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Journal of Clinical Research in... Jun 2024Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone...
INTRODUCTION
Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. This study aimed to investigate the molecular genetic etiology and determine the relationship between genotype and phenotype in OI patients with targeted next-generation sequencing (NGS).
METHOD
In patients with OI, a targeted NGS analysis panel (Illumina TruSight One) containing genes involved in collagen/bone synthesis was performed on the Illumina Nextseq550 platform.
RESULTS
Fifty-six patients (female/male: 25/31) from 46 different families were enrolled in the study. Consanguinity between parents was noted in 15 (32.6%) families. Clinically according to Sillence classification; 18(33.1%) patients were considered to type I, 1(1.7%) type II, 26(46.4%) type III and 11(19.6%) type IV. Median body weight was -1.1 (-6.8, - 2.5) SDS, and height was -2.3 (-7.6, - 1.2) SDS. Bone deformity was detected in 30 (53.5%) of the patients, while 31 (55.4%) were evaluated as mobile. Thirty-six (60.7%) patients had blue sclera, 13 (23.2%) had scoliosis, 12 (21.4%) had dentinogenesis imperfecta (DI), and 2 (3.6%) had hearing loss. Disease-causing variants in COL1A1 and COL1A2 genes were found in 24 (52.1%) and 6 (13%) families, respectively. In 8 (17.3%) of the remaining 16 (34.7%) families, the NGS panel revealed disease-causing variants in three different genes (FKBP10, SERPINF1, and P3H1). Nine (23.6%) of the variants detected in all investigated genes were not previously reported in the literature and were classified to be pathogenic according to ACMG guidelines pathogenity scores. In ten (21.7%) families, a disease-related variant was not found in a total of 13 OI genes included in the panel.
CONCLUSION
Genetic etiology was found in 38 (82.6%) of 46 families by targeted NGS analysis. In addition, 9 new variants were assessed in known OI genes which is a significant contribution to the literature.
PubMed: 38828893
DOI: 10.4274/jcrpe.galenos.2024.2022-12-8 -
Case Reports in Dentistry 2024Pulp involvement of immature permanent teeth with dentinogenesis imperfecta is challenging and could lead to extraction. A case of dentinogenesis imperfecta-induced...
Pulp involvement of immature permanent teeth with dentinogenesis imperfecta is challenging and could lead to extraction. A case of dentinogenesis imperfecta-induced periapical periodontitis of an immature permanent tooth was treated with regenerative endodontic treatment (RET), and root maturation was observed in 12-month follow-up. An 8-year-old girl presented acute pain and swelling in central mandibular region. Clinical and radiographic examination revealed "shell teeth" appearance of teeth 31, 41, and 42. Periapical lesion of tooth 31 was observed. Tooth 41 was previously treated with apexification. RET was planned and carried out for the necrotic tooth (tooth 31) with dentinogenesis imperfecta. The 1-, 3-, 7-, and 12-month postoperative recall revealed complete healing of periapical lesions. Root maturation characterized by elongation of root, thickening of dentinal walls, and closure of root apex was observed with radiographic examinations. We show that RET could be a desirable treatment for necrotic immature permanent teeth with dentinogenesis imperfecta and lead to resolution of endodontic lesions as well as maturation of dental root. The findings of this case suggest that RET should be considered by endodontist and pediatric dentist to treat teeth with similar dental anomalies and apical periodontitis.
PubMed: 38223911
DOI: 10.1155/2024/5128588 -
Medicine Jan 2024Dentinogenesis imperfecta (DI) is an autosomal-dominant disorder. The most common clinical manifestations, including obliterated tooth tissues and severe tooth wear,... (Review)
Review
RATIONALE
Dentinogenesis imperfecta (DI) is an autosomal-dominant disorder. The most common clinical manifestations, including obliterated tooth tissues and severe tooth wear, usually lead to tooth extractions. It remains a great challenge for dentists to preserve the residual tooth tissue and establish the esthetics and occlusion of dentitions.
PATIENTS CONCERNS
25-year-old twin sisters, who had suffered from dentinogenesis imperfecta type II for more than 10 years, presented with continuous tooth wear and discomfort from wearing a removable partial denture for more than 3 years.
