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JBMR Plus Dec 2020Osteogenesis imperfecta (OI) is characterized by bone fragility and secondary features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity,...
Osteogenesis imperfecta (OI) is characterized by bone fragility and secondary features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity, and short stature. It was thought that health-related quality of life (QoL) in patients with OI mainly depends on the severity of the skeletal deformities. However, it has become clear that additional factors can affect the QoL in all patients with OI. In this study, we compare dimensions of QoL in adults with OI with a control population. The SF-36 questionnaire was distributed among 330 adult patients with different OI types. Results were compared with two control populations from the Netherlands. Age-matched comparisons were made with one of the two control populations. The results were summarized in eight domains: general and mental health, physical and social function, bodily pain, vitality, and physical and emotional role. General health and physical function in all types of OI are low compared with controls, except patients with OI type 4 aged 55+ years. Bodily pain in patients with OI appeared significantly worse than in the control population. There was no significant difference between OI types regarding pain and vitality. Vitality was only in the OI type 1 group significantly lower compared with controls. Patients with OI type 1 had a significantly reduced mental health. Social functioning appeared most effective in type 3 around 20 years of age. QoL in adult patients with OI should be an important outcome measure in every OI clinic, but the amount of baseline data on this subject is sparse. This baseline measurement study is the largest study to date investigating QoL in adult patients with OI. The mean scores indicate that people with OI generally have a significantly lower QoL than the control population. Further qualitative evaluation of QoL and its influences is important for future management. © 2020 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 33354642
DOI: 10.1002/jbm4.10416 -
Bone Reports Dec 2020Osteogenesis imperfecta (OI) is a heterogeneous group of genetic disorders of connective tissue that cause skeletal fragility and extra-skeletal manifestations....
OBJECTIVES
Osteogenesis imperfecta (OI) is a heterogeneous group of genetic disorders of connective tissue that cause skeletal fragility and extra-skeletal manifestations. Classically, four different types of OI were distinguished. Type 5 OI was added due to its distinct clinical and radiographic features. In 2012, two independent groups identified a recurrent heterozygous c.-14C>T mutation in as the responsible genetic change for this type of OI. To our knowledge, cervical kyphosis has not been identified in the literature as a finding in type 5 OI patients. This is a retrospective review of a cohort of patients with type 5 OI and a description of associated cervical spine deformity.
METHODS
After institutional review board approval, a retrospective review identified 13 patients with type 5 OI. Clinical, radiologic, and genetic data from 2002 to 2020 were reviewed.
RESULTS
We identified 13 patients with clinical diagnosis of type 5 OI. Twelve had molecular confirmation and the classic , c.14C>T gene mutation was identified. The remaining individual did not undergo genetic testing. Dentinogenesis imperfecta was observed in one patient, while blue sclerae or hearing loss were not present. All patients had at least one fracture and four underwent intramedullary rodding. Radiologic features included subphyseal metaphyseal radiodense line in 12/13 patients (92%), interosseous membrane calcification in seven of 13 patients (54%) (more commonly noted in the upper extremities), and hypertrophic callus in six of 13 patients (46%). Thoracolumbar spinal deformities were seen in six of 13 patients (46%) with two of these individuals requiring surgery. Cervical kyphosis was noted in nine of 13 individuals (69%) ranging in age from 3 months to 22 years. Anterior wedging of the cervical vertebral bodies was noted in the absence of any fractures. Six of nine individuals demonstrated listhesis of C2-C3 or C3-C4 segment. Magnetic resonance imaging studies were performed and reviewed in patients with cervical kyphosis and subluxation; three patients showed narrowing of spinal canal without cervical cord compression and one asymptomatic patient showed impingement of the spinal cord.
CONCLUSIONS
Cervical kyphosis appears to be a common feature of type 5 OI. It can be a presenting and apparently life-long association and does not appear to be caused by vertebral body fractures. Evaluation for cervical kyphosis should be performed in patients with a suspected or confirmed diagnosis of type 5 OI. Furthermore, if cervical kyphosis is noted in an individual with OI, type 5 OI should be considered.Level of evidence: IV.
PubMed: 33304945
DOI: 10.1016/j.bonr.2020.100735 -
Frontiers in Physiology 2020Dentin dysplasia (DD) and dentinogenesis imperfecta (DGI) patients have abnormal structure, morphology, and function of dentin. DD-II, DGI-II, and DGI-III are caused by...
