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

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Journal of Cranio-Maxillo-Facial Surgery


journal homepage: www.jcmfs.com

Case report

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


syndrome
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 Htel-Dieu, Nantes, France
Laboratoire dIngnirie Osto-Articulaire et Dentaire, INSERM U791, Nantes, France
Laboratoire de Physiopathologie de la Rsorption Osseuse et Thrapie des Tumeurs Osseuses Primitives, INSERM U957, Nantes, France
d
Service de Chirurgie Maxillo-Faciale, Clinique Jules-Vernes, Nantes, France
e
Service de Chirurgie Maxillo-Faciale, Nouvelles Cliniques Nantaises, Nantes, France
b
c

a r t i c l e i n f o

a b s t r a c t

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

Radiculomegaly affecting incisors, canines or premolars is a rare radiological nding (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 congenital
glaucoma, oral and maxillofacial surgeons should be aware of the somatic anomalies potentially associated with radiculomegaly. We report a typical case of OFCDS and provide the rst description of the
microscopic dental anomalies associated with this syndrome.
2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights
reserved.

Keywords:
Macrodontia
Radiculomegaly
Oculo-facio-cardio-dental syndrome
BCOR
Dentine
Pulp stone

1. Introduction
Oculo-facio-cardio-dental syndrome (OFCDS) is a recently
described and extremely rare entity (Gorlin et al., 1996) also known
as Microphthalmia, syndromic 3 (MCOPS2; OMIM #300166) or as
Marashi-Gorlin syndrome. The clinical features of OFCDS are
microphthalmia and congenital cataracts with secondary glaucoma, dental radiculomegaly affecting predominantly the canines
and the premolars, cardiac defects (ventricular septal defect, atrial
septal defect and mitral valve abnormalities), characteristic face
and normal intelligence (Ng et al., 2004). OFCDS is an x-linked
dominant disorder caused by mutation in the BCL6 co-repressor
(BCOR) gene (Ng et al., 2004).
Dental disorders other than radiculomegaly are described in
OFCDS, such as delayed eruption, malposition, root dilaceration and
oligodontia (Schulze et al., 1999; Oberoi et al., 2005). The facial
features described to date include a long narrow face, high nasal

* Corresponding author. Service de Chirurgie Maxillo-Faciale et Stomatologie,


Centre Hospitalier Universitaire Htel-Dieu, 1 place Alexis Ricordeau, 44000
Nantes, France. Tel.: 44 33685967200; fax: 44 33145245998.
E-mail address: roman.khonsari@kcl.ac.uk (R.H. Khonsari).

bridge, bid/broad nasal tip, curved eyebrows and cleft lip and
palate (Schulze et al., 1999; Oberoi et al., 2005).
We report a case of OFCDS and provide the rst description of
dental histology in this syndrome. The specic dental anomalies we
report are of help in the understanding of the role of BCOR in
dentinogenesis.

2. Case report
A 36-year-old woman presented with acute cellulitis and abscess developing from the right mandibular canine (Fig. 1a). The
treatment included surgical drainage of the cervical collection and
extraction of the causal tooth. The patient had right microphthalmia and left glaucoma causing bilateral blindness. She had
no cleft lip or palate, no hearing disorders and no cutaneous softtissue syndactylies of hands of feet (Gorlin et al., 1996). She had a
heart murmur but refused further cardiac investigations. She also
declined screening for BCOR mutations. Despite the lack of genetic
evidence, the unique association of radiculomegaly, eye and heart
abnormalities led to the diagnosis of OFCDS. The patient was
informed of the risk of developing endocarditis due to her cardiac
abnormalities and lack of dental care.

1010-5182/$ e see front matter 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jcms.2013.05.020

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

Fig. 1. Oculo-facio-cardio-dental syndrome. (a) Orthopantomogram showing severe macrodontia; long canine root (red arrow) and large premolar root (blue arrow). (b) Sagittal
section 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 lower
view showing the length of the mandibulary canine root (red arrow).

