Introduction

Oculo-facio-cardio-dental (OFCD) is a sporadic syndrome (OFCD, MCOPS2; OMIM #300166) involving abnormalities in patients' eyes, face, heart, and teeth. As it was related to dental abnormalities, this condition may often be discovered by dentists.

In 1980, Hayward [1] was the first person to the relationship between a patient’s abnormally long teeth and congenital cataracts. In 1990, Marashi and Gorlin [2] reported three similar cases and hypothesized that abnormal root size and congenital cataracts could be characteristics of a specific syndrome. In 1993, Wilkie et al. [3] demonstrated a case of a mother and her daughter presenting with ocular, facial, cardiac, and dental abnormalities. He believed that it was an X-linked dominant disorder. Gorlin et al. [4] in 1996 named it OFCD syndrome. To date, there were no more than 100 OFCDs cases have been reported all over the world. In those reports, the most of patients were female. The study conducted by David Ng has demonstrated that OFCD syndrome is associated with a genetic variant located on the X chromosome [5].

Despite the presence of characteristic symptoms affecting the facial structures and teeth of patients, the rarity of the condition may increase the likelihood of misdiagnosis by physicians as other disorders [6, 7].

As a result, this article aims to summarize symptoms of this extremely rare syndrome and report an OFCD—diagnosed female patient with a discovery of a novel gene variant of BCOR. This was the first reported case of this syndrome in Viet Nam.

Case report

The case presents a 19-year-old Vietnamese female patient who came to the Maxillofacial Surgery Department of the National Hospital of Odonto-Stomatology in Ho Chi Minh City with a periapical infection and a fistula that had developed from her left mandibular canine. The patient's past medical history was obtained by interviewing both the patient and her mother, and all patient-specific information was de-identified. Written informed consent was obtained from the patient’s legal guardian for the publication of photographs and any accompanying information for the purpose of this case report.

Past medical history

Strabismus was detected at six months old. At the age of four, she was diagnosed with congenital cataracts. She underwent surgery to remove her cloudy lenses and had them replaced with new, artificial lenses (IOLs—Intraocular Lenses). At 14 years old, she was diagnosed with congenital cardiac diseases, including ostium secundum atrial septal defect, pulmonary artery hypertension and 4/4 leaky tricuspid valves. Furthermore, upon examining the patient's mother, we observed the presence of strabismus, even though no evidence of radiculomegaly was found on her panoramic radiograph.

There was no family history of any genetic diseases. The patient has two younger sisters with typical development. The patient's mother reported a fever and was hospitalized for one week at 22 weeks gestation. No abnormalities were detected during her mother's antenatal ultrasounds.

Extra-oral examination

Clinically, the patient presented with a long and broad face, as well as a concave facial profile in the lateral view. Other physical features included thick eyebrows, a broad and protrusive mandible, and eye abnormalities such as strabismus and microphthalmia on the left side. Visual impairment was present in both eyes, and there were no signs of secondary glaucoma. Additionally, a broad nasal tip with separation of anterior cartilage nasal was observed, along with a fistula on the left chin surrounded by an inflammatory area (Figs. 1, 2). There were no signs of hearing impairment, protruding or hypoplastic ears. The patient had normal pronunciation, but presented with intellectual disability.

Fig. 1
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Strabismus, microphthalmia on her left side

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Fig. 2
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Bifid nasal tip

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Limb examination

The patient presented with IV-toe camptodactyly and a I-hammer toe. There were no abnormalities detected in her hands (Figs. 3, 4). She did not have hearing impairment, protruding ears, or hypoplastic ears. Her pronunciation was normal, but she had intellectual disability. Radiograph examination revealed IV-toe camptodactyly and I-hammer toe, and her hand radiograph did not show any abnormality (Fig. 5).

Fig. 3
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Abnormal foot development (IV—toe camptodactyly and a I—hammer toe)

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Fig. 4
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Long and slender fingers

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Fig. 5
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Foot X-ray and hand X-ray

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Oral examination

The patient had a narrow, high-arched palate, with severely crowded teeth and multiple dental caries. Specifically, teeth 11, 12, 16, 21, 26, 32, 33, 36, 43, 46, and 47 had significant decay and required further dental treatments, including extractions and endodontic procedures. Additionally, glossitis was present (Fig. 6).

Fig. 6
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Intra examination showed high arched palate, many dental decays, and mal-occlusion with malposition of teeth 33, 34, 44, 25, heavy dental plaque, stomatitis, glossitis, and bifid uvula was also seen

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Radiograph findings

The Panoramic radiograph revealed a condition of severe crowding of the teeth with malposition of teeth 34, 44, retained roots of teeth 11, 12, 21, 26, 32, 33, 36, 43, 46 with many dental decays. The impacted tooth 24 was also noted. Additionally, the lower premolars and upper right second premolar showed signs of radiculomegaly. Furthermore, the lower anterior teeth had very long roots, and the 37 appeared taurodontic. The 48 was under-developed for 19 years of age. Notably, elongated canines' roots with open apices were demonstrated in all quadrants of her jaws. Moreover, a periapical infection was detected on her left mandibular canine through the panoramic radiograph (Fig. 7).

