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Sample records for hypomaturation amelogenesis imperfecta

  1. Enamel ultrastructure in pigmented hypomaturation amelogenesis imperfecta.

    PubMed

    Wright, J T; Lord, V; Robinson, C; Shore, R

    1992-10-01

    Hypomaturation amelogenesis imperfecta (AI) is a hereditary condition of enamel that is presumed to result from defects during the maturation stage of enamel development. This study characterized the enamel ultrastructure and enamel crystallite morphology, as well as the distribution of organic material in enamel affected with pigmented hypomaturation AI. Enamel exhibiting autosomal recessive pigmented hypomaturation AI was sectioned or fractured and examined using light microscopy, scanning electron microscopy and transmission electron microscopy. Enamel samples were treated with 30% NaOCl or 8 M urea to remove organic components and determine the effect of deproteinization on crystallite morphology. These were compared with untreated normal enamel samples. The enamel crystallites in hypomaturation AI exhibited considerable variability in size and morphology. Examination of deproteinized tissue indicated that the AI crystallites had a thick coating, presumably of organic or partially mineralized material, which was not visible in normal enamel. The results of this investigation provide further evidence that hypomaturation AI is associated with the retention of organic material that is most probably enamel protein. Enamel protein retention is likely to be involved in the inhibition of normal crystallite growth resulting in the morphological crystallite abnormalities associated with this disorder.

  2. Exonal deletion of SLC24A4 causes hypomaturation amelogenesis imperfecta.

    PubMed

    Seymen, F; Lee, K-E; Tran Le, C G; Yildirim, M; Gencay, K; Lee, Z H; Kim, J-W

    2014-04-01

    Amelogenesis imperfecta is a heterogeneous group of genetic conditions affecting enamel formation. Recently, mutations in solute carrier family 24 member 4 (SLC24A4) have been identified to cause autosomal recessive hypomaturation amelogenesis imperfecta. We recruited a consanguineous family with hypomaturation amelogenesis imperfecta with generalized brown discoloration. Sequencing of the candidate genes identified a 10-kb deletion, including exons 15, 16, and most of the last exon of the SLC24A4 gene. Interestingly, this deletion was caused by homologous recombination between two 354-bp-long homologous sequences located in intron 14 and the 3' UTR. This is the first report of exonal deletion in SLC24A4 providing confirmatory evidence that the function of SLC24A4 in calcium transport has a crucial role in the maturation stage of amelogenesis.

  3. Hypomaturation amelogenesis imperfecta caused by a novel SLC24A4 mutation.

    PubMed

    Herzog, Curtis R; Reid, Bryan M; Seymen, Figen; Koruyucu, Mine; Tuna, Elif Bahar; Simmer, James P; Hu, Jan C-C

    2015-02-01

    In this case report of autosomal recessive pigmented hypomaturation amelogenesis imperfecta (AI), we identify a novel homozygous missense mutation (g.165151 T>G; c.1317 T>G; p.Leu436 Arg) in SLC24A4, a gene encoding a potassium-dependent sodium-calcium exchanger that is critical for hardening dental enamel during tooth development.

  4. Hypomaturation Amelogenesis Imperfecta Caused By A Novel SLC24A4 Mutation

    PubMed Central

    Herzog, Curtis R.; Reid, Bryan M.; Seymen, Figen; Koruyucu, Mine; Tuna, Elif Bahar; Simmer, James P.; Hu, Jan C-C.

    2014-01-01

    In this case report of autosomal recessive pigmented hypomaturation amelogenesis imperfecta (AI), we identify a novel homozygous missense mutation (g.165151T>G; c.1317T>G; p.Leu436Arg) in SLC24A4, a gene encoding a potassium-dependent sodium-calcium exchanger that is critical for hardening dental enamel during tooth development. PMID:25442250

  5. Noninvasive esthetic treatment for hypomaturation amelogenesis imperfecta: a case report.

    PubMed

    Nahsan, Flávia Pardo Salata; Silva, Luciana Mendonça da; Lima, Thiago Mendes de; Bertocco, Verônica Pereira de Lima; Chui, Fabíola Mendonça da Silva; Martins, Leandro de Moura

    2016-01-01

    Enamel alterations, such as amelogenesis imperfecta, can compromise the harmony of the smile and the patient's self-esteem and may cause tooth sensitivity. A simple and effective treatment approach uses the natural stratification of composite resins to mask deficient enamel formation and mimic the natural appearance of the substrate. The operative steps and principles for restorative success are described in this case report with 36-month follow-up.

  6. Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta.

    PubMed

    El-Sayed, Walid; Parry, David A; Shore, Roger C; Ahmed, Mushtaq; Jafri, Hussain; Rashid, Yasmin; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2009-11-01

    Healthy dental enamel is the hardest and most highly mineralized human tissue. Though acellular, nonvital, and without capacity for turnover or repair, it can nevertheless last a lifetime. Amelogenesis imperfecta (AI) is a collective term for failure of normal enamel development, covering diverse clinical phenotypes that typically show Mendelian inheritance patterns. One subset, known as hypomaturation AI, is characterised by near-normal volumes of organic enamel matrix but with weak, creamy-brown opaque enamel that fails prematurely after tooth eruption. Mutations in genes critical to enamel matrix formation have been documented, but current understanding of other key events in enamel biomineralization is limited. We investigated autosomal-recessive hypomaturation AI in a consanguineous Pakistani family. A whole-genome SNP autozygosity screen identified a locus on chromosome 15q21.3. Sequencing candidate genes revealed a point mutation in the poorly characterized WDR72 gene. Screening of WDR72 in a panel of nine additional hypomaturation AI families revealed the same mutation in a second, apparently unrelated, Pakistani family and two further nonsense mutations in Omani families. Immunohistochemistry confirmed intracellular localization in maturation-stage ameloblasts. WDR72 function is unknown, but as a putative beta propeller is expected to be a scaffold for protein-protein interactions. The nearest homolog, WDR7, is involved in vesicle mobilization and Ca2+-dependent exocytosis at synapses. Vesicle trafficking is important in maturation-stage ameloblasts with respect to secretion into immature enamel and removal of cleaved enamel matrix proteins via endocytosis. This raises the intriguing possibility that WDR72 is critical to ameloblast vesicle turnover during enamel maturation.

  7. Amelogenesis imperfecta

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001578.htm Amelogenesis imperfecta To use the sharing features on this page, please enable JavaScript. Amelogenesis imperfecta is a tooth development disorder. It causes the ...

  8. Amelogenesis imperfecta: a clinician's challenge.

    PubMed

    Chamarthi, V; Varma, B R; Jayanthi, M

    2012-01-01

    Defective enamel formation can be explained as defects occurring at the stages of enamel formation. Quantitative defects in matrix formation leads to hypoplastic form of amelogenesis imperfecta. Inadequate mineralization of matrix leads to hypocalcification and hypomaturation variants. The demarcation of matrix formation and mineralization is not so distinct. This paper describes a case of a 7-year-old boy with amelogenesis imperfecta - Type IA i.e., hypoplastic pitted autosomal dominant.

  9. Genetics Home Reference: amelogenesis imperfecta

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions amelogenesis imperfecta amelogenesis imperfecta Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Amelogenesis imperfecta is a disorder of tooth development. This condition ...

  10. Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: a diagnostic dilemma.

    PubMed

    Hegde, Veda; Srikanth, K

    2014-01-01

    Amelogenesis imperfecta is a hereditary disorder with diverse clinical presentation, where enamel is the tissue that is primarily affected either quantitatively or qualitatively. Hypomaturation/hypoplastic amelogenesis imperfecta with taurodontism is a rare variant of amelogenesis imperfecta which is often confused with trichodentoosseous syndrome. We report a rare case of hereditary enamel defect with taurodontism associated with interradicular dentin dysplasia.

  11. Amelogenesis imperfecta

    PubMed Central

    Crawford, Peter JM; Aldred, Michael; Bloch-Zupan, Agnes

    2007-01-01

    Amelogenesis imperfecta (AI) represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations. PMID:17408482

  12. Homozygous and compound heterozygous MMP20 mutations in amelogenesis imperfecta.

    PubMed

    Gasse, B; Karayigit, E; Mathieu, E; Jung, S; Garret, A; Huckert, M; Morkmued, S; Schneider, C; Vidal, L; Hemmerlé, J; Sire, J-Y; Bloch-Zupan, A

    2013-07-01

    In this article, we focus on hypomaturation autosomal-recessive-type amelogenesis imperfecta (type IIA2) and describe 2 new causal Matrix metalloproteinase 20 (MMP20) mutations validated in two unrelated families: a missense mutation p.T130I at the expected homozygous state, and a compound heterozygous mutation having the same mutation combined with a nucleotide deletion, leading to a premature stop codon (p.N120fz*2). We characterized the enamel structure of the latter case using scanning electron microscopy analysis and microanalysis (Energy-dispersive X-ray Spectroscopy, EDX) and confirmed the hypomaturation-type amelogenesis imperfecta as identified in the clinical diagnosis. The mineralized content was slightly decreased, with magnesium substituting for calcium in the crystal structure. The anomalies affected enamel with minimal inter-rod enamel present and apatite crystals perpendicular to the enamel prisms, suggesting a possible new role for MMP20 in enamel formation.

  13. Amelogenesis imperfecta: an introduction.

    PubMed

    Gadhia, K; McDonald, S; Arkutu, N; Malik, K

    2012-04-27

    Amelogenesis imperfecta (AI) is an inherited disorder that is associated with mutations in five genes (AMEL; ENAM; MMP20; KLK4 and FAM83H) with a wide range of clinical presentations (phenotypes). It affects the structure and appearance of enamel of all teeth, both in the primary and secondary dentition. In this review paper, we look at the epidemiology, classification, aetiology, clinical description and diagnosis of AI. In the following three papers of this series, we aim to describe the role of paediatric dentists, orthodontists and restorative dentists in the clinical management of patients with AI.

  14. Amelogenesis imperfecta: the orthodontic perspective.

    PubMed

    Arkutu, N; Gadhia, K; McDonald, S; Malik, K; Currie, L

    2012-05-25

    Orthodontics in patients with amelogenesis imperfecta can be complicated by commonly occurring dental features in this group as well as patient factors. In this article we examine ways to avoid the common pitfalls of orthodontic management and the importance of adequate and timely liaison between the general dental practitioner and the multidisciplinary team.

  15. Enamel formation and amelogenesis imperfecta.

    PubMed

    Hu, Jan C-C; Chun, Yong-Hee P; Al Hazzazzi, Turki; Simmer, James P

    2007-01-01

    Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel.

  16. Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

    PubMed

    Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

    2011-02-01

    Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

  17. Multiple unerupted teeth with amelogenesis imperfecta in siblings.

    PubMed

    Hegde, Shruthi

    2012-05-01

    Amelogenesis imperfecta encompasses a group of inherited abnormalities that are generally considered to primarily affect the formation and/or calcification of enamel. This case report describes the unusual presentation of amelogenesis imperfecta in siblings as multiple unerupted teeth, multiple pulpal calcifications, and multiple dilacerations of roots along with the defect in the enamel. The intent of our report is to highlight a rare co-occurrence of amelogenesis imperfecta with multiple morphologic alterations in siblings.

  18. Periodontal management and restoration of an amelogenesis imperfecta patient: a case report.

    PubMed

    Horowitz, Robert A; Gautam, D K; Karol, Suneet; Kumari, Bindiya

    2014-02-01

    This report describes the treatment of a young male patient diagnosed with amelogenesis imperfecta (AI), a hereditary disorder that affects the enamel of both primary and permanent dentition. For management and rehabilitation, it is crucial to determine the type of AI-hypoplastic, hypomaturation, or hypocalcified. As with this patient, who presented with tricho-dento osseous syndrome, patients may present with associated expression of a syndrome (partial or full) and secondary changes in the periodontium. AI is a serious problem; therefore extensive treatment using a multidisciplinary approach must be instituted, especially if the patient is syndrome-associated.

  19. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity.

    PubMed

    Gundannavar, Gayatri; Rosh, Radhika M; Chandrasekaran, Shoba; Hussain, Ahad M

    2013-01-01

    This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

  20. MMP20 Hemopexin Domain Mutation in Amelogenesis Imperfecta

    PubMed Central

    Lee, S.-K.; Seymen, F.; Kang, H.-Y.; Lee, K.-E.; Gencay, K.; Tuna, B.; Kim, J.-W.

    2010-01-01

    Proteolytic enzymes serve important functions during dental enamel formation, and mutations in the kallikrein 4 (KLK4) and enamelysin (MMP20) genes cause autosomal-recessive amelogenesis imperfecta (ARAI). So far, only 1 KLK4 and 3 MMP20 mutations have been reported in ARAI kindreds. To determine whether ARAI in a family with a hypomaturation-type enamel defect is caused by mutations in the genes encoding enamel proteolytic enzymes, we performed mutational analysis on candidate genes. Mutational and haplotype analyses revealed an ARAI-causing point mutation (c.910G>A, p.A304T) in exon 6 of MMP20 that results in a single amino acid substitution in the hemopexin domain. Western blot analysis showed decreased expression of the mutant protein, but zymogram analysis demonstrated that this mutant was a functional protein. The proband and an affected brother were homozygous for the mutation, and both unaffected parents were carriers. The enamel of newly erupted teeth had normal thickness, but was chalky white and became darker with age. PMID:19966041

  1. [Genetic, clinical and molecular analysis of a family affected by amelogenesis imperfecta].

    PubMed

    Urzúa O, Blanca; Ortega P, Ana; Rodríguez M, Luis; Morales B, Irene

    2005-11-01

    Amelogenesis Imperfecta (AI) is a group of conditions where there is an abnormal formation of enamel in terms of quantity, structure and composition. AI is clinically and genetically heterogeneous, there are sex linked and autosomal versions, dominant and/or recessive, with phenotypes of hypoplastic, hypocalcified or hypomature enamel. Only recently, through clinical, genetic and molecular studies of affected families, phenotypic-genotypic correlations are being established in this group of anomalies. To carry out a genetic, clinical and molecular analysis of a Chilean family affected with an enamel malformation, which probably would correspond to Amelogenesis Imperfecta Dominant Autosomal (AIDA), of hypoplastic type, resulting from g.6395G>A mutation in the enamelin gene. A genealogical pattern was created for five generations. Five members of this family group were clinically examined, and four of them had a molecular analysis that consisted of the detection of a mutation in the enamelin gene using PCR. In this family, the enamel malformation presents a dominant autosomal pattern of inheritance. The clinical examination of the group allowed a diagnosis of Amelogenesis Imperfecta, of the hypoplastic local type. However, the molecular analysis revealed that the members analyzed did not exhibit the g.6395G>A mutation reported for the enamelin gene (ENAM). The enamel phenotype in this family could be explained by the presence of one of four other mutations recently described in this or another gene, thereby supporting the findings of allelic heterogeneity reported in the literature.

  2. Amelogenesis imperfecta: review of diagnostic findings and treatment concepts.

    PubMed

    Sabandal, Martin M I; Schäfer, Edgar

    2016-09-01

    Mineralization defects like amelogenesis imperfecta are often of hereditary origin. This article reviews the diagnostic findings and summarizes the suggested treatment approaches. Currently, there are no defined therapy recommendations available for patients suffering from amelogenesis imperfecta. The mentioned therapies are more or less equal but no comprehensive therapy recommendation is evident. When treating patients suffering from amelogenesis imperfecta, a comprehensive therapy of almost every dental discipline has to be considered. The earlier the diagnosis of amelogenesis imperfecta is confirmed, the better the outcome is. Optimal treatment approaches consist of early diagnosis and treatment approach and frequent dental recall appointments to prevent progressive occlusal wear or early destruction by caries. Full-mouth prosthetic treatment seems to be the best treatment option.

  3. Amelogenesis Imperfecta with Coronal Resorption: Report of Three Cases.

    PubMed

    Bhatia, Shannu K; Hunter, M Lindsay; Ashley, Paul F

    2015-12-01

    Intracoronal resorption of the permanent dentition in cases of amelogenesis imperfecta (AI) is a rare finding which poses an added complication to the already complex management of this condition. This paper presents three cases of AI associated with delayed eruption of permanent teeth in which asymptomatic intracoronal resorption occurred. CPD/Clinical Relevance: This paper highlights the fact that teeth affected with amelogenesis imperfecta may undergo asymptomatic intracoronal resorption which is only identifiable radiographically.

  4. Amelogenesis imperfecta and the treatment plan - interdisciplinary team approach.

    PubMed

    Suchancova, B; Holly, D; Janska, M; Stebel, J; Lysy, J; Thurzo, A; Sasinek, S

    2014-01-01

    Amelogenesis imperfecta is a set of hereditary defects representing mainly the development defects of enamel without the presence of whole-body symptoms. Developmental disorders can manifest a complete absence of enamel, which is caused by improper differentiation of ameloblasts. This article describes the diagnosis and treatment of a patient with amelogenesis imperfecta, as well as the need for interdisciplinary cooperation to achieve the best possible morphological, skeletal, functional and aesthetic rehabilitation of the patients with this diagnosis. Furthermore, the article reviews literature dealing with other anomalies occurring in association with amelogenesis imperfect (Fig. 12, Ref. 20).

  5. Amelogenesis Imperfecta: Genotype-Phenotype Studies in 71 Families

    PubMed Central

    Wright, J. Timothy; Torain, Melody; Long, Kimberly; Seow, Kim; Crawford, Peter; Aldred, Michael J.; Hart, P. Suzanne; Hart, Tom C.

    2011-01-01

    Amelogenesis imperfecta (AI) represents hereditary conditions affecting the quality and quantity of enamel. Six genes are known to cause AI (AMELX, ENAM, MMP20, KLK4, FAM83H, and WDR72). Our aim was to determine the distribution of different gene mutations in a large AI population and evaluate phenotype-genotype relationships. Affected and unaffected family members were evaluated clinically and radiographically by one examiner. Genotyping was completed using genomic DNA obtained from blood or saliva. A total of 494 individuals were enrolled, with 430 (224 affected, 202 unaffected, and 4 not definitive) belonging to 71 families with conditions consistent with the diagnosis of AI. Diverse clinical phenotypes were observed (i.e. hypoplastic, hypocalcified, and hypomaturation). Genotyping revealed mutations in all 6 candidate genes. A molecular diagnosis was made in 132 affected individuals (59%) and in 26 of the families (37%). Mutations involved 12 families with FAM83H (46%), 6 families with AMELX (23%), 3 families with ENAM (11%), 2 families with KLK4 and MMP20 (8% for each gene), and 1 family with a WDR72 mutation (4%). Phenotypic variants were associated with allelic FAM83H and AMELX mutations. Two seemingly unrelated families had the same KLK4 mutation. Families affected with AI where candidate gene mutations were not identified could have mutations not identifiable by traditional gene sequencing (e.g. exon deletion) or they could have promoter sequence mutations not evaluated in this study. However, the results suggest that there remain new AI causative genes to be identified. PMID:21597265

  6. Amelogenesis Imperfecta; Genes, Proteins, and Pathways

    PubMed Central

    Smith, Claire E. L.; Poulter, James A.; Antanaviciute, Agne; Kirkham, Jennifer; Brookes, Steven J.; Inglehearn, Chris F.; Mighell, Alan J.

    2017-01-01

    Amelogenesis imperfecta (AI) is the name given to a heterogeneous group of conditions characterized by inherited developmental enamel defects. AI enamel is abnormally thin, soft, fragile, pitted and/or badly discolored, with poor function and aesthetics, causing patients problems such as early tooth loss, severe embarrassment, eating difficulties, and pain. It was first described separately from diseases of dentine nearly 80 years ago, but the underlying genetic and mechanistic basis of the condition is only now coming to light. Mutations in the gene AMELX, encoding an extracellular matrix protein secreted by ameloblasts during enamel formation, were first identified as a cause of AI in 1991. Since then, mutations in at least eighteen genes have been shown to cause AI presenting in isolation of other health problems, with many more implicated in syndromic AI. Some of the encoded proteins have well documented roles in amelogenesis, acting as enamel matrix proteins or the proteases that degrade them, cell adhesion molecules or regulators of calcium homeostasis. However, for others, function is less clear and further research is needed to understand the pathways and processes essential for the development of healthy enamel. Here, we review the genes and mutations underlying AI presenting in isolation of other health problems, the proteins they encode and knowledge of their roles in amelogenesis, combining evidence from human phenotypes, inheritance patterns, mouse models, and in vitro studies. An LOVD resource (http://dna2.leeds.ac.uk/LOVD/) containing all published gene mutations for AI presenting in isolation of other health problems is described. We use this resource to identify trends in the genes and mutations reported to cause AI in the 270 families for which molecular diagnoses have been reported by 23rd May 2017. Finally we discuss the potential value of the translation of AI genetics to clinical care with improved patient pathways and speculate on the

  7. Shear bond strength of dentin and deproteinized enamel of amelogenesis imperfecta mouse incisors.

    PubMed

    Pugach, Megan K; Ozer, Fusun; Mulmadgi, Raj; Li, Yong; Suggs, Cynthia; Wright, J Timothy; Bartlett, John D; Gibson, Carolyn W; Lindemeyer, Rochelle G

    2014-01-01

    The purposes of this study were to: (1) investigate adhesion through shear bond strength (SBS) testing of a resin composite bonded with a self-etching bonding system (SEB) to amelogenesis imperfecta (AI)-affected deproteinized mouse enamel or dentin; and (2) compare wild-type (WT), amelogenin null (AmelxKO), and matrix metalloproteinase-20 null (Mmp20KO) enamel and dentin phenotypes using micro-CT and nanoindentation. Enamel incisor surfaces of WT, AmelxKO, and Mmp20KO mice were treated with SEB with and without sodium hypochlorite and tested for SBS. Incisor dentin was also treated with SEB and tested for SBS. These surfaces were further examined by scanning electron miscroscopy. Micro-CT and nanoindentation analyses were performed on mouse dentin and enamel. Data were analyzed for significance by analysis of variance. Deproteinization did not improve SBS of SEB to these AI-affected enamel surfaces. SBS of AmelxKO teeth was similar in dentin and enamel; however, it was higher in Mmp20KO dentin. The nanohardness of knockout enamel was significantly lower than WT, while knockout dentin nanohardness was not different from WT. Using animal amelogenesis imperfecta models, enamel sodium hypochlorite deproteinization of hypoplastic and hypoplastic-hypomaturation enamel did not increase shear bond strength, while removal of the defective enamel allowed optimal dentin bonding.

