Dentin Dysplasia, Type Ii

A number sign (#) is used with this entry because of evidence that dentin dysplasia type II (DTDP2) is caused by heterozygous mutation in the DSPP gene (125485) on chromosome 4q22.

Dentinogenesis imperfecta-1 (DGI1; 125490), also called dentinogenesis imperfecta Shields type II, is an allelic disorder.

Description

Dentin dysplasia type II is a defect of dentin formation in which the clinical appearance of the secondary teeth is normal, but the primary teeth may appear opalescent, similar to teeth affected by dentinogenesis imperfecta. The roots of the teeth are of normal shape and morphologic character. The pulp chambers and root canals of the anterior teeth and the premolars are shaped like thistle tubes because of the radicular extension of the pulp chamber. Most teeth show accumulations of pulp stones in these unusually shaped pulp chambers (summary by Kalk et al., 1998).

Also see dentin dysplasia type I (DTDP1; 125400).

Clinical Features

Shields et al. (1973) delineated a heritable dental defect in which the deciduous teeth are opalescent. Several other cases have been reported (Rao et al., 1970; Richardson and Fantin, 1970; Giansanti and Allen, 1974; Wald and Diner, 1974; Melnick et al., 1977). Clinically the primary dentition in type II dentin dysplasia appears opalescent, and radiographically the pulp chambers are obliterated, resembling dentinogenesis imperfecta (DGI1; 125490). However, unlike dentinogenesis imperfecta, the permanent teeth in dentin dysplasia, type II are normal in color and on radiographs have a thistle-tube pulp chamber configuration with pulp stones. Gorlin (1982) concluded that pulpal dysplasia as described by Rao et al. (1970) is the same disorder. Rao et al. (1970) reported a 5-year-old mentally retarded girl whose teeth, on dental radiographs, had ovoid crowns, small roots, and large root canals. The pulp chambers were larger than normal, ovoid, and extended into the root. Multiple pulp calcifications were noted in the pulp chambers of all deciduous and unerupted permanent teeth. A sib and both parents were unaffected.

Mapping

The similarity of the primary dentition phenotype between DGI1 and type II dentin dysplasia suggested that the gene for dentin dysplasia type II is allelic with the gene for Shields type II dentinogenesis imperfecta, the isolated form of dentinogenesis imperfecta that has been shown by linkage studies to be encoded by a gene on 4q13-q21. Dean et al. (1997) studied a 3-generation family in which 10 members were affected with dentin dysplasia type II. Microsatellite markers specific for the area of 4q linked to DGI1 were used. A maximum 2-point lod score of 4.2 at theta = 0.0 was obtained with SPP1 (166490) and D4S2691. Multipoint analysis gave a maximum lod score of 4.33. The candidate region for dentin dysplasia type II was approximately 14.1 cM, included SPP1 and 4 anonymous DNA markers, and overlapped the most likely location of the DGI1 locus. Dean et al. (1997) concluded that any candidate gene for DGI1 should also be considered a candidate gene for dentin dysplasia type II.

Molecular Genetics

On the basis of the phenotypic overlap between, and shared chromosomal location with, dentinogenesis imperfecta type II, it had been proposed that dentin dysplasia type II and dentinogenesis imperfecta type II are allelic. Rajpar et al. (2002) reported an asp6-to-tyr missense mutation (125485.0005) in the bicistronic dentin sialophosphoprotein gene (DSPP; 125485) in a family with dentin dysplasia type II. The substitution in the hydrophobic signal peptide domain caused a failure of translocation of the encoded proteins into the endoplasmic reticulum. The authors hypothesized that this would likely to lead to a loss of function of both dentin sialoprotein and dentin phosphoprotein.

In affected individuals spanning 3-generations of a Chinese family with dentin dysplasia type II, Song et al. (2008) identified a heterozygous frameshift mutation in the DSPP gene (125485.0008). Most teeth of the youngest patient, a 5-year-old girl, showed amber discoloration and severe attrition. Panoramic radiographs showed obliterated pulp chambers and root canals. Her mother's permanent teeth had a normal appearance but showed thistle-shaped pulp chambers and nearly obliterated root canals on radiographs. The affected grandfather had similar manifestations as his granddaughter.

Nomenclature

Dean et al. (1997) suggested that an updating of the nomenclature for the developmental disturbances of dentin is indicated, comparable to that presented by Aldred and Crawford (1995) for developmental disturbances in amelogenesis imperfecta.