Volume 39, Issue 6 , Pages 622-625, June 2010
Extreme oral manifestations in a Marfan-type syndrome
Article Outline
- Abstract
- Case report
- Discussion
- Competing interests
- Funding
- Ethical approval
- Acknowledgements
- References
- Copyright
Abstract
A 12-year-old girl with an otherwise typical Marfan syndrome (Ghent criteria fulfilled) presented with highly unusual oral manifestations consisting of supernumerary teeth and severe dental crowding. Pathological examination of the supernumerary teeth revealed an elevated number of pulpoliths. No mutation in the FBN1, TGFBR1 and TGFBR2 genes was identified despite exhaustive screening, suggesting that another gene defect could explain this association of marfanoid features with dental abnormalities.
Key words: marfan syndrome, Loeys–Dietz syndrome, dental crowding, supernumerary teeth, pulpoliths, FBN1, TGF-beta sub-unit receptors
Case report
A 12-year-old girl was referred to the maxillofacial surgery department for severe dental crowding and supernumerary teeth at high risk of bacterial endocarditis. She had a history of aortic root dilatation involving aortic sinuses with aortic and mitral valve insufficiency. She had been treated at 10 years of age with aortic homograft (calibre 25) with coronary replantation associated with mitral annuloplasty (Carpentier ring, calibre 32). Aorta, aortic valve and mitral valve pathological examination had shown myxoid degeneration and mucopolysaccharidic deposits.
At admission, the patient's height was 1.76
m (+3.8 SD) and she weighed 55kg. Her skull perimeter was 58cm (+3.4 SD). She had marked dolichostenomelia in absence of spine deformation, with an arm span to height ratio >1.05 and reduced upper to lower segment ratio (Fig. 1a). She presented with arachnodactyly of the hands and feet and joint hypermobility (thumb and wrist signs were positive). She had reduced extension of her elbows <170°. She reported no family history of developmental disease and had no siblings. At birth, she weighed 3.2kg, was 51cm and her skull diameter was 36cm. The heights of her mother and her father were 1.61m and 1.73m, respectively. Both had an unremarkable clinical examination.
Fig. 1.
(a) Reduced elbow extension <170°, true dolichostenomelia; (b) lateral facial views; (c) lateral Delaire's cephalometry showing skeletal class I, vertical anterior excess and open mandibular angle.
Her facial features included a broad forehead with frontal and bi-temporal bossing and a small nose with broad base and depressed bridge (Fig. 1b and c). Bite examination (Fig. 2a), orthopantomogram (Fig. 2b) and CT scan (Fig. 2c) showed supernumerary and impacted teeth (there were 36 definitive teeth) crown and root malformations and extreme dental crowding. The right superior quadrant was formed by the central and lateral incisors, the first and second premolar and the three molars; the canine had been previously extracted. The left superior quadrant was formed by the central incisor, a cluster containing seven teeth including one mesiodens and more posteriorly by four molars. The left inferior quadrant was formed by the central and lateral incisors, a cluster containing an impacted canine and four premolars and more posteriorly by three molars including a germ. In the inferior right quadrant, the premolars had highly deformed crowns and the third molar was missing. The palate was highly arched.
Fig. 2.
(a) Frontal bite views showing numerous dental mispositions; (b) orthopantomogram showing supernumerary teeth, pachydontia and dental crowding; (c) 3D reconstructions of jaw CT scan; extreme dental crowding and numerous included teeth.
Delaire's cephalometry revealed skeletal class I (no facial retrusion), vertical anterior excess predominantly affecting the chin with mandibular angle opening (Fig. 1c).
Chest radiograph did not reveal hypoplasic clavicles and the pelvic skeleton was normal. There were no apical blebs. Lumbar MRI showed moderate dural ectasia without posterior scalloping or involvement of the posterior roots. An ophthalmologic check up with skiascopy was normal.
According to the Ghent nosology5, the patient was diagnosed with Marfan syndrome (presence of a major criteria in the skeletal, cardiovascular and dural systems), even though her oral manifestations were highly unusual.
Dental pathology after oral surgery under antibiotic prophylactic treatment revealed numerous highly deformed teeth without macroscopic enamel defects, normal dentin and narrowed pulpar cavities filled with a high number of pulpoliths (Fig. 3a). Pulpoliths were of two types: organized in concentric layers (Fig. 3b) and without obvious organisation (Fig. 3c).
Fig. 3.
(a) Right maxillary molar (section) showing abnormal crown and pulpoliths; (b) thin mineralized slice of dental tissue (supernumerary molar) under polarized microscopy showing typical concentric architecture of pulpoliths at the limit between dentin and pulp next to zones with disorganized dentin (scale bar: 1
mm); (c) same preparation showing a single pulpolith in the pulpar cavity with radiating canaliculi (scale bar: 200μm).