Dentin dysplasia (DD) and dentinogenesis imperfecta (DGI) patients have abnormal structure, morphology, and function of dentin. DD-II, DGI-II, and DGI-III are caused by heterozygous mutations in the dentin sialophosphoprotein () gene in humans. Evidences have shown that loss of function of DSPP in knockout mice leads to phenotypes similar to DGI-III, and that the abnormal dentinogenesis is associated with decreased levels of DSPP, indicating that DSPP haploinsufficiency may play a role in dentinogenesis. Thus, to testify the haploinsufficiency of , we used a heterozygous mouse model to observe the phenotypes in the teeth and the surrounding tissues. We found that heterozygous mice displayed dentin phenotypes similar to DD-II at the ages of 12 and 18 months, which was characterized by excessive attrition of the enamel at the occlusal surfaces, thicker floor dentin of the pulp chamber, decreased pulp volume, and compromised mineralization of the dentin. In addition, the periodontium was also affected, exhibiting apical proliferation of the junctional epithelium, decreased height and width of the alveolar bone, and infiltration of the inflammatory cells, leading to the destruction of the periodontium. Both the dental and periodontal phenotypes were age-dependent, which were more severe at 18 months old than those at 12 months old. Our report is the first to claim the haploinsufficiency of gene and a DD-II mouse model, which can be further used to study the molecular mechanisms of DD-II.
PubMed: 33240110
DOI: 10.3389/fphys.2020.593626 -
International Journal of Clinical... 2020The aim and objective of this report is to describe the dental management of 11-year-old patient with type III osteogenesis imperfecta (OI).
AIM AND OBJECTIVE
The aim and objective of this report is to describe the dental management of 11-year-old patient with type III osteogenesis imperfecta (OI).
BACKGROUND
Osteogenesis imperfecta or brittle bone disease is caused by mutations in the collegen type I gene which is a heterogeneous rare connective tissue disorder. Dentinogenesis imperfecta, hearing impairment, scoliosis, sclera is blue, hyperlaxity of ligaments, and fragile skin are other common features. Individuals having positive family history suggest a straightforward diagnosis of OI but can be difficult in the absence of affected family.
CASE DESCRIPTION
We report a case of 11-year-old boy, with a chief complaint of pain and swelling on the lower left back tooth region which was associated with extraoral draining sinus. His medical history revealed multiple fractures sustained during routine handling. On examination, the child was pale, dyspneic, with rhizomelic dwarfism, and relative macrocephaly with frontal bossing. On the grounds of history taken, clinical examination and respective investigations carried out, we came to a conclusion of osteogenesis imperfect type III. As the child needs a special care, we planned for a conservative treatment approach.
CONCLUSION
The craniofacial abnormalities in OI-III affected person's impact on their dentofacial appearance and masticatory function. A detailed dental and craniofacial investigation is necessary in affected persons in order to identify any primary or secondary abnormalities. As soon as the deciduous teeth erupt, patients with OI should be evaluated with adequate dental treatment and oral hygiene instructions in order to reduce the need for extensive treatment.
CLINICAL SIGNIFICANCE
Although oral manifestations are seldom seen, dentist should be extremely alert while managing this fragile bone disease. Early diagnosis, increased awareness, and effective treatment plan will reduce the effects of this debilitating disease. An ounce of prevention is worth a pound of cure, especially when something has no cure.
HOW TO CITE THIS ARTICLE
Krishnamurthy NH, Chikkanarasaiah N, Nanjappa A, Fragile and Brittle Bone Disease or Osteogenesis Imperfecta: A Case Report. Int J Clin Pediatr Dent 2020;13(4):425-428.
PubMed: 33149419
DOI: 10.5005/jp-journals-10005-1792 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Oct 2020The bone morphogenetic protein (BMP) 1/tolloid (TLD) proteinase family is a group of important metalloproteinases, which play key roles in the growth and development of... (Review)
Review
The bone morphogenetic protein (BMP) 1/tolloid (TLD) proteinase family is a group of important metalloproteinases, which play key roles in the growth and development of tissues and organs via regulating the biosynthetic processing of the extracellular matrix. Clinical reports have revealed that mutations in the genes encoding BMP1/TLD proteinases lead to dentinogenesis imperfecta type Ⅰ, accompanied with osteogenesis imperfecta. Therefore, this proteinase family is essential for the development of hard tissues. In this study, we review the research progress in the function and mechanism of the BMP1/TLD proteinase family in the development of teeth and bone.
Topics: Bone Morphogenetic Protein 1; Bone Morphogenetic Proteins; Bone and Bones; Metalloproteases; Tolloid-Like Metalloproteinases
PubMed: 33085247
DOI: 10.7518/hxkq.2020.05.020 -
International Journal of Environmental... Sep 2020Dentinogenesis imperfecta (DGI) is a complex anomaly, not only by its structure but by treatment approach. The treatment protocol depends on the severity, behavior, and...
BACKGROUND
Dentinogenesis imperfecta (DGI) is a complex anomaly, not only by its structure but by treatment approach. The treatment protocol depends on the severity, behavior, and the age of the patient.
CASE DESCRIPTION
This paper presents two siblings' cases of DGI type II (DGI-II) with different treatment based on the patient's clinical severity, behavior, and age (mixed versus primary dentition). The first case involves a patient in the primary dentition with severe attrition leading to a reduction in the vertical dimension of occlusion (VDO) treated by the fabrication of complete overlay dentures. The second case involves a patient in the early mixed dentition treated with restorations and extractions.
CONCLUSION
Full mouth rehabilitation in the two patients dramatically improves function, aesthetics, and proved to be a significant psychological boost to the patient's well-being.
