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RESEARCH REPORT |
1 Department of Teratology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic;
2 Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Vinicna 7, 128 00 Prague 2, Czech Republic;
3 INSERM U595, 11 rue Humann, 67085 Strasbourg Cedex, France;
4 Université Louis Pasteur, Faculté de Chirurgie Dentaire, 67085 Strasbourg, France; and
5 Clinic of Plastic Surgery, Faculty Hospital Kralovske Vinohrady, Srobarova 50, 100 34 Prague 10, Czech Republic
* corresponding author, marhor{at}biomed.cas.cz
| ABSTRACT |
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KEY WORDS: lateral incisor dental epithelium human tooth development orofacial cleft dental anomalies
| INTRODUCTION |
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Upper lateral incisor abnormalities are frequently associated with different types of orofacial clefts (Jordan et al., 1966; Tsai et al., 1998). In children with a unilateral complete cleft lip and palate, Tsai et al.(1998) observed four distribution patterns of the primary upper lateral incisor on the cleft side: (a) one lateral incisor located distally to the alveolar cleft, (b) one lateral incisor located mesially to the alveolar cleft, (c) the absence of the lateral incisor, and (d) the presence of two lateral incisorsone tooth on each side of the alveolar cleft.
In a normal population, the prevalence of supernumerary teeth is less than 1% for the primary dentition (e.g., Ravn, 1971; Jarvinen and Lehtinen, 1981). However, in patients with a cleft lip, the incidence of a supernumerary lateral incisor varies between 40% and 73% in the primary dentition (Böhn, 1963; Hansen and Mehdinia, 2002). In the permanent dentition, supernumerary lateral incisors were found in 42% of cleft patients (Böhn, 1963). Supernumerary lateral incisors are more frequent in the deciduous dentition than in the permanent one (Böhn, 1963; Tsai et al., 1998; Hansen and Mehdinia, 2002).
The morphology of the human face is established between the 5th and 10th prenatal weeks. An upper jaw arch is formed by the fusion of the paired medial nasal and maxillary facial processes (Figs. 1A, 1B, 1D
). After ossification, the upper jaw consists of the maxillary bone and premaxilla, separated by the incisive suture. However, the incisive suture is not located where the embryonic facial processes fuse (Lisson and Kjaer, 1997; Tsai et al., 1998; Barteczko and Jacob, 2004). During prenatal development, the medial part of the maxillary process delivers material to the future premaxilla (Lisson and Kjaer, 1997; Barteczko and Jacob, 2004). The premaxilla carries the upper central and lateral incisors.
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The aim of our study was to search for the origin of the deciduous upper lateral incisor in normal human embryos at prenatal weeks 68, to elucidate the reasons for the developmental vulnerability of this tooth.
| MATERIALS & METHODS |
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Histology
After fixation in Bouin-Hollande fluid or in 10% formol, the heads were embedded in paraffin, cut in series of 10-µm-thick frontal sections, and stained with hematoxylin-eosin or by a modified Mallory method.
3D Reconstructions
3D reconstructions of the dental epithelium have been performed in a representative sample of 8 normal human embryos showing a longitudinal series of tooth development (Hovorakova et al., 2005). The right or left upper jaw quadrant was selected randomly (Table
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| RESULTS |
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ED 4244
The place of the earlier junction between the facial processes was still easily visible (Figs. 2C, 2D
). It was formed by an oblique ridge between the primary choana and dental epithelium, and by a furrow continuing from the dental epithelium in the antero-medial direction to the epithelium of the oral vestibule. The dental epithelium formed a continuous dental mound, with a clearly detectable fusion site between its two original components (Figs. 2C, 2D
; Appendix Fig. 4C). In the developmentaly more advanced embryo, tooth primordia began to be visible. The fusion site of the dental epithelia was detectable as a furrow on the germ of the lateral incisor (Appendix Fig. 4D).
ED 4446
The fusion site of the dental epithelia of the medial nasal and maxillary processes was detectable on the germ of the lateral incisor. The fusion line could also be detected in the prospective vestibular area (Appendix Figs. 4E, 4F).
Prenatal Week 8
The primordia of both deciduous incisors, canine and first molar, were apparent on the dental mound. A shallow furrow on the lateral incisor germ suggested the earlier fusion between the dental epithelia of the medial nasal and maxillary processes. This furrow continued into the vestibular epithelium (Fig. 2E
; Appendix Figs. 5A, 6).
Beginning of the 3rd Month
At this stage, no evidence of the fusion process was found in either the dental or in the adjacent epithelia (Appendix Fig. 5B).
| DISCUSSION |
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The present study focused on the origin of the epithelial component of the upper lateral incisor germ. We used a natural markerthe furrow at the previous fusion site between medial nasal and maxillary processes. This furrow could be traced up to prenatal week 8 (Fig. 2
; Appendix Figs. 4, 5, 6). This marker allowed us to detect the epithelial contributions of the medial nasal and maxillary processes in the lateral incisor germ.
