Imperfecta Dentinogenesis: a case report

Dentin defects represent a cluster of relatively rare heritable disorders affecting the formation and mineralization of dentin. Major clinical features include loss of enamel with extreme wear of exposed dentin, opalescent tooth discoloration, short roots with pulpal calcification and increased tooth mobility, and frequent periapical radiolucencies. Historically, these inherited conditions have been classified by Shields et al. (1) as either dentinogenesis imperfecta (DGI) types I, II and III, or dentin dysplasia (DD) types I and II. DGI type I is now universally designated as osteogenesis imperfecta with dentinogenesis imperfecta (OI/DGI) and is caused by type I collagen mutations. Among the genes expressing the non‐collagenous proteins in dentin, only the DSPP gene has been implicated in the etiology of DD type II and all DGI types, suggesting that heritable dentin defects can be viewed as a continuum rather than as distinct disease entities. Dental treatment strategies should aim to preserve the affected dentitions by protecting teeth from wear, restoring them to compliance with the specific structural characteristics of the defective dentin, and anticipating early tooth loss. Endodontic treatment of the affected teeth is very challenging because of the peculiar pulp morphology and most often has poor prognosis. If conventional therapy is not an option, periapical curettage and retrograde filling is a possible alternative, except in the case of teeth with short roots.

By the Shields classification, articulated over 30 years ago, inherited dentin defects are divided into 5 types: 3 types of dentinogenesis imperfecta (DGI), and 2 types of dentin dysplasia (DD). DGI type I is osteogenesis imperfecta (OI) with DGI. OI with DGI is caused, in most cases, by mutations in the 2 genes encoding type I collagen. Many genes are required to generate the enzymes that catalyze collagen's diverse post-translational modifications and its assembly into fibers, fibrils, bundles, and networks. Rare inherited diseases of bone are caused by defects in these genes, and some are occasionally found to include DGI as a feature. Appreciation of the complicated genetic etiology of DGI associated with bony defects splintered the DGI type I description into a multitude of more precisely defined entities, all with their own designations. In contrast, DD-II, DGI-II, and DGI-III, each with its own pattern of inherited defects limited to the dentition, have been found to be caused by various defects in DSPP (dentin sialophosphoprotein), a gene encoding the major non-collagenous proteins of dentin. Only DD-I, an exceedingly rare condition featuring short, blunt roots with obliterated pulp chambers, remains untouched by the revolution in genetics, and its etiology is still a mystery. A major surprise in the characterization of genes underlying inherited dentin defects is the apparent lack of roles played by the genes encoding the less-abundant non-collagenous proteins in dentin, such as dentin matrix protein 1 (DMP1), integrin-binding sialoprotein (IBSP), matrix extracellular phosphoglycoprotein (MEPE), and secreted phosphoprotein-1, or osteopontin (SPP1, OPN). This review discusses the development of the dentin extracellular matrix in the context of its evolution, and discusses the phenotypes and clinical classifications of isolated hereditary defects of tooth dentin in the context of recent genetic data respecting their genetic etiologies.

Hydroxyapatite crystal deposition and stabilization within the collagen matrix of bone and dentin have been linked to the presence of noncollagenous proteins (NCP). Dentinogenesis imperfecta (DI), a genetic disorder of dentin mineralization, is being studied as a model for the analysis of mineralization mechanisms. A comparative study of the NCP in normal human dentin and dentinogenesis imperfecta Type II (hereditary opalescent dentin) dentin has been performed. The proteins of each tissue were extracted and separated using a variety of techniques. The calcium-binding, highly phosphorylated protein phosphophoryn was one of the principal NCP in normal human teeth dentin, whereas there was no evidence for the presence of such a component in the DI teeth. These data imply that dentin phosphophoryn may be related in function to the mineralization process. A similar calcium-binding protein defect should be sought in the various types of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by fragile bones and skeletal deformities. Individuals with OI may have dental abnormalities such as dentinogenesis imperfecta (DI) type I, malocclusions, and unerupted or missing teeth. This review comprehensively examines these dental abnormalities to assess their prevalence among the OI population and explore potential differences across different clinical types of OI and pathogenic variants. In accordance with the PRISMA guidelines, a systematic literature search in PubMed, Embase, and Web of Science was conducted that included articles up to June 2024. Out of 672 articles screened, 34 were included. The included studies confirmed that dental abnormalities are prevalent in OI, with DI prevalence ranging from approximately 20 to 48%. Those with a more severe skeletal phenotype (OI type III/IV) exhibited more dental abnormalities than those with a milder skeletal phenotype (OI type I). Notably, OI type V individuals generally do not have DI, although a few isolated cases have been reported. The prevalence of occlusion types varied: Class I occlusion ranged from 14.8 to 50% and Class II malocclusion ranged from 0 to 37.5%, while Class III malocclusion from 4.1 to 84%. This differs from the general population, where Class III malocclusion is typically the least common. Open bites, cross-bites, and unerupted and missing teeth are also commonly reported, particularly in OI types III and IV. This review emphasizes the need for comprehensive dental examinations in OI due to the high prevalence of dental abnormalities. Additionally, the review draws attention to the lack of clear guidelines for diagnosing DI.

