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 55 kg. Her skull perimeter was 58 cm (+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. 1 a ). 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 3.2 kg, was 51 cm and her skull diameter was 36 cm. The heights of her mother and her father were 1.61 m and 1.73 m, respectively. Both had an unremarkable clinical examination.

(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. 1 b and c). Bite examination ( Fig. 2 a ), orthopantomogram ( Fig. 2 b) and CT scan ( Fig. 2 c) 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.

(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. 1 c).

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 nosology , 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. 3 a ). Pulpoliths were of two types: organized in concentric layers ( Fig. 3 b) and without obvious organisation ( Fig. 3 c).

(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: 200 μm).

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.