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The Saudi Dental Journal Oct 2013Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia....
Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia. This case report discusses the systemic and dental manifestations of OI and DI in a 4-year-old child, with moderate presentation of both disorders, who was treated at King Fahd Military Medical Complex in Dhahran. Dental treatment included the use of strip and stainless-steel crowns under local anesthesia, as well as behavior modification techniques. Rigorous home care instructions, including reinforcement of the oral hygiene practice and avoidance of any episode that may lead to bone fracture, were discussed with the parents. The case was reevaluated at 3-month follow-up visits, wherein the medical and dental histories were updated, the child's growth was monitored, periodic clinical and radiographic examinations were performed, and the oral hygiene was evaluated via the debris index score and caries risk assessment. Further treatment of the permanent dentition may be needed in the future.
PubMed: 24371383
DOI: 10.1016/j.sdentj.2013.10.004 -
Acta Medica Academica Aug 2021The aim of this paper is to describe the varying clinical and imaging manifestations of Osteogenesis Imperfecta (OI) in the fetus, the child, and the adult. OI is a...
The aim of this paper is to describe the varying clinical and imaging manifestations of Osteogenesis Imperfecta (OI) in the fetus, the child, and the adult. OI is a genetic disorder with mutation of Type 1 and non-type 1 collagen genes that results in disruption of multiple collagen based organ systems, most notably bones, often leading to "brittle bones". Additional features such as blue sclera, dentinogenesis imperfecta, joint and ligamentous hyperlaxity, hearing loss and cardiac defects may be present. Currently, there are at least 30 recognized genetic forms of OI. Given the multiple genes involved, variable genetic inheritance, and the wide range in phenotype, diagnosis can be challenging. While OI may sometimes be diagnosed in the fetus, patients with mild forms of OI may be diagnosed in childhood or even in adulthood. Imaging, including ultrasound, radiography, computed tomography, and magnetic resonance imaging, plays an important role in the diagnoses of OI in the fetus, the child, and the adult. Imaging is also crucial in identifying the many multisystem manifestations of OI. In particular, imaging can help differentiate manifestations of OI from injuries sustained in non-accidental trauma. Age, severity and manner of presentation of OI vary broadly depending on the specific genetic mutation involved, mode of inheritance, and age of the patient. Successful diagnosis of OI hinges on a detailed knowledge of the variable presentation and complications that may be encountered with this disease. CONCLUSION: In conclusion, OI comprises a heterogeneous group of genetic disorders responsible for bone fragility and additional connective tissue disorders, which can result in specific clinical and imaging findings in the fetus, the child, and the adult.
Topics: Adult; Fetus; Humans; Joint Instability; Mutation; Osteogenesis Imperfecta; Radiography
PubMed: 34847680
DOI: 10.5644/ama2006-124.343 -
Molecular Genetics & Genomic Medicine May 2018Dentinogenesis imperfecta (DI) is a rare debilitating hereditary disorder affecting dentin formation and causing loss of the overlying enamel. Clinically, DI sufferers...
BACKGROUND
Dentinogenesis imperfecta (DI) is a rare debilitating hereditary disorder affecting dentin formation and causing loss of the overlying enamel. Clinically, DI sufferers have a discolored and weakened dentition with an increased risk of fracture. The aims of this study were to assess genotype-phenotype findings in three families with DI-II with special reference to mutations in the DSPP gene and clinical, histological, and imaging manifestations.
METHODS
Nine patients participated in the study (two from family A, four from family B, and three from family C). Buccal swab samples were collected from all participants and extracted for genomic DNA. Clinical and radiographic examinations had been performed longitudinally, and the dental status was documented using photographic images. Four extracted and decalcified tooth samples were prepared for histological analysis to assess dysplastic manifestations in the dentin. Optical coherence tomography (OCT) was applied to study the health of enamel tissue from in vivo images and the effect of the mutation on the function and structure of the DSPP gene was analyzed using bioinformatics software programs.
RESULTS
The direct DNA sequence analysis revealed three distinct mutations, one of which was a novel finding. The mutations caused dominant phenotypes presumably by interference with signal peptide processing and protein secretion. The clinical and radiographic disturbances in the permanent dentition indicated interfamilial variability in DI-II manifestations, however, no significant intrafamilial variability was observed.
CONCLUSION
The different mutations in the DSPP gene were accompanied by distinct phenotypes. Enamel defects suggested deficit in preameloblast function during the early stages of amelogenesis.
