Case report: Early prosthetic treatment in children with ectodermal dysplasia

Abstract
BACKGROUND: Ectodermal dysplasia affects at least two ectoderm-derived structures such as hair, nails, skin, sweat glands and teeth. The dentition in hypohidrotic ectodermal dysplasia (XHED) is altered with many phenotypes ranging from oligodontia to anodontia. No consensus exists on the ideal age for beginning of prosthetic rehabilitation. CASE REPORT: A 2-year-old male patient with severe oligodontia in the primary dentition was referred for examination, evaluation and treatment. The child exhibited classical XLHED features with sparse hair, absence of eyelashes and eyebrows, severe hypohidrosis associated with heat intolerance and skin dryness. Radiographic examination revealed only intra-osseous maxillary primary canines. He presented an apparent prognathism of partially functional cause, retrusion of the maxillary and lateral deviation of the mandible. TREATMENT: The rehabilitation protocol was similar to an edentulous adult but extra care was taken to avoid discomfort to this very young patient. For example, alginate was used for the impressions for its neutral taste, ease of use, and quick setting speed. An hour was given for the child to adapt to the maxillary prosthesis and then the mandibular one was fitted. Denture adhesive was used to maximize retention. The child succeeded in eating some dry biscuits and drinking some water, demonstrating the exceptional potential for adaptation children usually present with at this very young age. FOLLOW-UP: Three months later, the prognathic tendency had vanished and he could eat hard food. Periodic recall visits were scheduled and at six months and normalization of oral functions was almost complete. Three year later, a new set of prostheses was made very easily as the child knew the protocol and was used to dentures wearing. CONCLUSIONS: Prosthetic rehabilitation must be done at the earliest age possible in order to maintain and correct the oral functions and prevent growth anomalies. It makes the subsequent treatment steps easier. Early rehabilitation and follow-up seems to be one of the keys to a successful treatment that help these children overcome their handicap and integrate them into society.

Background
Ectodermal dysplasia (ED) is an heterogeneous group of congenital conditions that affects at least two ectoderm derived structures such as hair, nails, skin, sweat glands and teeth [Pinheiro and Freire-Maia, 1994]. There were more than 170 clinically distinct hereditary syndromes where ED has been described, and different attempts of classification were proposed [Itin, 2009, Irvine, 2009]. Hypohidrotic/anhidrotic ectodermal dysplasia represents 80% of ED and ranges from 1 to 10 children out of 10 9 live births [Pinheiro and Freire-Maia, 1994]. The most frequent X-linked forms of HED/EDA (MIM305100, Christ Siemens Touraine Syndrome, XLHED) result from mutations in the EDA1 gene, located on chromosome Xq12-q13.1 and encoding ectodysplasin (MIM300451), a member of the Tumor Necrosis Factor (TNF) family [Kere et al., 1996]. It accounts for more than 50% of the cases. Mutations in the EDA receptor EDAR, located on chromosome 2q11-q13 (MIM604095), or in the EDAR-Associated Death Domain EDARADD, located on chromosome 1q42-q43 (MIM606603), have been shown to cause both autosomal recessive and dominant HED forms respectively [Monreal et al., 1999, Headon et al., 2001, Bal et al., 2007]. These three forms are clinically undistinguishable as they alter a single signal transduction pathway. Clinical HED characterization. A clinical triad characterizes HED: sparse/fine hair on scalp (alopecia/hypotrichosis), sweating anomalies (hypohydrosis or anhidrosis) and dental agenesis (oligodontia or hypodontia). XLHED patients usually have nail dystrophy (onchodysplasia). Typical clinical manifestations also include dryness of the skin, eyes, airways and mucous membranes presumably due to the defective development of several exocrine glands. HED/EDA can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose and prominent lips) and occasionally with absent nipples. Extraoral examination reveals common facial characteristics making the genetic syndrome easily recognizable: frontal prominence, wrinkles and increased pigmentation around the eyes, high cheekbone and depressed nasal bridge. In profile, patients tend to show an Angle class III occlusion, combined with a flat or concave profile, a reduced lip/nose angle and a marked nasolabial fold. An infantile form of deglutition with tongue interposition

