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Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 321e324

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Journal of Cranio-Maxillo-Facial Surgery

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Case report

Giant canine with dentine anomalies in oculo-facio-cardio-dentalsyndrome

Matthieu Larhant a, Sophie Sourice b, Fanny Grimaud a, Luis Cordoba c, Sophie Leveau d,Pascal Huet e, Pierre Corre a, Roman Hossein Khonsari a,*a Service de Chirurgie Maxillo-Faciale et Stomatologie, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, Franceb Laboratoire d’Ingéniérie Ostéo-Articulaire et Dentaire, INSERM U791, Nantes, Francec Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, INSERM U957, Nantes, Franced Service de Chirurgie Maxillo-Faciale, Clinique Jules-Vernes, Nantes, Francee Service de Chirurgie Maxillo-Faciale, Nouvelles Cliniques Nantaises, Nantes, France

a r t i c l e i n f o

Article history:Paper received 14 November 2012Accepted 27 May 2013

Keywords:MacrodontiaRadiculomegalyOculo-facio-cardio-dental syndromeBCORDentinePulp stone

* Corresponding author. Service de Chirurgie MaxCentre Hospitalier Universitaire Hôtel-Dieu, 1 plaNantes, France. Tel.: þ44 33685967200; fax: þ44 331

E-mail address: roman.khonsari@kcl.ac.uk (R.H. Kh

1010-5182/$ e see front matter � 2013 European Asshttp://dx.doi.org/10.1016/j.jcms.2013.05.020

a b s t r a c t

Radiculomegaly affecting incisors, canines or premolars is a rare radiological finding (Maden et al., 2010)but is pathognomomic of a rare x-linked dominant syndrome called oculo-facio-cardio-dental syndrome(OFCDS). As this syndrome includes cardiac malformations and can lead to blindness due to congenitalglaucoma, oral and maxillofacial surgeons should be aware of the somatic anomalies potentially asso-ciated with radiculomegaly. We report a typical case of OFCDS and provide the first description of themicroscopic dental anomalies associated with this syndrome.

� 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rightsreserved.

1. Introduction

Oculo-facio-cardio-dental syndrome (OFCDS) is a recentlydescribed and extremely rare entity (Gorlin et al., 1996) also knownas Microphthalmia, syndromic 3 (MCOPS2; OMIM #300166) or asMarashi-Gorlin syndrome. The clinical features of OFCDS aremicrophthalmia and congenital cataracts with secondary glau-coma, dental radiculomegaly affecting predominantly the caninesand the premolars, cardiac defects (ventricular septal defect, atrialseptal defect and mitral valve abnormalities), characteristic faceand normal intelligence (Ng et al., 2004). OFCDS is an x-linkeddominant disorder caused by mutation in the BCL6 co-repressor(BCOR) gene (Ng et al., 2004).

Dental disorders other than radiculomegaly are described inOFCDS, such as delayed eruption, malposition, root dilaceration andoligodontia (Schulze et al., 1999; Oberoi et al., 2005). The facialfeatures described to date include a long narrow face, high nasal

illo-Faciale et Stomatologie,ce Alexis Ricordeau, 4400045245998.onsari).

ociation for Cranio-Maxillo-Facial

bridge, bifid/broad nasal tip, curved eyebrows and cleft lip andpalate (Schulze et al., 1999; Oberoi et al., 2005).

We report a case of OFCDS and provide the first description ofdental histology in this syndrome. The specific dental anomalies wereport are of help in the understanding of the role of BCOR indentinogenesis.

2. Case report

A 36-year-old woman presented with acute cellulitis and ab-scess developing from the right mandibular canine (Fig. 1a). Thetreatment included surgical drainage of the cervical collection andextraction of the causal tooth. The patient had right micro-phthalmia and left glaucoma causing bilateral blindness. She hadno cleft lip or palate, no hearing disorders and no cutaneous soft-tissue syndactylies of hands of feet (Gorlin et al., 1996). She had aheart murmur but refused further cardiac investigations. She alsodeclined screening for BCOR mutations. Despite the lack of geneticevidence, the unique association of radiculomegaly, eye and heartabnormalities led to the diagnosis of OFCDS. The patient wasinformed of the risk of developing endocarditis due to her cardiacabnormalities and lack of dental care.

Surgery. Published by Elsevier Ltd. All rights reserved.

