Case report: hypodontia and short roots in a child with Fraser syndrome.
Abstract: BACKGROUND: Fraser syndrome is a rare autosomal recessive disorder of which there has only previously been one case reported in the dental literature. The main characteristics are cryptophthalmos, syndactyly and genital abnormalities. Orofacial findings reported are: facial asymmetry, cleft lip and palate, high arched palate, dental crowding, fusion of primary teeth, dental hypoplasia, malocclusion, and supragingival calculus. CASE REPORT: A 15 year old girl with Fraser syndrome attended Bradford and Airedale salaried dental services complaining of painful mandibular anterior teeth. On examination she presented with hypodontia, shortened roots, and the mandibular anteriors had a titanium trauma splint fixed to reduce the mobility. This had been placed 4 years previously by a paediatric specialist. However oral hygiene was poor around it and therefore the patient had calculus and gingivitis. TREATMENT: The splint was removed followed by subgingival scaling under local analgesia, fissure sealants of all posterior teeth, regular oral hygiene instruction and scaling, and occasional use of chlorhexidine gel. FOLLOW-UP: She has been reviewed regularly with frequent scalings over two years. CONCLUSION: This case reports the possibility of hypodontia and short roots being associated with Fraser syndrome.

Key words: Fraser syndrome, cryptophthalmos, hypodontia, short roots.
Article Type: Case study
Subject: Fraser syndrome (Diagnosis)
Fraser syndrome (Care and treatment)
Fraser syndrome (Case studies)
Tooth diseases (Diagnosis)
Tooth diseases (Care and treatment)
Tooth diseases (Case studies)
Authors: Keene, E.J.
Day, P.F.
Pub Date: 08/01/2011
Publication: Name: European Archives of Paediatric Dentistry Publisher: European Academy of Paediatric Dentistry Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 European Academy of Paediatric Dentistry ISSN: 1818-6300
Issue: Date: August, 2011 Source Volume: 12 Source Issue: 4
Geographic: Geographic Scope: United Kingdom Geographic Code: 4EUUK United Kingdom
Accession Number: 277106773
Full Text: Introduction

This case reports only the second case of Fraser Syndrome (FS) in the dental literature, and the first with hypodontia and shortened roots. FS is a very rare autosomal recessive multisystem disorder [Francannet et al., 1990) which was first described by George Fraser in 1962 [Fraser, 1962], who described the main characteristics as cryptophthalmos (fused upper and lower eyelids), syndactyly and genital abnormalities. The incidence has been estimated to be 0.43 per 100,000 live births and 11.06 per 100,000 still births [Martinez-Frias et al., 1994; Comstock et al., 2005]. Survival rates are very low and most affected individuals die before they reach 1 year of age [Impallomeni et al., 2006]. It affects males and females equally [Chattopadhyay et al., 1993]. It is thought to be caused by mutations in two human genes FRAS 1 and FREM 2 [McGregor et al., 2003]. These genes are involved in the structural adhesion of the skin epithelium to its underlying mesenchyme [Petrou et al., 2008]. The pathogenesis therefore involves abnormal epithelium integrity during pre-natal life [Comstock et al., 2005].

Other characteristics have been documented; abnormalities of respiratory tract [van Haelst et al., 2008], renal agenesis or malformation [Fraser, 1962; Pitera et al., 2008], mental retardation [Comstock et al., 2005], and anophthalia (absence of eye balls) [Slavotinek and Tifft, 2002]. Thomas et al. [1986] proposed major and minor diagnostic criteria which Slavotinek and Tifft [2002] adapted in 2002 using 117 patients from the literature (Table 1).

Using these criteria the diagnosis of FS can be made if either three major, or two major and two minor, or one major and three minor diagnostic criteria are present in a patient.