  8. Interdisciplinary approach to oral rehabilitation of patient with amelogenesis imperfecta.

    PubMed

    Yilmaz, Burak; Oz, Ulas; Yilmaz, Hasan Guney

    2014-03-01

    Amelogenesis imperfecta is a hereditary condition that affects the development of enamel, causing quantity, structural and compositional anomalies that involve all dentitions. Consequently, the effects can extend to both the primary and secondary dentitions. Patients with amelogenesis imperfecta may present with clinical difficulties, such as insufficient crown length, tooth sensitivity and orthodontic discrepancies, all of which can be resolved successfully with an interdisciplinary approach. This case report describes the interdisciplinary approach to the treatment of a 22-year-old patient with amelogenesis imperfecta. The proper alignment of anterior teeth and gingivo-cervical line was provided with orthodontic and periodontal treatments. All-ceramic crowns were placed on anterior, and metal-ceramic restorations were placed on posterior teeth to reduce sensitivity and improve esthetics with function. Improved esthetic appearance, reduced tooth sensitivity and the resolution of a potentially harmful psychosocial condition were achieved. Patient remained satisfied in the 12-month follow-up examination.

  9. Treatment considerations for patient with Amelogenesis Imperfecta: a review.

    PubMed

    Chen, Chiung-Fen; Hu, Jan Cc; Bresciani, Eduardo; Peters, Mathilde C; Estrella, Maria Regina

    Amelogenesis imperfecta (AI) is a group of inherited disorders primary affecting the structural of enamel. Patients with AI experience poor esthetic, excessive tooth sensitivity and compromised chewing function that dental treatments are frequently required at early age. This review describes the non-enamel implications, stage-specific management strategies and outcomes of selected restorative materials based on literature evidence.

  10. Rehabilitation of amelogenesis imperfecta using a reorganized approach: a case report.

    PubMed

    Chan, Kingsley H C; Ho, Edward H T; Botelho, Michael G; Pow, Edmond H N

    2011-05-01

    Amelogenesis imperfecta is a genetic disorder that causes defective enamel development in both the primary and permanent dentitions. Significant tooth structure damage often results in various pulpal symptoms, occlusal disharmony, impaired function, and esthetic disfigurement. These problems pose great challenges to the clinician when rehabilitating patients with amelogenesis imperfecta. This case report describes an uncomplicated and logical way to reorganize, temporize, and completely restore an extensively damaged dentition caused by amelogenesis imperfecta.

  11. Amelogenesis imperfecta and anterior open bite: Etiological, classification, clinical and management interrelationships.

    PubMed

    Alachioti, Xanthippi Sofia; Dimopoulou, Eleni; Vlasakidou, Anatoli; Athanasiou, Athanasios E

    2014-01-01

    Although amelogenesis imperfecta is not a common dental pathological condition, its etiological, classification, clinical and management aspects have been addressed extensively in the scientific literature. Of special clinical consideration is the frequent co-existence of amelogenesis imperfecta with the anterior open bite. This paper provides an updated review on amelogenesis imperfecta as well as anterior open bite, in general, and documents the association of these two separate entities, in particular. Diagnosis and treatment of amelogenesis imperfecta patients presenting also with anterior open bite require a lengthy, comprehensive and multidisciplinary approach, which should aim to successfully address all dental, occlusal, developmental, skeletal and soft tissue problems associated with these two serious clinical conditions.

  12. Restoring Function and Aesthetics in a Class II Division 1 Patient with Amelogenesis Imperfecta: A Clinical Report

    PubMed Central

    Doruk, Cenk; Ozturk, Firat; Sari, Fatih; Turgut, Mehmet

    2011-01-01

    Amelogenesis imperfecta (AI) encompasses a complicated group of hereditary conditions that cause developmental alterations in the structure of the enamel in the absence of a systemic disorder. AI primarily affects the quality and/or quantity of dental enamel, and it may affect all or only some of the teeth in the primary and/or permanent dentition. This clinical report describes the oral rehabilitation of a 21-year-old man diagnosed with hypomaturation-type AI. He presented with discolored and mutilated teeth. Cephalometrically, the patient has skeletal class II malocclusion due to mandibular deficiency considered as a result of maxillary constriction. The interdisciplinary approach was followed because of the complex needs of the patient. The aim of treatment was to restore aesthetics, improve malocclusion and masticatory function. Aesthetic and functional expectations were met with metal ceramic restorations. In this report, the interdisciplinary approach for a patient with AI and a malocclusion is described. PMID:21494393

  13. Amelogenesis Imperfecta Due to a Mutation of the Enamelin Gene: Clinical Case With Genotype-phenotype Correlations

    PubMed Central

    Lindemeyer, Rochelle G.; Gibson, Carolyn W.; Wright, Timothy J.

    2010-01-01

    The major protein components of the enamel matrix include the most abundant amelogenin proteins as well as less plentiful proteins such as enamelin and ameloblastin. The enamel defect in amelogenesis imperfecta (AI) generally results in enamel that is too thin (hypoplastic) or too soft (hypocalcification or hypomaturation). Previous reports indicate that mutations in the human enamelin gene (ENAM) cause hypoplastic AI through autosomaldominant inheritance patterns and patients may also exhibit an anterior open bite. Although crown resorption of unerupted teeth occurs more frequently in AI patients, this finding has not been previously associated with known ENAM mutations. The purpose of this article was to report the genotype-phenotype correlations for a 9-year, 11-month-old boy with a homozygous ENAM mutation (c.1258_1259insAG). PMID:20298654

  14. Clinical and molecular analysis of the enamelin gene ENAM in Colombian families with autosomal dominant amelogenesis imperfecta

    PubMed Central

    Gutiérrez, Sandra; Torres, Diana; Briceño, Ignacio; Gómez, Ana Maria; Baquero, Eliana

    2012-01-01

    In this study, we analyzed the phenotype, clinical characteristics and presence of mutations in the enamelin gene ENAM in five Colombian families with autosomal dominant amelogenesis imperfecta (ADAI). 22 individuals (15 affected and seven unaffected) belonging to five Colombian families with ADAI and eight individuals (three affected and five unaffected) belonging to three Colombian families with autosomal recessive amelogenesis imperfecta (ARAI) that served as controls for molecular alterations and inheritance patterns were studied. Clinical, radiographic and genetic evaluations were done in all individuals. Eight exons and three intron-exon boundaries were sequenced for mutation analysis. Two of the five families with ADAI had the hypoplasic phenotype, two had the hypocalcified phenotype and one had the hypomaturative phenotype. Anterior open bite and mandibular retrognathism were the most frequent skeletal abnormalities in the families with ADAI. No mutations were found. These findings suggest that ADAI in these Colombian families was unrelated to previously described mutations in the ENAM gene. These results also indicate that other regions not included in this investigation, such as the promoter region, introns and other genes should be considered as potential ADAI candidates. PMID:23055792

  15. Clinical and molecular analysis of the enamelin gene ENAM in Colombian families with autosomal dominant amelogenesis imperfecta.

    PubMed

    Gutiérrez, Sandra; Torres, Diana; Briceño, Ignacio; Gómez, Ana Maria; Baquero, Eliana

    2012-07-01

    In this study, we analyzed the phenotype, clinical characteristics and presence of mutations in the enamelin gene ENAM in five Colombian families with autosomal dominant amelogenesis imperfecta (ADAI). 22 individuals (15 affected and seven unaffected) belonging to five Colombian families with ADAI and eight individuals (three affected and five unaffected) belonging to three Colombian families with autosomal recessive amelogenesis imperfecta (ARAI) that served as controls for molecular alterations and inheritance patterns were studied. Clinical, radiographic and genetic evaluations were done in all individuals. Eight exons and three intron-exon boundaries were sequenced for mutation analysis. Two of the five families with ADAI had the hypoplasic phenotype, two had the hypocalcified phenotype and one had the hypomaturative phenotype. Anterior open bite and mandibular retrognathism were the most frequent skeletal abnormalities in the families with ADAI. No mutations were found. These findings suggest that ADAI in these Colombian families was unrelated to previously described mutations in the ENAM gene. These results also indicate that other regions not included in this investigation, such as the promoter region, introns and other genes should be considered as potential ADAI candidates.

  16. A Novel Homozygous WDR72 Mutation in Two Siblings with Amelogenesis Imperfecta and Mild Short Stature

    PubMed Central

    Kuechler, A.; Hentschel, J.; Kurth, I.; Stephan, B.; Prott, E.-C.; Schweiger, B.; Schuster, A.; Wieczorek, D.; Lüdecke, H.-J.

    2012-01-01

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of inherited defects of enamel formation. In isolated AI (no additional segregating features), mutations in at least 7 genes are known so far, causing dominant, recessive or X-linked AI and allowing the identification of the molecular etiology in 40–50% of affected families. We report on 2 siblings (an 11-year-old female and a 7-year-old male) born to consanguineous Turkish parents, with AI and mild, proportionate short stature. Both parents have normal teeth, but mother, maternal grandmother and great-grandfather are/were also of short stature. A spine X-ray performed in the girl excluded brachyolmia. Affymetrix GenomeWide SNP6.0 Array analysis identified no pathogenic copy number changes, but showed sharing of large homozygous regions, including chromosome band 15q21.3 containing the WDR72 gene. WDR72 sequence analysis in both siblings revealed homozygosity for a novel stop mutation in exon 10 (c.997A>T, p.Lys333X) explaining the AI phenotype. Mutations in WDR72 are a very rare cause of autosomal-recessive hypomaturation type of isolated AI. The mutation described in our patients specifies the diagnosis AI IIA3 and represents only the sixth WDR72 mutation reported so far. The WDR72 protein is critical for dental enamel formation, but its exact function is still unknown. PMID:23293580

  17. A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta.

    PubMed

    Poulter, James A; Brookes, Steven J; Shore, Roger C; Smith, Claire E L; Abi Farraj, Layal; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-04-15

    We identified a family in which pitted hypomineralized amelogenesis imperfecta (AI) with premature enamel failure segregated in an autosomal recessive fashion. Whole-exome sequencing revealed a missense mutation (c.586C>A, p.P196T) in the I-domain of integrin-β6 (ITGB6), which is consistently predicted to be pathogenic by all available programmes and is the only variant that segregates with the disease phenotype. Furthermore, a recent study revealed that mice lacking a functional allele of Itgb6 display a hypomaturation AI phenotype. Phenotypic characterization of affected human teeth in this study showed areas of abnormal prismatic organization, areas of low mineral density and severe abnormal surface pitting in the tooth's coronal portion. We suggest that the pathogenesis of this form of AI may be due to ineffective ligand binding of ITGB6 resulting in either compromised cell-matrix interaction or compromised ITGB6 activation of transforming growth factor-β (TGF-β) impacting indirectly on ameloblast-ameloblast interactions and proteolytic processing of extracellular matrix proteins via MMP20. This study adds to the list of genes mutated in AI and further highlights the importance of cell-matrix interactions during enamel formation.

  18. A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta

    PubMed Central

    Poulter, James A.; Brookes, Steven J.; Shore, Roger C.; Smith, Claire E. L.; Abi Farraj, Layal; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2014-01-01

    We identified a family in which pitted hypomineralized amelogenesis imperfecta (AI) with premature enamel failure segregated in an autosomal recessive fashion. Whole-exome sequencing revealed a missense mutation (c.586C>A, p.P196T) in the I-domain of integrin-β6 (ITGB6), which is consistently predicted to be pathogenic by all available programmes and is the only variant that segregates with the disease phenotype. Furthermore, a recent study revealed that mice lacking a functional allele of Itgb6 display a hypomaturation AI phenotype. Phenotypic characterization of affected human teeth in this study showed areas of abnormal prismatic organization, areas of low mineral density and severe abnormal surface pitting in the tooth's coronal portion. We suggest that the pathogenesis of this form of AI may be due to ineffective ligand binding of ITGB6 resulting in either compromised cell–matrix interaction or compromised ITGB6 activation of transforming growth factor-β (TGF-β) impacting indirectly on ameloblast–ameloblast interactions and proteolytic processing of extracellular matrix proteins via MMP20. This study adds to the list of genes mutated in AI and further highlights the importance of cell–matrix interactions during enamel formation. PMID:24319098

  19. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.

    PubMed

    Poulter, James A; Murillo, Gina; Brookes, Steven J; Smith, Claire E L; Parry, David A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-10-15

    Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid.

  20. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta

    PubMed Central

    Poulter, James A.; Murillo, Gina; Brookes, Steven J.; Smith, Claire E. L.; Parry, David A.; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2014-01-01

    Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid. PMID:24858907

  1. Immediate Desensitization in Teeth Affected by Amelogenesis Imperfecta.

    PubMed

    Moreira, Rudá França; Figueiredo, Rossana Gomes; Oliveira, Henrique Eduardo; Fonseca, Ana Christina Lamosa da; Miranda, Mauro Sayão de

    2016-01-01

    The aim of this paper was to describe a clinical case of immediate dental desensitization using a self-etch adhesive system in an adolescent patient diagnosed with amelogenesis imperfecta (AI). AI was associated with severe tooth sensitivity, treated by the application of a universal adhesive system for desensitization of the teeth affected by AI. Reduction of tooth sensitivity was assessed using a visual analog scale during all reevaluations. The technique was effective for reducing tooth sensitivity. It was concluded that the adhesive system for tooth desensitization had an immediate effect and maintained its effectiveness during a 12-month follow-up period.

  2. Amelogenesis imperfecta - lifelong management. Restorative management of the adult patient.

    PubMed

    Patel, M; McDonnell, S T; Iram, S; Chan, M F W-Y

    2013-11-08

    The biggest challenge restorative dentists face in rehabilitating patients with amelogenesis imperfecta (AI) is trying to restore aesthetics, function and occlusal stability while keeping the treatment as conservative as possible. The goals of treatment should be to prolong the life of the patient's own teeth and avoid or delay the need for extractions and subsequent replacement with conventional fixed, removable or implant retained prostheses. In order to achieve these goals a stepwise approach to treatment planning is required starting with the most conservative but aesthetically acceptable treatment. This article discusses the management of AI and presents the various treatment options available for restoring the adult patient who presents to the dentist with AI.

  3. Crown lengthening procedure in the management of amelogenesis imperfecta.

    PubMed

    Kalaivani, S; Manohar, Jenish; Shakunthala, P; Sujatha, S; Rajasekaran, S A; Karthikeyan, B; Kalaiselvan, S

    2015-08-01

    Full mouth rehabilitation includes a promising treatment planning and execution thus fulfilling esthetic, occlusal, and functional parameters maintaining the harmony of the stomatognathic system. Crown lengthening procedures have become an integral component of the esthetic armamentarium and are utilized with increasing frequency to enhance the appearance of restorations placed in the esthetic zone. Crown lengthening plays a role to create healthy relationship of the gingiva and bone levels so as to gain access to more of the tooth which can be restored, if it is badly worn, decayed or fractured, below the gum line. This paper highlights the full mouth crown lengthening procedure performed on a patient with amelogenesis imperfecta.

  4. Conservative treatment for amelogenesis imperfecta: a case report.

    PubMed

    Campos, Roberto Elias; Miranda Valdivia, Andrea Dolores Correia; Santos-Filho, Paulo Cesar de Freitas; Menezes, Murilo de Souza; de Oliveira Junior, Osmir Batista; Soares, Carlos Jose

    2014-01-01

    Amelogenesis imperfecta is a hereditary condition that can alter the thickness, color, and shape of tooth enamel. Recent adhesive materials and techniques have provided less invasive treatment options. This case report presents the treatment of a patient whose anterior teeth had color alterations, white spots, pits, and shape defects. Using a more conservative technique, the mandibular and maxillary anterior teeth were restored using veneer direct composite restorations. After 6 years, the restorations demonstrated no deterioration, and no pathology was seen in association with the rehabilitation.

  5. Crown lengthening procedure in the management of amelogenesis imperfecta

    PubMed Central

    Kalaivani, S.; Manohar, Jenish; Shakunthala, P.; Sujatha, S.; Rajasekaran, S. A.; Karthikeyan, B.; Kalaiselvan, S.

    2015-01-01

    Full mouth rehabilitation includes a promising treatment planning and execution thus fulfilling esthetic, occlusal, and functional parameters maintaining the harmony of the stomatognathic system. Crown lengthening procedures have become an integral component of the esthetic armamentarium and are utilized with increasing frequency to enhance the appearance of restorations placed in the esthetic zone. Crown lengthening plays a role to create healthy relationship of the gingiva and bone levels so as to gain access to more of the tooth which can be restored, if it is badly worn, decayed or fractured, below the gum line. This paper highlights the full mouth crown lengthening procedure performed on a patient with amelogenesis imperfecta. PMID:26538965

  6. Amelogenesis Imperfecta, Facial Esthetics and Snap-On Smile.

    PubMed

    Wilson, Lee; Bradshaw, Jonathan P; Marks, Murray K

    2015-01-01

    Amelogenesis imperfecta is a hereditary enamel protein disorder affecting deciduous and secondary crown formation. The prevalence ranges from 1:700 to 1:14,000 depending on the population. These teeth may be hypoplastic, hypomineralized, or hypermineralized and are often discolored, sensitive and caries vulnerable. Patients often present with psychosocial issues due to appearance. Primary teeth are often treated with stainless steel crowns while secondary teeth are treated with full coverage esthetic crowns. The presenting preteen male here was fitted with Snap-On Smile? (www.snaponsmile.com). This treatment option provided cosmetic enhancement of the patient's appearance besides stabilization without altering the primary and secondary dentition during adolescent development.

  7. LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta.

    PubMed

    Kim, J W; Seymen, F; Lee, K E; Ko, J; Yildirim, M; Tuna, E B; Gencay, K; Shin, T J; Kyun, H K; Simmer, J P; Hu, J C-C

    2013-10-01

    Amelogenesis imperfecta (AI) can be either isolated or part of a larger syndrome. Junctional epidermolysis bullosa (JEB) is a collection of autosomal-recessive disorders featuring AI associated with skin fragility and other symptoms. JEB is a recessive syndrome usually caused by mutations in both alleles of COL17A1, LAMA3, LAMB3, or LAMC2. In rare cases, heterozygous carriers in JEB kindreds display enamel malformations in the absence of skin fragility (isolated AI). We recruited two kindreds with autosomal-dominant amelogenesis imperfecta (ADAI) characterized by generalized severe enamel hypoplasia with deep linear grooves and pits. Whole-exome sequencing of both probands identified novel heterozygous mutations in the last exon of LAMB3 that likely truncated the protein. The mutations perfectly segregated with the enamel defects in both families. In Family 1, an 8-bp deletion (c.3446_3453del GACTGGAG) shifted the reading frame (p.Gly 1149Glufs*8). In Family 2, a single nucleotide substitution (c.C3431A) generated an in-frame translation termination codon (p.Ser1144*). We conclude that enamel formation is particularly sensitive to defects in hemidesmosome/basement-membrane complexes and that syndromic and non-syndromic forms of AI can be etiologically related.