Fig. 1. Oculo-facio-cardio-dental syndrome. (a) Orthopantomogram showing severe macrodontia; long canine root (red arrow) and large premolar root (blue arrow). (b) Sagittalsection from Cone-beam CT (CBCT) showing large central lower root (red arrow). (c) Sagittal section from CBCT showing large upper incisor root bulging into the maxillary sinus.(d) 3D reconstruction from CBCT in lateral view showing large mandibulary canine root reaching the lower border of the mandible (red arrow). (e) Same 3D reconstruction in lowerview showing the length of the mandibulary canine root (red arrow).

Fig. 2. Lateral cephalogram and Delaire’s archirectural analysis. The anterior cranial base angle is at 21� and the posterior cranial base angle is at 120� . The nose has the typicaloutline described in OFCDS (red arrow). Delaire’s analysis shows maxillary retrusion, vertical posterior insufficiency and anterior vertical symphysar excess leading to a low andretrusive chin (the theoretical chin position given by the analysis is indicated by a red dot).

Table 1Dental size in OFCDS compared to normal values. The giant teeth are marked in bold. m: missing tooth; var: variable size. The normal sizes are given into brackets (afterMarseiller, 1937).

8 7 6 5 4 3 2 1 1 2 3 4 5 6 7 816.2 (var) 20.3

(20.7)17.4(22.3)

20.8(21)

22.5(21)

39.5(26.5)

30.2(22)

18.8(22.5)

m(22.5)

34.5(22)

32.5(26.5)

24.2(21)

20.5(21)

19.5(22.3)

20.2(20.7)

16.5(var)

11.9 (var) 18.6(19.8)

18.5(21)

m(23.5)

32.7(23)

42.5(25.6)

28.7(22.1)

29.2(20.7)

22.2(20.7)

20.2(22.1)

40.5(25.6)

28.5(23)

25.5(23.5)

21.4(21)

20.3(19.8)

17.6(var)

M. Larhant et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 321e324322

Fig. 3. 3D reconstruction of the skull in OFCDS. The coronoid processes are hyper-trophic (right coronoid process: red arrow).

M. Larhant et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 321e324 323

Cone-beam computed tomography (CBCT) examination of thejaws revealed severe macrodontia affecting the roots of the in-cisors, canines and premolars (teeth 12, 13, 22, 23, 33, 34, 41, 42, 43and 44; see Table 1), as well as agenesis of teeth 21 and 45. Theroots of the maxillary lateral incisors were bulging into themaxillary sinuses (Fig. 1b and c). The apex of the mandibulary ca-nines extended to the lower border of the mandible (Fig. 1d and e).

Fig. 4. Dental anomalies in OFCDS. (a) Giant right mandibulary canine (scale bar: 2 cm) wsection, H&E staining. (c) Apex of the extracted canine in OFCDS: the dentine surrounding thto (b); longitudinal parasagittal section lateral to the apical aperture, H&E staining. (d) Closearrow), polarized light microscopy. (e) Dentineeenamel junction in a normal adult mandithickness, H&E staining. (f) Enameledentine junction in the extracted OFCDS canine; thinabnormalities seen in (d): spherical dentine depositions (red arrows) resembling pulp stonespulp cavity.

The typical aspect of the OFCDS nose could be seen on lateralcephalograms (Fig. 2, red arrow). Delaire’s architectural analysis(Olszewski et al., 2010) revealed bimaxillary retrusion, posteriorvertical insufficiency and anterior symphyseal vertical excess(Fig. 2). The coronoid processes were hypertrophic but did notinterfere with lower jaw function (Fig. 3).

Histological examination of the extracted canine (42.5 mm,Fig. 4a) revealed dentine abnormalities, predominantly around theopen apex (compare Fig. 4b and c), as well as thin enamel (compareFig. 4e and f). The open apex was in line with continuous caninegrowth leading to radiculomegaly.

More precisely, the dentine abnormalities consisted in disor-ganized dentine deposition and round concentric structures cor-responding to pulp stones, embedded into thewall of the root canal(Fig. 4d and g).

The histological dental characteristics of OFCDS thus combined(1) radiculomegaly with open apices of incisors, canines and pre-molars, (2) dentine formation disorders (disorganized dentinedeposition, pulp stones) and (3) thin enamel.