between dental arches (lingual dyspraxia) can persist [Vierucci et al., 1994, Johnson et al., 2002]. Craniofacial abnormalities worsen with age and involve three directions of space when patients are left untreated. XLHED patients have a thin maxillary alveolus and an important diminishment of the lower facial height. Oral examination shows an altered dentition in every kind of dysplasia with many phenotypes ranging from hypodontia to anodontia. In 1998, G kes et al. [1998] established the frequency of permanent tooth agenesis in adult patients: 42% were maxillary central incisors, 41% were first permanent maxillary molars, 39% were first permanent mandibular molars, 22% were canines. These results correlated with those of Bergendal and Dahl [1998] who also showed that true anodontia seldom occurs. Lexner and coworkers reported in 2007 a mean of 22 missing permanent teeth in 22 patients with XLHED. Remaining teeth are usually small and peg-shaped. Taurodontism is usual and molars might have modified cusp organization [Glavina et al., 2001, Vierucci et al., 1994]. Knife-edge alveolar ridges, disturbed occlusion and hyposalivation were also reported as prosthetic rehabilitation difficulties [Lesot et al., 2009, Levin, 1988, Bondarets et al., 2002]. Oral prosthetic rehabilitation. Abnormalities in the dental development in children imply a need for prosthetic management. Early diagnosis and multidisciplinary treatment are the keys of XLHED patient oral rehabilitation. While it is recognized that early intervention is necessary to help oral function to develop normally, no consensus exists on the ideal age for the beginning of treatment. Early treatment helps to avoid social problems which are frequent at school age [Bergendal, 2001]. Treatment usually starts with a partial denture, followed by complete removable prostheses, which may be implant-supported, or prosthodontics. The aim of this article is to present the early prosthetic rehabilitation of an XLHED 2 years-old-boy, associated with severe oligodontia in the primary dentition and the added benefits of conducting the prosthetic rehabilitation at this very young age.

Case Report
A 2-year, 3 month-old male patient of Japanese descent was referred to the Dept. of Pediatric Dentistry (Albert Chenevier-Henri Mondor Hospital, Health Services-Paris Hospitals AP-HP Crteil, France) in March 2006 for examination, evaluation and treatment. The XLHED diagnosis had been made in Japan at the age of 5 months. The information collected during the initial interview was only limited, as neither the child nor his family were fluent with French, but revealed at least an affected maternal uncle. The mother also presented with mild oligodontia, sparse eyebrows and eyelashes. The child exhibited classical HED features with sparse hair, absence of eyelashes and eyebrows, severe hypohidrosis associated with heat intolerance and skin dryness (Fig.1). The association of both HED features in a boy, his maternal uncle and mild phenotype in his mother highly suggest a XLHED. The molecular data of these families were previously reported [Cluzeau et al., 2010]. EDA1 gene sequencing shows a disease causing non described mutation in intron 7 (IVS7-1G>C). These mutations of the splicing acceptor site modify the structure of the protein. Observation of the facial characteristics showed a sunken nose bridge, a prominent forehead and everted lips. Beside the usual cranial features of ED, the child had a noticeable plagiocephaly and no teeth (Fig.2a, 2b). Nevertheless, a careful examination of the alveolar ridges showed that maxillary primary canines were present but intra-osseous (Fig.2c). He presented an apparent prognathism of partially functional cause, retrusion of the maxilla and lateral deviation of the mandible. The occlusal plane was skewed to the right side. The habit of lingual interposition between dental arches was strong, as the patient had never been fitted with prostheses. Furthermore, in a stressful situation he tended to suck on his tongue (Fig.1b) on the right side only, which may have worsened the facial asymmetry.

Figure 1. Frontal view photographs of a 2-year-old boy at initial examination showing A. HED features with sparse hair, absence of eyelashes and eyebrows, severe hypohidrosis, depressed nasal bridge, frontal prominence and everted lips, B. in a stressful situation sucking on his tongue .

Figure 2. Initial dental examination revealed agenesis of A. maxilla, B. mandible, C. intra osseous maxillary primary canines detected on panoramic radiograph.