PRACTICAL IMPLICATIONS
Early diagnosis and a multidisciplinary approach for patients with DGI to preserve the remaining teeth and rehabilitation for their function and aesthetics are essential for obtaining a favorable prognosis.
Topics: Child; Child, Preschool; Dental Implantation, Endosseous; Dental Prosthesis, Implant-Supported; Dentin; Dentinogenesis Imperfecta; Esthetics; Female; Humans; Male; Mouth Rehabilitation; Siblings; Tooth, Deciduous
PubMed: 32992978
DOI: 10.3390/ijerph17197029 -
Journal of Prosthodontics : Official... Oct 2020A 19-year-old female affected by dentinogenesis imperfecta type II (DI-II), a genetic disease that affects the structural integrity of the dentin, presented with a chief...
A 19-year-old female affected by dentinogenesis imperfecta type II (DI-II), a genetic disease that affects the structural integrity of the dentin, presented with a chief complaint of discolored teeth. For this patient, digital techniques, including digital smile design (DSD), the ARCUSdigma axiograph and computer-aided design/computer-aided manufacturing (CAD/CAM), were extensively used in all phases of the rehabilitation process. Compared to traditional analog methods, these digital techniques could reduce the constant confirmation of occlusion, promote communication between clinicians and dental technicians, achieve accurate occlusion with relatively high efficiency, and improve the efficacy of esthetic rehabilitation in the treatment of this patient with DI-II.
Topics: Adult; Computer-Aided Design; Dentinogenesis Imperfecta; Esthetics, Dental; Female; Humans; Young Adult
PubMed: 32803808
DOI: 10.1111/jopr.13237 -
Molecular Genetics & Genomic Medicine Aug 2020Wnt signaling pathway plays an important role in promoting ostergenesis. WNT1 mutations have been considered as a major cause of ostergenesis imperfect (OI). We...
BACKGROUND
Wnt signaling pathway plays an important role in promoting ostergenesis. WNT1 mutations have been considered as a major cause of ostergenesis imperfect (OI). We identified an OI patient with pathogenic consanguineous-derived homozygous WNT1 missense mutation.
METHODS
We designed and applied a panel of known 261 genes associated with hereditary bone diseases for targeted next-generation sequencing to examine clinically diagnosed OI patients. Detected mutations were confirmed by Sanger sequencing.
RESULTS
The female proband presented with severe OI with low bone density, multiple long bone fractures, short stature, and absence of dentinogenesis imperfect and brain malformation. She had congenital ptosis and exotropia with her left eye, and absence of blue sclera. The proband came from a consanguineous family and had a homozygous WNT1 missense mutation (c.677C>T, (p.S226L)). In addition, three other compound heterozygous mutations (c.1729C>T in FKBP10, c.1958A>C in FGFR3, c.760G>C in TRPV4) were also detected in her family members.
CONCLUSION
We report the first identified case of consanguineous derived homozygous WNT1 mutation leading to severe osteogenesis imperfecta with congenital ptosis and exotropia.
Topics: Adult; Aged; Blepharoptosis; Consanguinity; Exotropia; Female; Heterozygote; Homozygote; Humans; Male; Middle Aged; Mutation, Missense; Osteogenesis Imperfecta; Pedigree; Phenotype; Wnt1 Protein
PubMed: 32529806
DOI: 10.1002/mgg3.1350 -
Molecular Genetics & Genomic Medicine Aug 2020Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20...
BACKGROUND
Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation-type amelogenesis imperfecta (AI2A2; OMIM #612529). MMP20 is expressed in both odontoblasts and ameloblasts, but its function during dentinogenesis is unclear.
METHODS
We characterized 10 AI kindreds with MMP20 defects, characterized human third molars and/or Mmp20 mice by histology, Backscattered Scanning Electron Microscopy (bSEM), µCT, and nanohardness testing.
RESULTS
We identified six novel MMP20 disease-causing mutations. Four pathogenic variants were associated with exons encoding the MMP20 hemopexin-like (PEX) domain, suggesting a necessary regulatory function. Mutant human enamel hardness was softest (13% of normal) midway between the dentinoenamel junction (DEJ) and the enamel surface. bSEM and µCT analyses of the third molars revealed reduced mineral density in both enamel and dentin. Dentin close to the DEJ showed an average hardness number 62%-69% of control. Characterization of Mmp20 mouse dentin revealed a significant reduction in dentin thickness and mineral density and a transient increase in predentin thickness, indicating disturbances in dentin matrix secretion and mineralization.
CONCLUSION
These results expand the spectrum of MMP20 disease-causing mutations and provide the first evidence for MMP20 function during dentin formation.
Topics: Alleles; Amelogenesis Imperfecta; Animals; Dental Enamel; Dentin; Female; Male; Matrix Metalloproteinase 20; Mice; Mice, Inbred C57BL; Mutation; Pedigree
PubMed: 32495503
DOI: 10.1002/mgg3.1307