  8. Acid-etching effects in hypomineralized amelogenesis imperfecta. A microscopic and microanalytical study.

    PubMed

    Sánchez-Quevedo, Carmen; Ceballos, Gregorio; Rodríguez, Ismael Angel; García, José Manuel; Alaminos, Miguel

    2006-01-01

    The purpose of this study was to use quantitative x-ray microprobe analysis with scanning electron microscopy to define the morphostructural and calcification patterns in the enamel of teeth with the hypomineralized variant of amelogenesis imperfecta. We compared 5 fragments of permanent human canines from patients with clinically diagnosed hypomineralized amelogenesis imperfecta and 5 normal permanent canines from subjects without amelogenesis imperfecta. All specimens were etched with phosphoric acid for morphological and microanalytical examination. Two types of etching patterns were found; in addition, islets of pattern I were seen within areas of pattern II. Microanalysis detected no significant differences in calcium concentration between specimens with amelogenesis imperfecta and normal control specimens after acid etching. Pattern III was not observed. The changes and their distribution in the enamel structure after 30 s of acid etching are described in teeth with this rare disorder. Although these data seem to coincide with alterations in prism development, no alterations in calcium concentration were found.

  9. Amelogenesis imperfecta and anterior open bite: Etiological, classification, clinical and management interrelationships

    PubMed Central

    Alachioti, Xanthippi Sofia; Dimopoulou, Eleni; Vlasakidou, Anatoli; Athanasiou, Athanasios E

    2014-01-01

    Although amelogenesis imperfecta is not a common dental pathological condition, its etiological, classification, clinical and management aspects have been addressed extensively in the scientific literature. Of special clinical consideration is the frequent co-existence of amelogenesis imperfecta with the anterior open bite. This paper provides an updated review on amelogenesis imperfecta as well as anterior open bite, in general, and documents the association of these two separate entities, in particular. Diagnosis and treatment of amelogenesis imperfecta patients presenting also with anterior open bite require a lengthy, comprehensive and multidisciplinary approach, which should aim to successfully address all dental, occlusal, developmental, skeletal and soft tissue problems associated with these two serious clinical conditions. PMID:24987656

  10. Occurrence of epidermolysis bullosa along with Amelogenesis imperfecta in female patient of India.

    PubMed

    Javed, A P; Shenai, Prashanth; Chatra, Laxmikanth; Veena, K M; Rao, Prasanna Kumar; Prabhu, Rachana

    2013-11-01

    Epidermolysis bullosa (EB) is an inherited disorder, which is characteristically presented as skin blisters developing in response to minor injury. Junctional variety of EB is also associated with enamel hypoplasia. Amelogenesis imperfecta presents with abnormal formation of the enamel both in deciduous and permanent dentition. This article describes a previously unreported case of Amelogenesis imperfecta with complete loss of enamel in a young female patient with EB.

  11. Clinical findings and long-term managements of patients with amelogenesis imperfecta.

    PubMed

    Koruyucu, Mine; Bayram, Merve; Tuna, Elif Bahar; Gencay, Koray; Seymen, Figen

    2014-10-01

    The aim of this clinical case series is to present a diagnosis and different treatment methods of patients in different ages with amelogenesis imperfecta (AI) as well as further treatments during a 3-6 years follow-up period. A number of 31 patients (16 female, 15 male with a mean age of 10.77 ± 2.65 years) with AI have been examined for the study group between 2007 and 2010 years. A detailed anamnesis was recorded, followed by a clinical and radiological assessment of oral health. The types of AI classified for each patient according to clinical and radiographic evaluation. The main complaints of patients, presence of dental caries and dental anomalies were noted. Necessary treatments had been planned for the individual cases of AI. A number of 19 patients had hypoplastic (HP) form, and 10 patients showed hypomaturation (HM) form of AI, while one patient showed hypocalcified form of AI and one patient had HM-HP form with taurodontism. Main complaints were chiefly related to dissatisfactory esthetics and dental sensitivity. Caries prevalence index was 93.5%. Mean decayed, missing, filling permanent teeth (DMF) and DMF surface (DMFS) were found as 2.74 ± 1.71 and 6.23 ± 3.99; df (decayed, filling primary teeth) and dfs (decayed, filling primary teeth surface) were found as 3.12 ± 2.85 and 5.24 ± 4.97, respectively. All patients received individual clinical care, including preventive, restorative, and prosthetic treatments. Patients have scheduled for regular follow-up in every 3 months. Composite restorations were used as the most common treatment (25 patients, 80.6%). The treatment plan should be based on patient's age, type of defects and individual needs of the patients. Necessary treatment plan is essential, not only due to functional and aesthetic reasons, but also for the positive psychological impact on young patients.

  12. Case series: clinical findings and oral rehabilitation of patients with amelogenesis imperfecta.

    PubMed

    Markovic, D; Petrovic, B; Peric, T

    2010-08-01

    Children with amelogenesis imperfecta (AI) experience many oral difficulties including sensitivity and aesthetics. The methods of treating AI children are limited and therefore a program of care was evaluated in order to assess the clinical efficacy of providing preventive and restorative treatments. A non-randomised convenience sample of 12 patients with AI was evaluated. A comprehensive patient history was recorded, followed by a clinical and radiographic assessment of oral health. In 8/12 patients a hypoplastic form of AI was diagnosed, in 2/12 cases hypomaturation and in 2/12 cases hypocalcified form were noted. Chief complaints were mainly related to unsatisfactory aesthetics and dental sensitivity. In 8 patients there was active dental caries. Most of the patients had gingivitis and showed fair oral hygiene. The presence of non-enamel dental anomalies was recorded in 9 patients. All patients received meticulous preventive care. Initial treatment depended on AI type and oral health of the patient. During the transition period, both conventional and resin modified glassionomer cements, as well as composite resin materials, were used to restore posterior teeth. Direct composite resin restorations were used to improve the appearance of anterior teeth. In 4 patients a long-lasting interdisciplinary approach including orthodontics, metal-ceramic crowns and fixed partial dentures, and direct composite restorations was required. Follow-up periods varied between 2-11 years. All children have been regularly recalled at 3 monthly intervals. Caries prevalence has remained low during the follow-up postoperative period and patients have reported satisfaction with the treatment they have received. AI is associated with multiple non-enamel anomalies and requires a complex treatment. Treatment planning is related to the age of the patient, the type and severity of the disorder, and the oral health of the patient. Early diagnosis, preventive care and timely treatment are of

  13. Clinical findings and long-term managements of patients with amelogenesis imperfecta

    PubMed Central

    Koruyucu, Mine; Bayram, Merve; Tuna, Elif Bahar; Gencay, Koray; Seymen, Figen

    2014-01-01

    The aim of this clinical case series is to present a diagnosis and different treatment methods of patients in different ages with amelogenesis imperfecta (AI) as well as further treatments during a 3-6 years follow-up period. A number of 31 patients (16 female, 15 male with a mean age of 10.77 ± 2.65 years) with AI have been examined for the study group between 2007 and 2010 years. A detailed anamnesis was recorded, followed by a clinical and radiological assessment of oral health. The types of AI classified for each patient according to clinical and radiographic evaluation. The main complaints of patients, presence of dental caries and dental anomalies were noted. Necessary treatments had been planned for the individual cases of AI. A number of 19 patients had hypoplastic (HP) form, and 10 patients showed hypomaturation (HM) form of AI, while one patient showed hypocalcified form of AI and one patient had HM-HP form with taurodontism. Main complaints were chiefly related to dissatisfactory esthetics and dental sensitivity. Caries prevalence index was 93.5%. Mean decayed, missing, filling permanent teeth (DMF) and DMF surface (DMFS) were found as 2.74 ± 1.71 and 6.23 ± 3.99; df (decayed, filling primary teeth) and dfs (decayed, filling primary teeth surface) were found as 3.12 ± 2.85 and 5.24 ± 4.97, respectively. All patients received individual clinical care, including preventive, restorative, and prosthetic treatments. Patients have scheduled for regular follow-up in every 3 months. Composite restorations were used as the most common treatment (25 patients, 80.6%). The treatment plan should be based on patient's age, type of defects and individual needs of the patients. Necessary treatment plan is essential, not only due to functional and aesthetic reasons, but also for the positive psychological impact on young patients. PMID:25512739

  14. Dental rehabilitation of amelogenesis imperfecta using thermoformed templates.

    PubMed

    Sockalingam, Snmp

    2011-01-01

    Amelogenesis imperfecta represents a group of dental developmental conditions that are genomic in origin. Hypoplastic AI, hypomineralised AI or both in combination were the most common types seen clinically. This paper describes oral rehabilitation of a 9-year-old Malay girl with inherited hypoplastic AI using transparent thermoforming templates. The defective surface areas were reconstructed to their original dimensions on stone cast models of the upper and lower arches using composite, and transparent thermoform templates were fabricated on the models. The templates were used as crown formers to reconstruct the defective teeth clinically using esthetically matching composite. The usage of the templates allowed direct light curing of the composite, accurate reproducibility of the anatomic contours of the defective teeth, reduced chair-side time and easy contouring and placement of homogenous thickness of composite in otherwise inaccessible sites of the affected teeth.

  15. Amelogenesis Imperfecta and Screening of Mutation in Amelogenin Gene

    PubMed Central

    Oliveira, Fernanda Veronese; Gurgel, Carla Vecchione; Kobayashi, Tatiana Yuriko; Dionísio, Thiago José; Neves, Lucimara Teixeira; Santos, Carlos Ferreira; Machado, Maria Aparecida Andrade Moreira

    2014-01-01

    The aim of this study was to report the clinical findings and the screening of mutations of amelogenin gene of a 7-year-old boy with amelogenesis imperfecta (AI). The genomic DNA was extracted from saliva of patient and his family, followed by PCR and direct DNA sequencing. The c.261C>T mutation was found in samples of mother, father, and brother, but the mutation was not found in the sequence of the patient. This mutation is a silent mutation and a single-nucleotide polymorphism (rs2106416). Thus, it is suggested that the mutation found was not related to the clinical presence of AI. Further research is necessary to examine larger number of patients and genes related to AI. PMID:25045544

  16. Bilateral nephrocalcinosis and amelogenesis imperfecta: A case report.

    PubMed

    Patel, Alok; Jagtap, Chetana; Bhat, Chetan; Shah, Rohan

    2015-01-01

    Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect the quality and/or quantity of dental enamel. This paper describes the clinicopathological features of a patient who was born of nonconsanguineous parents and who presented with oral alterations, including yellow and misshapen teeth, intrapulpal calcifications, delayed tooth eruption, and gum enlargement. Scanning electron microscopy of the teeth revealed hypoplastic enamel, and a renal ultrasound detected bilateral nephrocalcinosis, leading to a diagnosis of AI and nephrocalcinosis syndrome. Since nephrocalcinosis is often asymptomatic and can be associated with impaired renal function, dentists who see children with a generalized and thin hypoplastic AI should consider a renal ultrasound scan and referral to a Nephrologist. Children with nephrocalcinosis should also be considered for a dental check.

  17. Esthetic and functional rehabilitation of mutilated dentition and loss of vertical dimension due to amelogenesis imperfecta.

    PubMed

    Mittal, Shweta; Tewari, Sanjay; Goel, Rajat

    2014-04-01

    Cases of severe attrition are a common finding. Among the congenital anomalies, amelogenesis imperfecta and dentinogenesis imperfecta are important conditions that may cause accelerated wear of teeth. The following case report describes the complete oral rehabilitation of a patient diagnosed with amelogenesis imperfecta. A detailed treatment plan was chalked out which included proper oral hygiene measures, restoration of carious teeth and endodontic treatment followed by foundation restorations of teeth that were crucial for the final prostheses. Patient was given transitional restorations for about 6 weeks with the aim of regaining the lost vertical dimensions. Final rehabilitation was done by fixed dental prostheses.

  18. Esthetic and functional rehabilitation of mutilated dentition and loss of vertical dimension due to amelogenesis imperfecta

    PubMed Central

    Mittal, Shweta; Tewari, Sanjay; Goel, Rajat

    2014-01-01

    Cases of severe attrition are a common finding. Among the congenital anomalies, amelogenesis imperfecta and dentinogenesis imperfecta are important conditions that may cause accelerated wear of teeth. The following case report describes the complete oral rehabilitation of a patient diagnosed with amelogenesis imperfecta. A detailed treatment plan was chalked out which included proper oral hygiene measures, restoration of carious teeth and endodontic treatment followed by foundation restorations of teeth that were crucial for the final prostheses. Patient was given transitional restorations for about 6 weeks with the aim of regaining the lost vertical dimensions. Final rehabilitation was done by fixed dental prostheses. PMID:25565735

  19. Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.

    PubMed

    Prasad, M K; Laouina, S; El Alloussi, M; Dollfus, H; Bloch-Zupan, A

    2016-12-01

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis.

  20. Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report.

    PubMed

    Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

    2015-09-01

    Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

  1. Scanning electron microscopy and calcification in amelogenesis imperfecta in anterior and posterior human teeth.

    PubMed

    Sánchez-Quevedo, M C; Ceballos, G; García, J M; Rodríguez, I A; Gómez de Ferraris, M E; Campos, A

    2001-07-01

    Teeth fragments from members of a family clinically and genetically diagnosed as having amelogenesis imperfecta were studied by scanning electron microscopy and X-ray microprobe analysis to establish the morphological patterns and the quantitative concentration of calcium in the enamel of anterior (canine, incisor) and posterior (premolar and molar) teeth. The prism patterns in the enamel of teeth from both regions were parallel or irregularly decussate, with occasional filamentous prisms accompanied by small, irregularly rounded formations. Prismless enamel showed the R- and P-type patterns. Calcium levels in enamel of amelogenesis imperfecta and control teeth differed significantly between anterior and posterior teeth, indicating that the factors that influence normal mineralization in different regions of the dental arch are not altered in the process of amelogenesis imperfecta.

  2. Diagnosis and esthetic functional rehabilitation of a patient with amelogenesis imperfecta.

    PubMed

    Oliveira, Ilione Kruschewsky Costa Sousa; Fonseca, Jussara de Fatima Barbosa; do Amaral, Flavia Lucisano Botelho; Pecorari, Vanessa Gallego Arias; Basting, Roberta Tarkany; França, Fabiana Mantovani Gomes

    2011-06-01

    Amelogenesis imperfecta is a hereditary disease that causes structural anomalies in dental enamel of both the primary and permanent dentition. The anomaly may present a variety of clinical forms and appearances, with its main characteristics being the loss of tooth structure, compromised esthetic appearance, and dental sensitivity. The aim of this study was to present the clinical report of a 16-year-old patient with severely compromised esthetics as a result of amelogenesis imperfecta of the hypocalcified type who was rehabilitated with composite resin and ceramic crowns.

  3. Target gene analyses of 39 amelogenesis imperfecta kindreds.

    PubMed

    Chan, Hui-Chen; Estrella, Ninna M R P; Milkovich, Rachel N; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C

    2011-12-01

    Previously, mutational analyses identified six disease-causing mutations in 24 amelogenesis imperfecta (AI) kindreds. We have since expanded the number of AI kindreds to 39, and performed mutation analyses covering the coding exons and adjoining intron sequences for the six proven AI candidate genes [amelogenin (AMELX), enamelin (ENAM), family with sequence similarity 83, member H (FAM83H), WD repeat containing domain 72 (WDR72), enamelysin (MMP20), and kallikrein-related peptidase 4 (KLK4)] and for ameloblastin (AMBN) (a suspected candidate gene). All four of the X-linked AI families (100%) had disease-causing mutations in AMELX, suggesting that AMELX is the only gene involved in the aetiology of X-linked AI. Eighteen families showed an autosomal-dominant pattern of inheritance. Disease-causing mutations were identified in 12 (67%): eight in FAM83H, and four in ENAM. No FAM83H coding-region or splice-junction mutations were identified in three probands with autosomal-dominant hypocalcification AI (ADHCAI), suggesting that a second gene may contribute to the aetiology of ADHCAI. Six families showed an autosomal-recessive pattern of inheritance, and disease-causing mutations were identified in three (50%): two in MMP20, and one in WDR72. No disease-causing mutations were found in 11 families with only one affected member. We conclude that mutation analyses of the current candidate genes for AI have about a 50% chance of identifying the disease-causing mutation in a given kindred.

  4. Minimally invasive rehabilitation of a patient with amelogenesis imperfecta.

    PubMed

    Büchi, Dominik; Fehmer, Vincent; Sailer, Irene; Wolleb, Karin; Jung, Ronald

    2014-01-01

    This case report describes a minimally invasive step-by-step approach to treat a patient with amelogenesis imperfecta. This is a genetic developmental disorder of the dental enamel, which clinically manifests as white and dark discolorations of the teeth. The clinical examination did not reveal the true depth of the staining. Therefore, a step-wise treatment approach was chosen. The first step consisted of a home bleaching procedure, which led to a slight improvement of the esthetic appearance, but the stains were still clearly visible. The next step was the application of a microabrasion technique. This led to further improvement, but not to a satisfactory result for this patient who had high esthetic expectations. Thus, the third step was undertaken: it was planned to restore the maxillary incisors and canines with ceramic veneers. The dental technician prepared a wax-up, which served as a basis for a clinical mock-up. After discussing the mock-up and the treatment plan with the patient, crown lengthening was performed on teeth 11 and 23 to improve the pink esthetics. Subsequently, the teeth were prepared in a minimally invasive way and a final impression was taken. Following try-in, the six veneers were inserted with resin cement.

  5. Target gene analyses of 39 amelogenesis imperfecta kindreds

    PubMed Central

    Chan, Hui-Chen; Estrella, Ninna M. R. P.; Milkovich, Rachel N.; Kim, Jung-Wook; Simmer, James P.; Hu, Jan C-C.

    2012-01-01

    Previously, mutational analyses identified six disease-causing mutations in 24 amelogenesis imperfecta (AI) kindreds. We have since expanded the number of AI kindreds to 39, and performed mutation analyses covering the coding exons and adjoining intron sequences for the six proven AI candidate genes [amelogenin (AMELX), enamelin (ENAM), family with sequence similarity 83, member H (FAM83H), WD repeat containing domain 72 (WDR72), enamelysin (MMP20), and kallikrein-related peptidase 4 (KLK4)] and for ameloblastin (AMBN) (a suspected candidate gene). All four of the X-linked AI families (100%) had disease-causing mutations in AMELX, suggesting that AMELX is the only gene involved in the aetiology of X-linked AI. Eighteen families showed an autosomal-dominant pattern of inheritance. Disease-causing mutations were identified in 12 (67%): eight in FAM83H, and four in ENAM. No FAM83H coding-region or splice-junction mutations were identified in three probands with autosomal-dominant hypocalcification AI (ADHCAI), suggesting that a second gene may contribute to the aetiology of ADHCAI. Six families showed an autosomal-recessive pattern of inheritance, and disease-causing mutations were identified in three (50%): two in MMP20, and one in WDR72. No disease-causing mutations were found in 11 families with only one affected member. We conclude that mutation analyses of the current candidate genes for AI have about a 50% chance of identifying the disease-causing mutation in a given kindred. PMID:22243262

  6. Dental management of amelogenesis imperfecta patients: a primer on genotype-phenotype correlations.

    PubMed

    Ng, F K; Messer, L B

    2009-01-01

    Amelogenesis imperfecta (AI) represents a group of hereditary conditions which affects enamel formation in the primary and permanent dentitions. Mutations in genes critical for amelogenesis result in diverse phenotypes characterized by variably thin and/or defective enamel. To date, mutations in 5 genes are known to cause AI in humans. Understanding the molecular etiologies and associated inheritance patterns can assist in the early diagnosis of this condition. Recognition of genotype-phenotype correlations will allow clinicians to guide genetic testing and select appropriate management strategies for patients who express different phenotypes. The purpose of this paper was to provide a narrative review of the current literature on amelogenesis imperfecta, particularly regarding recent advances in the identification of candidate genes and the patterns of inheritance.

  7. Microtensile bond strength to enamel affected by hypoplastic amelogenesis imperfecta.

    PubMed

    Yaman, Batu Can; Ozer, Fusun; Cabukusta, Cigdem Sozen; Eren, Meltem M; Koray, Fatma; Blatz, Markus B

    2014-02-01

    This study compared the microtensile bond strengths (μTBS) of two different self-etching (SE) and etchand- rinse (ER) adhesive systems to enamel affected by hypoplastic amelogenesis imperfecta (HPAI) and analyzed the enamel etching patterns created by the two adhesive systems using scanning electron microscopy (SEM). Sixteen extracted HPAI-affected molars were used for the bond strength tests and 2 molars were examined under SEM for etching patterns. The control groups consisted of 12 healthy third molars for μTBS tests and two molars for SEM. Mesial and distal surfaces of the teeth were slightly ground flat. The adhesive systems and composite resin were applied to the flat enamel surfaces according to the manufacturers' instructions. The tooth slabs containing composite resin material on their mesial and distal surfaces were cut in the mesio-distal direction with a slow-speed diamond saw. The slabs were cut again to obtain square, 1-mm-thick sticks. Finally, each stick was divided into halves and placed in the μTBS tester. Bond strength tests were performed at a speed of 0.5 mm/min. Data were analyzed with two-way ANOVA and Tukey's tests. There was no significant difference between the bond strength values of ER and SE adhesives (p > 0.05). However, significant differences were found between HPAI and control groups (p < 0.05). HPAI-affected enamel surfaces exhibited mild intra- and inter-prismatic enamel etching patterns after orthophosphoric acid application, while conditioning of HPAI-affected enamel with SE primer created a slightly rough and grooved surface. SE and ER adhesive systems provide similar bond strengths to HPAI-affected enamel surfaces.