Topics: Adolescent; Adult; Child; Child, Preschool; Dental Enamel; Dentin; Dentinogenesis Imperfecta; Family; Female; Genotype; Humans; Male; Middle Aged; Mutation; Netherlands; Pedigree; Phenotype; Sequence Analysis, DNA; Tooth
PubMed: 29512331
DOI: 10.1002/mgg3.375 -
Indian Journal of Dental Research :... 2010In oral cavity, the spectrum of diseases due to genetic alterations ranges from developmental disturbances of teeth to the pre-cancerous and cancerous lesions. Of late,... (Review)
Review
In oral cavity, the spectrum of diseases due to genetic alterations ranges from developmental disturbances of teeth to the pre-cancerous and cancerous lesions. Of late, significant progress has been made in the molecular analysis of tumors. With molecular genetic testing emerging as diagnostic, prognostic, and therapeutic approach, a review of genetic alterations ranging from the development of oro-facial structures to the tumors in the head and neck region are addressed in this article. The functional regulatory aspect of genes in relation to oro-facial structures are discussed separately, i.e., in relation to tooth genesis, tooth agenesis (non-syndromic, syndromic), tooth structural alterations, syndromic oro-facial defects, bone diseases, skin diseases (genodermatoses), and malignant tumors. In this literature, various genes involved in the development of the oro-facial structures and tooth in particular are discussed. The genetic basis of disorders in the tooth development (agenesis, hypodontia), tooth structural defects like amelogenesis imperfecta (AI), dentinogenesis imperfecta (DI), and oro-facial structural alterations (various syndromes) are explained.
Topics: Anodontia; Craniofacial Abnormalities; Ectodermal Dysplasia; Genes, Homeobox; Humans; Odontogenesis; Tooth Abnormalities
PubMed: 20657100
DOI: 10.4103/0970-9290.66646 -
European Journal of Medical Genetics Dec 2019Osteogenesis imperfecta (OI) type V is an ultrarare heritable bone disorder caused by the heterozygous c.-14C > T mutation in IFITM5. The oro-dental and craniofacial...
Osteogenesis imperfecta (OI) type V is an ultrarare heritable bone disorder caused by the heterozygous c.-14C > T mutation in IFITM5. The oro-dental and craniofacial phenotype has not been described in detail, which we therefore undertook to evaluate in a multicenter study (Brittle Bone Disease Consortium). Fourteen individuals with OI type V (age 3-50 years; 10 females, 4 males) underwent dental and craniofacial assessment. None of the individuals had dentinogenesis imperfecta. Six of the 9 study participants (66%) for whom panoramic radiographs were obtained had at least one missing tooth (range 1-9). Class II molar occlusion was present in 8 (57%) of the 14 study participants. The facial profile was retrusive and lower face height was decreased in 8 (57%) individuals. Cephalometry, performed in three study participants, revealed a severely retrusive maxilla and mandible, and moderately to severly retroclined incisors in a 14-year old girl, a protrusive maxilla and a retrusive mandible in a 14-year old boy. Cone beam computed tomograpy scans were obtained from two study participants and demonstrated intervertebral disc calcification at the C2-C3 level in one individual. Our study observed that OI type V is associated with missing permanent teeth, especially permanent premolar, but not with dentinogenesis imperfecta. The pattern of craniofacial abnormalities in OI type V thus differs from that in other severe OI types, such as OI type III and IV, and could be described as a bimaxillary retrusive malocclusion with reduced lower face height and multiple missing teeth.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Osteogenesis Imperfecta; Phenotype
PubMed: 30593885
DOI: 10.1016/j.ejmg.2018.12.011 -
The Chinese Journal of Dental Research Mar 2024The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3... (Review)
Review
The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3 (DGI-III) and dentine dysplasia type 2 (DD-II). These three disorders may have similar molecular mechanisms involved in bridging the DSPP mutations and the resulting abnormal dentine mineralisation. The DSPP encoding proteins DSP (dentine sialoprotein) and DPP (dentine phosphoprotein) are positive regulators of dentine formation and perform a function during dentinogenesis. The present review focused on the recent findings and viewpoints regarding the relationship between DSPP and dentinogenesis as well as mineralisation from multiple perspectives, involving studies relating to spatial structure and tissue localisation of DSPP, DSP and DPP, the biochemical characteristics and biological function of these molecules, and the causative role of the proteins in phenotypes of the knockout mouse model and in hereditary dentine defects.
Topics: Animals; Mice; Calcification, Physiologic; Calcinosis; Dentin; Dentinogenesis Imperfecta; Disease Models, Animal; Mice, Knockout; Humans; Sialoglycoproteins; Phosphoproteins
PubMed: 38546516
DOI: 10.3290/j.cjdr.b5136791 -
A homozygous mutation causes osteogenesis and dentinogenesis imperfecta with craniofacial anomalies.JBMR Plus May 2024Osteogenesis imperfecta (OI) is a heterogeneous spectrum of hereditary genetic disorders that cause bone fragility, through various quantitative and qualitative defects...
Osteogenesis imperfecta (OI) is a heterogeneous spectrum of hereditary genetic disorders that cause bone fragility, through various quantitative and qualitative defects of type 1 collagen, a triple helix composed of two α1 and one α2 chains encoded by and , respectively. The main extra-skeletal manifestations of OI include blue sclerae, opalescent teeth, and hearing impairment. Moreover, multiple genes involved in osteoblast maturation and type 1 collagen biosynthesis are now known to cause recessive forms of OI. In this study a multiplex consanguineous family of two affected males with OI was recruited for genetic screening. To determine the causative, pathogenic variant(s), genomic DNA from two affected family members were analyzed using whole exome sequencing, autozygosity mapping, and then validated with Sanger sequencing. The analysis led to the mapping of a homozygous variant previously reported in SP7/OSX, a gene encoding for Osterix, a transcription factor that activates a repertoire of genes involved in osteoblast and osteocyte differentiation and function. The identified variant (c.946C > T; p.Arg316Cys) in exon 2 of results in a pathogenic amino acid change in two affected male siblings and develops OI, dentinogenesis imperfecta, and craniofacial anomaly. On the basis of the findings of the present study, :c. 946C > T is a rare homozygous variant causing OI with extra-skeletal features in inbred Arab populations.