Fig. 7
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Panoramic panoramic radiograph revealed seriously crowding teeth, many dental caries and radiculomegaly canine with open apices

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Genetic analyses

Genomic DNA was extracted from peripheral blood using the GeneJET™ Whole Blood Genomic DNA Purification Mini Kit (Thermo Fisher Scientific, MA, USA). Genomic DNA was used to amplify exons 1 through 15 and the exon–intron boundaries of the BCOR gene using pairs of PCR primers designed by our own. Purified PCR products were sequenced in both directions using Big Dye Version 3.1 and an ABI 3500 Genetic Analyzer (Applied Biosystems, CA, USA). As a result, the patient was found to be heterozygous for a novel single-base deletion within intron 11 (IVS11-2delA) of the BCOR (Fig. 8).

Fig. 8
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BCOR gene sequencing results: detected heterozygous variant IVS11-2delA on intron 11 of BCOR gene

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Diagnosis and treatment

The patient was diagnosed with periapical infection resulting from her left mandibular canine, and was found to have OFCD syndrome. The treatment plan included a root canal treatment for the affected tooth followed by an extraoral apicoectomy to remove the fistula on her left chin (Figs. 9, 10).

Fig. 9
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Panoramic film after root canal treatment

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Fig. 10
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Extraoral apicoectomy with a fistula removal

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Follow up

The patient experienced no pain or discomfort in the surgical area. An OPG was taken two weeks post-surgery, and no abnormalities were observed on the X-ray. The patient was re-examined 4 months after surgery and reported no chin pain. At that moment, we did not conduct an X-ray. No adverse events were documented.

Discussion

OFCD is a rare genetic syndrome with no more than 100 cases reported in literature [8,9,10], characterized by ocular, facial, cardiac, and dental abnormalities. Early and definitive diagnosis of this syndrome is considered problematic. However, OFCD syndrome has some specific dental symptoms, including an extreme elongation of canine roots and an open apex. Fortunately, these signs could be easily identified on panoramic dental radiograph.

OFCD syndrome has been misdiagnosed as maternal exposure to rubella during pregnancy [6, 11, 12]. However, in some cases, abnormal symptoms in the teeth, particularly radiculomegaly, and the absence of maternal rubella infection during pregnancy, help to differentiate the diagnosis [13]. In addition to the four main symptoms (including ocular, facial, cardiac, and dental), OFCDs patients often have the abnormality in the ears (hearing impairment, protruding ears, hypoplastic ears) [10, 12, 14], extremities (toe syndactyly, hammer toes, radioulnar synostosis) [6, 10, 15] and mental retardation [6, 10, 16]. Numerous cases with several BCOR variants have been reported in the medical literature [8, 9, 13, 14, 17,18,19,20,21,22,23,24,25,26,27] (see Table 1). In our report, the patient's chief complaint was the appearance of a fistula developing from her left mandibular canine. She was then indicated to take a panoramic radiograph, and we found that all her canine teeth had extreme elongation with their apex opening. Clinical examination and medical history demonstrated that this patient had abnormalities in her eyes (congenital cataract, cross-eyed), her face (long and narrow faces, bifid nasal tip) (Fig. 2), and her heart (ostium secundum atrial septal defect, pulmonary artery hypertension, and 4/4 leaky tricuspid valves). We speculated that this patient might have an OFCD syndrome. Therefore, we decided to take a screening for BCOR variants. The result showed that a heterozygous deletion variant IVS 11-2delA was detected in intron 11 of gene BCOR, a novel variant. With these above symptoms, this patient was planned to receive thorough treatment, including extracting all her root teeth, filling all decayed teeth, undergoing a root canal treatment for the left mandibular canine, and having an extraoral apicoectomy with a fistula removal on her left chin. OFCD is a rare syndrome affecting many organs. Early identification of this disease helps prevent oral complications and endocarditis progression due to caries teeth. As a result, we could combine a wide range of specialties to provide patients with comprehensive care.

Table 1 Literature review of case report with BCOR variant
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Conclusion

Radiculomegaly is a crucial dental symptom that is highly specific to OFCDs. This syndrome is often detected by dentists during dental panoramic radiograph examinations. Therefore, dentists play an essential role in identifying and diagnosing this OFCD syndrome. Dentists should identify patients who may have the condition and refer them to geneticists for further examination and testing. In other words, patients need an accurate diagnosis to receive prophylactic treatment for other related conditions.