  8. Novel MMP20 and KLK4 Mutations in Amelogenesis Imperfecta.

    PubMed

    Seymen, F; Park, J-C; Lee, K-E; Lee, H-K; Lee, D-S; Koruyucu, M; Gencay, K; Bayram, M; Tuna, E B; Lee, Z H; Kim, Y-J; Kim, J-W

    2015-08-01

    In order to achieve highly mineralized tooth enamel, enamel proteinases serve the important function of removing the remaining organic matrix in the mineralization and maturation of the enamel matrix. Mutations in the kallikrein 4 (KLK4), enamelysin (MMP20), and WDR72 genes have been identified as causing hypomaturation enamel defects in an autosomal-recessive hereditary pattern. In this report, 2 consanguineous families with a hypomaturation-type enamel defect were recruited, and mutational analysis was performed to determine the molecular genetic etiology of the disease. Whole exome sequencing and autozygosity mapping identified novel homozygous mutations in the KLK4 (c.620_621delCT, p.Ser207Trpfs*38) and MMP20 (c.1054G>A, p.Glu352Lys) genes. Further analysis on the effect of the mutations on the translation, secretion, and function of KLK4 and MMP20 revealed that mutant KLK4 was degraded intracellularly and became inactive while mutant MMP20 was expressed at a normal level but secreted only minimally with proteolytic function.

  9. Isolation and characterization of dental epithelial cells derived from amelogenesis imperfecta rat.

    PubMed

    Adiningrat, A; Tanimura, A; Miyoshi, K; Hagita, H; Yanuaryska, R D; Arinawati, D Y; Horiguchi, T; Noma, T

    2016-03-01

    Disruption of the third zinc finger domain of specificity protein 6 (SP6) presents an enamel-specific defect in a rat model of amelogenesis imperfecta (AMI rats). To understand the molecular basis of amelogenesis imperfecta caused by the Sp6 mutation, we established and characterized AMI-derived rat dental epithelial (ARE) cells. ARE cell clones were isolated from the mandibular incisors of AMI rats, and amelogenesis-related gene expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Localization of wild-type SP6 (SP6WT) and mutant-type SP6 (SP6AMI) was analyzed by immunocytochemistry. SP6 transcriptional activity was monitored by rho-associated protein kinase 1 (Rock1) promoter activity with its specific binding to the promoter region in dental (G5 and ARE) and non-dental (COS-7) epithelial cells. Isolated ARE cells were varied in morphology and gene expression. Both SP6WT and SP6AMI were mainly detected in nuclei. The promoter analysis revealed that SP6WT and SP6AMI enhanced Rock1 promoter activity in G5 cells but that enhancement by SP6AMI was weaker, whereas no enhancement was observed in the ARE and COS-7 cells, even though SP6WT and SP6AMI bound to the promoter in all instances. ARE cell clones can provide a useful in vitro model to study the mechanism of SP6-mediated amelogenesis imperfecta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta.

    PubMed

    Seymen, Figen; Kim, Youn Jung; Lee, Ye Ji; Kang, Jenny; Kim, Tak-Heun; Choi, Hwajung; Koruyucu, Mine; Kasimoglu, Yelda; Tuna, Elif Bahar; Gencay, Koray; Shin, Teo Jeon; Hyun, Hong-Keun; Kim, Young-Jae; Lee, Sang-Hoon; Lee, Zang Hee; Zhang, Hong; Hu, Jan C-C; Simmer, James P; Cho, Eui-Sic; Kim, Jung-Wook

    2016-11-03

    Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families. Families 1, 4, and 5 were affected by the homozygous ACPT mutation c.713C>T (p.Ser238Leu), family 2 by the homozygous ACPT mutation c.331C>T (p.Arg111Cys), family 3 by the homozygous ACPT mutation c.226C>T (p.Arg76Cys), and family 6 by the compound heterozygous ACPT mutations c.382G>C (p.Ala128Pro) and 397G>A (p.Glu133Lys). Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. Immunohistochemical analysis confirmed localization of ACPT in secretory-stage ameloblasts. The study results provide evidence for the crucial function of ACPT during amelogenesis.

  11. Amelogenesis imperfecta with multiple impacted teeth and skeletal class III malocclusion: complete mouth rehabilitation of a young adult.

    PubMed

    Patil, Pravinkumar G; Patil, Smita P

    2014-01-01

    Amelogenesis imperfecta is an autosomal dominant disorder. It is a group of hereditary diseases showing abnormal enamel density and crown malformation. This clinical report describes the oral rehabilitation of a young adult diagnosed with a variant of hypoplastic amelogenesis imperfecta with multiple impacted teeth and skeletal class III malocclusion. The treatment procedures of teeth extractions, endodontic treatment of remaining teeth followed by post and core restorations, esthetic and functional crown lengthening, and metal ceramic fixed dental prostheses were performed sequentially in the maxillary arch. The mandibular arch was restored with an overdenture. One-year follow-up revealed satisfactory results.

  12. Chairside treatment of amelogenesis imperfecta, including establishment of a new vertical dimension with resin nanoceramic and intraoral scanning.

    PubMed

    Zimmermann, Moritz; Koller, Christina; Hickel, Reinhard; Kühnisch, Jan

    2016-09-01

    Amelogenesis imperfecta is a hereditary disease affecting the structural development of tooth substance. This clinical report describes a 1-visit chairside treatment of an 8-year-old patient with amelogenesis imperfecta, using computer-aided design and computer-aided manufacturing (CAD-CAM) technology. Intraoral scanning was performed using the Cerec Omnicam. Thirteen resin nanoceramic crowns (Lava Ultimate) were fabricated chairside by using a Cerec MCXL milling unit and seated adhesively. The patient's treatment included establishing a new occlusal vertical dimension and new centric relationship. Reevaluation after 6 months showed a stable situation.

  13. Amelogenesis Imperfecta and Generalized Gingival Overgrowth Resembling Hereditary Gingival Fibromatosis in Siblings: A Case Report

    PubMed Central

    Yaprak, Emre; Subaşı, Meryem Gülce; Avunduk, Mustafa; Aykent, Filiz

    2012-01-01

    Amelogenesis imperfecta (AI) is a group of hereditary disorders primarily characterized by developmental abnormalities in the quantity and/or quality of enamel. There are some reports suggesting an association between AI and generalized gingival enlargement. This paper describes the clinical findings and oral management of two siblings presenting both AI and hereditary gingival fibromatosis (HGF) like generalized gingival enlargements. The treatment of gingival enlargements by periodontal flap surgery was successful in the management of the physiologic gingival form for both patients in the 3-year follow-up period. Prosthetic treatment was also satisfactory for the older patient both aesthetically and functionally. PMID:23091740

  14. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

    PubMed Central

    Gasse, Barbara; Prasad, Megana; Delgado, Sidney; Huckert, Mathilde; Kawczynski, Marzena; Garret-Bernardin, Annelyse; Lopez-Cazaux, Serena; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Stoetzel, Corinne; Bloch-Zupan, Agnès; Sire, Jean-Yves

    2017-01-01

    Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI. PMID:28659819

  15. Full mouth rehabilitation of a patient with amelogenesis imperfecta: a case report.

    PubMed

    Rajesh, P; Prasad, Maruthi; Haldal, Sindhu

    2014-07-01

    Amelogenesis imperfecta (AI) is a hereditary disorder expressing a group of conditions which cause developmental alterations in the structure of enamel. This disorder has an adverse impact on oral health and also hampers the quality of life of the individual causing physiologic problems. The treatment of such patients would not only upgrade their quality-of-life, but also improve their self-esteem. The correction of such severely worn out dentition may require extensive restorative treatment to achieve appropriate results. It is important to identify the factors that contribute to the excessive wear and loss of vertical dimension. The correction of the defects has to be done without violating the biologic or mechanical principles. Full mouth rehabilitation in such patients improves esthetics, function and comfort. The following case report presents a systematic approach in rehabilitating a case of AI hypoplastic type using full mouth metal reinforced porcelain restorations.

  16. Exclusion of known gene for enamel development in two Brazilian families with amelogenesis imperfecta.

    PubMed

    Santos, Maria C L G; Hart, P Suzanne; Ramaswami, Mukundhan; Kanno, Cláudia M; Hart, Thomas C; Line, Sergio R P

    2007-01-31

    Amelogenesis imperfecta (AI) is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DNA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI.

  17. Amelogenesis imperfecta: functional and esthetic restoration of a severely compromised dentition.

    PubMed

    Williams, W P; Becker, L H

    2000-06-01

    The treatment of patients with severe forms of amelogenesis imperfecta presents an interesting challenge to the dental team. A 16-year-old girl presented with a severely compromised occlusion and poor esthetics that had lowered her self-esteem. Preoperative investigations included the determination of completion of growth, an accurate diagnostic waxup, and an evaluation of clinical crown lengths. Periodontal full-flap surgery was planned to lengthen clinical crowns and create gingival harmony. This was to be followed by placement of 28 complete crowns to restore occlusal function and gain a pleasing esthetic result. All-porcelain crowns were placed from premolar to premolar in each arch (20 crowns), and porcelain-fused-to-metal crowns were placed on each molar tooth in each arch (8 crowns). The final treatment result provided this patient with a mutually protective occlusion and with esthetics that greatly enhanced her self-image.

  18. Full Mouth Rehabilitation of a Patient with Amelogenesis Imperfecta: A Case Report

    PubMed Central

    Rajesh, P; Prasad, Maruthi; Haldal, Sindhu

    2014-01-01

    Amelogenesis imperfecta (AI) is a hereditary disorder expressing a group of conditions which cause developmental alterations in the structure of enamel. This disorder has an adverse impact on oral health and also hampers the quality of life of the individual causing physiologic problems. The treatment of such patients would not only upgrade their quality-of-life, but also improve their self-esteem. The correction of such severely worn out dentition may require extensive restorative treatment to achieve appropriate results. It is important to identify the factors that contribute to the excessive wear and loss of vertical dimension. The correction of the defects has to be done without violating the biologic or mechanical principles. Full mouth rehabilitation in such patients improves esthetics, function and comfort. The following case report presents a systematic approach in rehabilitating a case of AI hypoplastic type using full mouth metal reinforced porcelain restorations. PMID:25214738

  19. Restoring function and esthetics in a patient with amelogenesis imperfecta: a case report.

    PubMed

    Sengun, Abdulkadir; Ozer, Füsun

    2002-03-01

    Amelogenesis imperfecta is a hereditary disorder that affects enamel on primary and permanent teeth. It is a rare dental disease but represents a major restorative challenge for the dentist. A 14-year-old boy presented with sensitive, discolored, and mutilated teeth and a decreased vertical dimension of occlusion. The aim of treatment was to reduce dental sensitivity, to restore esthetics, and to correct the vertical dimension of occlusion. To modify the occlusion, and to protect the dentin from chemical and thermal attacks, nickel-chrome onlays were placed on the molars. To improve the esthetics of the incisors and premolars, resin composite restorations were applied. The patient was regularly recalled during the postoperative period. Radiographic and clinical examinations 10 months posttreatment revealed no evidence of disorders associated with the restored teeth or their supporting structures.

  20. Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta.

    PubMed

    Polok, Bozena; Escher, Pascal; Ambresin, Aude; Chouery, Eliane; Bolay, Sylvain; Meunier, Isabelle; Nan, Francis; Hamel, Christian; Munier, Francis L; Thilo, Bernard; Mégarbané, André; Schorderet, Daniel F

    2009-02-01

    Cone-rod dystrophies are inherited dystrophies of the retina characterized by the accumulation of deposits mainly localized to the cone-rich macular region of the eye. Dystrophy can be limited to the retina or be part of a syndrome. Unlike nonsyndromic cone-rod dystrophies, syndromic cone-rod dystrophies are genetically heterogeneous with mutations in genes encoding structural, cell-adhesion, and transporter proteins. Using a genome-wide single-nucleotide polymorphism (SNP) haplotype analysis to fine map the locus and a gene-candidate approach, we identified homozygous mutations in the ancient conserved domain protein 4 gene (CNNM4) that either generate a truncated protein or occur in highly conserved regions of the protein. Given that CNNM4 is implicated in metal ion transport, cone-rod dystrophy and amelogenesis imperfecta may originate from abnormal ion homeostasis.

  1. Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

    PubMed

    Wang, Xin; Zhao, Yuming; Yang, Yuan; Qin, Man

    2015-01-01

    Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI). Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB), while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16) in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11) in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X) in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

  2. Rehabilitation of a patient with amelogenesis imperfecta using porcelain veneers and CAD/CAM polymer restorations: A clinical report.

    PubMed

    Saeidi Pour, Reza; Edelhoff, Daniel; Prandtner, Otto; Liebermann, Anja

    2015-01-01

    The complete dental rehabilitation of patients with a vertical dimension loss (VDL) caused by structural enamel deficits associated with amelogenesis imperfecta (AI) represents a difficult challenge for restorative teams. Accurate analysis and treatment planning that includes esthetic and functional evaluations and adequate material selection are important prerequisites for successful results. Long-term provisional restorations play an important role in exploring and elucidating the patients' esthetic demands and functional needs. Restorative treatment options can vary from requiring only oral hygiene instructions to extensive dental restorations that include composite fillings, ceramic veneers, metal-ceramic, or all-ceramic crowns. This case report describes a full-mouth rehabilitation of a patient with amelogenesis imperfecta including the case planning, bite replacement, preparation, and restoration setting steps with an experimental CAD/CAM polymer and porcelain veneers.

  3. Interdisciplinary treatment of a patient with amelogenesis imperfecta, a skeletal Class III relationship, and an anterior open bite.

    PubMed

    Marşan, Gülnaz; Aksu, Irem Sakarya; Kurt, Hanefi; Kuvat, Samet Vasfi; Cura, Nil

    2010-01-01

    An adult woman with amelogenesis imperfecta, a skeletal Class III relationship, long face syndrome, and a severe anterior open bite received interdisciplinary treatment (orthodontics, orthognathic surgery, and prosthodontics). Presurgical orthodontic treatment was followed by a maxillary posterior impaction with anterior advancement and a mandibular setback. After surgery, the patient received ceramic crowns. Function and esthetics were successfully re-established. © 2010 BY QUINTESSENCE PUBLISHING CO, INC.

  4. Impact of moderate and severe hypodontia and amelogenesis imperfecta on quality of life and self-esteem of adult patients.

    PubMed

    Hashem, Atef; Kelly, Alan; O'Connell, Brian; O'Sullivan, Michael

    2013-08-01

    The objective of this study was to investigate the impact of moderate and severe hypodontia and amelogenesis imperfecta on the quality of life and self-esteem of affected adult patients. Forty one adult patients (aged 18-45 years) with clinical and radiological diagnoses of moderate to severe hypodontia and twenty seven patients diagnosed with amelogenesis imperfecta were age and gender matched with a control group of patients attending for routine dental care. Subjects completed the Oral Health Impact Profile [OHIP-49] and Rosenberg Self Esteem Scale. A paired t-test was used to analyse data; the test alpha level was set at P ≤ 0.05. The results for hypodontia patients were significantly different from controls in six out of the seven OHIP-49 domains, the exception being the Handicap domain. Total scores were also significantly different between the two groups (P=0.003). Self-esteem was not significantly different between the two groups (P=0.98). For amelogenesis imperfecta patients the results were significantly different from control patients in four out of the seven domains of the OHIP-49 and also in the total scores (P=0.01). When self-esteem was investigated there was no significant differences between the two groups (P=0.92). Moderate to severe hypodontia and amelogenesis imperfecta have marked negative impacts on the Oral Health Related quality of life of this patient population relative to controls. However, self-esteem was not significantly affected. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta.

    PubMed

    Parry, David A; Smith, Claire E L; El-Sayed, Walid; Poulter, James A; Shore, Roger C; Logan, Clare V; Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu; Harada, Akihiro; Zhang, Hong; Koruyucu, Mine; Seymen, Figen; Hu, Jan C-C; Simmer, James P; Ahmed, Mushtaq; Jafri, Hussain; Johnson, Colin A; Inglehearn, Chris F; Mighell, Alan J

    2016-10-06

    Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the pH of the developing enamel matrix. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with amelogenesis imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion, and a missense variant) were predicted to result in loss of function. GPR68 encodes a proton-sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localization of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation.

  6. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta.

    PubMed

    Wang, Shih-Kai; Choi, Murim; Richardson, Amelia S; Reid, Bryan M; Lin, Brent P; Wang, Susan J; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C

    2014-04-15

    Integrins are cell-surface adhesion receptors that bind to extracellular matrices (ECM) and mediate cell-ECM interactions. Some integrins are known to play critical roles in dental enamel formation. We recruited two Hispanic families with generalized hypoplastic amelogenesis imperfecta (AI). Analysis of whole-exome sequences identified three integrin beta 6 (ITGB6) mutations responsible for their enamel malformations. The female proband of Family 1 was a compound heterozygote with an ITGB6 transition mutation in Exon 4 (g.4545G > A c.427G > A p.Ala143Thr) and an ITGB6 transversion mutation in Exon 6 (g.27415T > A c.825T > A p.His275Gln). The male proband of Family 2 was homozygous for an ITGB6 transition mutation in Exon 11 (g.73664C > T c.1846C > T p.Arg616*) and hemizygous for a transition mutation in Exon 6 of Nance-Horan Syndrome (NHS Xp22.13; g.355444T > C c.1697T > C p.Met566Thr). These are the first disease-causing ITGB6 mutations to be reported. Immunohistochemistry of mouse mandibular incisors localized ITGB6 to the distal membrane of differentiating ameloblasts and pre-ameloblasts, and then ITGB6 appeared to be internalized by secretory stage ameloblasts. ITGB6 expression was strongest in the maturation stage and its localization was associated with ameloblast modulation. Our findings demonstrate that early and late amelogenesis depend upon cell-matrix interactions. Our approach (from knockout mouse phenotype to human disease) demonstrates the power of mouse reverse genetics in mutational analysis of human genetic disorders and attests to the need for a careful dental phenotyping in large-scale knockout mouse projects.

  7. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta

    PubMed Central

    Wang, Shih-Kai; Choi, Murim; Richardson, Amelia S.; Reid, Bryan M.; Lin, Brent P.; Wang, Susan J.; Kim, Jung-Wook; Simmer, James P.; Hu, Jan C.-C.

    2014-01-01

    Integrins are cell-surface adhesion receptors that bind to extracellular matrices (ECM) and mediate cell–ECM interactions. Some integrins are known to play critical roles in dental enamel formation. We recruited two Hispanic families with generalized hypoplastic amelogenesis imperfecta (AI). Analysis of whole-exome sequences identified three integrin beta 6 (ITGB6) mutations responsible for their enamel malformations. The female proband of Family 1 was a compound heterozygote with an ITGB6 transition mutation in Exon 4 (g.4545G > A c.427G > A p.Ala143Thr) and an ITGB6 transversion mutation in Exon 6 (g.27415T > A c.825T > A p.His275Gln). The male proband of Family 2 was homozygous for an ITGB6 transition mutation in Exon 11 (g.73664C > T c.1846C > T p.Arg616*) and hemizygous for a transition mutation in Exon 6 of Nance–Horan Syndrome (NHS Xp22.13; g.355444T > C c.1697T > C p.Met566Thr). These are the first disease-causing ITGB6 mutations to be reported. Immunohistochemistry of mouse mandibular incisors localized ITGB6 to the distal membrane of differentiating ameloblasts and pre-ameloblasts, and then ITGB6 appeared to be internalized by secretory stage ameloblasts. ITGB6 expression was strongest in the maturation stage and its localization was associated with ameloblast modulation. Our findings demonstrate that early and late amelogenesis depend upon cell–matrix interactions. Our approach (from knockout mouse phenotype to human disease) demonstrates the power of mouse reverse genetics in mutational analysis of human genetic disorders and attests to the need for a careful dental phenotyping in large-scale knockout mouse projects. PMID:24305999

  8. The Use of Mouse Models to Investigate Shear Bond Strength in Amelogenesis Imperfecta

    PubMed Central

    Pugach, M.K.; Ozer, F.; Li, Y.; Sheth, K.; Beasley, R.; Resnick, A.; Daneshmehr, L.; Kulkarni, A.B.; Bartlett, J.D.; Gibson, C.W.; Lindemeyer, R.G.