A review of the literature shows oro-facial abnormalities are infrequently described in relation to FS. The findings reported currently are: facial asymmetry in 10% of cases [McGregor et al., 2003], cleft lip and palate ranging from 2-11%, a high arched palate in 12% [Slavotinek and Tifft, 2002], ankyloglossia [Gupta and Saxena, 1962; Ide and Wollschlaeger, 1969; Gattuso et al., 1987; Boyd et al., 1988], dental crowding [Ide and Wollschlaeger, 1969; Diniz et al., 2007], fusion of primary teeth [Bialer and Wilson, 1988; Bierich et al., 1991], and dental hypoplasia [Thomas et al., 1986]. Other findings in one case report [Diniz et al., 2007] were malocclusion, absence of lingual fraenum, parched lips, supragingival calculus, and moderate gingivitis.

Case report

A 15 year-old girl with FS presented to Bradford and Airedale Salaried Dental Services (SDS) complaining of painful lower anterior teeth. Her parents were first cousins and she was the first and only child in her family to have FS.

Medical history. She had several features of FS: cryptophthalmos and anophthalmia with facial asymmetry (Fig. 1), syndactyly (Fig. 2), a single left kidney, narrow airway in which she required a tracheostomy fitted for a general anaesthetic for a hysterectomy. She had short stature for her age and was below the 3rd percentile for height and weight. She had no signs of developmental delay or learning difficulties.

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Dental history. She had previously been seen by other dentists in the service. On clinical examination (Fig. 3) she was in the full permanent dentition with congenitally missing 15, 25, 35, 42 and 45. She had a high vaulted palate. Her occlusion was Class II molars with Class II division I incisors with an overjet of 13mm, anterior open bite of 4mm and bilateral posterior crossbite. The maxillary incisor 12 was in a palatal position with 13 buccally placed. Both her and her parents were not concerned about her dental appearance so no further orthodontic opinion was sought.

Radiographic examination This confirmed hypodontia and also showed her third molars to be missing (Fig. 4). All her teeth appeared to have very short tapered roots with the mandibular anteriors being especially short (Fig. 5) and presented with grade 3 mobility. She had been seen 4 years previously within the SDS and as a result of the mobility a splint from 33 to 43 had been fitted in an attempt to protect these teeth from further trauma. The titanium trauma splint was still in situ but was now associated with gross calculus, gingivitis and gingival recession. All her teeth had extrinsic staining but were caries free. She and her family were warned of the poor long term prognosis of all her teeth, especially the mandibular anteriors.

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Treatment

The treatment performed was oral hygiene instruction, removal of the splint, gross scaling around mandibular anteriors under local analgesia, reapplication of deficient fissure sealants , and regular two monthly appointments for supragingival scalings. Periodic use of chlorhexidine gel for a week at a time instead of toothpaste was used. She was very co-operative and scored Frankl ++ [Frankl et al., 1962] for behaviour.

Follow up

Since the removal of the splint she has been reviewed every four months with scalings and oral hygiene instruction for one and a half years. The lower anteriors have reduced mobility of grade 1 (Figs. 6 and 7).

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Discussion

Fraser syndrome is a rare syndrome which is more frequent in consanguineous parents. This case presented with several of the criteria for FS and reports hypodontia and short roots. The lower anterior teeth presented with a poor long term prognosis as a consequence of their shorts roots and increased mobility. Optimal oral hygiene and maintenance of good gingival health is essential to maintain their presence within the dentition.

Using this case and the details from the previous dental case in the literature both cases report the following oral findings: crowding, malocclusion, high arched palate, and supragingival calculus. Since this is the first reported case of hypodontia and short roots these cannot be concluded as being common findings or associated with the syndrome but may simply be a coincidence. Further case reports may help to clarify this. The dental treatment consisted of regular scalings and use of chlorhexidine gel together with the removal of a splint which inhibited cleaning of her teeth in this area.

Conclusion

The present case is the first report to describe hypodontia and shortened roots in Fraser syndrome.

References

Bialer MG, Wilson WG. Syndromic cryptophthalmos. Amer J Med Genetics 1988; 30:835-837.