The double-stranded DNA sequencing of exons and intronic borders of the following genes involved in Marfan type I and II syndromes (MIM#154700 and 154705) was conducted: FBN1, 65 coding and 3 non-coding exons; TGFBR2, 7 exons; and TGFBR1, 9 exons. For the first two genes, FBN1 and TGFBR2, large deletions and duplications were screened using the multiplex ligation-dependent probe amplification genetic dosage technique (MRC-Holland, according to the manufacturer's instructions). None of these tests showed significant variations. Fibroblast culture on skin biopsy for transcript studies and whole genome-comparative genomic hybridisation array could not be conducted because the patient's family refused further follow-up.
Discussion
According to the Ghent nosology5, three major and three minor skeletal system criteria, one major and one minor cardiovascular system criteria and one major dural criterium were found in this case. This set of symptoms allowed the unambiguous diagnosis of Marfan syndrome (MFS). None of the craniofacial manifestations of MFS are part of these major diagnostic criteria2 (Table 1), so in this case, the presence of unusual oral signs did not interfere with the diagnosis of MFS.
Table 1. Craniofacial manifestations in Marfan syndrome.
| • Long and narrow face (dolichocephaly) |
| • High palatal vault with maxillary constriction and teeth crowding |
| • Mandibular and maxillar retrognathia |
| • Temporomandibular joint hypermobility |
| • Enamel defects and poor gingival conditions |
| • Abnormal dentin formation |
| • Oral calculus |
| • Pulpoliths |
The dental malformations in this case were more similar to cleidocranial dysplasia (CCD) than MFS. The diagnosis of CDD was highly unlikely because this syndrome is always associated with short stature and the patient had no clavicular hypoplasia or pelvic skeletal abnormality.
The cephalometric anomalies in MFS include vertical midface hypoplasia, maxillary and mandibular retroposition and increased palatal height3. MFS patients have an increased rate of chronic airway obstruction due to high nasal resistance1. This ‘long face syndrome’ due to mouth breathing in childhood may be the combined consequence of airway obstruction and intrinsic growth disorders linked to the fibrillinopathy3, 4. This set of craniofacial anomalies was found in the present case (Fig. 1c).
Patients with MFS often exhibit three types of dental anomalies involving dentin formation: root deformities; calcified pulp inclusions; and abnormal pulp shape2, 4. These deformations were found in the present case (Fig. 3). They may be explained by multiple endothelial ruptures in pulpar vessels or by abnormal mechanical constraints around the tooth germ due to periosteal and stromal microfibrillar dysfunction.
Airway obstruction and dentin formation disorders do not account for all the craniofacial anomalies found in this case, and not for the supernumerary teeth (Fig. 2).
Despite exhaustive genetic screening, no causative mutation in the FBN1, TGFBR1 and TGFBR2 genes was identified. This could be a failure of the genetic tests to detect, for instance, particular deep intronic mutations, but the unusual dental characteristics of this young patient suggest the possibility of the involvement of a distinctive gene. None of the genes involved in MFS is known to lead to the formation of supernumerary teeth6. Several clinical characteristics in this patient indicate that her presentation may be the consequence of excessive TGFβ signalling7. Both the clinical and pathological cardiovascular signs match animal model and human study results on TGFβ over-expression in Marfan and Marfan-related disorders such as the Loeys–Dietz syndrome9. TGFβ is required in dentin formation8; its overexpression could result in pulpolith formation (Fig. 3). The causal gene, if discovered, could bring some important insights to the understanding of fibrillin metabolism and its links with dental morphogenesis.
The treatment of dental anomalies is a key issue in the follow-up of MFS patients. MFS patients have a high frequency of cardiovascular disorders and may theoretically have an abnormal bone response to mechanical stress. Three points have to be taken into account by maxillofacial surgeons: the use of local anaesthesia containing epinephrine needs careful management; high-risk protocols to prevent bacteraemia during and after oral surgery are mandatory; and alveolar bone may not react as expected to orthopaedic or orthodontic treatments.
Competing interests
None declared.
Funding
None.
Ethical approval
Not required.
Acknowledgements
Special thanks to Pr. PJ de Coster for his critical comments on the manuscript.
References
- . Influence of maxillary morphology on nasal airway resistance in Marfan's syndrome. Acta Otolaryngol. 2000;120:410–413
- . Oral manifestations of patients with Marfan syndrome: a case-control study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93:564–572
- . Craniofacial structure in Marfan syndrome: a cephalometric study. Am J Med Genet. 2004;131A:240–248
- . Orofacial manifestations of congenital fibrillin deficiency: pathogenesis and clinical diagnostics. Ped Dent. 2004;26:535–537
- . Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996;62:417–426
- . Unraveling the molecular mechanisms that lead to supernumerary teeth in mice and men: current concepts and novel approaches. Cells Tissues Organs. 2007;186:60–69
- . Marfan's syndrome. Lancet. 2005;366:1965–1976
- . Cell autonomous requirement for TGFβ signaling during odontoblast differentiation and dentin matrix formation. Mech Dev. 2007;124:409–415
- . Genetic basis of thoracic aortic aneurysms and aortic dissections. Am J Med Genet. 2005;139C:10–16
PII: S0901-5027(10)00009-3
doi:10.1016/j.ijom.2010.01.006
© 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
Volume 39, Issue 6 , Pages 622-625, June 2010
