. Developmental delays in both motor and speech domains were noted by age two years, although she responded well to early intervention. At age five years, the patient was referred for genetic evaluation based on the presence of congenital cataract. Clinical examination revealed subtle dysmorphic features, including microphthalmia and a depressed nasal bridge. Initial dental examination showed delayed tooth eruption and fused primary mandibular incisors. According to the parents, the first tooth had erupted around the age of 1.5 years. Despite slightly reduced motor activity, overall neurodevelopment was within normal limits. Initial growth delay had normalized over time. Cardiac evaluation at the time showed no structural heart anomalies. However, a follow-up echocardiogram later demonstrated increased trabeculation in the left ventricle and an accessory chord, interpreted as a normal anatomical variant. Genetic testing revealed a likely pathogenic nonsense variant in the BCOR, confirming the diagnosis of oculo-facio-cardio-dental (OFCD) syndrome. Neither parents nor the patient’s two brothers were genetically tested; all appeared clinically unaffected. At age 7.5 years, the patient was referred to the Resource Centre for Rare Oral Diseases, Copenhagen University Hospital, Rigshospitalet for a specialized dental assessment. Radiographic assessment included six panoramic X-rays taken at age 7.5, 8 (Fig. 1 ), 9, 10, 11 and age 12 at Copenhagen University Hospital. These panoramic X-rays, combined with clinical findings, formed the basis for the assessment of the dentitions. Anomalies in the number of teeth Clinical examination showed eruption of the primary dentition; however, hypodontia was present in the incisal region of the lower jaw, where only a single but markedly broad primary mandibular central incisor was present, suggesting a possible fusion anomaly. Panoramic radiography confirmed the suspected fusion of the primary mandibular central incisors (#71 and #81), with root formation observed only on #81. The X-ray showed agenesis of the permanent mandibular left central incisor (#31). Anomalies in crown and root morphology Coronal fusion of #71 and #81 was radiographically evident, with root formation limited to #81. Macrodontia was observed in the maxillary permanent central and lateral incisors (#21, #22). The root morphology of those present primary incisors and canines appeared elongated and gracile. Calibrated measurements on the panoramic X-ray demonstrated an up till 6.31 mm increase in tooth length (see Table 2 ) compared to normative values [ 9 ]. Radiculomegaly, defined as excessive root elongation, could therefore be confirmed in 11 (#53, #52, #51, #61, #62, #63, #73, #72, #81, #82, #83) of the 11 present primary incisors and canines. Anomalies in tooth maturation The permanent incisors and canines were in initial stages of root development, stages R¼ - Ri for incisors and Cc - Ri for canines, corresponding to the average dental age of a 5.5-6.5-year-old [ 10 ]. In contrast, development of premolars and molars aligned with the chronological age of 7.5 years. Delayed development and maturation were noted in teeth #13, #12, #11, #21, #22, #23, #32, #33, #41, #42 and #43. Anomalies in dental hard tissues No anomalies were identified in dental hard tissues based on clinical and radiographic examination. Anomalies in tooth position Panoramic X-ray revealed that #11 was rotated 90 degrees and #21 exhibited a distally angulated eruption path. Anomalies in tooth eruption and shedding Clinically, the mandibular permanent first molars had fully erupted, whereas the maxillary counterparts (#16, #26) remained unerupted at the time of assessment. According to the Atlas of Human Tooth Development and Eruption [ 10 ], this eruption delay corresponds to 1–2 years. Delayed physiological root resorption was observed in teeth #52, #51, #72, and #82. Root length of these teeth could be clearly assessed in the X-ray and appeared intact, without signs of resorption. This was noteworthy given the developmental stage of their permanent successors. Case 2 ● General information Case 2 is a female born full-term after an uneventful pregnancy. She was hospitalized shortly after birth because of failure to thrive and jaundice. Due to abnormal facial appearance a karyotype was done but came back normal. Echocardiography was unremarkable. She was diagnosed with microphthalmia and bilateral congenital cataracts and underwent early lens removal. Subsequent ophthalmia on the left eye resulted in significantly impaired vision. Secondary glaucoma was diagnosed later in childhood, further reducing vision. Mild bilateral hearing loss was also reported. Syndactyly of the second and third toes was noted. Early motor development was slightly delayed possibly due to vision impairment and recurrent surgery and treatment but normalized within the first two years. Overall cognitive and mental function were within normal limits. The girl was referred to the Resource Centre for Rare Oral Diseases, Aarhus University Hospital, at the age of 12 years due to findings of dental agenesis and disturbances of tooth eruption noted by the municipal school dental service. Facial examination revealed deep-set eyes, microphthalmia and ptosis. She had a high nasal bridge, broad nasal tip with separated nasal cartilages and increased lower facial height. The palate was narrow, and multiple dental anomalies and eruption disturbances were evident. According to her parents, tooth eruption had been delayed, with the first tooth erupting around the age of one. At this time a clinical diagnosis of OFCD syndrome was proposed. At age 14 she underwent surgery for scoliosis. At age 24 she was referred to the Department of Clinical Genetics, Aalborg University Hospital. Genetic analysis revealed a variant of unknown significance in BCOR gene which after confirmation of its de novo origin was reclassified as likely pathogenic. Radiographic assessment included two panoramic X-rays: one taken at age 9 at the municipal school dental service and another at age 12 (Fig. 2 ). These panoramic X-rays, combined with clinical findings, formed the basis for the assessment of the dentitions. Anomalies in tooth number The patient had agenesis of the permanent maxillary lateral incisors (#12 and #22). Anomalies in crown and root morphology Radiculomegaly was evident in the primary teeth #72, #63, #73 and #83. The maxillary permanent central incisors exhibited pronounced cingula forming distinct talon-cusp-like tubercles and the roots demonstrated unusually wide pulp canals. The initial root development of the permanent canines appeared remarkably broad and divergent. Anomalies in tooth maturation Development of the permanent premolars appeared mildly delayed on the panoramic X-ray at age 12, particularly in teeth #34 and #44. The permanent canines were at an earlier stage of development, with root formation corresponding to an average dental age of 8.5–9.5 years, indicating a delay of approximately 3 years. The right permanent mandibular central incisor #41 remained immature, with root development consistent with that of a 7-year-old child, representing a 5-year delay. Anomalies in dental hard tissues Pulp stone-like calcifications were observed apically in teeth #13, #34, #43, and #44. Anomalies in tooth position Both permanent maxillary canines, #13 and #23, had drifted mesially. The permanent maxillary right canine, #13, was horizontally positioned in the jaw. Both permanent mandibular canines were deeply impacted. In addition, #43 was mesioangulated, and #33 was rotated 90 degrees. Additionally, two permanent mandibular incisors were rotated 90 degrees, due to crowding of the permanent lower anterior teeth, particularly #41, #31, and #32, all of which appeared deeply impacted in the mandible on the panoramic radiograph taken at age 9. Anomalies in eruption and shedding On the panoramic radiograph taken at age 9, persistence of primary teeth #82, #81, #71 and #72 was noted. These teeth would typically have been shed by age 6–7. By age 12, primary teeth #63, #72, #73 and #83 remained without signs of physiological root resorption. The permanent incisors #41, #31, and #32 were at an eruption stage consistent with that of a 5-6-year-old, indicating an estimated eruption delay of approximately three years. 