Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta – A retrospective cohort study

Abstract

Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2). Dentinogenesis imperfecta (DGI) and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI. The clinical examination included radiographic evaluations. Teeth from 81 individuals were available for histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29% of the individuals (44/152) and through isolated histological findings in another 19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with a glycine substitution located C-terminal of p.Gly305 exhibited DGI in both dentitions while no individual (0/7) with a mutation N-terminal of this point exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2 mutation, 80% (8/10) of those with a glycine substitution located C terminal of p.Gly211 exhibited DGI in both dentitions while no individual (0/5) with a mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition. DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had missense mutations where glycine to serine was the most prevalent substitution (53%). Taurodontism occurred in 18% and retention of permanent second molars in 31% of the adolescents. Dental aberrations are strongly associated with qualitatively changed collagen I. The varying expressivity of DGI is related to the location of the collagen I mutation. Genotype information may be helpful in identifying individuals with OI who have an increased risk of dental aberrations.

Cone‐Beam Computed Tomography of Osteogenesis Imperfecta Types III and IV: Three‐Dimensional Evaluation of Craniofacial Features and Upper Airways

“…Craniofacial and dentoalveolar abnormalities are present in mild, moderate, and severe types of OI. Cephalometric studies have revealed that dentoalveolar structures and the condylar processes are often vertically underdeveloped in OI types III and IV . Clinically, the hypoplastic maxilla and reduced vertical and transverse dimensions result in a malocclusion, such as bilateral open bite or cross bite, and counterclockwise (overclosing) rotation of the mandible .…”

Dentinogenesis imperfecta type II in Swedish children and adolescents

“…A study by Lagana et al [21] reported an impaction prevalence of 3.9% in a group of 4706 aged 8−12-years. Retention of permanent second molars is a frequent finding in OI [5, 6, 22], but was not found in any individuals in this cohort. Pulpal obliteration occurred in 100% of the children in the present study.…”

“…Clinically, the following signs were evaluated: retained teeth (failure of eruption), malocclusion, and DGI indicators – pathologic discoloration, attrition, and fractures. Radiographically, these signs were evaluated: number of tooth germs, extended pulp chambers (taurodontism), and DGI indicators – bulbous crowns with cervical constriction, pulpal obliteration, and short roots [5]. Individuals with suspected OI were referred to the national OI multidisciplinary pediatric team at Astrid Lindgren Children’s Hospital for further examination and diagnosis.…”

“…Depending on type of OI, reported prevalences of DGI-I in patients with OI range from 8 to 100%. Children with a more severe type of OI often present with a more severe dental phenotype [5–8]. …”

Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research

“…A frequent dental abnormality in OI is dentinogenesis imperfecta, which is caused by dysplastic dentin and can lead to dental discoloration, tooth fracture, and attrition . Genotype–phenotype correlation studies show that the large majority of patients with OI types III and IV caused by qualitative mutations have dentinogenesis imperfecta, whereas only a small minority of individuals with COL1A1 haploinsufficiency mutations have dentinogenesis imperfecta that is visible on clinical inspection . Beyond dentinogenesis imperfecta, tooth agenesis is a common finding in OI .…”