Clinical, histopathologic and genetic diagnosis in osteogenesis imperfecta and dentinogenesis imperfecta

Sammanfattning: The aims of this thesis were to investigate (1) dental aberrations in a large sample of unrelated patients with different types and forms of OI, (2) degree of dentin dysplasia in relation to type and form of OI and clinical, radiographic, and microscopic manifestations and type of DI, and (3) genotypes and phenotypes in two families with DI type II with special reference to clinical, radiographic, and histopathologic manifestations. In study I, morphological and clinical variation in the expression of DI within one family was described. The differences led to differences in treatment. It was emphasized that attrition should be prevented in order to avoid loss of vertical height and development of periapical lesions. In study II, conducted in young patients with OI, the spectrum of disturbances in tooth development ranged from no detectable abnormalities in 22% to severe abnormalities in 47% of the patients. This stresses the importance of a detailed and thorough dental investigation. Among patients with mild forms of the disease, where the medical diagnosis may be uncertain, demonstration of disturbances in dental development can be crucial for establishing a correct diagnosis. Two scoring systems were introduced in study III, one for assessing the degree of clinical and radiographic manifestations (CRS) and one for assessing the degree of dysplastic manifestations in dentin (DDS). Their utility was demonstrated in a large sample of teeth from patients with OI and DI. The DDS system proved valuable when the CRS system failed, the most significant finding being subclinical histological manifestations of DI in patients with OI but without clinical or radiographic signs of DI. Thus, these subtle dysplastic changes are most likely an expression of genetic disturbances associated with OI and should not be diagnosed as DI, but rather be termed histologic manifestations of dysplastic dentin associated with OI. In study IV, mutations in the DSPP gene in two families with DI type II were described. The families presented with different missense mutations, and none of the patients had any evidence of hearing loss. Members of each family presented with a similar pattern of disturbances as assessed clinically, radiographically, and histopathologically. In contrast, drastic differences were found between the two families. The data indicate the presence of a genotype-phenotype correlation in DI type II. In combination with previous reports, the data also indicate that DI type II may be allelic with DI type III and dentin dysplasia type II (DD type II), and the diseases may thus represent a spectrum rather than distinct entities.