3.2. Summary of Clinical Findings Table 1 summarizes the findings from the two Danish (case 1 and case 2 ) and the six selected OFCD syndrome cases [ 11 – 16 ], with documented anomalies in the primary dentition. Only five cases had radiographic documentation of the dentition needed for assessment of e.g., root morphology. The most prominent phenotypic feature in the primary dentition was the presence of radiculomegaly in all cases, where relevant data were available (5/5; 100%). In total, 31 primary teeth (14 canines and 17 incisors) were recorded with radiculomegaly for the 5 cases (see Table 3 ). The tooth type most frequently affected would seem to be the canine and more frequently in the mandible than in the maxilla. All five cases had radiculomegaly of at least one canine, and 4/5 had radiculomegaly of at least one incisor. Case 1 had radiculomegaly of 11 teeth (4 canines and 7 incisors). Case 7 [ 15 ] had radiculomegaly of 8 teeth (2 canines and 6 incisors), and Case 4 [ 12 ] had radiculomegaly of 7 teeth (4 canines and 3 incisors). Because the data were not reported consistently across all eight published cases, the denominators below reflect only those cases with relevant information. Delayed eruption of primary teeth was documented in all three cases for which eruption data were available (3/3; 100%). Delayed shedding or persistence was reported in all six cases with shedding data (6/6; 100%). Fusion of primary teeth was observed in five of the eight cases with sufficient documentation (5/8; 63%), and all fusions involved incisors. Agenesis of primary teeth was identified in three of the five cases with complete agenesis data (3/5; 60%), with each of these patients missing two primary incisors. It was established that crown formation of the mandibular first permanent molar was complete, as evidenced by its developmental stage corresponding to stage R¾ in the Liversidge classification. Therefore, the reference crown height for this tooth, defined for the completed crown stage, was used for calibration. In the panoramic x-ray, the crown height of the mandibular first permanent molar was measured to be 10 mm. Based on the known actual crown height from Liversidge’s data, a multiplication factor was applied to convert radiographic measurements into estimated true tooth lengths for patient 1. 4. Discussion Although more than 30 case reports and small patient series of OFCD syndrome have been published to date, the majority focus primarily on ocular, cardiac, or craniofacial manifestations. Dental findings are often mentioned only briefly and without sufficient clinical detail, particularly regarding anomalies in the primary dentition, even though it is well established that dental anomalies may affect both the primary and permanent dentitions [ 15 , 17 ]. In many reports, radiographic documentation and intraoral photographs are absent, and anomalies in tooth morphology, eruption patterns, and root formation are described only in general terms. This limited documentation is reflected in specific examples, where the dental component is reduced to a short remark, such as “teeth with radiculomegaly” [ 18 ] or a simple table entry of “Radiculomegaly” without details of the affected teeth [ 19 ]. The authors of an article describing a OFCD case, a nine-year-old was noted to have “not had dental problems,” while it was also mentioned that “parents reported she had long roots of her teeth” [ 20 ], however, the source or basis of this parental observation was not clarified in the article. Ragge et al. (2019) [ 18 ] reported that among 85 examined OFCD cases, four were recorded without dental anomalies. It is possible that additional dental findings might have been identified in those cases if more detailed data or specialist dental assessment had been available. These examples illustrate how key dental diagnostic indicators can occasionally be underrecognized. One contributing factor may be that many OFCD-related publications originate from medical specialities outside dentistry, such as ophthalmology, medical genetics or cardiology, and are often published in subspeciality medical journals [ 13 , 14 , 18 , 19 ]. While this reflects the multisystemic nature of OFCD syndrome, it may also explain why the dental findings are inconsistently described and only rarely evaluated in a systematic or standardized manner. In several publications, it appears that no dental professionals were involved in the clinical evaluation or authorship, which may account for some of the variability in terminology and interpretation of dental features. These challenges underscore the complexity of drawing consistent conclusions from the existing literature. Potential sources of bias include selection bias, as cases may be included or excluded depending on the completeness of clinical and radiographic records, and information bias, resulting from differences in clinical expertise or documentation quality. This makes it difficult to establish a reliable and comparable dataset across published cases. For example, Hilton et al. (2009) [ 4 ] reported on 30 females with OFCD syndrome, of whom eight had documented findings in the primary dentition. While six of these eight showed delayed eruption and/or persistence, the primary dentition was not analyzed in a structured manner. Similarly, Yamashita et al. (2023) [ 13 ] concluded that radiculomegaly was a feature limited to the permanent dentition and could not yet be assessed in their pediatric patient. Sauvestre et al. (2024) [ 11 ] likewise stated that radiculomegaly could not be identified in 13 younger patients included in their review. Our findings suggest that this statement may reflect limitations in the available radiographic data or the absence of dental specialists involved in the evaluation, rather than a true lack of radiculomegaly in early dentition. When appropriate imaging is available, and interpreted by clinicians with dental expertise, radiculomegaly can often be detected already in the primary or early mixed dentition. In support of this, Nishiguchi et al. (2018) [ 15 ] described a case of remarkable radiculomegaly in the primary dentition of a child with OFCD, reinforcing the relevance of dental findings in early diagnosis. Given that radiculomegaly in primary teeth is exceedingly rare in the general population (< 0.001%), and that agenesis of primary teeth is also uncommon (0.6%; Ravn, 1971) [ 21 ], the presence of either anomaly should prompt consideration of an underlying syndrome. In this light, early dental assessment may serve as an important diagnostic gateway to identifying OFCD syndrome at an earlier stage, particularly in children who have not yet developed recognizable ocular or cardiac findings. The underlying mechanisms of radiculomegaly in OFCD syndrome remain incompletely understood. However, experimental studies suggest that the BCOR gene may play a role in dentinogenesis and root elongation. For example, Surapornsawasd et al. (2014) [ 5 ] found that BCOR is expressed in dental pulp and periodontal ligament cells, while Larhant et al. 2014, [ 7 ] proposed that root elongation in OFCD syndrome may be linked to disturbed dentinogenesis, noting that BCOR silencing in mice results in dentine abnormalities, and that dental mesenchymal stem cells from OFCD patients show increased dentine formation potential. These findings support the hypothesis that BCOR may play a role in dentinogenesis and in regulation of dental root development, although further studies of these mechanisms are needed. Overall, our study contributes to the emerging recognition of the primary dentition as a relevant site for early diagnosis of OFCD syndrome. A structured dental assessment, particularly when conducted by pediatric dentists familiar with OFCD syndrome, may enable identification of characteristic features such as radiculomegaly, fusion, and delayed eruption or shedding, years before a definitive diagnosis might otherwise be made. Earlier recognition at the dental level can in turn prompt timely referral for comprehensive genetic testing and targeted evaluation by ophthalmology, cardiology, and other relevant specialties, allowing associated ocular and cardiac manifestations to be detected and managed at an earlier stage. This reinforces the value of interdisciplinary collaboration and highlights the need for increased dental awareness in rare syndromic disorders. 