Dentinogenesis imperfecta (DI) is characterized by abnormal dentine formation owing to a mutation of dentine sialophosphoprotein. It is usually an autosomal dominant disorder that affects both primary and permanent teeth. The prominent clinical feature is the opalescent hue of teeth. Radiographically, bulbous crowns, cervical constriction and short roots can be seen. Early diagnosis is essential in DI because these patients may experience aesthetic, functional and emotional problems. Management requires a multidisciplinary approach, starting with enhanced preventive strategies to preserve the remaining tooth structures. The following case report describes a child with DI type II who was managed by improving functional and aesthetic aspects. CPD/Clinical relevance: Dental professionals should be able diagnose dentinogenesis imperfecta and understand what early intervention can achieve.

The dentin sialophosphoprotein (DSPP) gene (4q21.3) encodes two major noncollagenous dentin matrix proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Defects in the human gene encoding DSPP cause inherited dentin defects, and these defects can be associated with bilateral progressive high-frequency sensorineural hearing loss. Clinically, five different patterns of inherited dentin defects are distinguished and are classified as dentinogenesis imperfecta (DGI) types I, II, and III, and dentin dysplasia types I and II. The genetic basis for this clinical heterogeneity is unknown. Among the 11 members recruited from the studied kindred, five were affected with autosomal dominant DGI type II. The mutation (g.1188C-->G, IVS2-3C-->G) lay in the third from the last nucleotide of intron 2 and changed its sequence from CAG to GAG. The mutation was correlated with the affection status and was absent in 104 unaffected individuals (208 alleles) with the same ethnic and geological background. The proband was in the primary dentition stage and presented with multiple pulp exposures. The occlusal surface of his dental enamel was generally abraded, and the dentin was heavily worn and uniformly shaded brown. The dental pulp chambers appeared originally to be within normal limits without any sign of obliteration, but over time (by age 4), the pulp chambers became partially or completely obliterated. The oldest affected member (age 59) showed mild hearing loss at high-frequency (8 kHz). Permanent dentition was severely affected in the adults, who had advanced dental attrition, premature loss of teeth, and extensive dental reconstruction.

To explore the clinical and genetic characteristics of a Chinese pedigree affected with hereditary dentinogenesis imperfecta (DGI) type II. Clinical data of the pedigree members were collected. Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing. Clinical characteristics of the affected family members have included amber teeth along with significant attrition, constricted roots and dentine hypertrophy leading to pulpal obliteration, which were suggestive of DGI type II. All of the affected members were found to have harbored a novel heterozygous c.2837delA (p.Asp946Valfs*368) variant of the DSPP gene which was predicted to be likely pathogenic. The c.2837delA variant of the DSPP gene probably underlay the disease in this pedigree. Above finding has expanded the variant spectrum of DSPP gene and provided a basis for molecular diagnosis and genetic counseling for this pedigree.

Chapter X - Diseases of the Musculoskeletal System and Joints correlated to the Oral Tissues

Dentinogenesis Imperfecta: A Case Report

To demonstrate the field of application and prospects of individually modeled indirect composite restorations for the treatment of children and adolescents based on a case of dentinogenesis imperfecta. Dental malformations can affect single or multiple teeth. In most cases, direct composite fillings can be placed. However, in severe cases, these restorations may be more challenging and error-prone, especially when occlusal adjustments are necessary. Since composite materials do not require a specific lamination strength and are easy to repair, they can be applied using the indirect technique, enabling conservation of more sound hard tissue than is possible when conventional restorations are used. A young patient with dentinogenesis imperfecta type II underwent interdisciplinary full-mouth rehabilitation due to massive tooth wear and loss of vertical occlusion. First, a check bite was taken, and vertical occlusion was increased using overdentures. Six months later, a construction bite was taken over the existing overdentures (focusing on the sagittal dimension) to move the mandibular position more towards the anterior, correcting the skeletal Class II malocclusion. This resulted in a Class I intercuspidation with harmonization of the facial proportions. After a further six months, all teeth were restored using individually modeled indirect composite restorations, which preserved most of the sound hard tissue and restored esthetics and function. Indirect composite restorations can be a valuable tool for improving occlusion, esthetics and function in the treatment of children and adolescents.