PubMed: 38562913
DOI: 10.1093/jbmrpl/ziae026 -
Bone Reports Jun 2022Metaphyseal corner fractures and posterior rib fractures are thought to only occur in settings of inflicted injury. We describe a case of siblings who presented with...
PURPOSE
Metaphyseal corner fractures and posterior rib fractures are thought to only occur in settings of inflicted injury. We describe a case of siblings who presented with metaphyseal corner fractures and multiple posterior rib fractures who were later found to carry mutations, a rare cause of Osteogenesis Imperfecta (OI) known as Bruck syndrome. This clinical presentation led to a literature review examining fracture types in OI and inflicted injury.
CASES
A 15-month-old male presented with multiple healing fractures of varying ages including posterior rib and metaphyseal corner fractures with no history of significant trauma. He had joint laxity, short stature and Wormian bones. His diagnosis of Bruck Syndrome led to investigations in his sibling at birth, which demonstrated the same fracture pattern including multiple posterior rib and metaphyseal corner fractures. They both had pathogenic compound heterozygous variants.
LITERATURE REVIEW AND RESULTS
We performed a literature review evaluating the fracture pattern in cases investigated for inflicted injury and found to have OI. Fourteen articles reported 78 children with OI initially diagnosed as inflicted injury. Of these children, 71 (91%) were diagnosed with milder forms of OI (Sillence type I and IV). Sixty-four children (81%) had clinical signs of OI including blue sclera, dentinogenesis imperfecta, short stature, joint laxity and limb bowing. Fifteen (19%) children had fractures of high specificity for inflicted injury including metaphyseal corner fractures and posterior rib fractures and 58 (74%) had fractures of moderate specificity for inflicted injury such as bilateral fractures and fractures of different ages.
CONCLUSION
Metaphyseal corner fractures and posterior rib fractures are highly associated with inflicted injury, but they have been reported in children with OI. Bruck syndrome, a rare and severe form of OI can present with metaphyseal and posterior rib fractures, including at birth. When features of OI are present in children with metaphyseal corner fractures and/or posterior rib fractures are present, genetic testing may be warranted.
PubMed: 35242891
DOI: 10.1016/j.bonr.2022.101171 -
Indian Journal of Dental Research :... 2019Dentinogenesis Imperfecta and dentin dysplasia are genetic oral diseases inherited in a simple autosomal dominant mode, with high penetrance and a low mutation rate.... (Review)
Review
Dentinogenesis Imperfecta and dentin dysplasia are genetic oral diseases inherited in a simple autosomal dominant mode, with high penetrance and a low mutation rate. Both of them are present with bulbous crowns, marked cervical constrictions, severe attritions, few periapical radiolucencies, and premature tooth loss. The diagnosis is based on family history, and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Here, we present a case with overlapping features of both dentinogenesis imperfecta and dentin dysplasia asserting both the anomalies to be part of the same continuum of the genetic event.
Topics: Dentin; Dentin Dysplasia; Dentinogenesis Imperfecta; Extracellular Matrix Proteins; Humans; Pedigree; Phosphoproteins; Sialoglycoproteins
PubMed: 31745067
DOI: 10.4103/ijdr.IJDR_318_18 -
Orthodontics & Craniofacial Research May 2007The synthesis of tooth development biology with human studies focusing on inherited conditions that specifically interfere with tooth development is improving our... (Review)
Review
The synthesis of tooth development biology with human studies focusing on inherited conditions that specifically interfere with tooth development is improving our understanding of normal and pathological tooth formation. The type of inherited dental malformations observed in a given kindred relate to when, during odontogenesis, the defective gene is critically expressed. Information about the protein encoded by the defective gene and the resulting dental phenotype helps us understand the major processes underway at different stages during tooth development. Genes affecting early tooth development (PAX9, MSX1, and AXIN2) are associated with familial tooth agenesis or oligodontia. Genes expressed by odontoblasts (COL1A1, COL1A2, and DSPP), and ameloblasts (AMELX, ENAM, MMP20, and KLK4) during the crown formation stage, are associated with dentinogenesis imperfecta, dentin dysplasia, and amelogenesis imperfecta. Late genes expressed during root formation (ALPL and DLX3) are associated with cementum agenesis (hypophosphatasia) and taurodontism. Understanding the relationships between normal tooth development and the dental pathologies associated with inherited diseases improves our ability to diagnose and treat patients suffering the manifestations of inherited dental disorders.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Hypophosphatasia; Mutation; Odontogenesis; Tooth Abnormalities
PubMed: 17552940
DOI: 10.1111/j.1601-6343.2007.00384.x