DIAGNOSIS
Intraoral examination showed extensive tooth wear with enamel exfoliation and typical amber-brown color with an opalescent discoloration. Their panoramic radiographs revealed completely obliterated tooth tissues and severe tooth wear.
INTERVENTIONS AND OUTCOMES
The dentitions were restored with post-and-core crowns and pin lays after preparing root post paths and pin holes guided by computer-aided design/computer-aided manufacturing (CAD/CAM) procedures, resulting in a successful repair.
LESSONS
Severe tooth wear and tooth tissue obliteration are typical clinical manifestations in DI-affected dentitions, increasing the complexity and difficulty in dental restorations. Early diagnosis and appropriate treatments are essential to achieve a favorable prognosis. CAD/CAM procedures, permitting accurate and effective treatment, possess promising potential in the treatment of DI-affected dentitions.
Topics: Adult; Humans; Crowns; Dentinogenesis Imperfecta; Mouth Rehabilitation; Tooth; Tooth Wear; Female
PubMed: 38277536
DOI: 10.1097/MD.0000000000036882 -
Journal of Applied Oral Science :... 2023Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteogenesis imperfecta (OI) is a rare genetic disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. OI is also known as brittle bone disease.
OBJECTIVE
This study aims to describe the prevalence of dental anomalies (except dentinogenesis imperfecta) in individuals with OI, and compare the prevalence of dental anomalies between individuals with and without OI and between individuals with different types of OI.
SEARCH METHODS
Searches in PubMed, Web of Science, Scopus, Ovid, and gray literature were performed in October 2022.
SELECTION CRITERIA
Observational studies (with or without a comparison group) that evaluated the prevalence of dental anomalies in individuals with OI. Data collection and analysis: Data items were extracted by two authors. Quality assessment employing the Joanna Briggs Institute checklists and meta-analyses was conducted. Results were provided in prevalence values and odds ratio (OR) / 95% confidence interval (CI). Strength of evidence was determined.
RESULTS
Eighteen studies were included. Most prevalent dental anomalies in individuals with OI included pulp obliteration (46.4%), dental impaction (33.5%), dental impaction of second molars (27%), and tooth agenesis (23.9%). Individuals with OI type III/IV had 20.16-fold greater chance of exhibiting tooth discoloration in comparison with individuals with OI type I (CI: 1.10-370.98). In comparison with the group without OI, the individuals with OI had 6.90-fold greater chance of exhibiting dental impaction (CI: 1.54-31.00). High methodological quality was found in 47% of the studies. Strength of evidence was low or very low.
CONCLUSIONS
Pulp obliteration, dental impaction, and tooth agenesis were the most prevalent dental anomalies in the OI group. Individuals with OI were more likely to have dental impaction than individuals without OI. Individuals with OI type III/IV (severe-moderate) are more likely to have tooth discoloration than individuals with OI type I (mild).
Topics: Humans; Osteogenesis Imperfecta; Prevalence; Tooth Discoloration
PubMed: 37672427
DOI: 10.1590/1678-7757-2023-0040 -
Cureus Feb 2024This is a case report presenting a female patient in her twenties suffering from severely stained, unaesthetic, and worn-out teeth since her childhood. It was a major...
This is a case report presenting a female patient in her twenties suffering from severely stained, unaesthetic, and worn-out teeth since her childhood. It was a major aesthetic and functional concern for her. This clinical presentation describes the prosthetic rehabilitation of a patient with generalized discolored and worn-out teeth to have enhanced aesthetics and masticatory function of the patient. This is a referred case of dentinogenesis imperfecta- II (DGI-II) from the Department of Oral Medicine and Radiology and Oral Pathology, as diagnosed by them after a thorough clinical, radiographical, and histopathological examination. DGI is a disorder of teeth characterized by discoloration and rapid wear and belongs to a group of disorders of the development of teeth. Due to the rapid wear and generalized intrinsically stained and discolored teeth, there is a loss of vertical dimension of occlusion (VDO) and an unesthetic look of the patient respectively. Therefore, the main objective of the case report is to re-establish the aesthetic and regain the VDO and functionality of the damaged teeth using the Pankey Mann Schuyler philosophy in which the first anterior teeth were rehabilitated with porcelain fused to metal (PFM) crowns based on aesthetics and phonetics of the patient. This was followed by posterior PFM crowns based on Broadrick's flag analysis for posterior occlusal plane determination and centric occlusion.
