Osteogenesis imperfecta tooth level phenotype analysis: Cross-sectional study

Abstract

Introduction: Dental anomalies in Osteogenesis imperfecta (OI), such as tooth discoloration, pulp obliteration (calcified dental pulp space), and taurodontism (enlarged dental pulp space) vary between and within patients. To better understand the associations and variations in these anomalies, a cross-sectional study was designed to analyze the dental phenotype in OI patients at the individual tooth type.

Method: A cohort of 171 individuals with OI type I, III and IV, aged 3-55 years, were recruited and evaluated for tooth discoloration, pulp obliteration, and taurodontism at the individual tooth level, using intraoral photographs and panoramic radiographs.

Results: Genetic variants were identified in 154 of the participants. Patients with Helical α1 and α2 glycine substitutions presented the highest prevalence of tooth discoloration, while those with α1 Haploinsufficiency had the lowest (<10%). C-propeptide variants did not cause discoloration but resulted in the highest pulp obliteration prevalence (~%20). The prevalence of tooth discoloration and pulp obliteration was higher in OI types III and IV and increased with age. Tooth discoloration was mainly observed in teeth known to have thinner enamel (i.e. lower anterior), while pulp obliteration was most prevalent in the first molars. A significant association was observed between pulp obliteration and tooth discoloration, and both were associated with a lack of occlusal contact. Taurodontism was only found in permanent teeth and affected mostly first molars, and its prevalence decreased with age.

Conclusion: The dental phenotype evaluation at the tooth level revealed that different genetic variants and associated clinical phenotypes affect each tooth type differently, and genetic variants are better predictors of the dental phenotype than the type of OI. Our results also suggest that tooth discoloration is most likely an optical phenomenon inversely proportional to enamel thickness, and highly associated with pulp obliteration. In turn, pulp obliteration is proportional to patient age, it is associated with malocclusion and likely related to immature progressive dentin deposition. Taurodontism is an isolated phenomenon that is probably associated with delayed pulpal maturation.

Keywords: Connective tissue; Dentin; Dentinogenesis; Oral medicine; Osteogenesis Imperfecta; Tooth abnormalities.

Figure 1.

1) 31 years old female with OI Type I. 2) 16 years old female with OI type III. 3) 17 years old male with OI type IV. a) upper occlusal view, b) frontal view, c) lower occlusal view. c) right side, d) left side, f) panoramic x-ray.

Figure 2.

The prevalence of the clinical and dental phenotype of OI patients as a function of their genetic variants a) The number of patients associated with different types of variants as a function of their OI type. b) The number of discolored teeth in different OI types. c) The number of obliterated teeth in different OI types. d) The number of teeth with taurodontism in different OI types. e) The number of discolored teeth associated with the different types of variants. f) The number of obliterated teeth associated with the different types of variants. g) The number of teeth with taurodontism associated with different variant types.

Figure 3.

The prevalence of dentinogenesis imperfecta in permanent and deciduous teeth. b) The prevalence of pulp obliteration in different OI types in each tooth type. c) The prevalence of Taurodontism in permanent teeth. * indicates a significant difference.

Figure 4.

Tooth level analysis of OI patients as a function of their type of variant. a) The prevalence of tooth discoloration in each tooth type as a function of type of variant. b) the prevalence of obliterated in each tooth type as a function of type of variant. c) The prevalence of taurodontism in each tooth type as a function of type of variant.

Figure 5.

Variants in Col 1A1 and Col1A2. a) Normal collagen formation: 2 Pro α1 and 1 pro α2 are essential for the normal formation for the triple helix; change in the 2:1 ratio will result in a reduction of collagen production as in b). b) Haploinsufficiency variant affecting Pro α1 or Pro α2 would result in less collagen and a mild clinical phenotype (OI type I). c) Point variant, especially the Glycine substitution, would result in abnormal collagen structure. The severity will be dependent on the affected gene (Pro α1 or Pro α2). d)c-propeptide is the start point for the formation of the triple helix, and a mutation at this site will result in a loose bundle of collagen fibres and is associated with moderate to severe OI clinical phenotypes (OI types IV and III). e) Splice site variant is associated with a wide range of clinical phenotypes, where the site and type of variant will determine the severity. Skipping mutation is usually associated with a more severe form of OI, while insertions or deletion are associated with a mild form.