    2011-01-01

    Patients with amelogenesis imperfecta (AI) have defective enamel; therefore, bonded restorations of patients with AI have variable success rates. To distinguish which cases of AI may have good clinical outcomes with bonded materials, we evaluated etching characteristics and bond strength of enamel in mouse models, comparing wild-type (WT) with those having mutations in amelogenin (Amelx) and matrix metalloproteinase-20 (Mmp20), which mimic 2 forms of human AI. Etched enamel surfaces were compared for roughness by scanning electron microscopy (SEM) images. Bonding was compared through shear bond strength (SBS) studies with 2 different systems (etch-and-rinse and self-etch). Etched enamel surfaces of incisors from Amelx knock-out (AmelxKO) mice appeared randomly organized and non-uniform compared with WT. Etching of Mmp20KO surfaces left little enamel, and the etching pattern was indistinguishable from unetched surfaces. SBS results were significantly different when AmelxKO and Mmp20KO enamel surfaces were compared. A significant increase in SBS was measured for all samples when the self-etch system was compared with the etch-and-rinse system. We have developed a novel system for testing shear bond strength of mouse incisors with AI variants, and analysis of these data may have important clinical implications for the treatment of patients with AI. PMID:21917602

  9. Multidisciplinary Approach for Restoring Function and Esthetics in a Patient with Amelogenesis Imperfecta: A Clinical Report

    PubMed Central

    Kamble, Vaibhav D; Parkhedkar, Rambhau D

    2013-01-01

    Amelogenesis Imperfecta (AI) is a genetically determined and enamel mineralization defect reported, depicted as “Hereditary brown teeth.” AI is characterized as a clinical entity and its clinical manifestations, histological appearance, and genetic pattern are characterized by their heterogeneity. The need for prosthodontic management of this group of patients varies. Some patients need oral hygiene instructions only, whereas others need extensive dental treatment that includes composite restorations, metal ceramic crowns, all ceramic crowns, porcelain veneers. A 20-year-old male patient presented with sensitive, discoloured, and mutilated teeth, with a decreased vertical dimension of occlusion. The 4-year recall examination revealed no pathology associated with the full mouth rehabilitation, and the patient’s aesthetic and functional expectations were satisfied. The rehabilitation included all-ceramic crowns on anterior teeth and metal-ceramic crowns on posterior teeth following endodontic treatment and a crown-lengthening procedure for eliminating tooth sensitivity, improving the aesthetics and occlusion, and for restoring function. PMID:24551735

  10. Amelogenesis Imperfecta: Rehabilitation and Brainstorming on the Treatment Outcome after the First Year

    PubMed Central

    İzgi, Ayça Deniz; Kale, Ediz; Niğiz, Remzi

    2015-01-01

    Amelogenesis imperfecta (AI) affects enamel on primary and permanent dentition. This hereditary disorder is characterized by loss of enamel, poor esthetics, and hypersensitivity. Functional and cosmetic rehabilitation is challenging with variety of treatment options. This report presents the treatment of an AI patient using conventional fixed dentures and discusses issues related to posttreatment complications and prosthetic treatment outcome after 1 year of follow-up. A 19-year-old male AI patient with impaired self-esteem presented with hypersensitive, discolored, and mutilated teeth. Clinical examination revealed compromised occlusion and anterior open-bite. After hygiene maintenance full-coverage porcelain-fused-to-metal fixed restorations were indicated and applied. At the end of the treatment acceptable functional and esthetic results could be achieved. However, nearly a year after treatment a gingival inflammation in the esthetic zone complicated the outcome. Insufficient oral hygiene was to be blamed. Tooth sensitivity present from early childhood in these patients may prevent oral hygiene from becoming a habit. The relaxation due to relieve of hypersensitivity after treatment makes oral hygiene learning difficult. Continuous oral hygiene maintenance motivation may be crucial for the success of the treatment of AI patients. Treatment of AI patients should be carefully planned and an acceptable risk-benefit balance should be established. PMID:26783475

  11. Deletion of amelotin exons 3–6 is associated with amelogenesis imperfecta

    PubMed Central

    Smith, Claire E.L.; Murillo, Gina; Brookes, Steven J.; Poulter, James A.; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2016-01-01

    Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective dental enamel formation. Amelotin (AMTN) is a secreted protein thought to act as a promoter of matrix mineralization in the final stage of enamel development, and is strongly expressed, almost exclusively, in maturation stage ameloblasts. Amtn overexpression and Amtn knockout mouse models have defective enamel with no other associated phenotypes, highlighting AMTN as an excellent candidate gene for human AI. However, no AMTN mutations have yet been associated with human AI. Using whole exome sequencing, we identified an 8,678 bp heterozygous genomic deletion encompassing exons 3-6 of AMTN in a Costa Rican family segregating dominant hypomineralised AI. The deletion corresponds to an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 residues. Exfoliated primary teeth from an affected family member had enamel that was of a lower mineral density compared to control enamel and exhibited structural defects at least some of which appeared to be associated with organic material as evidenced using elemental analysis. This study demonstrates for the first time that AMTN mutations cause non-syndromic human AI and explores the human phenotype, comparing it with that of mice with disrupted Amtn function. PMID:27412008

  12. Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate.

    PubMed

    Brookes, Steven J; Barron, Martin J; Boot-Handford, Ray; Kirkham, Jennifer; Dixon, Michael J

    2014-05-01

    Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease.

  13. Simple recessive mutation in ENAM is associated with amelogenesis imperfecta in Italian Greyhounds.

    PubMed

    Gandolfi, Barbara; Liu, Hongwei; Griffioen, Layle; Pedersen, Niels C

    2013-08-01

    We report a familial enamel hypoplasia in Italian Greyhounds resembling non-syndromic autosomal recessive amelogenesis imperfecta (AI) of humans. The condition uniformly affects deciduous and permanent teeth and is manifested by enamel roughening/thinning and brownish mottling. Affected teeth are often small and pointed with increased gaps. However, basic tooth structure is usually maintained throughout life, and fractures and dental cavities are not a serious problem as in humans. No tissues or organs other than teeth were affected by this mutation, and there was no relationship between enamel hypoplasia and either autoimmunity or periodontal disease, which also are prevalent in the breed. The enamel hypoplasia was associated with a 5-bp deletion in exon 10 of the enamelin (ENAM) gene. The prevalence of the enamel defect in Italian Greyhounds was 14%, and 30% of dogs with normal teeth were carriers. Genome analyses suggest that the trait is under inadvertent positive selection. Based on the deletion detected in the ENAM gene, a genetic test was developed for identifying mutation carriers, which would enable breeders to manage the trait.

  14. A Randomized Controlled Trial of Crown Therapy in Young Individuals with Amelogenesis Imperfecta.

    PubMed

    Pousette Lundgren, G; Morling Vestlund, G I; Trulsson, M; Dahllöf, G

    2015-08-01

    Amelogenesis imperfecta (AI) is a rare, genetically determined defect in enamel mineralization. Existing treatment recommendations suggest resin-composite restorations until adulthood, although such restorations have a limited longevity. New crown materials allow for minimal preparation techniques. The aim of this study was to compare the quality and longevity of 2 crown types-Procera and IPS e.max Press-in adolescents and young adults with AI. A secondary aim was to document adverse events. We included 27 patients (11 to 22 y of age) with AI in need of crown therapy in a randomized controlled trial using a split-mouth technique. After placing 119 Procera crowns and 108 IPS e.max Press crowns following randomization, we recorded longevity, quality, adverse events, and tooth sensitivity. After 2 y, 97% of the crowns in both crown groups had excellent or acceptable quality. We found no significant differences in quality between Procera and IPS e.max Press crowns. Tooth sensitivity was significantly reduced after crown therapy (P < 0.001). Endodontic complications occurred in 3% of crowns. The results show that it is possible to perform crown therapy with excellent results and without severe complications in young patients with AI. The study is registered at http://www.controlled-trials.com (ISRCTN70438627).

  15. A new locus for autosomal dominant amelogenesis imperfecta on chromosome 8q24.3.

    PubMed

    Mendoza, Gustavo; Pemberton, Trevor J; Lee, Kwanghyuk; Scarel-Caminaga, Raquel; Mehrian-Shai, Ruty; Gonzalez-Quevedo, Catalina; Ninis, Vasiliki; Hartiala, Jaana; Allayee, Hooman; Snead, Malcolm L; Leal, Suzanne M; Line, Sergio R P; Patel, Pragna I

    2007-01-01

    Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically diverse forms of defective tooth enamel development. AI has been reported to exhibit a variety of inheritance patterns, and several loci have been identified that are associated with AI. We have performed a genome-wide scan in a large Brazilian family segregating an autosomal dominant form of AI and mapped a novel locus to 8q24.3. A maximum multipoint LOD score of 7.5 was obtained at marker D8S2334 (146,101,309 bp). The disease locus lies in a 1.9 cM (2.1 Mb) region according to the Rutgers Combined Linkage-Physical map, between a VNTR marker (at 143,988,705 bp) and the telomere (146,274,826 bp). Ten candidate genes were identified based on gene ontology and microarray-facilitated gene selection using the expression of murine orthologues in dental tissue, and examined for the presence of a mutation. However, no causative mutation was identified.

  16. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    PubMed Central

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development. PMID:25705526

  17. Amelogenesis Imperfecta: Rehabilitation and Brainstorming on the Treatment Outcome after the First Year.

    PubMed

    İzgi, Ayça Deniz; Kale, Ediz; Niğiz, Remzi

    2015-01-01

    Amelogenesis imperfecta (AI) affects enamel on primary and permanent dentition. This hereditary disorder is characterized by loss of enamel, poor esthetics, and hypersensitivity. Functional and cosmetic rehabilitation is challenging with variety of treatment options. This report presents the treatment of an AI patient using conventional fixed dentures and discusses issues related to posttreatment complications and prosthetic treatment outcome after 1 year of follow-up. A 19-year-old male AI patient with impaired self-esteem presented with hypersensitive, discolored, and mutilated teeth. Clinical examination revealed compromised occlusion and anterior open-bite. After hygiene maintenance full-coverage porcelain-fused-to-metal fixed restorations were indicated and applied. At the end of the treatment acceptable functional and esthetic results could be achieved. However, nearly a year after treatment a gingival inflammation in the esthetic zone complicated the outcome. Insufficient oral hygiene was to be blamed. Tooth sensitivity present from early childhood in these patients may prevent oral hygiene from becoming a habit. The relaxation due to relieve of hypersensitivity after treatment makes oral hygiene learning difficult. Continuous oral hygiene maintenance motivation may be crucial for the success of the treatment of AI patients. Treatment of AI patients should be carefully planned and an acceptable risk-benefit balance should be established.

  18. Management of Amelogenesis Imperfecta: A 15-Year Case History of Two Siblings.

    PubMed

    Dursun, E; Savard, E; Vargas, C; Loison-Robert, L; Cherifi, H; Bdeoui, F; Landru, M-M

    Amelogenesis imperfecta (AI) is a heterogenous genetic disorder that interferes with normal enamel formation in the absence of systemic disorders. The patients' main concerns are caries susceptibility, poor esthetics, and generalized sensitivity. There is a broad clinical spectrum, from discolorations to consequent enamel alterations. This case report describes the 15-year case study and the full-mouth rehabilitation of two siblings affected by a hypocalcified AI. Clinical Considerations: In these two patients, conservative care with stainless steel crowns and direct composite restorations was undertaken to restore function and esthetics and to reduce sensitivities in primary and mixed dentitions. The difficulties in monitoring resulted in severe infectious complications (dental abscess with cutaneous fistula), important dental defects, and loss of spaces with subsequent malocclusion. In the young adult dentition, they were treated by extractions, root canal therapies, and new restorations: stainless steel crowns for permanent molars, direct composite restorations (with strip crowns) for incisors and maxillary canines (to improve the crown morphology as well as to mask the discolorations and the malpositions), and adjusted composite crown molds using a thermoforming procedure for premolars and the mandibular canines. The main difficulties were rapid tooth surface loss, bonding to atypical enamel, developing dentition, long-term follow-up. Restoring function and esthetics in AI-affected patients is a challenge from primary to adult dentition. Early corrections are essential to avoid dental damage and for psychological benefits. This clinical report highlights the adhesive rehabilitation for anterior and premolar areas and the difficulty of patient follow-up.

  19. Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate

    PubMed Central

    Brookes, Steven J.; Barron, Martin J.; Boot-Handford, Ray; Kirkham, Jennifer; Dixon, Michael J.

    2014-01-01

    Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease. PMID:24362885

  20. Variation in dental and skeletal open bite malocclusion in humans with amelogenesis imperfecta.

    PubMed

    Ravassipour, Darren B; Powell, Cynthia M; Phillips, Ceib L; Hart, P Suzanne; Hart, Thomas C; Boyd, Courtney; Wright, J Tim

    2005-07-01

    The amelogenesis imperfectas (AI) are a diverse group of genetic disorders primarily affecting the quality and or quantity of enamel, however, affected individuals often have an open bite malocclusion. Three main AI types are recognized based on the perceived developmental mechanisms involved and the enamel phenotype. The purpose of this investigation was to evaluate the association of the AI enamel defect with craniofacial features characteristic of an open bite malocclusion. The sample consisted of 54 AI affected and 34 unaffected family members from 18 different kindreds. Lateral cephalograms were digitized and measurements evaluated for vertical plane alterations using Z-scores. Forty two percent of AI affected individuals and 12% of unaffected family members had dental or skeletal open bite malocclusions. Skeletal open bite malocclusion was variably expressed in AI affected individuals. The enamel phenotype severity did not necessarily correspond with the presence or severity of open bite malocclussion. Open bite malocclusion occurred in individuals with AI caused by mutations in the AMELX and ENAM genes even though these genes are considered to be predominantly or exclusively expressed in teeth. Affected AI individuals with cephalometric values meeting our criteria of skeletal open bite malocclusion were observed in all three major AI types. The pathophysiological relationship between AI associated enamel defects and open bite malocclusion remains unknown.

  1. Phenotype-genotype correlations in mouse models of amelogenesis imperfecta caused by Amelx and Enam mutations.

    PubMed

    Coxon, Thomas Liam; Brook, Alan Henry; Barron, Martin John; Smith, Richard Nigel

    2012-01-01

    Mutations in human and in mouse orthologous genes Amelx and Enam result in a diverse range of enamel defects. In this study we aimed to investigate the phenotype-genotype correlation between the mutants and the wild-type controls in mouse models of amelogenesis imperfecta using novel measurement approaches. Ten hemi-mandibles and incisors were dissected from each group of Amelx(WT), Amelx(X/Y64H), Amelx(Y/Y64H), Amelx(Y64H/Y64H), and Enam(WT), Enam(Rgsc395) heterozygous and Enam(Rgsc395) homozygous mice. Their macro-morphology, colour and micro-topography were assessed using bespoke 2D and 3D image analysis systems and customized colour and whiteness algorithms. The novel methods identified significant differences (p ≤ 0.05) between the Amelx groups for mandible and incisor size and enamel colour and between the Enam groups for incisor size and enamel colour. The Amelx(WT) mice had the largest mandibles and incisors, followed in descending order of size by the Amelx(X/Y64H), Amelx(Y/Y64H) and Amelx(Y64H/Y64H) mice. Within the Enam groups the Enam(WT) incisors were largest and the Enam(Rgsc395) heterozygous mice were smallest. The effect on tooth morphology was also reflected by the severity of the enamel defects in the colour and whiteness assessment. Amelogenin affected mandible morphology and incisor enamel formation, while enamelin only affected incisors, supporting the multifunctional role of amelogenin. The enamelin mutation was associated with earlier forming enamel defects. The study supported the critical involvement of amelogenin and enamelin in enamel mineralization.

  2. Amelogenesis imperfecta and other biomineralization defects in Fam20a and Fam20c null mice.

    PubMed

    Vogel, P; Hansen, G M; Read, R W; Vance, R B; Thiel, M; Liu, J; Wronski, T J; Smith, D D; Jeter-Jones, S; Brommage, R

    2012-11-01

    The FAM20 family of secreted proteins consists of three members (FAM20A, FAM20B, and FAM20C) recently linked to developmental disorders suggesting roles for FAM20 proteins in modulating biomineralization processes. The authors report here findings in knockout mice having null mutations affecting each of the three FAM20 proteins. Both Fam20a and Fam20c null mice survived to adulthood and showed biomineralization defects. Fam20b (-/-) embryos showed severe stunting and increased mortality at E13.5, although early lethality precluded detailed investigations. Physiologic calcification or biomineralization of extracellular matrices is a normal process in the development and functioning of various tissues (eg, bones and teeth). The lesions that developed in teeth, bones, or blood vessels after functional deletion of either Fam20a or Fam20c support a significant role for their encoded proteins in modulating biomineralization processes. Severe amelogenesis imperfecta (AI) was present in both Fam20a and Fam20c null mice. In addition, Fam20a (-/-) mice developed disseminated calcifications of muscular arteries and intrapulmonary calcifications, similar to those of fetuin-A deficient mice, although they were normocalcemic and normophosphatemic, with normal dentin and bone. Fam20a gene expression was detected in ameloblasts, odontoblasts, and the parathyroid gland, with local and systemic effects suggesting both local and/or systemic effects for FAM20A. In contrast, Fam20c (-/-) mice lacked ectopic calcifications but were severely hypophosphatemic and developed notable lesions in both dentin and bone to accompany the AI. The bone and dentin lesions, plus the marked hypophosphatemia and elevated serum alkaline phosphatase and FGF23 levels, are indicative of autosomal recessive hypophosphatemic rickets/osteomalacia in Fam20c (-/-) mice.

  3. Perturbed Amelogenin Secondary Structure Leads to Uncontrolled Aggregation in Amelogenesis Imperfecta Mutant Proteins*

    PubMed Central

    Lakshminarayanan, Rajamani; Bromley, Keith M.; Lei, Ya-Ping; Snead, Malcolm L.; Moradian-Oldak, Janet

    2010-01-01

    Mutations in amelogenin sequence result in defective enamel, and the diverse group of genetically altered conditions is collectively known as amelogenesis imperfecta (AI). Despite numerous studies, the detailed molecular mechanism of defective enamel formation is still unknown. In this study, we have examined the biophysical properties of a recombinant murine amelogenin (rM180) and two point mutations identified from human DNA sequences in two cases of AI (T21I and P41T). At pH 5.8 and 25 °C, wild type (WT) rM180 and mutant P41T existed as monomers, and mutant T21I formed lower order oligomers. CD, dynamic light scattering, and fluorescence studies indicated that rM180 and P41T can be classified as a premolten globule-like subclass protein at 25 °C. Thermal denaturation and refolding monitored by CD ellipticity at 224 nm indicated the presence of a strong hysteresis in mutants compared with WT. Variable temperature tryptophan fluorescence and dynamic light scattering studies showed that WT transformed to a partially folded conformation upon heating and remained stable. The partially folded conformation formed by P41T, however, readily converted into a heterogeneous population of aggregates. T21I existed in an oligomeric state at room temperature and, upon heating, rapidly formed large aggregates over a very narrow temperature range. Thermal denaturation and refolding studies indicated that the mutants are less stable and exhibit poor refolding ability compared with WT rM180. Our results suggest that alterations in self-assembly of amelogenin are a consequence of destabilization of the intrinsic disorder. Therefore, we propose that, like a number of other human diseases, AI appears to be due to the destabilization of the secondary structure as a result of amelogenin mutations. PMID:20929860

  4. Amelogenesis Imperfecta in Two Families with Defined AMELX Deletions in ARHGAP6

    PubMed Central

    Hu, Jan C.-C.; Chan, Hui-Chen; Simmer, Stephen G.; Seymen, Figen; Richardson, Amelia S.; Hu, Yuanyuan; Milkovich, Rachel N.; Estrella, Ninna M. R. P.; Yildirim, Mine; Bayram, Merve; Chen, Chiung-Fen; Simmer, James P.