Genetic disorders of the dentin are known for several years, and reviews have been published mainly in the form of case reports. Dentinogenesis imperfecta (DI) is a disease characterized by an abnormal formation and abnormal structure of the dentin, generally affecting both primary and permanent dentition. The only epidemiological data available were published in 1975 by Witkop, who estimated the incidence of dentinogenesis imperfecta to be between 1/6000 and 1/8000. We present a case of DI III with an unusual presentation of rhizomegaly, dilacerations of the root, and taurodontism, seldom reported in the English literature for any genetic disorder of dentin. Clinical management is challenging in such cases, as the literature mentions that only an early diagnosis and early treatment with periodic follow-up can help improve the quality of life. Psychological and genetic counseling along with a multidisciplinary approach is mandatory for the cases such as the one presented here. Patient education and motivation had a paramount role in making the patient accept the treatment.

Tooth development is regulated by sequential and reciprocal epithelium-mesenchymal interactions and their related molecular signaling pathways, such as bone morphogenetic proteins (BMPs). Among the 14 types of BMPs, BMP9 (also known as growth differentiation factor 2) is one of the most potent BMPs to induce osteogenic differentiation of mesenchymal stem cells. The purpose of this study was to examine potential roles of BMP9 signaling in tooth development. First, we detected the expression pattern of BMP9 in tooth germ during postnatal tooth development, and we found that BMP9 was widely expressed in odontoblasts, ameloblasts, dental pulp cells, and osteoblasts in alveolar bones. Then, we established a BMP9-KO mouse model. Gross morphological examination revealed that the tooth cusps of BMP9-KO mice were significantly abraded with shorter roots. Micro-computed tomography and three-dimensional reconstruction analysis indicated that the first molars of the BMP9-KO mice exhibited a reduced thickness dentin, enlarged pulp canals, and shortened roots, resembling the phenotypes of the common hereditary dental disease dentinogenesis imperfecta. Further, the alveolar bone of the BMP9-KO mutants was found to be shorter and had a decreased mineral density and trabecular thickness and bone volume fraction compared with that of the wild-type control. Mechanistically, we demonstrated that both dentin sialophosphoprotein and dentin matrix protein 1 were induced in dental stem cells by BMP9, whereas their expression was reduced when BMP9 was silenced. Further studies are required to determine whether loss of or decreased BMP9 expression is clinically associated with dentinogenesis imperfecta. Collectively, our results strongly suggest that BMP9 may play an important role in regulating dentinogenesis and tooth development. Further research is recommended into the therapeutic uses of BMP9 to regenerate traumatized and diseased tissues and for the bioengineering of replacement teeth.

Osteogenesis imperfecta (OI) is a heterogeneous group of genetic disorders that affect connective tissue integrity, with bone fragility being the cardinal feature. Evidence of this debilitating disorder dates back to 1000 B.C. Skeletons of mummies from this period reveal abnormal growth patterns similar to those of OI patients. Ivar the Boneless, the Danish prince who led the Scandinavian invasion of England, was believed to have such severe OI that he had to be carried into battle on a shield because he was unable to walk. The hallmarks of OI include bone fragility, osteoporosis, dentinogenesis imperfecta, blue sclera, easy bruising, joint laxity, and scoliosis. The severity of OI symptoms ranges from prenatal death to mild osteopenia without limb deformity. Variations in the clinical manifestations of OI relate directly to the heterogeneity of genetic defects in type I collagen genes (Ibsen 1967; Kuiviniemi, Tromp, and Prockop 1991). Although bone fragility is the hallmark of OI, other tissues in which type I collagen is the primary structural protein are also affected. These include skin, tendon, ligament, and dentin. Diagnosis is based upon clinical, genetic, and radiographic findings. The incidence of OI ranges from 1 per 20,000 to 1 per 50,000 live births (Ashton et al. 1980; Byers and Steiner 1992). There is no predilection for race, gender, or ethnic origin.

journal's founding editor-in-chief, Dr. Opitz, who was one of the first physicians to recognize and characterize human congenital anomaly syndromes.

Pulp canal calcification (PCC) is common in patients with dentinogenesis imperfecta (DGI). We present endodontic management of multiple anterior and posterior teeth with PCCs in a patient with DGI type II using guided endodontics. A 26-year-old female patient was diagnosed with DGI type II. Clinical examination revealed palatal cusp fracture in tooth #13, microcracks in tooth #14, and a sinus tract in the maxillary right buccal vestibule related to tooth #13. Periapical radiographs revealed PCCs in all teeth, and periapical radiolucencies in several teeth. Due to difficult negotiation of canal orifices, guided endodontic approach was planned. Cone-beam computed tomography (CBCT) was requested and obtained. Intraoral scanning was performed, and CBCT and intraoral scanning data were superimposed. A template was designed and 3D printed. The root canal orifices were successfully negotiated and endodontic treatments were successfully accomplished. At the 1-year follow-up, the endodontically treated teeth were asymptomatic, and periapical lesions were healing.