Table 1
Dental 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 (after
Marseiller, 1937).
8
16.2 (var)
11.9 (var)

7
20.3
(20.7)
18.6
(19.8)

6
17.4
(22.3)
18.5
(21)

5
20.8
(21)
m
(23.5)

4
22.5
(21)
32.7
(23)

3
39.5
(26.5)
42.5
(25.6)

2
30.2
(22)
28.7
(22.1)

1
18.8
(22.5)
29.2
(20.7)

1
m
(22.5)
22.2
(20.7)

2
34.5
(22)
20.2
(22.1)

3
32.5
(26.5)
40.5
(25.6)

4
24.2
(21)
28.5
(23)

5
20.5
(21)
25.5
(23.5)

6
19.5
(22.3)
21.4
(21)

7
20.2
(20.7)
20.3
(19.8)

8
16.5
(var)
17.6
(var)

Fig. 2. Lateral cephalogram and Delaires archirectural analysis. The anterior cranial base angle is at 21 and the posterior cranial base angle is at 120 . The nose has the typical
outline described in OFCDS (red arrow). Delaires analysis shows maxillary retrusion, vertical posterior insufciency and anterior vertical symphysar excess leading to a low and
retrusive chin (the theoretical chin position given by the analysis is indicated by a red dot).

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

323

The typical aspect of the OFCDS nose could be seen on lateral


cephalograms (Fig. 2, red arrow). Delaires architectural analysis
(Olszewski et al., 2010) revealed bimaxillary retrusion, posterior
vertical insufciency and anterior symphyseal vertical excess
(Fig. 2). The coronoid processes were hypertrophic but did not
interfere with lower jaw function (Fig. 3).
Histological examination of the extracted canine (42.5 mm,
Fig. 4a) revealed dentine abnormalities, predominantly around the
open apex (compare Fig. 4b and c), as well as thin enamel (compare
Fig. 4e and f). The open apex was in line with continuous canine
growth leading to radiculomegaly.
More precisely, the dentine abnormalities consisted in disorganized dentine deposition and round concentric structures corresponding to pulp stones, embedded into the wall 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 premolars, (2) dentine formation disorders (disorganized dentine
deposition, pulp stones) and (3) thin enamel.
3. Discussion

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

Cone-beam computed tomography (CBCT) examination of the


jaws revealed severe macrodontia affecting the roots of the incisors, canines and premolars (teeth 12, 13, 22, 23, 33, 34, 41, 42, 43
and 44; see Table 1), as well as agenesis of teeth 21 and 45. The
roots of the maxillary lateral incisors were bulging into the
maxillary sinuses (Fig. 1b and c). The apex of the mandibulary canines extended to the lower border of the mandible (Fig. 1d and e).

Syndromes with macrodontia are very rare and dental overgrowth only affects the crowns in most cases. A well-characterized
syndrome with large teeth is oto-dental dysplasia (OMIM
#166750), an autosomal dominant microdeletion of chromosome
11q13 causing grossly enlarged canines and molars (globodontia)
and sensorineural hearing loss. 11q13 microdeletion affects multiple genes, including FGF3, but no obvious mechanism has been
proposed to date to explain the dental disorders (Gregory-Evans
et al., 2007). Nevertheless, globodontia in oto-renal dysplasia affects crowns and is very different from the radiculomegaly reported
in OFCDS.
Overgrowth syndromes such as Proteus syndrome (Adolphs
et al., 2004) and Sotos syndrome (Cohen, 1999) as well as syndromes including hormonal disorders such as Berardinelli-Seip