3. Discussion

Syndromes with macrodontia are very rare and dental over-growth only affects the crowns in most cases. A well-characterizedsyndrome with large teeth is oto-dental dysplasia (OMIM#166750), an autosomal dominant microdeletion of chromosome11q13 causing grossly enlarged canines and molars (globodontia)and sensorineural hearing loss. 11q13 microdeletion affects multi-ple genes, including FGF3, but no obvious mechanism has beenproposed to date to explain the dental disorders (Gregory-Evanset al., 2007). Nevertheless, globodontia in oto-renal dysplasia af-fects crowns and is very different from the radiculomegaly reportedin OFCDS.

Overgrowth syndromes such as Proteus syndrome (Adolphset al., 2004) and Sotos syndrome (Cohen, 1999) as well as syn-dromes including hormonal disorders such as Berardinelli-Seip

ith open apex (red arrow). (b) Apex of a normal adult mandibular canine; longitudinale canal is abnormal (blue arrow) and the shape of the apex is distorted when comparedview of the boxed area in (c); irregular dentine deposition in the walls of the canal (redbulary canine; the red arrow points to the enamel and the red bar indicates enamelenamel (vertical red bar and red arrow), H&E staining. (g) Close view of the dentineembedded into the canal walls, polarized light microscopy. dt: dentine; en: enamel; pc:

M. Larhant et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 321e324324

lipoatrophic diabetes syndrome (Solanki et al., 2008) can be asso-ciated with dental gigantism but the anomaly is never exclusive tothe roots as in OFCDS.

Similarly, third molar overgrowth characterizes Ekman-Westborg & Julin syndrome (Ekman-Westborg and Julin, 1974),and central incisor overgrowth is a main sign in KBG syndrome(Sirmaci et al., 2011) but the dental morphology in these syndromeshas little in common with OFCDS.

Macrodontia can also occur in conditions as diverse as Cockaynesyndrome (Bloch-Zupan et al., 2013), SchinzeleGiedion syndrome(Cooke et al., 2002), congenital infiltrating lipomatosis (Kamal et al.,2010; Keramidas et al., 2012), or may even be isolated (Groper,1987), without ever mimicking the characteristic dental pheno-type of OFCDS. Radiculomegaly affecting incisors, canines andpremolars (Table 1) is thus typical of OFCDS.

When confronted with incisor, canine or premolar radi-culomegaly, maxillofacial surgeons and dentists are in the frontlinefor the diagnosis of OFCDS. From a therapeutic point of view, afterscreening for heart and eye disorders, it is crucial to avoid dentaldecay due to the difficulties in performing endodontic treatmentand the risk of endocarditis. Caries prevention and treatment iscrucial due to the presence of cardiac malformations in OFCDS.Specific endodontic techniques have to be applied due to root lengthand open apices (Maden et al., 2010; Pace et al., 2011). Devitalizationhas even been proposed as a preventive procedure for radi-culomegaly, and subsequently for its consequences such as increasein vertical dimension (Fig. 2 and Maden et al., 2010). Furthermore,patientswith OFCDS oftenpresent as challenging orthodontic cases.Braces alone (Sakaguchi et al., 2012) or associated with traction onskeletal anchoring (Uribe et al., 2011) have proven successful in therepositioning of giant canines, without reported ankylosis.

The role of BCOR (B-cell lymphoma 6 co-repressor) e a gene alsoassociated with acute myeloid leukemiae is not well understood inthe genesis of radiculomegaly in OFCDS (Ng et al., 2004). Interest-ingly, Bcor silencing in the oral mesenchyme of mice causes dentineabnormalities (Cai et al., 2010), and dental mesenchymal stem cellsfrom patients with OFCDS show an increase in dentine formationpotential (Fan et al., 2009). Furthermore, the role of Bcor in regu-latingmesenchymal cell proliferation has been demonstrated in thecervical loop of mouse incisors and in molar roots (Lapthanasupkulet al., 2012). These results are in line with the phenotype observedin OFCDS and contribute to the understanding of the role of BCOR indentinogenesis, but the direct involvement of BCOR in root for-mation still needs to be clarified.

4. Conclusion

From a practical point of view, the main issues in OFCDS are (1)ophthalmological follow-up in order to avoid the complications ofcongenital glaucoma poor follow-up in our case led to bilateralblindness), (2) treatment of the cardiac abnormalities and (3) oralhygiene and early caries treatment, as endodontic treatment ofgiant roots is challenging and dental infections can be life-threatening in patients with at-risk cardiac malformations.

Ethical approvalNot required.

FundingNone.

Competing interestsNone declared.

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