    2012-01-01

    Amelogenesis imperfecta (AI) is a group of inherited conditions featuring isolated enamel malformations. About 5% of AI cases show an X-linked pattern of inheritance, which are caused by mutations in AMELX. In humans there are two, non-allelic amelogenin genes: AMELX (Xp22.3) and AMELY (Yp11.2). About 90% of amelogenin expression is from AMELX, which is nested within intron 1 of the gene encoding Rho GTPase activating protein 6 (ARHGAP6). We recruited two AI families and determined that their disease-causing mutations were partial deletions in ARHGAP6 that completely deleted AMELX. Affected males in both families had a distinctive enamel phenotype resembling “snow-capped” teeth. The 96,240 bp deletion in family 1 was confined to intron 1 of ARHGAP6 (g.302534_398773del96240), but removed alternative ARHGAP6 promoters 1c and 1d. Analyses of developing teeth in mice showed that ARHGAP6 is not expressed from these promoters in ameloblasts. The 52,654 bp deletion in family 2 (g.363924_416577del52654insA) removed ARHGAP6 promoter 1d and exon 2, precluding normal expression of ARHGAP6. The male proband of family 2 had slightly thinner enamel with greater surface roughness, but exhibited the same pattern of enamel malformations characteristic of males in family 1, which themselves showed minor variations in their enamel phenotypes. We conclude that the enamel defects in both families were caused by amelogenin insufficiency, that deletion of AMELX results in males with a characteristic snow-capped enamel phenotype, and failed ARHGAP6 expression did not appreciably alter the severity of enamel defects when AMELX was absent. PMID:23251683

  5. Cone-rod dystrophy and amelogenesis imperfecta (Jalili syndrome): phenotypes and environs.

    PubMed

    Jalili, I K

    2010-11-01

    To report a new phenotype with additional data on the oculo-dental syndrome of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) caused by mutations on CNNM4, a metal transporter, with linkage at achromatopsia locus 2q11 (Jalili syndrome). Three siblings aged 5, 6, and 10 years from a six-generation Arab family in Gaza City underwent full systemic, ophthalmic, and dental examinations, investigations and detailed genealogy. Subjects presented at early childhood with visual impairment and abnormal dentition together with photophobia and fine nystagmus increasing under photopic conditions, in the presence of normal fundi. Electrophysiologically, photopic flicker responses were impaired; scotopic responses were extinguished at the age of 10 years. Anterior open bite accompanied AI in all siblings. The syndrome formed 83% of CRD cases in the Gaza Strip, which has a prevalence of 1 : 10,000. On the basis of clinical features and electrophysiology, two phenotypes exist: an infancy onset form with progressive macular lesion and an early childhood onset form with normal fundi. More prevalent than previously thought, Jalili syndrome presents a model of the effect of different mutations of the same genetic defect, observations of the same phenotype at different stages of the natural history of the disease, and the influence of epigenetic and tissue-specific factors as causes of phenotypic variability. The paper calls for action to tackle consanguinity in endogamous communities, addresses the possible role of high fluoride levels in groundwater as a trigger for genetic mutations, and the use of red-tinted filter in cone disorders.

  6. Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression.

    PubMed

    Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

    2016-05-05

    Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2(f/f);Bmp4(f/f)ameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling.

  7. Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression

    PubMed Central

    Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H.; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

    2016-01-01

    Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2f/f;Bmp4f/fameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling. PMID:27146352

  8. Esthetic treatment of a diffuse amelogenesis imperfecta using pressed lithium disilicate and feldspathic ceramic restorations: 5-year follow up.

    PubMed

    Savi, Andrea; Turillazzi, Oliviero; Crescini, Aldo; Manfredi, Maddalena

    2014-01-01

    The treatment of a diffuse and severe case of amelogenesis imperfecta represents a challenge for the dental team and in particular for the dentist who perform the prosthetic restorations. The enamel alterations, which are characteristic of the disease, determine different problems that need to be carefully planned and solved before the beginning of the treatment, with particular regard to the materials used to perform the restorations. In order to create the best conditions to perform the prosthetic restoration, the treatment plan should be multidisciplinary. In addition, the young age of the patients usually affected by the disease imposes a very conservative and cautious approach. The main goals of the therapy are represented by the need to protect the occlusal dental surfaces from the abrasion and provide a satisfactory esthetic result. In particular, dental abrasions if not treated may determine the loss of the vertical dimension as well as a diffuse and marked dentinal hypersensitivity. A correct treatment plan and the use of the new adhesive ceramic materials made it possible to obtain good results both from a functional and esthetic point of view with a much more conservative approach compared with the traditional one. This clinical report describes the prosthetic rehabilitation of an adult female patient with a diffuse amelogenesis imperfecta using feldspathic ceramics for the esthetic regions and monolithic lithium disilicate material for the posterior areas. © 2014 Wiley Periodicals, Inc.

  9. Amelogenesis imperfecta associated with dental follicular-like hamartomas and generalised gingival enlargement.

    PubMed

    O'Connell, S; Davies, J; Smallridge, J; Vaidyanathan, M

    2014-10-01

    Amelogenesis imperfecta (AI) is an inherited disorder characterised by generalised defects of dental enamel, but has been associated with other dental and medical conditions. It affects the appearance and structure of teeth, both in the primary and secondary dentition. AI in the presence of dental follicular hamartomas and gingival hyperplasia is rare and the management presents several challenges to the clinician. This article describes a case of a girl who presented to the paediatric department at the age of 7 years complaining of discomfort when eating and that she was unhappy with the appearance of her anterior teeth. The patient was born in the UK but she and her family were African and of Kenyan origin. She was otherwise fit and well. Investigations included clinical, radiographic and pathological examination as well as cone beam computed tomography imaging and X-ray Microtomography of extracted primary teeth. A diagnosis of AI in the presence of dental follicular hamartomas and generalised gingival hyperplasia was made, which had resulted in the delayed eruption of permanent teeth and an associated anterior open bite. There was no family history of dental defects. Initial treatment included preventative advice and the application of preformed metal crowns on all primary molars. Extraction of all remaining primary incisors was carried out followed by gingivectomy around the maxillary permanent incisors, mandibular central incisors and maxillary left second primary molar. Composite resin reconstruction of all permanent incisors and mandibular primary canines was complicated by the poor quality of enamel. Orthodontic extrusion of the anterior incisors was carried out to improve surface area for bonding with some success. A multidisciplinary team managed this case and decided that no surgical intervention of the dental follicular hamartomas was warranted. The patient coped well with treatment and attended for regular review over an 8-year period. She was

  10. Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta.

    PubMed

    Parry, David A; Brookes, Steven J; Logan, Clare V; Poulter, James A; El-Sayed, Walid; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Sayed, Jihad; Raïf, El Mostafa; Shore, Roger C; Dashash, Mayssoon; Barron, Martin; Morgan, Joanne E; Carr, Ian M; Taylor, Graham R; Johnson, Colin A; Aldred, Michael J; Dixon, Michael J; Wright, J Tim; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2012-09-07

    Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.

  11. Whole-Exome sequencing identifies FAM20A mutations as a cause of amelogenesis imperfecta and gingival hyperplasia syndrome.

    PubMed

    O'Sullivan, James; Bitu, Carolina C; Daly, Sarah B; Urquhart, Jill E; Barron, Martin J; Bhaskar, Sanjeev S; Martelli-Júnior, Hercilio; dos Santos Neto, Pedro Eleuterio; Mansilla, Maria A; Murray, Jeffrey C; Coletta, Ricardo D; Black, Graeme C M; Dixon, Michael J

    2011-05-13

    Amelogenesis imperfecta (AI) describes a clinically and genetically heterogeneous group of disorders of biomineralization resulting from failure of normal enamel formation. AI is found as an isolated entity or as part of a syndrome, and an autosomal-recessive syndrome associating AI and gingival hyperplasia was recently reported. Using whole-exome sequencing, we identified a homozygous nonsense mutation in exon 2 of FAM20A that was not present in the Single Nucleotide Polymorphism database (dbSNP), the 1000 Genomes database, or the Centre d'Etude du Polymorphisme Humain (CEPH) Diversity Panel. Expression analyses indicated that Fam20a is expressed in ameloblasts and gingivae, providing biological plausibility for mutations in FAM20A underlying the pathogenesis of this syndrome.

  12. Interdisciplinary Full Mouth Rehabilitation of a Patient with Amelogenesis Imperfecta: A Case Report with 8 Years Follow-up

    PubMed Central

    Sreedevi, S; Sanjeev, R; Ephraim, Rena; Joseph, Mathai

    2014-01-01

    This case report deals with the interdisciplinary approach of a 28-year-old lady with Amelogenesis imperfecta of the hypoplastic kind. The patient came with a chief illness of worn out teeth, unsatisfactory esthetics and severe sensitivity of teeth. Her family history revealed a related situation in her father’s brother and her sister. On clinical assessment, the crowns of all teeth were worn out. The plan of the treatment was to protect as much tooth structure, restore the vertical dimension, and improve esthetics and masticatory function. The treatment procedures involved prosthodontic, endodontic, and periodontic interventions. After recording the vertical height, endodontic treatment and crown lengthening were performed with respect to the lower anteriors. The lost vertical height was regained in stages by insertion of full coverage crowns for all the teeth. The patient’s esthetic and functional needs were met with systematic and sequential interdisciplinary treatment approach. PMID:25628493

  13. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta.

    PubMed

    Huckert, Mathilde; Stoetzel, Corinne; Morkmued, Supawich; Laugel-Haushalter, Virginie; Geoffroy, Véronique; Muller, Jean; Clauss, François; Prasad, Megana K; Obry, Frédéric; Raymond, Jean Louis; Switala, Marzena; Alembik, Yves; Soskin, Sylvie; Mathieu, Eric; Hemmerlé, Joseph; Weickert, Jean-Luc; Dabovic, Branka Brukner; Rifkin, Daniel B; Dheedene, Annelies; Boudin, Eveline; Caluseriu, Oana; Cholette, Marie-Claude; Mcleod, Ross; Antequera, Reynaldo; Gellé, Marie-Paule; Coeuriot, Jean-Louis; Jacquelin, Louis-Frédéric; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Van Hul, Wim; Bertola, Debora; Dollé, Pascal; Verloes, Alain; Mortier, Geert; Dollfus, Hélène; Bloch-Zupan, Agnès

    2015-06-01

    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder.

  14. Interdisciplinary Full Mouth Rehabilitation of a Patient with Amelogenesis Imperfecta: A Case Report with 8 Years Follow-up.

    PubMed

    Sreedevi, S; Sanjeev, R; Ephraim, Rena; Joseph, Mathai

    2014-01-01

    This case report deals with the interdisciplinary approach of a 28-year-old lady with Amelogenesis imperfecta of the hypoplastic kind. The patient came with a chief illness of worn out teeth, unsatisfactory esthetics and severe sensitivity of teeth. Her family history revealed a related situation in her father's brother and her sister. On clinical assessment, the crowns of all teeth were worn out. The plan of the treatment was to protect as much tooth structure, restore the vertical dimension, and improve esthetics and masticatory function. The treatment procedures involved prosthodontic, endodontic, and periodontic interventions. After recording the vertical height, endodontic treatment and crown lengthening were performed with respect to the lower anteriors. The lost vertical height was regained in stages by insertion of full coverage crowns for all the teeth. The patient's esthetic and functional needs were met with systematic and sequential interdisciplinary treatment approach.

  15. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta

    PubMed Central

    Huckert, Mathilde; Stoetzel, Corinne; Morkmued, Supawich; Laugel-Haushalter, Virginie; Geoffroy, Véronique; Muller, Jean; Clauss, François; Prasad, Megana K.; Obry, Frédéric; Raymond, Jean Louis; Switala, Marzena; Alembik, Yves; Soskin, Sylvie; Mathieu, Eric; Hemmerlé, Joseph; Weickert, Jean-Luc; Dabovic, Branka Brukner; Rifkin, Daniel B.; Dheedene, Annelies; Boudin, Eveline; Caluseriu, Oana; Cholette, Marie-Claude; Mcleod, Ross; Antequera, Reynaldo; Gellé, Marie-Paule; Coeuriot, Jean-Louis; Jacquelin, Louis-Frédéric; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Van Hul, Wim; Bertola, Debora; Dollé, Pascal; Verloes, Alain; Mortier, Geert; Dollfus, Hélène; Bloch-Zupan, Agnès

    2015-01-01

    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder. PMID:25669657

  16. A large X-chromosomal deletion is associated with microphthalmia with linear skin defects (MLS) and amelogenesis imperfecta (XAI).

    PubMed

    Hobson, Grace M; Gibson, Carolyn W; Aragon, Melissa; Yuan, Zhi-an; Davis-Williams, Angelique; Banser, Linda; Kirkham, Jennifer; Brook, Alan H

    2009-08-01

    A female patient is described with clinical symptoms of both microphthalmia with linear skin defects (MLS or MIDAS) and dental enamel defects, having an appearance compatible with X-linked amelogenesis imperfecta (XAI). Genomic DNA was purified from the patient's blood and semiquantitative multiplex PCR revealed a deletion encompassing the amelogenin gene (AMELX). Because MLS is also localized to Xp22, genomic DNA was subjected to array comparative genomic hybridization, and a large heterozygous deletion was identified. Histopathology of one primary and one permanent molar tooth showed abnormalities in the dental enamel layer, and a third tooth had unusually high microhardness measurements, possibly due to its ultrastructural anomalies as seen by scanning electron microscopy. This is the first report of a patient with both of these rare conditions, and the first description of the phenotype resulting from a deletion encompassing the entire AMELX gene. More than 50 additional genes were monosomic in this patient. 2009 Wiley-Liss, Inc.

  17. Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth

    PubMed Central

    Li, Li-Li; Liu, Pei-Hong; Xie, Xiao-Hua; Ma, Su; Liu, Chao; Chen, Li; Qin, Chun-Lin

    2016-01-01

    FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20Aflox/flox mice, we created K14-Cre;Fam20Aflox/flox (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues. PMID:27281036

  18. Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth.

    PubMed

    Li, Li-Li; Liu, Pei-Hong; Xie, Xiao-Hua; Ma, Su; Liu, Chao; Chen, Li; Qin, Chun-Lin

    2016-06-30

    FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20A(flox/flox) mice, we created K14-Cre;Fam20A(flox/flox) (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.

  19. Mutations in CNNM4 Cause Jalili Syndrome, Consisting of Autosomal-Recessive Cone-Rod Dystrophy and Amelogenesis Imperfecta

    PubMed Central

    Parry, David A.; Mighell, Alan J.; El-Sayed, Walid; Shore, Roger C.; Jalili, Ismail K.; Dollfus, Hélène; Bloch-Zupan, Agnes; Carlos, Roman; Carr, Ian M.; Downey, Louise M.; Blain, Katharine M.; Mansfield, David C.; Shahrabi, Mehdi; Heidari, Mansour; Aref, Parissa; Abbasi, Mohsen; Michaelides, Michel; Moore, Anthony T.; Kirkham, Jennifer; Inglehearn, Chris F.

    2009-01-01

    The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization. PMID:19200525

  20. Full-mouth adhesive rehabilitation in a case of amelogenesis imperfecta: a 5-year follow-up case report.

    PubMed

    Gerdolle, David; Mortier, Eric; Richard, Adeline; Vailati, Francesca

    2015-01-01

    Amelogenesis imperfecta (AI) is a hereditary disorder caused by mutations of genes primarily involved in the enamel formation. Several different types of AI have been identified, based on the phenotype and on the mode of inheritance. Regardless of the type, the dental treatment tends to be the same, favoring the complete removal of the compromised enamel late in the patient's life. With the new dentistry guidelines that orient clinicians towards minimal invasiveness, it should be mandatory to intercept patients affected by AI earlier, not only to protect the dentition from further degradation but also to help patients improve their self-esteem. This article examines the restorative dentistry performed on a 24-year-old Caucasian female suffering from the hypoplastic type of AI, using only adhesive procedures. Due to the complex needs of the patient, an interdisciplinary approach was followed, involving orthodontics, periodontics, and restorative dentistry. A full-mouth adhesive rehabilitation was achieved by means of direct composite restorations, veneer/onlays and facial/palatal veneers. No elective endodontic therapy was necessary for restorative purposes. The esthetics, mechanics, and biological success were achieved and maintained. The bond to the enamel did not show signs of degradation (eg, discoloration or infiltration) even after 5 years of function. This is encouraging as it shows that adhesive techniques may be a reliable approach even in the presence of a compromised enamel layer.

  1. Noninvasive and Multidisciplinary Approach to the Functional and Esthetic Rehabilitation of Amelogenesis Imperfecta: A Pediatric Case Report

    PubMed Central

    de Souza, Juliana Feltrin; Fragelli, Camila Maria Bullio; Paschoal, Marco Aurélio Benini; Campos, Edson Alves; Cunha, Leonardo Fernandes; Losso, Estela Maris; Cordeiro, Rita de Cássia Loiola

    2014-01-01

    Case Report. An 8-year-old girl with amelogenesis imperfecta (AI) reported unsatisfactory aesthetics, difficulty in mastication, and dental hypersensitivity. The intraoral examination observed mixed dentition, malocclusion in anteroposterior relationships, anterior open bite, and dental asymmetry. A hypoplastic form of AI was diagnosed in the permanent dentition. A multidisciplinary planning was performed and divided into preventive, orthopedic, and rehabilitation stages. Initially, preventive treatment was implemented, with fluoride varnish applications, in order to protect the fragile enamel and reduce the dental sensitivity. In the second stage, the patient received an interceptive orthopedic treatment to improve cross-relationship of the arches during six months. Finally, the rehabilitation treatment was executed to establish the vertical dimension. In the posterior teeth, indirect composite resin crowns were performed with minimally invasive dental preparation. Direct composite resin restorations were used to improve the appearance of anterior teeth. Follow-Up. The follow-up was carried out after 3, 6, 12, and 18 months. After 18 months of follow-up, The restoration of integrity, oral hygiene, and patient satisfaction were observed . Conclusion. Successful reduction of the dental hypersensitivity and improvement of the aesthetic and functional aspects as well as quality of life were observed. PMID:25061528

  2. Amelogenesis Imperfecta and Early Restorative Crown Therapy: An Interview Study with Adolescents and Young Adults on Their Experiences

    PubMed Central

    Wickström, Anette; Hasselblad, Tove; Dahllöf, Göran

    2016-01-01

    Patients with Amelogenesis imperfecta (AI) can present with rapid tooth loss or fractures of enamel as well as alterations in enamel thickness, color, and shape; factors that may compromise aesthetic appearance and masticatory function. The aim was to explore the experiences and perceptions of adolescents and young adults living with AI and receiving early prosthetic therapy. Seven patients with severe AI aged 16 to 23 years who underwent porcelain crown therapy participated in one-to-one individual interviews. The interviews followed a topic guide consisting of open-ended questions related to experiences of having AI. Transcripts from the interviews were analyzed using thematic analysis. The analysis process identified three main themes: Disturbances in daily life, Managing disturbances, and Normalization of daily life. These themes explain the experiences of patients living with enamel disturbances caused by AI and receiving early crown therapy. Experiences include severe pain and sensitivity problems, feelings of embarrassment, and dealing with dental staff that lack knowledge and understanding of their condition. The patients described ways to manage their disturbances and to reduce pain when eating or drinking, and strategies for meeting other people. After definitive treatment with porcelain crown therapy, they described feeling like a normal patient. In conclusion the results showed that adolescents and young adults describe a profound effect of AI on several aspects of their daily life. PMID:27359125

  3. Mutations in C4orf26, Encoding a Peptide with In Vitro Hydroxyapatite Crystal Nucleation and Growth Activity, Cause Amelogenesis Imperfecta

    PubMed Central

    Parry, David A.; Brookes, Steven J.; Logan, Clare V.; Poulter, James A.; El-Sayed, Walid; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Sayed, Jihad; Raïf, El Mostafa; Shore, Roger C.; Dashash, Mayssoon; Barron, Martin; Morgan, Joanne E.; Carr, Ian M.; Taylor, Graham R.; Johnson, Colin A.; Aldred, Michael J.; Dixon, Michael J.; Wright, J. Tim; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2012-01-01

    Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein’s phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis. PMID:22901946

  4. Amelogenesis Imperfecta Caused by N-Terminal Enamelin Point Mutations in Mice and Men is driven by Endoplasmic Reticulum Stress.

    PubMed

    Brookes, Steven J; Barron, Martin J; Smith, Claire E L; Poulter, James A; Mighell, Alan J; Inglehearn, Chris F; Brown, Catriona J; Rodd, Helen; Kirkham, Jennifer; Dixon, Michael J

    2017-03-11

    "Amelogenesis imperfecta" (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel. However, enamel secreted thereafter was structurally abnormal; presumably due to the UPR modulating ameloblast behaviour and function in an attempt to relieve ER stress. Homozygous mutant mice failed to produce enamel. We also identified a novel heterozygous ENAMp.L31R mutation causing AI in humans. We hypothesise that ER stress is the aetiological factor in this case of human AI as it shared the characteristic phenotype described above for the Enamp.S55I mouse. We previously demonstrated that AI in mice carrying the Amelxp.Y64H mutation is a proteinopathy. The current data indicate that AI in Enamp.S55I mice is also a proteinopathy, and based on comparative phenotypic analysis, we suggest that human AI resulting from the ENAMp.L31R mutation is another proteinopathic disease. Identifying a common aetiology for AI resulting from mutations in two different genes opens the way for developing pharmaceutical interventions designed to relieve ER stress or modulate the UPR during enamel development to ameliorate the clinical phenotype.

  5. Complex morphological and molecular genetic examination of amelogenesis imperfecta: a case presentation of two Czech siblings with a non-syndrome form of the disease.