5. Conclusions The present study demonstrates a consistent pattern of anomalies in the primary dentition of patients with OFCD syndrome. Radiculomegaly of canines and incisors, delayed eruption and shedding were present in all cases with radiographs available, while fusion and agenesis were observed in approximately 60% of cases. All recorded anomalies predominantly involved the canine–incisor regions. These findings indicate that dental anomalies in OFCD syndrome are not limited to the permanent dentition but may also be present in the primary dentition. Although based on a limited dataset, the results align with previous case reports and highlight the important role of oral health professionals in recognizing early phenotypic features of the syndrome. The syndrome-specific triad of radiculomegaly, delayed eruption, and persistence of teeth should therefore be regarded as equally relevant in the primary as in the permanent dentition. Early clinical and radiographic evaluation by an experienced pediatric dentist is essential, as dental findings may provide key clues for the diagnosis in combination with genetic testing. Such early recognition not only enables appropriate dental treatment but also facilitates earlier detection and management of OFCD’s ocular, cardiac, and other systemic manifestations, benefiting both the patient and their family as well as the wider healthcare team. Abbreviations BCOR BCL6 Corepressor OFCD Oculo-Facio-Cardio-Dental syndrome CBCT Cone Beam Computed Tomography Declarations Ethics approval and consent to participate This study is a retrospective case series combined with a literature review. No experimental procedures or interventions were performed, and all data were obtained from existing clinical records and diagnostic material collected as part of routine clinical care. According to Danish legislation, retrospective studies based solely on previously collected clinical data do not require approval from a regional ethics committee. Therefore, formal ethics committee approval was not required for this study. Informed consent for participation and use of clinical data and images for research and publication purposes was obtained from all patients and/or their parents or legal guardians. The study was conducted in accordance with the Declaration of Helsinki (2024 revision). Consent for publication Written informed consent for publication of anonymized clinical and radiographic information was obtained from the parents/legal guardians of both Danish patients included in this study. Availability of data and materials All data supporting the findings of this study are included within the article. Additional details can be made available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research received no external funding. Authors’ contributions MV designed the study, performed the literature review, collected and analyzed dental and radiographic data, prepared tables and figures, and drafted the manuscript. SK contributed to the interpretation of dental findings, manuscript structure, and critical revisions. CK contributed to manuscript revisions. XH contributed to manuscript revisions. AS contributed genetic expertise, variant interpretation, and manuscript revisions. LR contributed to the genetic evaluation and verification of BCOR variants. NVH supervised the project, contributed to study design and interpretation, and critically revised the manuscript. All authors read and approved the final manuscript. Acknowledgements The authors thank the families who consented to the use of clinical and radiographic data in this study. The authors also acknowledge the support of the Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital, Rigshospitalet and the Resource Centre for Rare Oral Diseases, Copenhagen University Hospital, Rigshospitalet. References Wamstad JA, Corcoran CM, Keating AM, Bardwell VJ. Role of the transcriptional corepressor BCOR in embryonic stem cell differentiation and early embryonic development. PLoS ONE. 2008;3(7):e2814. 10.1371/journal.pone.0002814 . Marashi AH, Gorlin RJ. Radiculomegaly of canine teeth and congenital cataracts: confirmation of a syndrome. Am J Med Genet. 1992;42(1):143. 10.1002/ajmg.1320420132 . Ng D, Thakker N, Corcoran CM, Donnai D, Perveen R, Schneider A, et al. Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR. Nat Genet. 2004;36:411–6. Hilton E, Johnston J, Whalen S, Okamoto N, Hatsukawa Y, Nishio J, et al. BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects. Eur J Hum Genet. 2009;17:1325–35. Surapornsawasd T, Ogawa T, Tsuji M, Moriyama K. Oculofaciocardiodental syndrome: novel BCOR mutations and expression in dental cells. J Hum Genet. 2014;59:314–20. Batkova A, Havlovicova M, Nocar A, Dudakova L, Macek M, Liskova P, et al. Dental abnormalities observed in the oculo-facio-cardio-dental (OFCD) syndrome present in two Czech families bearing novel de novo BCOR pathogenic variants. BMC Oral Health. 2024;24(1):1264. 10.1186/s12903-024-05005-y . Larhant M, Sourice S, Grimaud F, Cordoba L, Leveau S, Huet P, et al. Giant canine with dentine anomalies in oculo-facio-cardio-dental syndrome. J Craniomaxillofac Surg. 2014;42(4):321–4. Schulze BRB, Horn D, Kobelt A, Tariverdian G, Stellzig A. 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Yamashita T, Hotta J, Jogu Y, Sakai E, Ono C, Bamba H, et al. Oculofaciocardiodental syndrome caused by a novel BCOR variant. Hum Genome Var. 2023;10(1):18–4. Hamid R, Duncan L, Colazo JM, Morgan TM, Joos KM, Ban Y. Two cases of oculofaciocardiodental (OFCD) syndrome due to X-linked BCOR mutations presenting with infantile hemangiomas: phenotypic overlap with PHACE syndrome. Case Rep Genet. 2019;2019:1–8. Nishiguchi M, Sasaki Y, Satoh K, Kamasaki Y, Kondo Y, Fujiwara T. Long-term observation of a case of oculo-facio-cardio-dental syndrome that showed remarkable radiculomegaly of primary teeth. J Transl Sci. 2018;5:1–4. 10.15761/JTS.1000257 . Oberoi S, Winder AE, Johnston J, Vargervik K, Slavotinek AM. Case reports of oculofaciocardiodental syndrome with unusual dental findings. Am J Med Genet A. 2005;136A(3):275–7. Kantaputra P. BCOR mutations and unstoppable root growth: a commentary on oculofaciocardiodental syndrome: novel BCOR mutations and expression in dental cells. J Hum Genet. 2014;59:297–9. Ragge N, Isidor B, Bitoun P, et al. Expanding the phenotype of the X-linked BCOR. Hum Genet. 2019;138:1051–69. Moleiro A, Oliveira J, Grangeia A, et al. Ocular severe involvement in oculofaciocardiodental syndrome: description of a case series. Eur J Ophthalmol. 2024;34(1):NP6–11. 10.1177/11206721231170406 . Morgan T, Colazo JM, Duncan L, Hamid R, Joos K. Two cases of oculofaciocardiodental (OFCD) syndrome due to X-linked BCOR mutations presenting with infantile hemangiomas: phenotypic overlap with PHACE syndrome. Case Rep Genet. 2019;2019:9382640. 10.1155/2019/9382640 . Ravn JJ. Aplasia, supernumerary teeth and fused teeth in the primary dentition: an epidemiologic study. Scand J Dent Res. 1971;79(1):1–6. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7989161","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":583612058,"identity":"32acddc2-0870-4870-a2e1-3e719bc6307d","order_by":0,"name":"Mellanie Vendt","email":"data:image/png;base64,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","orcid":"","institution":"Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital - Rigshospitalet","correspondingAuthor":true,"prefix":"","firstName":"Mellanie","middleName":"","lastName":"Vendt","suffix":""},{"id":583612059,"identity":"d232c7cf-b0ed-46c9-8b7f-dc593250b93c","order_by":1,"name":"Sven Kreiborg","email":"","orcid":"","institution":"Pediatric Dentistry and Clinical Genetics, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen","correspondingAuthor":false,"prefix":"","firstName":"Sven","middleName":"","lastName":"Kreiborg","suffix":""},{"id":583612061,"identity":"7c5c7dcd-fa5e-49f5-8c7e-2f9a5ec7f114","order_by":2,"name":"Casper Kruse","email":"","orcid":"","institution":"Center for Oral Health in Rare Diseases, Department of Maxillofacial Surgery, Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Casper","middleName":"","lastName":"Kruse","suffix":""},{"id":583612062,"identity":"b510c364-82cc-4646-98f1-aca5a2e5d777","order_by":3,"name":"Xenia B. Hermann","email":"","orcid":"","institution":"Center for Oral Health in Rare Diseases, Department of Maxillofacial Surgery, Copenhagen University Hospital - Rigshospitalet","correspondingAuthor":false,"prefix":"","firstName":"Xenia","middleName":"B.","lastName":"Hermann","suffix":""},{"id":583612063,"identity":"e36c03c5-1368-46bf-80c9-1bcda027e442","order_by":4,"name":"Anne E. Rothmann Sørensen","email":"","orcid":"","institution":"Department of Clinical Genetics, Aalborg University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Anne","middleName":"E. Rothmann","lastName":"Sørensen","suffix":""},{"id":583612064,"identity":"3a937c49-498b-4973-bb7b-ed99502b429f","order_by":5,"name":"Laura Kirstine Sønderberg Roos","email":"","orcid":"","institution":"Department of Clinical Genetics, Copenhagen University Hospital - Rigshospitalet","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"Kirstine Sønderberg","lastName":"Roos","suffix":""},{"id":583612067,"identity":"2cd17fa2-9bc0-4583-b8bb-76cf4355f9d7","order_by":6,"name":"Nuno V. Hermann","email":"","orcid":"","institution":"Pediatric Dentistry and Clinical Genetics, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen","correspondingAuthor":false,"prefix":"","firstName":"Nuno","middleName":"V.","lastName":"Hermann","suffix":""}],"badges":[],"createdAt":"2025-10-30 12:08:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7989161/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7989161/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101643668,"identity":"2dab2812-0112-48a0-a7b6-bd66814683fa","added_by":"auto","created_at":"2026-02-02 08:11:19","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":749308,"visible":true,"origin":"","legend":"\u003cp\u003ePanoramic x-ray of case 1 showing prolonged retention of primary teeth, delayed eruption of permanent teeth, teeth fusion and radiculomegaly in the primary canines and incisors.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7989161/v1/5ba59c4e3676a94fdd714b19.jpeg"},{"id":101754048,"identity":"dd50d63d-f3f0-4dad-aa29-32af76c2b72f","added_by":"auto","created_at":"2026-02-03 10:41:27","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":565768,"visible":true,"origin":"","legend":"\u003cp\u003ePanoramic x-ray of case 2 showing prolonged retention of primary teeth, delayed eruption of permanent teeth, radiculomegaly in primary canines and incisors.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7989161/v1/3738cc8a6ccb46da67e28dc5.jpeg"},{"id":101880706,"identity":"1addccec-78e3-483b-be2b-76a011a79350","added_by":"auto","created_at":"2026-02-04 15:05:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1833891,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7989161/v1/b9a027b5-0294-4d65-929e-630cc95d0917.pdf"},{"id":101643664,"identity":"56d1e732-968c-44bb-b39b-8d5cf970fdde","added_by":"auto","created_at":"2026-02-02 08:11:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":29946,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7989161/v1/f621f2f8ca31f0cb17f5d54f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Anomalies of the Primary Dentition in Patients with Oculo-Facio-Cardio-Dental (OFCD) Syndrome","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOculo-Facio-Cardio-Dental (OFCD) syndrome is a rare X-linked dominant disorder caused by pathogenic variants in the BCOR gene, which encodes the BCL6 corepressor protein. This protein remains incompletely understood; however, it has a critical function as a key transcriptional regulator during early embryogenesis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The estimated prevalence of OFCD syndrome is less than 1 per million and is observed almost exclusively in females due to the presumed embryonic lethality in males [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The cardinal features of the syndrome were delineated by Marashi and Gorlin (1992) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], and the causative gene was identified in 2004 by Ng et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe syndrome primarily affects structures derived from the ectoderm and neural crest, including the eyes, facial region, heart, and dentition. Commonly reported ocular anomalies in patients with OFCD syndrome include congenital cataract, microphthalmia, and progressive loss of vision. Characteristic facial features comprise a long, narrow face, high nasal bridge, and broad nasal tip with widely spaced nasal cartilages. Cardiac abnormalities vary but may include atrial or ventricular septal defects, mild cardiomegaly, and mitral valve prolapse. In some cases, skeletal anomalies such as syndactyly of the toes and radioulnar synostosis have also been reported [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe cardinal dental hallmark of OFCD syndrome is radiculomegaly (abnormally elongated dental roots) in the permanent dentition, especially affecting the canines but also observed in incisors and premolars [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Other reported dental anomalies include tooth agenesis, fusion, malposition, and markedly delayed eruption of teeth [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Considering the extreme rarity of radiculomegaly in the permanent canines in the general population, this trait is considered pathognomonic of OFCD syndrome [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, the value of this trait as a diagnostic marker is limited by the fact that the diagnosis cannot be made with certainty until adolescence, when the patient is 13\u0026ndash;15 years of age and the roots of the canines fully developed. Since variations in the BCOR gene have been shown to promote dentinogenesis and increase proliferation of periodontal ligament cells [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], it would seem likely that the primary dentition would be affected as well. However, most published case reports and reviews so far have focused exclusively on the permanent dentition [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIf the primary dentition, like the permanent dentition, shows a syndrome-specific pattern of dental anomalies, including radiculomegaly, these traits could be identified by age 3\u0026ndash;4 years, leading to a much earlier diagnosis and possible earlier treatment intervention which would be of great value for the patient.\u003c/p\u003e \u003cp\u003eThese facts underscore a clear need for a systematic investigation of the phenotype of the primary dentition in OFCD syndrome.\u003c/p\u003e \u003cp\u003eTo our knowledge, no publications have systematically correlated early dental findings with the later diagnosis of OFCD syndrome caused by pathogenic BCOR variants. This may represent a missed opportunity for an earlier identification of the syndrome, especially given that dental anomalies may be present well before other signs become clinically evident. Although many patients present with congenital cataract and microphthalmia, these ocular features can be subtle or mild; in such cases, characteristic dental anomalies, alone or in combination with mild eye findings, may constitute the first striking feature in early childhood and should prompt consideration of OFCD syndrome.\u003c/p\u003e \u003cp\u003eThis study aims to fill that knowledge-gap by providing a structured and detailed description of the phenotype of the primary dentition in reported patients with OFCD syndrome. A literature review on the syndrome was carried out with this focus in combination with description of two new Danish cases. Our goal is to highlight the importance of identifying early dental signs that could facilitate an earlier recognition and diagnosis of OFCD syndrome; especially in cases where ocular or cardiac anomalies may not yet have prompted further genetic evaluation.