Treatment

The rehabilitation protocol was similar to that of a completely edentulous adult but some extra care was taken to avoid discomfort to this very young patient. It involved the steps of primary impression, secondary impression, vertical dimension assessment and recording, choice of prosthetic teeth, validation of the aesthetics and functions with a wax mockup of the prosthesis, installation of the prosthesis and final adjustments. Primary and secondary impressions. Taking impressions usually involves some discomfort from the patient's point of view. Extra care was observed when dealing with this patient, as impressions were the first step of the prosthetic rehabilitation. He needed to be introduced to the material and tools used. A mandibular impression was performed first as this is usually less difficult and allowed a better cooperation for the following procedures. Given the child's young age, the usual choice of impression material was altered in order to avoid material with any bad taste, foul smell or long setting time, such as polysulphur or polyether based materials [Kotsiomiti et al., 2000]. Accordingly, an alginate was used for the primary impressions for its neutral taste, ease of use, and rapid setting. Commercially available small size impression trays were chosen (Fig.3a) and from the resultant cast, modified trays were made. Alginate was also used for the secondary impressions to minimize the child's discomfort during the procedure (Fig.3b). Impressions were of questionable but sufficient quality. Figure 3: Method of taking clinical impressions: A. alginate was used for primary impressions (in commercially impression trays; B. secondary impressions (in individualized trays) and to minimize the child's discomfort during the procedure a neutral taste, ease of use, and quick setting speed giving impressions of questionable but sufficient quality; C. wax made occlusion trays were used for the assessment and recording of the vertical dimension. Vertical dimension and occlusion recording. Wax made occlusion trays were used for the assessment and recording of the vertical dimension (Fig.3c). They prefigured the position of the prosthetic teeth. The position of the inter incisor point was first noted in accordance with the medial line of the face. Height and shape of the maxillary occlusal line was adjusted to provide the support the maxillary lip needed to achieve good aesthetic effect. The prospective occlusal line was arbitrarily determined, parallel with the Camper plane [Huth et al., 2002]. Then occlusion was recorded and new vertical dimension was determined during this process with regard to the following criteria: general facial aesthetics, lip position, comparison between the lower, middle, and higher facial heights. Aesthetic and functional test. Prosthetic temporary teeth (Bambino tooth, MAJOR Prodotti Dentari S.p.A., Moncalieri, Italy; existing in two shades only) were used (Fig.4a). The shade was chosen according to the child's complexion. The validity of the previous work was tested with wax mock-ups of the prostheses and minor adjustments were completed (Fig.4b). Paediatric prostheses are bound by the same aesthetic and functional criteria as 'adult' prostheses. They should naturally integrate in the facial environment; mimicking real teeth by offering a good labial support with facial height restoration and nasolabial fold decrease. The tooth layout in this case was adapted to the clinical situation: prosthetic space was sparse in terms of height and arch length so no second primary molars were used (Fig.4c). Figure 4. Photographs showing prostheses construction: A. choice of temporary prosthetic teeth; B. validation of the aesthetics and functions with a wax mock-up of the prosthesis; C. prosthetic space was sparse in terms of height and arch length so no second primary molars were used. Prostheses fitting. The prostheses were then fitted, one at a time, beginning with the maxillary prosthesis. Some time was given to the child to adapt to the volume/size of the maxillary prosthesis (about 60 minutes). As this first patient/prosthesis contact could be decisive in denture acceptance, denture adhesive was used to maximize retention. Instability due to prosthetic imperfection or novelty could lead to a sensation of respiratory obstruction and rejection. Once the maxillary prosthesis was accepted, the mandibular one was fitted (Fig.5a). While observing the child's reaction, explanations were given to his parents about specific care measures to be taken with the prostheses. The child was asked to eat some dry biscuits and drink some water. He succeeded in this task demonstrating the exceptional potential for adaptation children usually present at this very young age. The prothesis should also be worn at night if possible.

Follow-up
A recall visit was arranged for four days later when no mucosal lesions or difficulty of adaptation were noted nor reported by the boy's parents (Fig.5b). One and a half months later, an oral examination showed no mucosal lesions, but a tendency for mandibular protrusion. He did not lose weight but was eating soft

food only. Another month and a half later, the mandibular protrusion had vanished and he was eating hard food. Periodic recall visits were scheduled and at 6-month intervals, normalization of oral functions was almost complete (Fig.5c, 5d). With the prostheses removed, we observed that the child spontaneously adopted a relaxed position that corresponded to the vertical dimension given by the prostheses. The lateral sliding of the mandible was greatly reduced. The child wore the prostheses without the aid of denture adhesive by that time. Figure 5. Photographs and radiographs showing: A. the lower prosthesis being fitted after one hour adaptation to the upper one; B. at recall visit was four days after fitting prostheses; C. wearing dentures at six months recall with normalization of oral functions almost complete ; D. as confirmed by cephalometric radiograph with prostheses in place. A new set of prostheses was constructed three years after the last examination. Making a new set of dentures was easier as the boy knew the protocol and was used to wearing dentures. Subsequent sets were a lot easier to make as the child now knows the protocol and is used to wearing dentures. However, a new set can be necessary, sooner after if the first set did not functions satisfactorily or the child has not adapted to them.