PubMed: 38469028
DOI: 10.7759/cureus.53978 -
The Journal of Clinical Pediatric... Mar 2024Children with dentinogenesis imperfecta require restorative or prosthodontic treatment to minimize the aesthetic and functional impact of the condition. This clinical...
Children with dentinogenesis imperfecta require restorative or prosthodontic treatment to minimize the aesthetic and functional impact of the condition. This clinical case report describes the oral rehabilitation procedure in a 12-year-old patient with dentinogenesis imperfecta type II using nanoceramic resin crowns fabricated with Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM) technology and the patient's progression over eight years. This minimal intervention approach enabled functional and aesthetic reestablishment along with tooth wear prevention. The result simplified an extensive prosthetic procedure and facilitated an affordable rehabilitation for the young patient while providing excellent long-term outcomes.
Topics: Child; Humans; Dentinogenesis Imperfecta; Crowns; Computer-Aided Design; Dental Prosthesis Design
PubMed: 38548649
DOI: 10.22514/jocpd.2024.047 -
Endocrine Journal Jul 2023Osteogenesis imperfecta (OI) is an inherited disease characterized by bone fragility due to impaired type I collagen. Although orthopedic management is improving, other... (Review)
Review
Osteogenesis imperfecta (OI) is an inherited disease characterized by bone fragility due to impaired type I collagen. Although orthopedic management is improving, other complications are poorly understood. We describe three patients with OI with unruptured intracranial aneurysm (IA) detected by magnetic resonance angiography (MRA) screening of 14 patients. Case 1 was a 73-year-old woman with type 1 OI with blue sclera, vertebral compression fractures, and impaired hearing. Lumbar spine bone mineral density (BMD) was preserved (young adult mean (YAM): 86%). MRA revealed an IA in the right internal carotid artery. Case 2 was a 43-year-old man with type 4 OI and leg-length discrepancy due to left femoral neck fracture. Lumbar spine BMD was decreased (YAM: 61%). MRA showed an IA in the left anterior cerebral artery. Case 3 was a 35-year-old woman with type 3 OI with blue sclera, dentinogenesis imperfecta, deformity of the long bones, and severe scoliosis. She had undergone spine surgery and needed wheelchair assistance. The YAM of the femoral neck BMD was 71%. MRA indicated an IA in the right posterior communicating artery. The prevalence of IA in our series of patients with OI was 21%, which is higher than the reported prevalence of unruptured IA in the Japanese general population (2.2%), suggesting that IA may be a complication of OI. Our literature review revealed no cases of OI with unruptured IA, but 11 cases of OI with subarachnoid hemorrhage. IA seems unrelated to OI type, sex, or age. We recommend MRA of adults with OI.
Topics: Male; Female; Young Adult; Humans; Aged; Adult; Osteogenesis Imperfecta; Intracranial Aneurysm; Fractures, Compression; Spinal Fractures; Collagen Type I; Bone Density
PubMed: 37164684
DOI: 10.1507/endocrj.EJ22-0620 -
The American Journal of Case Reports Dec 2023BACKGROUND Osteogenesis imperfecta (OI) is a rare genetic disease that results from mutations in type 1 collagen (COL1) or its interacting proteins. Such mutations lead...