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003eA structured literature search was conducted in PubMed in May 2025 using the following search terms: (oculo facio cardio dental syndrome [Title/Abstract]) OR (OFCD[Title/Abstract]) OR (radiculomegaly [Title/Abstract])\u003c/p\u003e \u003cp\u003eThe search yielded 92 articles published between December 1990 and May 2025. Filters were applied to include only case reports, clinical studies, reviews, and systematic reviews, narrowing the dataset to 60 articles. Among these, only studies describing cases with genetically confirmed OFCD syndrome with molecular verification of a pathogenic BCOR gene variant were selected, resulting in 15 eligible articles describing 27 individual patient cases. From this cohort, we further selected only the patient cases that contained documented findings related to the primary dentition. Eighteen patient cases met this criterion. However, 12 of these patient cases relied solely on general statements or anecdotal observations on the dentition provided by caregivers or authors, without radiographic or clinical documentation. These cases were deemed insufficient for detailed phenotypic analysis.\u003c/p\u003e \u003cp\u003eThe remaining six cases provided objective and verifiable data including clinical photographs, panoramic radiographs, or cone beam CT images describing anomalies in the primary dentition. Accordingly, these six cases were included in the final review. In addition, we have included two identified Danish patients with genetically confirmed diagnosis of OFCD syndrome, whose cases have not previously been published, and we present detailed descriptions of their primary dentition.\u003c/p\u003e \u003cp\u003eIn total, eight cases with genetically confirmed OFCD syndrome and documented anomalies in the primary dentition were thus extracted and analyzed.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eA detailed presentation and structured assessment of the two Danish cases is first provided. As these patients have been followed longitudinally, information on the primary as well as the permanent dentition is included. Subsequently, the relevant findings are summarized in a comprehensive table (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) for the two Danish patients and the six additional patients included in the study.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCase Reports\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 1\u003c/strong\u003e \u003cp\u003e● \u003cem\u003eGeneral information\u003c/em\u003e\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 1\u003c/strong\u003e \u003cp\u003eis a female born by planned cesarean section at 39\u0026thinsp;+\u0026thinsp;0 weeks of gestation following an uneventful pregnancy. At 10 days of age, she was hospitalized due to neonatal jaundice. During this admission, a congenital malformation of the female genital tract was identified. At 7 weeks of age, she was diagnosed with bilateral congenital cataracts and underwent early ophthalmic surgery.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eDevelopmental delays in both motor and speech domains were noted by age two years, although she responded well to early intervention. At age five years, the patient was referred for genetic evaluation based on the presence of congenital cataract. Clinical examination revealed subtle dysmorphic features, including microphthalmia and a depressed nasal bridge. Initial dental examination showed delayed tooth eruption and fused primary mandibular incisors. According to the parents, the first tooth had erupted around the age of 1.5 years. Despite slightly reduced motor activity, overall neurodevelopment was within normal limits. Initial growth delay had normalized over time. Cardiac evaluation at the time showed no structural heart anomalies. However, a follow-up echocardiogram later demonstrated increased trabeculation in the left ventricle and an accessory chord, interpreted as a normal anatomical variant.\u003c/p\u003e \u003cp\u003eGenetic testing revealed a likely pathogenic nonsense variant in the BCOR, confirming the diagnosis of oculo-facio-cardio-dental (OFCD) syndrome. Neither parents nor the patient\u0026rsquo;s two brothers were genetically tested; all appeared clinically unaffected.\u003c/p\u003e \u003cp\u003eAt age 7.5 years, the patient was referred to the Resource Centre for Rare Oral Diseases, Copenhagen University Hospital, Rigshospitalet for a specialized dental assessment.\u003c/p\u003e \u003cp\u003eRadiographic assessment included six panoramic X-rays taken at age 7.5, 8 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), 9, 10, 11 and age 12 at Copenhagen University Hospital. These panoramic X-rays, combined with clinical findings, formed the basis for the assessment of the dentitions.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in the number of teeth\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eClinical examination showed eruption of the primary dentition; however, hypodontia was present in the incisal region of the lower jaw, where only a single but markedly broad primary mandibular central incisor was present, suggesting a possible fusion anomaly. Panoramic radiography confirmed the suspected fusion of the primary mandibular central incisors (#71 and #81), with root formation observed only on #81. The X-ray showed agenesis of the permanent mandibular left central incisor (#31).\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in crown and root morphology\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eCoronal fusion of #71 and #81 was radiographically evident, with root formation limited to #81. Macrodontia was observed in the maxillary permanent central and lateral incisors (#21, #22).\u003c/p\u003e \u003cp\u003eThe root morphology of those present primary incisors and canines appeared elongated and gracile. Calibrated measurements on the panoramic X-ray demonstrated an up till 6.31 mm increase in tooth length (see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) compared to normative values [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Radiculomegaly, defined as excessive root elongation, could therefore be confirmed in 11 (#53, #52, #51, #61, #62, #63, #73, #72, #81, #82, #83) of the 11 present primary incisors and canines.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in tooth maturation\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThe permanent incisors and canines were in initial stages of root development, stages R\u0026frac14; - Ri for incisors and Cc - Ri for canines, corresponding to the average dental age of a 5.5-6.5-year-old [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In contrast, development of premolars and molars aligned with the chronological age of 7.5 years.\u003c/p\u003e \u003cp\u003eDelayed development and maturation were noted in teeth #13, #12, #11, #21, #22, #23, #32, #33, #41, #42 and #43.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in dental hard tissues\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eNo anomalies were identified in dental hard tissues based on clinical and radiographic examination.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in tooth position\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003ePanoramic X-ray revealed that #11 was rotated 90 degrees and #21 exhibited a distally angulated eruption path.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in tooth eruption and shedding\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eClinically, the mandibular permanent first molars had fully erupted, whereas the maxillary counterparts (#16, #26) remained unerupted at the time of assessment. According to the Atlas of Human Tooth Development and Eruption [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], this eruption delay corresponds to 1\u0026ndash;2 years. Delayed physiological root resorption was observed in teeth #52, #51, #72, and #82. Root length of these teeth could be clearly assessed in the X-ray and appeared intact, without signs of resorption. This was noteworthy given the developmental stage of their permanent successors.