Discussion
Providing early prosthetic care for very young partially or completely edentulous patients seems advisable. Indeed being edentulous has many consequences: poor aesthetics, speech impairment, deforming lingual habits, and a poor nutrition due to the fact that mastication is difficult or impossible. Furthermore, primary teeth are necessary for the acquisition and maturation of diverse functions, which are important for normal growth. Agenesis is seldom associated with normality and might lead to abnormal functions and dysmorphosis. These troubles are of the utmost importance during growth. Early intervention is needed to help a child to develop normal oral functions (speech, deglutition, mastication). Psychological benefits are as important as dental benefits brought by the prostheses [Bergendal, 2002]. Apparent prognathism. Anterior protruding of the mandible can cause an apparent prognathism as a consequence of the diminished facial height, the lowering of the occlusal plane and the lack of incisal lock. Diminishment of the lower part of the face is caused by the absence of alveolar bone but can also be a consequence of an insufficient development of the basal bone. Basal growth is limited by a low lingual position; the tongue tends to grow laterally between the dental arches. Transversal maxillary growth stays limited and a true Angle class III can develop with maxillary brachignathism and mandibular prognathism. A primary deglutition mechanism can persist in absence of prosthetic rehabilitation and abnormal lingual habits usually develop [Vierucci et al., 1994, Johnson et al., 2002]. Growth of maxillary and mandible occur more harmoniously when prosthetic rehabilitation happens early, when normal mastication, swallowing and speech are restored and abnormal functions are eliminated. Apparent prognathism can be reduced by the use of prostheses [Vierucci et al., 1994, Johnson et al., 2002, Sforza et al., 2006]. Early treatment. After treating more than 40 patients with ED, we consider that the sooner the prosthetic rehabilitation begins, the better the results will be in term of functions, social integration and self-esteem of the patient. Taking care of patients at such a very young age is a complex task but the social benefits for the child are enormous while he/she is supposedly mature enough to recognize social handicaps [Kotsiomiti et al., 2000]. Apart from the benefits offered in term of functions and aesthetics, the 'learning' set of prostheses set allows a child to overcome their social handicap while beginning to go to school and live in their community. The learning prosthetic set. Our main objective was to have this child learn how to function with prostheses: how to wear them, swallow, masticate, speak and smile with them. This first set of dentures is a 'learning' prosthetic set. Making such dentures when a child is very young is difficult. Nevertheless, they are well tolerated despite the questionable precisenessof the impressions and the compromise made to accommodate the prostheses to a child. These learning prostheses did not conform to the classical rules of prosthodontics but still presented good retention and stabilization without the need for denture adhesive. We attributed this good result to the fact that very young children adapt very well and manage to keep their dentures in place using tongue and cheek muscles when necessary. Follow-up and parental motivation. These are key points for the success of this kind of prosthetic rehabilitation. The younger the child, the more important it is; oral hygiene instructions should be given to parents for the care of their child's prothesis and any natural teeth that may be present. The prostheses should be worn during nighttime to allow for a better integration.

Conclusion
Early dental management of children with ectodermal dysplasia is advisable and prosthetic rehabilitation must be done at the earliest age possible in order to maintain and correct the oral functions. Not only does it help such children cope with future social handicap(s) implied by the edentulism, it also takes advantage of the great adaptability the children present at this age. It permits the development of functions as soon as possible and makes the subsequent treatment steps easier. Furthermore, the sooner the growth abnormalities are prevented, the less serious their extent is. Early rehabilitation and follow-up seems to be one of the keys to a successful treatment, which help these children overcome their handicap and integrate our smile driven society.
Acknowledgements
The authors wish to extend their gratitude to our prosthetic technicians M. Alain Kleiner and M. Stphane Hurtado; as well as Drs Lucile Dahan and Romain Jacq for the clinical and bibliographic assistance. We thank Dr Smail Hadj-Rabia and Prof Christine Bodemer (Dermatology Dept, Necker-Enfants Malades Hospital, Paris, France) for their help in reviewing the manuscript.