Fig. 4. Dental anomalies in OFCDS. (a) Giant right mandibulary canine (scale bar: 2 cm) with open apex (red arrow). (b) Apex of a normal adult mandibular canine; longitudinal
section, H&E staining. (c) Apex of the extracted canine in OFCDS: the dentine surrounding the canal is abnormal (blue arrow) and the shape of the apex is distorted when compared
to (b); longitudinal parasagittal section lateral to the apical aperture, H&E staining. (d) Close view of the boxed area in (c); irregular dentine deposition in the walls of the canal (red
arrow), polarized light microscopy. (e) Dentineeenamel junction in a normal adult mandibulary canine; the red arrow points to the enamel and the red bar indicates enamel
thickness, H&E staining. (f) Enameledentine junction in the extracted OFCDS canine; thin enamel (vertical red bar and red arrow), H&E staining. (g) Close view of the dentine
abnormalities seen in (d): spherical dentine depositions (red arrows) resembling pulp stones embedded into the canal walls, polarized light microscopy. dt: dentine; en: enamel; pc:
pulp cavity.

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

lipoatrophic diabetes syndrome (Solanki et al., 2008) can be associated with dental gigantism but the anomaly is never exclusive to
the roots as in OFCDS.
Similarly, third molar overgrowth characterizes EkmanWestborg & 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 syndromes
has little in common with OFCDS.
Macrodontia can also occur in conditions as diverse as Cockayne
syndrome (Bloch-Zupan et al., 2013), SchinzeleGiedion syndrome
(Cooke et al., 2002), congenital inltrating lipomatosis (Kamal et al.,
2010; Keramidas et al., 2012), or may even be isolated (Groper,
1987), without ever mimicking the characteristic dental phenotype of OFCDS. Radiculomegaly affecting incisors, canines and
premolars (Table 1) is thus typical of OFCDS.
When confronted with incisor, canine or premolar radiculomegaly, maxillofacial surgeons and dentists are in the frontline
for the diagnosis of OFCDS. From a therapeutic point of view, after
screening for heart and eye disorders, it is crucial to avoid dental
decay due to the difculties in performing endodontic treatment
and the risk of endocarditis. Caries prevention and treatment is
crucial due to the presence of cardiac malformations in OFCDS.
Specic endodontic techniques have to be applied due to root length
and open apices (Maden et al., 2010; Pace et al., 2011). Devitalization
has even been proposed as a preventive procedure for radiculomegaly, and subsequently for its consequences such as increase
in vertical dimension (Fig. 2 and Maden et al., 2010). Furthermore,
patients with OFCDS often present as challenging orthodontic cases.
Braces alone (Sakaguchi et al., 2012) or associated with traction on
skeletal anchoring (Uribe et al., 2011) have proven successful in the
repositioning of giant canines, without reported ankylosis.
The role of BCOR (B-cell lymphoma 6 co-repressor) e a gene also
associated with acute myeloid leukemia e is not well understood in
the genesis of radiculomegaly in OFCDS (Ng et al., 2004). Interestingly, Bcor silencing in the oral mesenchyme of mice causes dentine
abnormalities (Cai et al., 2010), and dental mesenchymal stem cells
from patients with OFCDS show an increase in dentine formation
potential (Fan et al., 2009). Furthermore, the role of Bcor in regulating mesenchymal cell proliferation has been demonstrated in the
cervical loop of mouse incisors and in molar roots (Lapthanasupkul
et al., 2012). These results are in line with the phenotype observed
in OFCDS and contribute to the understanding of the role of BCOR in
dentinogenesis, but the direct involvement of BCOR in root formation still needs to be claried.

4. Conclusion
From a practical point of view, the main issues in OFCDS are (1)
ophthalmological follow-up in order to avoid the complications of
congenital glaucoma poor follow-up in our case led to bilateral
blindness), (2) treatment of the cardiac abnormalities and (3) oral
hygiene and early caries treatment, as endodontic treatment of
giant roots is challenging and dental infections can be lifethreatening in patients with at-risk cardiac malformations.

Ethical approval
Not required.

Funding
None.
Competing interests
None declared.

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