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 2\u003c/strong\u003e \u003cp\u003e● \u003cem\u003eGeneral information\u003c/em\u003e\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 2\u003c/strong\u003e \u003cp\u003eis a female born full-term after an uneventful pregnancy. She was hospitalized shortly after birth because of failure to thrive and jaundice. Due to abnormal facial appearance a karyotype was done but came back normal. Echocardiography was unremarkable. She was diagnosed with microphthalmia and bilateral congenital cataracts and underwent early lens removal. Subsequent ophthalmia on the left eye resulted in significantly impaired vision. Secondary glaucoma was diagnosed later in childhood, further reducing vision. Mild bilateral hearing loss was also reported. Syndactyly of the second and third toes was noted. Early motor development was slightly delayed possibly due to vision impairment and recurrent surgery and treatment but normalized within the first two years. Overall cognitive and mental function were within normal limits.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eThe girl was referred to the Resource Centre for Rare Oral Diseases, Aarhus University Hospital, at the age of 12 years due to findings of dental agenesis and disturbances of tooth eruption noted by the municipal school dental service.\u003c/p\u003e \u003cp\u003eFacial examination revealed deep-set eyes, microphthalmia and ptosis. She had a high nasal bridge, broad nasal tip with separated nasal cartilages and increased lower facial height. The palate was narrow, and multiple dental anomalies and eruption disturbances were evident. According to her parents, tooth eruption had been delayed, with the first tooth erupting around the age of one. At this time a clinical diagnosis of OFCD syndrome was proposed. At age 14 she underwent surgery for scoliosis.\u003c/p\u003e \u003cp\u003eAt age 24 she was referred to the Department of Clinical Genetics, Aalborg University Hospital. Genetic analysis revealed a variant of unknown significance in BCOR gene which after confirmation of its de novo origin was reclassified as likely pathogenic.\u003c/p\u003e \u003cp\u003eRadiographic assessment included two panoramic X-rays: one taken at age 9 at the municipal school dental service and another at age 12 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). These panoramic X-rays, combined with clinical findings, formed the basis for the assessment of the dentitions.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in tooth number\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThe patient had agenesis of the permanent maxillary lateral incisors (#12 and #22).\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in crown and root morphology\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eRadiculomegaly was evident in the primary teeth #72, #63, #73 and #83. The maxillary permanent central incisors exhibited pronounced cingula forming distinct talon-cusp-like tubercles and the roots demonstrated unusually wide pulp canals. The initial root development of the permanent canines appeared remarkably broad and divergent.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in tooth maturation\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eDevelopment of the permanent premolars appeared mildly delayed on the panoramic X-ray at age 12, particularly in teeth #34 and #44. The permanent canines were at an earlier stage of development, with root formation corresponding to an average dental age of 8.5\u0026ndash;9.5 years, indicating a delay of approximately 3 years. The right permanent mandibular central incisor #41 remained immature, with root development consistent with that of a 7-year-old child, representing a 5-year delay.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in dental hard tissues\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003ePulp stone-like calcifications were observed apically in teeth #13, #34, #43, and #44.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in tooth position\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eBoth permanent maxillary canines, #13 and #23, had drifted mesially. The permanent maxillary right canine, #13, was horizontally positioned in the jaw. Both permanent mandibular canines were deeply impacted. In addition, #43 was mesioangulated, and #33 was rotated 90 degrees. Additionally, two permanent mandibular incisors were rotated 90 degrees, due to crowding of the permanent lower anterior teeth, particularly #41, #31, and #32, all of which appeared deeply impacted in the mandible on the panoramic radiograph taken at age 9.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eAnomalies in eruption and shedding\u003c/em\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eOn the panoramic radiograph taken at age 9, persistence of primary teeth #82, #81, #71 and #72 was noted. These teeth would typically have been shed by age 6\u0026ndash;7. By age 12, primary teeth #63, #72, #73 and #83 remained without signs of physiological root resorption. The permanent incisors #41, #31, and #32 were at an eruption stage consistent with that of a 5-6-year-old, indicating an estimated eruption delay of approximately three years.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Summary of Clinical Findings\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the findings from the two Danish (case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and case \u003cspan refid=\"FPar3\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and the six selected OFCD syndrome cases [\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], with documented anomalies in the primary dentition. Only five cases had radiographic documentation of the dentition needed for assessment of e.g., root morphology. The most prominent phenotypic feature in the primary dentition was the presence of radiculomegaly in all cases, where relevant data were available (5/5; 100%). In total, 31 primary teeth (14 canines and 17 incisors) were recorded with radiculomegaly for the 5 cases (see Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The tooth type most frequently affected would seem to be the canine and more frequently in the mandible than in the maxilla. All five cases had radiculomegaly of at least one canine, and 4/5 had radiculomegaly of at least one incisor. Case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e had radiculomegaly of 11 teeth (4 canines and 7 incisors). Case 7 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] had radiculomegaly of 8 teeth (2 canines and 6 incisors), and Case 4 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] had radiculomegaly of 7 teeth (4 canines and 3 incisors). Because the data were not reported consistently across all eight published cases, the denominators below reflect only those cases with relevant information.\u003c/p\u003e \u003cp\u003eDelayed eruption of primary teeth was documented in all three cases for which eruption data were available (3/3; 100%). Delayed shedding or persistence was reported in all six cases with shedding data (6/6; 100%). Fusion of primary teeth was observed in five of the eight cases with sufficient documentation (5/8; 63%), and all fusions involved incisors. Agenesis of primary teeth was identified in three of the five cases with complete agenesis data (3/5; 60%), with each of these patients missing two primary incisors.\u003c/p\u003e\u003cp\u003eIt was established that crown formation of the mandibular first permanent molar was complete, as evidenced by its developmental stage corresponding to stage R\u0026frac34; in the Liversidge classification. Therefore, the reference crown height for this tooth, defined for the completed crown stage, was used for calibration. In the panoramic x-ray, the crown height of the mandibular first permanent molar was measured to be 10 mm. Based on the known actual crown height from Liversidge\u0026rsquo;s data, a multiplication factor was applied to convert radiographic measurements into estimated true tooth lengths for patient 1.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eAlthough more than 30 case reports and small patient series of OFCD syndrome have been published to date, the majority focus primarily on ocular, cardiac, or craniofacial manifestations. Dental findings are often mentioned only briefly and without sufficient clinical detail, particularly regarding anomalies in the primary dentition, even though it is well established that dental anomalies may affect both the primary and permanent dentitions [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In many reports, radiographic documentation and intraoral photographs are absent, and anomalies in tooth morphology, eruption patterns, and root formation are described only in general terms.