BACKGROUND: The oculo-facio-cardio-dental syndrome (OFCD) is an ultra-rare multiple congenital anomaly. This report describes clinical findings emphasising dental phenotype in five, molecularly confirmed, female cases from two Czech families. CASE PRESENTATION: Dental examinations were carried out. An orthopantomogram was taken in three patients, and all patients' intraoral cavities and teeth were photographed. Exome sequencing was performed in both probands. Results were validated by Sanger DNA sequencing which was also used to follow segregation of the variants in first-degree relatives. Dental abnormalities and congenital cataracts were present in all five cases, whilst other signs were variable and included facial dysmorphism, microphthalmia, and cardiac and skeletal abnormalities. Two individuals had cleft lip and/or cleft palate. Radiculomegaly occurred in three patients with permanent teeth and was diagnosed on orthopantomograms. Two patients had agenesis of permanent teeth. Malocclusion was also present in two patients due to crowding and a Class III malocclusion and mandibular overjet. De novo novel pathogenic variants in the BCOR gene were identified; c.2382del p.(Lys795Argfs*12) and c.3914dup p.(Gln1306Alafs*20) and co-segregated with the disease in each family. CONCLUSIONS: The OFCD syndrome has a unique dental phenotype and dentists should be aware of signs of this ultra-rare genetic disorder. All patients with congenital cataracts and dental abnormalities, including those without a family history, should be referred for genetic testing and indicated to specialised dental care.

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University Motol University Hospital Prague Czech Republic

Department of Ophthalmology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Stomatology 2nd Faculty of Medicine Charles University Motol University Hospital Prague Czech Republic

Zobrazit více v PubMed

Fan Z, Yamaza T, Lee JS, Yu J, Wang S, Fan G, et al. BCOR regulates mesenchymal stem cell function by epigenetic mechanisms. Nat Cell Biol. 2009;11(8):1002–9. 10.1038/ncb1913. PubMed PMC

Schulze BR, Horn D, Kobelt A, Tariverdian G, Stellzig A. Rare dental abnormalities seen in oculo-facio-cardio-dental (OFCD) syndrome: three new cases and review of nine patients. Am J Med Genet. 1999;82(5):429–35. 10.1002/(sici)1096-8628(19990219)82:5%3C429::aid-ajmg13%3E3.0.co;2-s. PubMed

Mezad-Koursh D, Rosenfeld E, Bachar Zipori A, Zur D, Elhanan E, Ben-Shachar S. A rare genotype of biallelic mosaic variants in BCOR gene causing a bilateral ocular anterior segment dysgenesis and cataracts. Eur J Hum Genet. 2023;31(1):125–7. 10.1038/s41431-022-01195-7. PubMed PMC

Verma G, Singh GK, Tandon P, Verma SL. A rare syndrome with unusual dental findings: Oculo-Facio-cardio-dental syndrome. J Oral Maxillofac Pathol. 2014;18(2):331. 10.4103/0973-029X.140928. PubMed PMC

Hayward JR. Cuspid gigantism. Oral Surg Oral Med Oral Pathol. 1980;49(6):500–1. 10.1016/0030-4220(80)90070-5. PubMed

Martinho J, Ferreira H, Paulo S, Paula A, Marto CM, Carrilho E, Marques-Ferreira M. Oculo-Facio-Cardio-Dental Syndrome: a Case Report about a Rare Pathological Condition. Int J Environ Res Public Health. 2019;16(6):928. 10.3390/ijerph16060928. PubMed PMC

Ragge N, Isidor B, Bitoun P, Odent S, Giurgea I, Cogne B, et al. Expanding the phenotype of the X-linked BCOR microphthalmia syndromes. Hum Genet. 2019;138(8–9):1051–69. 10.1007/s00439-018-1896-x. PubMed