BACKGROUND Osteogenesis imperfecta (OI) is a rare genetic disease that results from mutations in type 1 collagen (COL1) or its interacting proteins. Such mutations lead to defects in bone structure, causing brittle bones, short stature, hearing loss, and dental problems, among others. The current classification system arranges OI into types according to a clinical phenotype that includes the severity of the disease and a combination of specific features, such as blue sclerae and dental abnormalities. CASE REPORT Here, we present a clinical report of a 3-year-old boy diagnosed with OI in utero who has been followed by our pediatric clinic postnatally. The patient was born with multiple bone fractures, a small head circumference, and blue sclerae and later had a concomitant diagnosis of dentinogenesis imperfecta (DI). Soon after birth, the patient was started on bisphosphonate and calcium/vitamin D treatment. The patient's OI type was inconclusive due to the dramatic difference between perinatal and postnatal phenotypes, the presence of blue sclerae, and the additional diagnosis of DI. The patient experienced only 1 new bone fracture postnatally, had normal anthropometric measurements except for short stature, and was healthy. CONCLUSIONS This clinical case is unique owing to the dramatic perinatal and mild postnatal OI phenotypes. This and the unique combination of postnatal features demonstrate that classical OI typing could be inconclusive in atypical disease presentation. This case may demonstrate a new classification possibility outside the current OI nomenclature. However, the potential beneficial role of pharmacological treatment in the clinical outcome of OI cannot be excluded.
Topics: Male; Child; Humans; Child, Preschool; Collagen Type I; Osteogenesis Imperfecta; Mutation; Phenotype
PubMed: 38148598
DOI: 10.12659/AJCR.942239 -
Journal of the American Dental... May 2024Orthodontic treatment for patients with dentinogenesis imperfecta (DGI) can be risky because of the fragility of their dental hard tissue. Although the Invisalign (Align...
BACKGROUND
Orthodontic treatment for patients with dentinogenesis imperfecta (DGI) can be risky because of the fragility of their dental hard tissue. Although the Invisalign (Align Technology) clear aligner system should be a suitable orthodontic appliance for patients with DGI, to the authors' knowledge, there has been no related research.
CASE DESCRIPTION
A 28-year-old woman with DGI sought treatment with a 1 mm open bite, edge-to-edge occlusion of the central incisors, and a bilateral Class III cusp-to-cusp molar relationship. Invisalign was applied for her treatment, and after 3 and one-half years of orthodontic therapy, a normal overjet and overbite were achieved, accompanied by retraction of the lower lip as well as a bilateral Class I molar relationship. In addition, there was no iatrogenic injury to the patient's teeth.
PRACTICAL IMPLICATIONS
The Invisalign system may be a suitable orthodontic appliance for patients with DGI because clear aligners lessen the tensile stress to the teeth, decrease the number and area of bonds to the teeth, and offer protective effects through a full wrap of plastic that covers the crowns of the teeth.
Topics: Humans; Female; Adult; Dentinogenesis Imperfecta; Orthodontic Appliances, Removable; Tooth Movement Techniques; Orthodontics, Corrective; Orthodontic Appliance Design
PubMed: 38573273
DOI: 10.1016/j.adaj.2024.01.007 -
European Journal of Medical Genetics Nov 2023Pathogenic variants in SPARC cause a rare autosomal recessive form of osteogenesis imperfecta (OI), classified as OI type XVII, which was first reported in 2015. Only...
Pathogenic variants in SPARC cause a rare autosomal recessive form of osteogenesis imperfecta (OI), classified as OI type XVII, which was first reported in 2015. Only six patient cases with this specific form of OI have been reported to date. The SPARC protein plays a crucial role in the calcification of collagen in bone, synthesis of the extracellular matrix, and the regulation of cell shape. In this case report, we describe the phenotype of two patients with SPARC-related OI, including a patient with two novel pathogenic variants in the SPARC gene. Targeted Next Generation Sequencing revealed new compound heterozygous variants (c.484G > A p.(Glu162Lys)) and c.496C > T p.(Arg166Cys)) in one patient and a homozygous nonsense pathogenic variant (c.145C > T p.(Gln49*)) in the other. In line with previously reported cases, the two OI patients presented delayed motor development, muscular weakness, scoliosis, and multiple fractures. Interestingly, our study reports for the first time the occurrence of dentinogenesis imperfecta. The study also reports the effectiveness of bisphosphonate treatment for OI type XVII. This article enhances the genetic, clinical, therapeutic, and radiological understanding of SPARC-related OI.
Topics: Humans; Osteogenesis Imperfecta; Mutation; Phenotype; Homozygote; Bone and Bones; Collagen Type I; Osteonectin
PubMed: 37758164
DOI: 10.1016/j.ejmg.2023.104857