\u003c/p\u003e \u003cp\u003eThis limited documentation is reflected in specific examples, where the dental component is reduced to a short remark, such as \u0026ldquo;teeth with radiculomegaly\u0026rdquo; [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] or a simple table entry of \u0026ldquo;Radiculomegaly\u0026rdquo; without details of the affected teeth [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The authors of an article describing a OFCD case, a nine-year-old was noted to have \u0026ldquo;not had dental problems,\u0026rdquo; while it was also mentioned that \u0026ldquo;parents reported she had long roots of her teeth\u0026rdquo; [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], however, the source or basis of this parental observation was not clarified in the article. Ragge et al. (2019) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] reported that among 85 examined OFCD cases, four were recorded without dental anomalies. It is possible that additional dental findings might have been identified in those cases if more detailed data or specialist dental assessment had been available. These examples illustrate how key dental diagnostic indicators can occasionally be underrecognized. One contributing factor may be that many OFCD-related publications originate from medical specialities outside dentistry, such as ophthalmology, medical genetics or cardiology, and are often published in subspeciality medical journals [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile this reflects the multisystemic nature of OFCD syndrome, it may also explain why the dental findings are inconsistently described and only rarely evaluated in a systematic or standardized manner. In several publications, it appears that no dental professionals were involved in the clinical evaluation or authorship, which may account for some of the variability in terminology and interpretation of dental features. These challenges underscore the complexity of drawing consistent conclusions from the existing literature. Potential sources of bias include selection bias, as cases may be included or excluded depending on the completeness of clinical and radiographic records, and information bias, resulting from differences in clinical expertise or documentation quality. This makes it difficult to establish a reliable and comparable dataset across published cases. For example, Hilton et al. (2009) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] reported on 30 females with OFCD syndrome, of whom eight had documented findings in the primary dentition. While six of these eight showed delayed eruption and/or persistence, the primary dentition was not analyzed in a structured manner. Similarly, Yamashita et al. (2023) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] concluded that radiculomegaly was a feature limited to the permanent dentition and could not yet be assessed in their pediatric patient. Sauvestre et al. (2024) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] likewise stated that radiculomegaly could not be identified in 13 younger patients included in their review.\u003c/p\u003e \u003cp\u003eOur findings suggest that this statement may reflect limitations in the available radiographic data or the absence of dental specialists involved in the evaluation, rather than a true lack of radiculomegaly in early dentition. When appropriate imaging is available, and interpreted by clinicians with dental expertise, radiculomegaly can often be detected already in the primary or early mixed dentition. In support of this, Nishiguchi et al. (2018) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] described a case of remarkable radiculomegaly in the primary dentition of a child with OFCD, reinforcing the relevance of dental findings in early diagnosis.\u003c/p\u003e \u003cp\u003eGiven that radiculomegaly in primary teeth is exceedingly rare in the general population (\u0026lt;\u0026thinsp;0.001%), and that agenesis of primary teeth is also uncommon (0.6%; Ravn, 1971) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], the presence of either anomaly should prompt consideration of an underlying syndrome. In this light, early dental assessment may serve as an important diagnostic gateway to identifying OFCD syndrome at an earlier stage, particularly in children who have not yet developed recognizable ocular or cardiac findings.\u003c/p\u003e \u003cp\u003eThe underlying mechanisms of radiculomegaly in OFCD syndrome remain incompletely understood. However, experimental studies suggest that the BCOR gene may play a role in dentinogenesis and root elongation. For example, Surapornsawasd et al. (2014) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] found that BCOR is expressed in dental pulp and periodontal ligament cells, while Larhant et al. 2014, [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] proposed that root elongation in OFCD syndrome may be linked to disturbed dentinogenesis, noting that BCOR silencing in mice results in dentine abnormalities, and that dental mesenchymal stem cells from OFCD patients show increased dentine formation potential. These findings support the hypothesis that BCOR may play a role in dentinogenesis and in regulation of dental root development, although further studies of these mechanisms are needed.\u003c/p\u003e \u003cp\u003eOverall, our study contributes to the emerging recognition of the primary dentition as a relevant site for early diagnosis of OFCD syndrome. A structured dental assessment, particularly when conducted by pediatric dentists familiar with OFCD syndrome, may enable identification of characteristic features such as radiculomegaly, fusion, and delayed eruption or shedding, years before a definitive diagnosis might otherwise be made. Earlier recognition at the dental level can in turn prompt timely referral for comprehensive genetic testing and targeted evaluation by ophthalmology, cardiology, and other relevant specialties, allowing associated ocular and cardiac manifestations to be detected and managed at an earlier stage. This reinforces the value of interdisciplinary collaboration and highlights the need for increased dental awareness in rare syndromic disorders.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThe present study demonstrates a consistent pattern of anomalies in the primary dentition of patients with OFCD syndrome. Radiculomegaly of canines and incisors, delayed eruption and shedding were present in all cases with radiographs available, while fusion and agenesis were observed in approximately 60% of cases. All recorded anomalies predominantly involved the canine\u0026ndash;incisor regions.\u003c/p\u003e \u003cp\u003eThese findings indicate that dental anomalies in OFCD syndrome are not limited to the permanent dentition but may also be present in the primary dentition. Although based on a limited dataset, the results align with previous case reports and highlight the important role of oral health professionals in recognizing early phenotypic features of the syndrome.\u003c/p\u003e \u003cp\u003eThe syndrome-specific triad of radiculomegaly, delayed eruption, and persistence of teeth should therefore be regarded as equally relevant in the primary as in the permanent dentition. Early clinical and radiographic evaluation by an experienced pediatric dentist is essential, as dental findings may provide key clues for the diagnosis in combination with genetic testing. Such early recognition not only enables appropriate dental treatment but also facilitates earlier detection and management of OFCD\u0026rsquo;s ocular, cardiac, and other systemic manifestations, benefiting both the patient and their family as well as the wider healthcare team.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBCOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBCL6 Corepressor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOFCD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOculo-Facio-Cardio-Dental syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCBCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCone Beam Computed Tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a retrospective case series combined with a literature review. No experimental procedures or interventions were performed, and all data were obtained from existing clinical records and diagnostic material collected as part of routine clinical care.