Aalfs CM, Oosterwijk JC, Van Schooneveld MJ, Begeman CJ, Wabeke KB, Hennekam RC. Cataracts, radiculomegaly, septal heart defects and hearing loss in two unrelated adult females with normal intelligence and similar facial appearance: confirmation of a syndrome? Clin Dysmorphol. 1996;5:93–103. 10.1097/00019605-199604000-00001. PubMed

Hilton EN, Manson FD, Urquhart JE, Johnston JJ, Slavotinek AM, Hedera P, Stattin EL, Nordgren A, Biesecker LG, Black GC. Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination. Hum Mol Genet. 2007;16:1773–82. 10.1093/hmg/ddm125. PubMed

Gorlin RJ, Marashi AH, Obwegeser HL. Oculo-Facio-cardio-dental (OFCD) syndrome. Am J Med Genet. 1996;63(1):290–2. 10.1002/(SICI)1096-8628(19960503)63:1%3C290::AID-AJMG47%3E3.0.CO;2-G. PubMed

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(4):411–6. 10.1038/ng1321. PubMed

Hu Q, Mai J, Xiang Q, Zhou B, Liu S, Wang J. A novel deletion mutation in the BCOR gene is associated with oculo-facio-cardio-dental syndrome: a case report. BMC Pediatr. 2022;22(1):82. 10.1186/s12887-022-03148-x. PubMed PMC

Huynh KD, Fischle W, Verdin E, Bardwell VJ. BCoR, a novel corepressor involved in BCL-6 repression. Genes Dev. 2000;14(14):1810–23. PubMed PMC

Horn D, Chyrek M, Kleier S, Luttgen S, Bolz H, Hinkel GK, Korenke GC, Riess A, Schell-Apacik C, Tinschert S, Wieczorek D, Gillessen-Kaesbach G, Kutsche K. Novel mutations in BCOR in three patients with oculo-facio-cardio-dental syndrome, but none in Lenz microphthalmia syndrome. Eur J Hum Genet. 2005;13(5):563–9. PubMed

ADA. Clinical Practice Guidelines and Dental Evidence. https://www.ada.org/resources/research/science-and-research-institute/evidence-based-dental-research

Ensenberger MG, Thompson J, Hill B, Homick K, Kearney V, Mayntz-Press KA, et al. Developmental validation of the PowerPlex 16 HS System: an improved 16-locus fluorescent STR multiplex. Forensic Sci Int Genet. 2010;4(4):257–64. 10.1016/j.fsigen.2009.10.007. PubMed

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24. 10.1038/gim.2015.30. PubMed PMC

Yamashita T, Hotta J, Jogu Y, Sakai E, Ono C, Bamba H, Suzuki H, Yamada M, Takenouchi T, Kosaki K, Yorifuji T, Hamazaki T, Seto T. Oculofaciocardiodental syndrome caused by a novel BCOR variant. Hum Genome Var. 2023;10(1):18. 10.1038/s41439-023-00244-x. PubMed PMC

Lozic B, Ljubkovic J, Panduric DG, Saltvig I, Kutsche K, Krzelj V, et al. Oculo-Facio-cardio-dental syndrome in three succeeding generations: genotypic data and phenotypic features. Braz J Med Biol Res. 2012;45(12):1315–9. 10.1590/s0100-879x2012007500150. PubMed PMC

Kawamoto T, Motohashi N, Ohyama K. A case of oculo-facio-cardio-dental syndrome with integrated orthodontic-prosthodontic treatment. Cleft Palate Craniofac J. 2004;41(1):84–94. 10.1597/02-133. PubMed

Davoody A, Chen IP, Nanda R, Uribe F, Reichenberger EJ. Oculofaciocardiodental syndrome: a rare case and review of the literature. Cleft Palate Craniofac J. 2012;49(5):e55–60. 10.1597/10-256. PubMed PMC

Smith MH, Cohen DM, Bhattacharyya I, Islam NM, Kashtwari D. Radiculomegaly: a case report of this rare dental finding with review of the associated oculo-facio-cardio-dental syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;126(4):e220–7. 10.1016/j.oooo.2018.02.011. PubMed