In humans, a thickened odontogenic epithelium can be identified in the 5th embryonic week on all the medial nasal and maxillary processes before their fusion (Ooë, 1957). The fusion of all components of the facial processes does not occur simultaneously. In macaques, the obliteration of the groove between the facial processes lags behind in the alveolus, compared with that in the lip (Wei et al., 2000). Generally, it is believed that the fusion of the human frontonasal, maxillary, and mandibular processes is complete by ED 38 (Tonge, 1967). The 3D reconstructions performed here clearly documented the fusion site between the medial nasal and maxillary processes. Although the facial processes proper have been fused, the thickenings of the dental epithelium were still separate at ED 4042 (Figs. 2A, 2B
; Appendix Figs. 4A, 4B). They fused as late as at ED 4244 (Figs. 2C, 2D
; Appendix Fig. 4C). Until prenatal week 8, the former fusion was indicated by a furrow on the lateral incisor germ that continued to the adjacent oral epithelia (Fig. 2E
; Appendix Figs. 4D4G, 5A, 6). Compared with the fusion of other components of the facial processes, the fusion of the dental epithelia was delayed (Figs. 1A1E
, 2A, 2B
). The delay was estimated to be about 46 days.
At the fusion site of the facial processes, the germ of the upper lateral incisor emerged, comprised of epithelium from both the medial nasal and maxillary processes (Fig. 2
; Appendix Fig. 4). Analysis of the present data, documenting the composite origin of the lateral incisor (Fig. 2
; Appendix Figs. 4, 5, 6), fits with the observation that the original maxillary facial processes participate in the development of the premaxilla (Lisson and Kjaer, 1997; Barteczko and Jacob, 2004). On the premaxilla, the upper incisors erupt. In 1957, Ooë had already proposed, on the basis of his model of 3D reconstruction, that the human upper lateral incisor germ can have its origin partly in the medial nasal and partly in the maxillary process. By 3D reconstructions, a contribution of the maxillary process to incisor formation has also been demonstrated in the mouse (Peterkova et al., 1993). In the macaque, the developmental origin of the upper lateral incisor has been localized entirely on the maxillary process (Wei et al., 2000).
The complex origin of the human upper lateral deciduous incisor can explain its developmental vulnerability, resulting in anomalies of number, shape, and size, frequently associated with orofacial clefts (Böhn, 1963; Hansen and Mehdinia, 2002). The presumed double origin of the upper lateral incisor (Ooë, 1957) has been used to explain the high incidence of two lateral incisors adjacent to the cleft, mesially and distally, in patients with a complete cleft lip and palate (CLP) (Tsai et al., 1998) (Figs. 1F
, 3A
). The CLP formation is caused by the non-fusion of the medial nasal and maxillary processes, resulting from their insufficient development (hypoplasia) (Ferguson, 1991). We suggest that the non-fusion of the facial processes leads to the non-fusion of the two components of the lateral incisor (Figs. 1C, 1F
). Their separate development may finally give rise to two lateral incisors, one on each side of the cleft (Figs. 1F
, 3A
).
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Moreover, the patients with supernumerary lateral incisors in an intact jaw can be at increased risk to carry some genetic predisposition for orofacial clefts. The presence of a supernumerary lateral incisor in otherwise clinically normal individuals could be used as a marker of possible cleft predisposition. As a similar marker, the ultrasonographic detection of orbicularis oris muscle defects has been proposed (Martin et al., 2000).
Beside the supernumeraries, other dental anomalies can be observed in the lateral incisor region in cleft patients: one lateral incisor distal to the alveolar cleft, one lateral incisor mesial to the alveolar cleft, and the absence of a lateral incisor on the cleft side.
The above-mentioned anomalies may be within the same spectrum and may be ranked according to the degree of hypoplasia (tissue insufficiency) of the facial processes. In humans, the fusion of facial processes proceeds from deeper to superficial. As fusion fails earlier, the more relevant (deeper) orofacial cleft occurs. Accordingly, the failing development of one or both components of the lateral incisor can be expected in more relevant cleft types that also affect hard tissues (cleft lip and alveolar process, CLP). One small lateral incisor located mesial or lateral to the alveolar cleft can reflect development of only one component of the lateral incisor (on the less hypoplastic facial process), while the second component (on the more hypoplastic process) did not form. The absence of the lateral incisor can be explained by the hypoplasia of both facial processes, including both components of the lateral incisor. From this aspect, the absence of the lateral incisor mesially and/or distally to the cleft could be the marker of the tissue insufficiency of the corresponding medial nasal and/or maxillary process. In contrast, the supernumerary lateral incisor might be more often associated with those cleft forms affecting only soft tissues (isolated soft-tissue cleft lip).
The type of lateral incisor pattern could be used to subclassify patients with different forms of cleft into separate etiologic categories. The etiology of clefting according to the lateral incisor phenotype can be tested in families, specially in non-cleft siblings of cleft patients. The significantly higher frequency of dental anomalies has been found in the non-cleft siblings of cleft patients, compared with the control non-cleft group (Schroeder and Green, 1975). However, a precise ranking of patients into groups according to orofacial cleft type is necessary before the evaluation of the genetic background of this defect can proceed.
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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Received September 23, 2004; Last revision September 1, 2005; Accepted October 3, 2005
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