\u003c/p\u003e\n\u003cp\u003eAccording to Danish legislation, retrospective studies based solely on previously collected clinical data do not require approval from a regional ethics committee. Therefore, formal ethics committee approval was not required for this study.\u003c/p\u003e\n\u003cp\u003eInformed consent for participation and use of clinical data and images for research and publication purposes was obtained from all patients and/or their parents or legal guardians. The study was conducted in accordance with the Declaration of Helsinki (2024 revision).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of anonymized clinical and radiographic information was obtained from the parents/legal guardians of both Danish patients included in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the findings of this study are included within the article. Additional details can be made available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMV designed the study, performed the literature review, collected and analyzed dental and radiographic data, prepared tables and figures, and drafted the manuscript.\u003c/p\u003e\n\u003cp\u003eSK contributed to the interpretation of dental findings, manuscript structure, and critical revisions.\u003c/p\u003e\n\u003cp\u003eCK contributed to manuscript revisions.\u003c/p\u003e\n\u003cp\u003eXH contributed to manuscript revisions.\u003c/p\u003e\n\u003cp\u003eAS contributed genetic expertise, variant interpretation, and manuscript revisions.\u003c/p\u003e\n\u003cp\u003eLR contributed to the genetic evaluation and verification of BCOR variants.\u003c/p\u003e\n\u003cp\u003eNVH supervised the project, contributed to study design and interpretation, and critically revised the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the families who consented to the use of clinical and radiographic data in this study. The authors also acknowledge the support of the Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital, Rigshospitalet and the Resource Centre for Rare Oral Diseases, Copenhagen University Hospital, Rigshospitalet.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWamstad JA, Corcoran CM, Keating AM, Bardwell VJ. Role of the transcriptional corepressor BCOR in embryonic stem cell differentiation and early embryonic development. PLoS ONE. 2008;3(7):e2814. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0002814\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0002814\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarashi AH, Gorlin RJ. Radiculomegaly of canine teeth and congenital cataracts: confirmation of a syndrome. 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J Hum Genet. 2014;59:297\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRagge N, Isidor B, Bitoun P, et al. Expanding the phenotype of the X-linked BCOR. Hum Genet. 2019;138:1051\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoleiro A, Oliveira J, Grangeia A, et al. Ocular severe involvement in oculofaciocardiodental syndrome: description of a case series. Eur J Ophthalmol. 2024;34(1):NP6\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/11206721231170406\u003c/span\u003e\u003cspan address=\"10.1177/11206721231170406\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorgan T, Colazo JM, Duncan L, Hamid R, Joos K. Two cases of oculofaciocardiodental (OFCD) syndrome due to X-linked BCOR mutations presenting with infantile hemangiomas: phenotypic overlap with PHACE syndrome. Case Rep Genet. 2019;2019:9382640. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2019/9382640\u003c/span\u003e\u003cspan address=\"10.1155/2019/9382640\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRavn JJ. Aplasia, supernumerary teeth and fused teeth in the primary dentition: an epidemiologic study. Scand J Dent Res. 1971;79(1):1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Oculo-Facio-Cardio-Dental syndrome, OFCD, children, primary dentition, radiculomegaly, long roots, dental anomalies","lastPublishedDoi":"10.21203/rs.3.rs-7989161/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7989161/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOculo-Facio-Cardio-Dental (OFCD) syndrome is a rare X-linked dominant disorder caused by pathogenic variants in BCOR gene primarily affecting structures derived from ectoderm and neural crest, including the eyes, facial region, heart, and dentition. The cardinal dental hallmark is radiculomegaly in the permanent dentition, especially affecting the canines but also observed in incisors and premolars. Since variations in the BCOR gene have been shown to promote dentinogenesis, it seems likely that the primary dentition would be affected as well. However, most of the literature on the subject so far has focused on the permanent dentition. The aim of the present study was to provide a detailed description of the phenotype of the primary dentition in OFCD syndrome.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eLiterature review including patients with genetically verified OFCD syndrome with focus on the primary dentition in combination with description of two new Danish cases.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe most prominent phenotypic feature in the primary dentition was the presence of radiculomegaly in all cases, where relevant data were available. The tooth type most frequently affected was the canine (mandible\u0026thinsp;\u0026gt;\u0026thinsp;maxilla) followed by the incisors. Delayed eruption of primary teeth and later shedding/persistence was also noted together with fusion of the primary teeth.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings indicate that radiculomegaly in OFCD syndrome may be present already in the primary dentition. Therefore, early clinical and radiographic evaluation by an experienced pediatric dentist is essential, as dental findings may provide key clues for the diagnosis, and in combination with genetic testing may lead to timely and sufficient treatment intervention resulting in improved oral quality of life for the patient and support earlier recognition and management of OFCD\u0026rsquo;s ocular, cardiac, and other systemic manifestations.\u003c/p\u003e","manuscriptTitle":"Anomalies of the Primary Dentition in Patients with Oculo-Facio-Cardio-Dental (OFCD) Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-02 08:09:48","doi":"10.21203/rs.3.rs-7989161/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-19T17:44:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"145956984625507538005397364445051784016","date":"2026-02-12T18:53:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-12T16:36:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T19:38:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"320710667603530662031241914505075396764","date":"2026-02-05T13:32:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-04T09:25:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"154227175626012882369995610382908113858","date":"2026-02-04T05:53:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"128995127551891144991740921955779720792","date":"2026-02-03T14:26:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"84136203867030894767929857255630583661","date":"2026-01-31T18:59:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-29T13:25:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-25T07:18:07+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-17T06:44:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-12T16:55:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2025-12-12T16:46:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"765b2e8c-15b0-4a3d-9a7b-a43fe210cb41","owner":[],"postedDate":"February 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-06T06:59:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-02 08:09:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7989161","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7989161","identity":"rs-7989161","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}