Bierich JR, Christie M, Heinrich JJ et al. New observations on midline defects: coincidence of anophthalmos, microphthalmos and cryptophthalmos with hypothalamic disorders. Europ J Pediatr 1991; 150:246-249.

Boyd PA, Keeling JW, Lindenbaum RH. Fraser syndrome (cryptophthalmos-syndactyly syndrome): a review of eleven cases with postmortem findings. Amer J Med Genetics 1988; 31:159-168.

Chattopadhyay A, Kher AS, Udwadia et al. Fraser syndrome. J Postgrad Med 1993; 39:228-230.

Comstock JM, Putnam AR, Opitz JM et al. Prenatal death in Fraser syndrome. Fetal Pediatr Pathol 2005; 24:223-238.

Diniz MB, Lima LM, Sacono NT et al. Clinical manifestations and oral findings in Fraser syndrome. J Dent Child 2007; 74:231-235.

Francannet C, Lefrancois P, Dechelotte P et al. Fraser syndrome with renal agenesis in two consanguineous Turkish families. Amer J Med Genetics 1990; 36:477-479.

Frankl SN, Shiere FR, Fogels SHR. Should the parent remain with the child in the dental operatory? J Dent Child 1962; 29:150-163.

Fraser GR. Our genetic 'load'. A review of some aspects of genetic variation. Ann Hum Genet 1962; 25:387-415.

Gattuso J, Patton MA, Baraitser M. The clinical spectrum of the Fraser syndrome: reports of three new cases and review. J Med Genetics 1987; 24:549-555.

Gupta SP, Saxena RC. Cryptophthalmos. Br J Ophthalmol 1962; 46:629-632.

Ide CH, Wollschlaeger PB. Multiple congenital abnormalities associated with cryptophthalmia. Arch Ophthalmol 1969; 81:638-644.

Impallomeni M, Subramanian D, Mahmood N et al. Fraser syndrome in a 96-year-old female. Age Ageing 2006; 35:642-643.

Martinez-Frias ML, Bermejo E, Sanchez OT et al. Sclerocornea, hypertelorism, syndactyly, and ambiguous genitalia. Amer J Med Genetics 1994; 49:195-197.

McGregor L, Makela V, Darling SM et al. Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet 2003; 34:203-208.

Petrou P, Makrygiannis AK, Chalepakis G. The Fras1/Frem family of extracellular matrix proteins: structure, function, and association with Fraser syndrome and the mouse pleb phenotype. Connect Tissue Res 2008; 49:277-282.

Pitera JE, Scambler PJ, Woolf AS. Fras1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli. Hum Mol Genetics 2008; 17:3953-3964.

Slavotinek AM, Tifft CJ. Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes. J Med Genetics 2002; 39:623-633.

Thomas IT, Frias JL, Felix V et al. Isolated and syndromic cryptophthalmos. Amer J Med Genetics 1986; 25:85-98.

van Haelst MM, Maiburg M, Baujat G et al. Molecular study of 33 families with Fraser syndrome new data and mutation review. Amer J Med Genetics 2008; 146A:2252-2257.

E.J. Keene, Bradford and Airedale Salaried Dental Service, P.F. Day, Dept Paediatric Dentisty Leeds Dental Institute, UK

Postal address: E. Keene, Department of Paediatric Dentistry, Leeds. Dental Institute, Worsely Building, Clarendon Way, Leeds, LS2 9LU

Email: emily.keene@nhs.net
Table 1. Revised Diagnostic
Criteria for Fraser Syndrome.

Major criteria                 Minor criteria

Syndactyly                     Anorectal defects

Cryptophthalmos spectrum       Dysplastic ears

Urinary tract abnormalities    Skull ossification defects

Ambiguous genitalia            Umbilical abnormalities

Laryngeal and tracheal         Nasal anomalies
anomalies

Positive family history

Ref: Slavotinek and Tifft [2002]
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