    PubMed

    Kripnerova, Tereza; Krulisova, Veronika; Ptakova, Nikola; Macek, Milan; Dostalova, Tatjana

    2014-01-01

    Amelogenesis imperfecta (AI) is an overarching term for a group of rare inherited disorders of hard tooth tissues. It is characterized by various defects in proper enamel formation. AI is a severe disorder that affects both the aesthetics and function of the dentition, with affected teeth increasingly suffering from dental caries. Therefore, early diagnosis and lifelong stomatological interventions are important. Due to the complex nature of AI family history, stomatological, radiographic, and molecular genetic examinations should be part of the diagnostic portfolio. Additionally, we utilized new visualization methods for the assessment of teeth demineralization. We present a case report of two affected Czech sisters (6 and 8 years old) with clinically defined AI. These are the first Czech cases in which comprehensive clinical and genetic analysis had been carried out and reflect the complex clinical nature, positive treatment options, and limitations of candidate-gene molecular genetic testing.

  6. Enamel defects in extracted and exfoliated teeth from patients with Amelogenesis Imperfecta, measured using the extended enamel defects index and image analysis

    PubMed Central

    Smith, R.N.; Elcock, C.; Abdellatif, A.; Bäckman, B.; Russell, J.M.; Brook, A.H.

    2009-01-01

    Aims To enhance the phenotypic description and quantification of enamel defects from a North Sweden sample of extracted and exfoliated teeth originating from families with Amelogenesis Imperfecta by use of the extended enamel defects index (EDI) and image analysis to demonstrate the comparable reliability and value of the additional measurements. Methods and results The sample comprised 109 deciduous and 7 permanent teeth from 32 individuals of 19 families with Amelogenesis Imperfecta in Northern Sweden. A special holder for individual teeth was designed and the whole sample was examined using the extended EDI and an image analysis system. In addition to the extended EDI definitions, the calibrated images were measured for tooth surface area, defect area and percentage of surface affected using image analysis techniques. The extended EDI was assessed using weighted and unweighted Kappa statistics. The reliability of imaging and measurement was determined using Fleiss’ intra-class correlation coefficient (ICCC). Kappa values indicated good or excellent intra-operator repeatability and inter-operator reproducibility for the extended EDI. The Fleiss ICCC values indicated excellent repeatability for the image analysis measurements. Hypoplastic pits on the occlusal surfaces were the most frequent defect in this sample (82.6%). The occlusal surface displayed the most post-eruptive breakdown (39.13%) whilst the incisal portion of the buccal surfaces showed most diffuse opacities (53.4%). Image analysis methods demonstrated the largest mean hypoplastic pit areas were on the lingual surfaces. The largest mean post-eruptive breakdown areas were on the lingual surfaces of posterior teeth. The largest mean demarcated opacity areas were found on the labial surfaces. Conclusions The extended EDI and the standardised image acquisition and analysis system provided additional information to conventional measurement techniques. Additional phenotypic variables were described. PMID

  7. Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta.

    PubMed

    Poulter, James A; El-Sayed, Walid; Shore, Roger C; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-01-01

    The conventional approach to identifying the defective gene in a family with an inherited disease is to find the disease locus through family studies. However, the rapid development and decreasing cost of next generation sequencing facilitates a more direct approach. Here, we report the identification of a frameshift mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta (AI). Whole-exome sequencing of three affected family members and subsequent filtering of shared variants, without prior genetic linkage, sufficed to identify the pathogenic variant. Simultaneous analysis of multiple family members confirms segregation, enhancing the power to filter the genetic variation found and leading to rapid identification of the pathogenic variant. LAMB3 encodes a subunit of Laminin-5, one of a family of basement membrane proteins with essential functions in cell growth, movement and adhesion. Homozygous LAMB3 mutations cause junctional epidermolysis bullosa (JEB) and enamel defects are seen in JEB cases. However, to our knowledge, this is the first report of dominant AI due to a LAMB3 mutation in the absence of JEB.

  8. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation.

    PubMed

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian G; Juncker, Inger; Nyegaard, Mette; Børglum, Anders D; Poulsen, Sven; Hertz, Jens M

    2011-11-01

    BACKGROUND.  Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES.  The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study the phenotypic variation of the enamel in affected family members. RESULTS.  Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION.  We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients.

  9. Identification of the first multi-exonic WDR72 deletion in isolated amelogenesis imperfecta, and generation of a WDR72-specific copy number screening tool.

    PubMed

    Hentschel, Julia; Tatun, Dana; Parkhomchuk, Dmitri; Kurth, Ingo; Schimmel, Bettina; Heinrich-Weltzien, Roswitha; Bertzbach, Sabine; Peters, Hartmut; Beetz, Christian

    2016-09-15

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous disorder of tooth development which is due to aberrant deposition or composition of enamel. Both syndromic and isolated forms exist; they may be inherited in an X-linked, autosomal recessive, or autosomal dominant manner. WDR72 is one of ten currently known genes for recessive isolated AI; nine WDR72 mutations affecting single nucleotides have been described to date. Based on whole exome sequencing in a large consanguineous AI pedigree, we obtained evidence for presence of a multi-exonic WDR72 deletion. A home-made multiplex ligation-dependent probe amplification assay was used to confirm the aberration, to narrow its extent, and to identify heterozygous carriers. Our study extends the mutational spectrum for WDR72 to include large deletions, and supports a relevance of the previously proposed loss-of-function mechanism. It also introduces an easy-to-use and highly sensitive tool for detecting WDR72 copy number alterations.

  10. Improved protocol to purify untagged amelogenin – Application to murine amelogenin containing the equivalent P70 → T point mutation observed in human amelogenesis imperfecta

    PubMed Central

    Buchko, Garry W.; Shaw, Wendy J.

    2015-01-01

    Amelogenin is the predominant extracellular protein responsible for converting carbonated hydroxyapatite into dental enamel, the hardest and most heavily mineralized tissue in vertebrates. Despite much effort, the precise mechanism by which amelogenin regulates enamel formation is not fully understood. To assist efforts aimed at understanding the biochemical mechanism of enamel formation, more facile protocols to purify recombinantly expressed amelogenin, ideally without any tag to assist affinity purification, are advantageous. Here we describe an improved method to purify milligram quantities of amelogenin that exploits its high solubility in 2% glacial acetic acid under conditions of low ionic strength. The method involves heating the frozen cell pellet for two 15 min periods at −70 °C with 2 min of sonication in between, dialysis twice in 2% acetic acid (1:250 v/v), and reverse phase chromatography. A further improvement in yield is obtained by resuspending the frozen cell pellet in 6 M guanidine hydrochloride in the first step. The acetic acid heating method is illustrated with a murine amelogenin containing the corresponding P70 → T point mutation observed in an human amelogenin associated with amelogenesis imperfecta (P71T), while the guanidine hydrochloride heating method is illustrated with wild type murine amelogenin (M180). The self-assembly properties of P71T were probed by NMR chemical shift perturbation studies as a function of protein (0.1–1.8 mM) and NaCl (0–367 mM) concentration. Relative to similar studies with wild type murine amelogenin, P71T self-associates at lower protein or salt concentrations with the interactions initiated near the N-terminus. PMID:25306873

  11. A mutation in the mouse Amelx tri-tyrosyl domain results in impaired secretion of amelogenin and phenocopies human X-linked amelogenesis imperfecta

    PubMed Central

    Barron, Martin J.; Brookes, Steven J.; Kirkham, Jennifer; Shore, Roger C.; Hunt, Charlotte; Mironov, Aleksandr; Kingswell, Nicola J.; Maycock, Joanne; Shuttleworth, C. Adrian; Dixon, Michael J.

    2010-01-01

    Amelogenesis imperfecta (AI) describes a broad group of clinically and genetically heterogeneous inherited defects of dental enamel bio-mineralization. Despite identification of a number of genetic mutations underlying AI, the precise causal mechanisms have yet to be determined. Using a multi-disciplinary approach, we describe here a mis-sense mutation in the mouse Amelx gene resulting in a Y → H substitution in the tri-tyrosyl domain of the enamel extracellular matrix protein amelogenin. The enamel in affected animals phenocopies human X-linked AI where similar mutations have been reported. Animals affected by the mutation have severe defects of enamel bio-mineralization associated with absence of full-length amelogenin protein in the developing enamel matrix, loss of ameloblast phenotype, increased ameloblast apoptosis and formation of multi-cellular masses. We present evidence to demonstrate that affected ameloblasts express but fail to secrete full-length amelogenin leading to engorgement of the endoplasmic reticulum/Golgi apparatus. Immunohistochemical analysis revealed accumulations of both amelogenin and ameloblastin in affected cells. Co-transfection of Ambn and mutant Amelx in a eukaryotic cell line also revealed intracellular abnormalities and increased cytotoxicity compared with cells singly transfected with wild-type Amelx, mutant Amelx or Ambn or co-transfected with both wild-type Amelx and Ambn. We hypothesize that intracellular protein–protein interactions mediated via the amelogenin tri-tyrosyl motif are a key mechanistic factor underpinning the molecular pathogenesis in this example of AI. This study therefore successfully links phenotype with underlying genetic lesion in a relevant murine model for human AI. PMID:20067920

  12. Improved protocol to purify untagged amelogenin - Application to murine amelogenin containing the equivalent P70→T point mutation observed in human amelogenesis imperfecta.

    PubMed

    Buchko, Garry W; Shaw, Wendy J

    2015-01-01

    Amelogenin is the predominant extracellular protein responsible for converting carbonated hydroxyapatite into dental enamel, the hardest and most heavily mineralized tissue in vertebrates. Despite much effort, the precise mechanism by which amelogenin regulates enamel formation is not fully understood. To assist efforts aimed at understanding the biochemical mechanism of enamel formation, more facile protocols to purify recombinantly expressed amelogenin, ideally without any tag to assist affinity purification, are advantageous. Here we describe an improved method to purify milligram quantities of amelogenin that exploits its high solubility in 2% glacial acetic acid under conditions of low ionic strength. The method involves heating the frozen cell pellet for two 15min periods at ∼70°C with 2min of sonication in between, dialysis twice in 2% acetic acid (1:250 v/v), and reverse phase chromatography. A further improvement in yield is obtained by resuspending the frozen cell pellet in 6M guanidine hydrochloride in the first step. The acetic acid heating method is illustrated with a murine amelogenin containing the corresponding P70→T point mutation observed in an human amelogenin associated with amelogenesis imperfecta (P71T), while the guanidine hydrochloride heating method is illustrated with wild type murine amelogenin (M180). The self-assembly properties of P71T were probed by NMR chemical shift perturbation studies as a function of protein (0.1-1.8mM) and NaCl (0-367mM) concentration. Relative to similar studies with wild type murine amelogenin, P71T self-associates at lower protein or salt concentrations with the interactions initiated near the N-terminus.

  13. Improved protocol to purify untagged amelogenin – Application to murine amelogenin containing the equivalent P70→T point mutation observed in human amelogenesis imperfecta

    SciTech Connect

    Buchko, Garry W.; Shaw, Wendy J.

    2014-10-13

    Amelogenin is the predominant extracellular protein responsible for converting carbonated hydroxyapatite into dental enamel, the hardest and most heavily mineralized tissue in vertebrates. Despite much effort, the precise mechanism by which amelogenin regulates enamel formation is not fully understood. To assist efforts aimed at understanding the biochemical mechanism of enamel formation, more facile protocols to purify recombinantly expressed amelogenin, ideally without any tag to assist affinity purification, are advantageous. Here we describe an improved method to purify milligram quantities of amelogenin that exploits its high solubility in 2% glacial acetic acid under conditions of low ionic strength. The method involves heating the frozen cell pellet for two 15 min periods at ~70 ºC with two minutes of sonication in between, dialysis twice in 2% acetic acid (1:250 v/v), and reverse phase chromatography. A further improvement in yield is obtained by resuspending the frozen cell pellet in 6 M guanidine hydrochloride in the first step. The acetic acid heating method is illustrated with a murine amelogenin containing the corresponding P70→T point mutation observed in an human amelogenin associated with amelogenesis imperfecta (P71T), while the guanidine hydrochloride heating method is illustrated with wild type murine amelogenin (M180). The self-assembly properties of P71T were probed by NMR chemical shift perturbation studies as a function of protein (0.1 to 1.8 mM) and NaCl (0 to 367 mM) concentration. In conclusion, relative to similar studies with wild type murine amelogenin, P71T self-associates at lower protein or salt concentrations with the interactions initiated near the N-terminus.

  14. Improved protocol to purify untagged amelogenin – Application to murine amelogenin containing the equivalent P70→T point mutation observed in human amelogenesis imperfecta

    DOE PAGES

    Buchko, Garry W.; Shaw, Wendy J.

    2014-10-13

    Amelogenin is the predominant extracellular protein responsible for converting carbonated hydroxyapatite into dental enamel, the hardest and most heavily mineralized tissue in vertebrates. Despite much effort, the precise mechanism by which amelogenin regulates enamel formation is not fully understood. To assist efforts aimed at understanding the biochemical mechanism of enamel formation, more facile protocols to purify recombinantly expressed amelogenin, ideally without any tag to assist affinity purification, are advantageous. Here we describe an improved method to purify milligram quantities of amelogenin that exploits its high solubility in 2% glacial acetic acid under conditions of low ionic strength. The method involvesmore » heating the frozen cell pellet for two 15 min periods at ~70 ºC with two minutes of sonication in between, dialysis twice in 2% acetic acid (1:250 v/v), and reverse phase chromatography. A further improvement in yield is obtained by resuspending the frozen cell pellet in 6 M guanidine hydrochloride in the first step. The acetic acid heating method is illustrated with a murine amelogenin containing the corresponding P70→T point mutation observed in an human amelogenin associated with amelogenesis imperfecta (P71T), while the guanidine hydrochloride heating method is illustrated with wild type murine amelogenin (M180). The self-assembly properties of P71T were probed by NMR chemical shift perturbation studies as a function of protein (0.1 to 1.8 mM) and NaCl (0 to 367 mM) concentration. In conclusion, relative to similar studies with wild type murine amelogenin, P71T self-associates at lower protein or salt concentrations with the interactions initiated near the N-terminus.« less

  15. Amelogenesis imperfecta with bilateral nephrocalcinosis.

    PubMed

    Poornima, P; Katkade, Shashikant; Mohamed, Roshan Noor; Mallikarjuna, Rachappa

    2013-05-24

    A 12-year-old patient presented with a severe delay of eruption in permanent maxillary and mandibular incisors. On examination, there was over-retained primary teeth and delayed eruption of permanent teeth. Retained primary teeth showed light yellow discolouration whereas permanent teeth were distinct yellow with thin or little enamel. Subsequent imaging revealed all the premolars except maxillary left first premolar showed signs of intra-alveolar coronal resorption, nephrocalcinosis with bilateral multiple calculi and small papillary tip calcifications, marked increase in alkaline phosphatase. Subsequent dental treatment for restoring the functional and aesthetic requirement followed by appropriate treatment for renal problem was undertaken.

  16. A Functional Study of Mutations in K+-dependent Na+-Ca2+ Exchangers Associated with Amelogenesis Imperfecta and Non-syndromic Oculocutaneous Albinism.

    PubMed

    Jalloul, Ali H; Rogasevskaia, Tatiana P; Szerencsei, Robert T; Schnetkamp, Paul P M

    2016-06-17

    K(+)-dependent Na(+)/Ca(2+) exchangers belong to the solute carrier 24 (SLC24A1-5) gene family of membrane transporters. Five different gene products (NCKX1-5) have been identified in humans, which play key roles in biological processes including vision, olfaction, and skin pigmentation. NCKXs are bi-directional membrane transporters that transport 1 Ca(2+)+K(+) ions in exchange for 4 Na(+) ions. Recent studies have linked mutations in the SLC24A4 (NCKX4) and SLC24A5 (NCKX5) genes to amylogenesis imperfecta (AI) and non-syndromic oculocutaneous albinism (OCA6), respectively. Here, we introduced mutations found in patients with AI and OCA6 into human SLC24A4 (NCKX4) cDNA leading to single residue substitutions in the mutant NCKX4 proteins. We measured NCKX-mediated Ca(2+) transport activity of WT and mutant NCKX4 proteins expressed in HEK293 cells. Three mutant NCKX4 cDNAs represent mutations found in the SCL24A4 gene and three represent mutations found in the SCL24A5 gene involving residues conserved between NCKX4 and NCKX5. Five mutant proteins had no observable NCKX activity, whereas one mutation resulted in a 78% reduction in transport activity. Total protein expression and trafficking to the plasma membrane (the latter with one exception) were not affected in the HEK293 cell expression system. We also analyzed two mutations in a Drosophila NCKX gene that have been reported to result in an increased susceptibility for seizures, and found that both resulted in mutant proteins with significantly reduced but observable NCKX activity. The data presented here support the genetic analyses that mutations in SLC24A4 and SLC24A5 are responsible for the phenotypic defects observed in human patients.

  17. Learning about Osteogenesis Imperfecta

    MedlinePlus

    ... genetic terms used on this page. Learning About Osteogenesis Imperfecta What is Osteogenesis imperfecta? What are the symptoms ... imperfecta Additional Resources on Osteogenesis imperfecta What is Osteogenesis imperfecta? Osteogenesis imperfecta (OI) is a genetic disorder that ...

  18. Osteogenesis imperfecta

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001573.htm Osteogenesis imperfecta To use the sharing features on this page, please enable JavaScript. Osteogenesis imperfecta is a condition causing extremely fragile bones. Causes ...

  19. Osteogenesis Imperfecta

    MedlinePlus

    ... imperfecta (OI) is a genetic disorder in which bones break easily. Sometimes the bones break for no known reason. OI can also ... you make collagen, a protein that helps make bones strong. OI can range from mild to severe, ...

  20. Osteogenesis imperfecta.

    PubMed

    Marini, Joan C; Forlino, Antonella; Bächinger, Hans Peter; Bishop, Nick J; Byers, Peter H; Paepe, Anne De; Fassier, Francois; Fratzl-Zelman, Nadja; Kozloff, Kenneth M; Krakow, Deborah; Montpetit, Kathleen; Semler, Oliver

    2017-08-18

    Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure. In the past decade, (mostly) recessive, dominant and X-linked defects in a wide variety of genes encoding proteins involved in type I collagen synthesis, processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells have been shown to cause osteogenesis imperfecta. The large number of causative genes has complicated the classic classification of the disease, and although a new genetic classification system is widely used, it is still debated. Phenotypic manifestations in many organs, in addition to bone, are reported, such as abnormalities in the cardiovascular and pulmonary systems, skin fragility, muscle weakness, hearing loss and dentinogenesis imperfecta. Management involves surgical and medical treatment of skeletal abnormalities, and treatment of other complications. More innovative approaches based on gene and cell therapy, and signalling pathway alterations, are under investigation.

  1. Osteogenesis Imperfecta Foundation

    MedlinePlus

    ... Better Bones Upcoming Events Online Store What is Osteogenesis Imperfecta? Osteogenesis Imperfecta (OI) is a genetic bone disorder ... known as "brittle bone disease." Learn More The Osteogenesis Imperfecta Foundation The OI Foundation provides medically verified information ...

  2. [Osteogenesis imperfecta].

    PubMed

    Hamuy, J; Nissen Abente, J C; Rolón Arámbulo, P R; Campuzano de Rolón, A E

    1976-01-01

    Our clinical files on osteogenesis imperfecta are brought up-to-date reviewing a total of 33,555 cases admitted between 4/XII/48 and 31/VIII/76. From these, 5 clinical cases were found. The extreme rareness of this regional pathology in our Cátedra y Sericio de Pediatría, which is the largest concentration center in Paraguay had led us to make this publication. From our casuistics, we may single out a three-month-old infant which would be a case of congenital osteogenesis imperfecta. The remaining 4 would correspond to cases of late osteogenesis imperfecta. Generalized osteoporosis was present in 3 patients and all of them showed blue sclera the same as fractures of femur. Fractures of radius, tibia and fibula were seen in 2 cases. The humerus was fractured in one patient and the ulna in another one. Three patients were under one year old, another one was on his second year and the last one was a school ager. An audiologic examination was normal in the nine-year-old patient. In the other 4 cases, it was not possible to carry out such test.

  3. Osteogenesis imperfecta.

    PubMed

    Forlino, Antonella; Marini, Joan C

    2016-04-16

    Osteogenesis imperfecta is a phenotypically and molecularly heterogeneous group of inherited connective tissue disorders that share similar skeletal abnormalities causing bone fragility and deformity. Previously, the disorder was thought to be an autosomal dominant bone dysplasia caused by defects in type I collagen, but in the past 10 years discoveries of novel (mainly recessive) causative genes have lent support to a predominantly collagen-related pathophysiology and have contributed to an improved understanding of normal bone development. Defects in proteins with very different functions, ranging from structural to enzymatic and from intracellular transport to chaperones, have been described in patients with osteogenesis imperfecta. Knowledge of the specific molecular basis of each form of the disorder will advance clinical diagnosis and potentially stimulate targeted therapeutic approaches. In this Seminar, together with diagnosis, management, and treatment, we describe the defects causing osteogenesis imperfecta and their mechanism and interrelations, and classify them into five groups on the basis of the metabolic pathway compromised, specifically those related to collagen synthesis, structure, and processing; post-translational modification; folding and cross-linking; mineralisation; and osteoblast differentiation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Transcriptional factor DLX3 promotes the gene expression of enamel matrix proteins during amelogenesis.

    PubMed

    Zhang, Zhichun; Tian, Hua; Lv, Ping; Wang, Weiping; Jia, Zhuqing; Wang, Sainan; Zhou, Chunyan; Gao, Xuejun

    2015-01-01

    Mutation of distal-less homeobox 3 (DLX3) is responsible for human tricho-dento-osseous syndrome (TDO) with amelogenesis imperfecta, indicating a crucial role of DLX3 in amelogenesis. However, the expression pattern of DLX3 and its specific function in amelogenesis remain largely unknown. The aim of this study was to investigate the effects of DLX3 on enamel matrix protein (EMP) genes. By immunohistochemistry assays of mouse tooth germs, stronger immunostaining of DLX3 protein was identified in ameloblasts in the secretory stage than in the pre-secretory and maturation stages, and the same pattern was found for Dlx3 mRNA using Realtime PCR. In a mouse ameloblast cell lineage, forced expression of DLX3 up-regulated the expression of the EMP genes Amelx, Enam, Klk4, and Odam, whereas knockdown of DLX3 down-regulated these four EMP genes. Further, bioinformatics, chromatin immunoprecipitation, and luciferase assays revealed that DLX3 transactivated Enam, Amelx, and Odam through direct binding to their enhancer regions. Particularly, over-expression of mutant-DLX3 (c.571_574delGGGG, responsible for TDO) inhibited the activation function of DLX3 on expression levels and promoter activities of the Enam, Amelx, and Odam genes. Together, our data show that DLX3 promotes the expression of the EMP genes Amelx, Enam, Klk4, and Odam in amelogenesis, while mutant-DLX3 disrupts this regulatory function, thus providing insights into the molecular mechanisms underlying the enamel defects of TDO disease.

  5. The Unfolded Protein Response in Amelogenesis and Enamel Pathologies

    PubMed Central

    Brookes, Steven J.; Barron, Martin J.; Dixon, Michael J.; Kirkham, Jennifer

    2017-01-01

    During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other “professional” secretory cells, ameloblasts employ the unfolded protein response (UPR) to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum)/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI) and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.

  6. Congenital adrenal hyperplasia with localized aggressive periodontitis and amelogenesis imperfecta.

    PubMed

    Ajlan, Sumaiah Abdulbaqi

    2015-11-01

    Congenital adrenal hyperplasia (CAH) is an inherited medical condition that implies defects in steroid biosynthesis. The dental findings of a female patient with CAH are reported. The patient suffered from severe periodontal tissue destruction, obvious enamel defects, as well as some occlusal problems. The management approach is presented and the possibility of interrelation of her dental findings with her medical condition is discussed.

  7. Osteogenesis Imperfecta Issues: Constipation

    MedlinePlus

    ... Constipation is a problem for some people with osteogenesis imperfecta. Constipation is defined as a decrease in frequency ... to a more serious problem called rectal prolapse. Osteogenesis Imperfecta Foundation • 804 W. Diamond Ave, Suite 210 • Gaithersburg, ...

  8. Genetics Home Reference: dentinogenesis imperfecta

    MedlinePlus

    ... abnormalities. Type I occurs in people who have osteogenesis imperfecta , a genetic condition in which bones are brittle ... Dentinogenesis imperfecta type I occurs as part of osteogenesis imperfecta , which is caused by mutations in one of ...

  9. Genetics Home Reference: osteogenesis imperfecta

    MedlinePlus

    ... Email Facebook Twitter Home Health Conditions osteogenesis imperfecta osteogenesis imperfecta Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Osteogenesis imperfecta (OI) is a group of genetic disorders that ...

  10. Osteogenesis imperfecta/lobstein syndrome associated with dentinogenesis imperfecta.

    PubMed

    Lingaraju, Naresh; Nagarathna, P J; Vijayalakshmi, R; Sheshadri, P

    2013-01-01

    Osteogenesis imperfecta is a collagen related disorder characterized by increased bone fragility and low bone mass. The important oral finding in osteogenesis imperfect is the presence of dentinogenesis imperfecta. This article presents a case of osteogenesis imperfecta (type IV B) with dentinogenesis imperfecta where a 7-year-old girl had opalacent primary teeth associated with severe bone deformity, scoliosis, barrel shaped rib cage, and short stature. The clinical, radiographic ad histologic features are reviewed along with management aspects.

  11. Myths about OI (Osteogenesis Imperfecta)

    MedlinePlus

    ... Based on the OI Foundation publication Introduction to Osteogenesis Imperfecta: A Guide for Medical Professionals, Individuals and Families ... for Children, editor, 2013. Page updated August, 2015. © Osteogenesis Imperfecta Foundation, 2015 Privacy Policy

  12. Dentinogenesis imperfecta associated with osteogenesis imperfecta

    PubMed Central

    Biria, Mina; Abbas, Fatemeh Mashhadi; Mozaffar, Sedighe; Ahmadi, Rahil

    2012-01-01

    This paper presents a case with dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta. Systemic and dental manifestations of OI and its medical and dental treatments are discussed in this paper. A 5-year-old child with the diagnosis of OI was referred to the Dental School of Shaid Beheshti University of Medical Sciences. On clinical examination yellow/brown discoloration of primary teeth with the attrition of the exposed dentin and class III malocclusion was observed. Enamel of first permanent molars was hypoplastic. Radiographic examinations confirmed the diagnosis of DI. A histological study was performed on one of the exfoliating teeth, which showed abnormal dentin. Primary teeth with DI were more severely affected compared to permanent teeth; enamel disintegration occurred in teeth with DI, demonstrating the need for restricts recalls for these patients. PMID:23162594

  13. Retinoic Acid Excess Impairs Amelogenesis Inducing Enamel Defects

    PubMed Central

    Morkmued, Supawich; Laugel-Haushalter, Virginie; Mathieu, Eric; Schuhbaur, Brigitte; Hemmerlé, Joseph; Dollé, Pascal; Bloch-Zupan, Agnès; Niederreither, Karen

    2017-01-01

    Abnormalities of enamel matrix proteins deposition, mineralization, or degradation during tooth development are responsible for a spectrum of either genetic diseases termed Amelogenesis imperfecta or acquired enamel defects. To assess if environmental/nutritional factors can exacerbate enamel defects, we investigated the role of the active form of vitamin A, retinoic acid (RA). Robust expression of RA-degrading enzymes Cyp26b1 and Cyp26c1 in developing murine teeth suggested RA excess would reduce tooth hard tissue mineralization, adversely affecting enamel. We employed a protocol where RA was supplied to pregnant mice as a food supplement, at a concentration estimated to result in moderate elevations in serum RA levels. This supplementation led to severe enamel defects in adult mice born from pregnant dams, with most severe alterations observed for treatments from embryonic day (E)12.5 to E16.5. We identified the enamel matrix proteins enamelin (Enam), ameloblastin (Ambn), and odontogenic ameloblast-associated protein (Odam) as target genes affected by excess RA, exhibiting mRNA reductions of over 20-fold in lower incisors at E16.5. RA treatments also affected bone formation, reducing mineralization. Accordingly, craniofacial ossification was drastically reduced after 2 days of treatment (E14.5). Massive RNA-sequencing (RNA-seq) was performed on E14.5 and E16.5 lower incisors. Reductions in Runx2 (a key transcriptional regulator of bone and enamel differentiation) and its targets were observed at E14.5 in RA-exposed embryos. RNA-seq analysis further indicated that bone growth factors, extracellular matrix, and calcium homeostasis were perturbed. Genes mutated in human AI (ENAM, AMBN, AMELX, AMTN, KLK4) were reduced in expression at E16.5. Our observations support a model in which elevated RA signaling at fetal stages affects dental cell lineages. Thereafter enamel protein production is impaired, leading to permanent enamel alterations. PMID:28111553

  14. Dentinogenesis imperfecta: a case report.

    PubMed

    Subramaniam, P; Mathew, S; Sugnani, S N

    2008-06-01

    Dentinogenesis imperfecta is an autosomal dominant disorder of tooth development characterized by the presence of opalescent dentin, resulting in a dusky blue to brownish discoloration of the teeth. This condition is genetically and clinically heterogeneous; it may affect only the teeth or it may be associated with the osteogenesis imperfecta. Dentinogenesis imperfecta has been subdivided into three types: type I is associated with osteogenesis imperfecta; in type II there is no associated osteogenesis imperfecta; and when the condition is associated with the Brandywine triracial isolate and large pulp chambers it is classified as type III. This report describes a 16-year-old female patient who showed the characteristic dental features of dentinogenesis imperfecta type II. The etiology and prevalence of the disorder, and a comprehensive treatment plan, will be briefly reviewed.

  15. Prosthodontic rehabilitation of dentinogenesis imperfecta.

    PubMed

    Goud, Anil; Deshpande, Saee

    2011-04-01

    Dentinogenesis imperfecta and its prosthodontic management is a challenging task. Treatment protocol varies according to clinical case. Although various reports in the literature suggest general guidelines for treatment planning, the present case report describes a full mouth rehabilitation of a young patient with dentinogenesis imperfecta treated by maxillary fixed partial dentures and mandibular fiber reinforced overdenture with metal occlusal surfaces.

  16. Prosthodontic rehabilitation of dentinogenesis imperfecta

    PubMed Central

    Goud, Anil; Deshpande, Saee

    2011-01-01

    Dentinogenesis imperfecta and its prosthodontic management is a challenging task. Treatment protocol varies according to clinical case. Although various reports in the literature suggest general guidelines for treatment planning, the present case report describes a full mouth rehabilitation of a young patient with dentinogenesis imperfecta treated by maxillary fixed partial dentures and mandibular fiber reinforced overdenture with metal occlusal surfaces. PMID:21957394

  17. Child Abuse or Osteogenesis Imperfecta?

    MedlinePlus

    Child Abuse or Osteogenesis Imperfecta? A child is brought into the emergency room with a fractured leg. The parents are unable to explain how ... the fractures is not child abuse. It is osteogenesis imperfecta , or OI. OI is a genetic disorder characterized ...

  18. MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

    PubMed Central

    Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L.; Hacia, Joseph G.; Paine, Michael L.

    2017-01-01

    Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI. PMID:28287144

  19. Osteogenesis imperfecta as a complication of pregnancy.

    PubMed

    Key, T C; Horger, E O

    1978-01-01

    Osteogenesis imperfecta is a complex disorder that rarely complicates pregancy. The successful obstetric management of a patient with severe osteogensis imperfecta is presented along with a detailed review of maternal osteogenesis imperfecta in the recent English literature. A review of the disease process, its complications, and associated disorders is presented.

  20. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia

    PubMed Central

    Barron, Martin J; McDonnell, Sinead T; MacKie, Iain; Dixon, Michael J

    2008-01-01

    The hereditary dentine disorders, dentinogenesis imperfecta (DGI) and dentine dysplasia (DD), comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP), suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome), permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a number of options including

  1. Osteogenesis imperfecta: diagnosis and treatment.

    PubMed

    Palomo, Telma; Vilaça, Tatiane; Lazaretti-Castro, Marise

    2017-08-31

    Here we summarize the diagnosis of osteogenesis imperfecta, discuss newly discovered genes involved in osteogenesis imperfecta, and review the management of this disease in children and adults. Mutations in the two genes coding for collagen type I, COL1A1 and COL1A2, are the most common cause of osteogenesis imperfecta. In the past 10 years, defects in at least 17 other genes have been identified as responsible for osteogenesis imperfecta phenotypes, with either dominant or recessive transmission. Intravenous bisphosphonate infusions are the most widely used medical treatment. This has a marked effect on vertebra in growing children and can lead to vertebral reshaping after compression fractures. However, bisphosphonates are less effective for preventing long-bone fractures. At the moment, new therapies are under investigation. Despite advances in the diagnosis and treatment of osteogenesis imperfecta, more research is needed. Bisphosphonate treatment decreases long-bone fracture rates, but such fractures are still frequent. New antiresorptive and anabolic agents are being investigated but efficacy and safety of these drugs, especially in children, need to be better established before they can be used in clinical practice.

  2. Bmp2 Deletion Causes an Amelogenesis Imperfecta Phenotype Via Regulating Enamel Gene Expression

    PubMed Central

    GUO, FENG; FENG, JUNSHENG; WANG, FENG; LI, WENTONG; GAO, QINGPING; CHEN, ZHUO; SHOFF, LISA; DONLY, KEVIN J.; GLUHAK-HEINRICH, JELICA; CHUN, YONG HEE PATRICIA; HARRIS, STEPHEN E.; MACDOUGALL, MARY; CHEN, SHUO

    2015-01-01

    Although Bmp2 is essential for tooth formation, the role of Bmp2 during enamel formation remains unknown in vivo. In this study, the role of Bmp2 in regulation of enamel formation was investigated by the Bmp2 conditional knock out (Bmp2 cKO) mice. Teeth of Bmp2 cKO mice displayed severe and profound phenotypes with asymmetric and misshaped incisors as well as abrasion of incisors and molars. Scanning electron microscopy analysis showed that the enamel layer was hypoplastic and enamel lacked a typical prismatic pattern. Teeth from null mice were much more brittle as tested by shear and compressive moduli. Expression of enamel matrix protein genes, amelogenin, enamelin, and enamel-processing proteases, Mmp-20 and Klk4 was reduced in the Bmp2 cKO teeth as reflected in a reduced enamel formation. Exogenous Bmp2 up-regulated those gene expressions in mouse enamel organ epithelial cells. This result for the first time indicates Bmp2 signaling is essential for proper enamel development and mineralization in vivo. PMID:25545831

  3. Bmp2 deletion causes an amelogenesis imperfecta phenotype via regulating enamel gene expression.

    PubMed

    Guo, Feng; Feng, Junsheng; Wang, Feng; Li, Wentong; Gao, Qingping; Chen, Zhuo; Shoff, Lisa; Donly, Kevin J; Gluhak-Heinrich, Jelica; Chun, Yong Hee Patricia; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

    2015-08-01

    Although Bmp2 is essential for tooth formation, the role of Bmp2 during enamel formation remains unknown in vivo. In this study, the role of Bmp2 in regulation of enamel formation was investigated by the Bmp2 conditional knock out (Bmp2 cKO) mice. Teeth of Bmp2 cKO mice displayed severe and profound phenotypes with asymmetric and misshaped incisors as well as abrasion of incisors and molars. Scanning electron microscopy analysis showed that the enamel layer was hypoplastic and enamel lacked a typical prismatic pattern. Teeth from null mice were much more brittle as tested by shear and compressive moduli. Expression of enamel matrix protein genes, amelogenin, enamelin, and enamel-processing proteases, Mmp-20 and Klk4 was reduced in the Bmp2 cKO teeth as reflected in a reduced enamel formation. Exogenous Bmp2 up-regulated those gene expressions in mouse enamel organ epithelial cells. This result for the first time indicates Bmp2 signaling is essential for proper enamel development and mineralization in vivo.

  4. Osteogenesis imperfecta: pathophysiology and treatment.

    PubMed

    Hoyer-Kuhn, Heike; Netzer, Christian; Semler, Oliver

    2015-07-01

    Osteogenesis imperfecta is a rare hereditary disease mostly caused by mutations impairing collagen synthesis and modification. Recently recessive forms have been described influencing differentiation and activity of osteoblasts and osteoclasts. Most prominent signs are fractures due to low traumata and deformities of long bones and vertebrae. Additional patients can be affected by dwarfism, scoliosis Dentinogenesis imperfecta, deafness and a blueish discoloration of the sclera. During childhood state of the art medical treatment are i.v. bisphosphonates to increase bone mass and to reduce fracture rate. Surgical interventions are needed to treat fractures, to correct deformities and should always be accompanied by physiotherapeutic and rehabilitative interventions.

  5. The Spine in Patients With Osteogenesis Imperfecta.

    PubMed

    Wallace, Maegen J; Kruse, Richard W; Shah, Suken A

    2017-02-01

    Osteogenesis imperfecta is a genetic disorder of type I collagen. Although multiple genotypes and phenotypes are associated with osteogenesis imperfecta, approximately 90% of the mutations are in the COL1A1 and COL1A2 genes. Osteogenesis imperfecta is characterized by bone fragility. Patients typically have multiple fractures or limb deformity; however, the spine can also be affected. Spinal manifestations include scoliosis, kyphosis, craniocervical junction abnormalities, and lumbosacral pathology. The incidence of lumbosacral spondylolysis and spondylolisthesis is higher in patients with osteogenesis imperfecta than in the general population. Use of diphosphonates has been found to decrease the rate of progression of scoliosis in patients with osteogenesis imperfecta. A lateral cervical radiograph is recommended in patients with this condition before age 6 years for surveillance of craniocervical junction abnormalities, such as basilar impression. Intraoperative and anesthetic considerations in patients with osteogenesis imperfecta include challenges related to fracture risk, airway management, pulmonary function, and blood loss.

  6. Scanning Еlectron Мicroscopy of Еnamel and Dentin of Тeeth with Hypocalcified Аmelogenesis Imperfecta.

    PubMed

    Belcheva, Ani B; Philipov, Ivan At; Tomov, Georgi T

    2016-03-01

    The histological features of teeth with hypocalcified amelogenesis imperfecta (AI) have been poorly studied, which calls into question the effectiveness of modern adhesive techniques used in the treatment of these noncarious defects. The aim of this study was to investigate the morphological features of the enamel and dentin of teeth with AI using scanning electron microscopy (SEM), and compare these features with those of healthy teeth. We examined four primary teeth extracted on indication from a 10-year-old girl with hypocalcified amelogenesis imperfecta. The same number of primary teeth extracted from healthy subjects was used as controls. The morphological characteristics of the enamel and dentin are described after investigating the teeth and photographing the specimens with scanning electron microscope. The SEM photos of the enamel of AI teeth show presence of external defects, incorrectly oriented enamel prisms and enlarged interprism spaces. Thickening of the peritubular dentin and partially obliterated dentinal tubules characterize the dentin of these teeth. The enamel and dentin of teeth affected by hypocalcified AI diff er considerably from normal hard dental structures in their morphological characteristics.

  7. Osteogenesis imperfecta: cesarean deliveries in identical twins.

    PubMed

    Dinges, E; Ortner, C; Bollag, L; Davies, J; Landau, R

    2015-02-01

    Osteogenesis imperfecta is a congenital disorder resulting in multiple fractures and extremely short stature, usually necessitating cesarean delivery. Identical twins with severe osteogenesis imperfecta each of whom underwent a cesarean delivery with different anesthetic modalities are presented. A review of the literature and anesthetic options for cesarean delivery and postoperative analgesia for women with osteogenesis imperfecta are discussed. Copyright © 2015. Published by Elsevier Ltd.

  8. Hypercalcaemia in osteogenesis imperfecta treated with pamidronate

    PubMed Central

    Williams, C; Smith, R; Ball, R; Wilkinson, H

    1997-01-01

    Accepted 10 September 1996
 The response to the bisphophosphonate, pamidronate, is reported in a child with osteogenesis imperfecta who had recurrent symptomatic hypercalcaemia after immobilisation following fractures. Oral clodronate was effective in the prevention of immobilisation hypercalcaemia in the same child. The bisphosphonates may have other roles in osteogenesis imperfecta by decreasing bone turnover.

 PMID:9068314

  9. Surface integrity governs the proteome of hypomineralized enamel.

    PubMed

    Mangum, J E; Crombie, F A; Kilpatrick, N; Manton, D J; Hubbard, M J

    2010-10-01

    Growing interest in the treatment and prevention of Molar/Incisor Hypomineralization (MIH) warrants investigation into the protein composition of hypomineralized enamel. Hypothesizing abnormality akin to amelogenesis imperfecta, we profiled proteins in hypomineralized enamel from human permanent first molars using a biochemical approach. Hypomineralized enamel was found to have from 3- to 15-fold higher protein content than normal, but a near-normal level of residual amelogenins. This distinguished MIH from hypomaturation defects with high residual amelogenins (amelogenesis imperfecta, fluorosis) and so typified it as a hypocalcification defect. Second, hypomineralized enamel was found to have accumulated various proteins from oral fluid and blood, with differential incorporation depending on integrity of the enamel surface. Pathogenically, these results point to a pre-eruptive disturbance of mineralization involving albumin and, in cases with post-eruptive breakdown, subsequent protein adsorption on the exposed hydroxyapatite matrix. These insights into the pathogenesis and properties of hypomineralized enamel hold significance for prevention and treatment of MIH.

  10. Bisphosphonate therapy for osteogenesis imperfecta.

    PubMed

    Dwan, Kerry; Phillipi, Carrie A; Steiner, Robert D; Basel, Donald

    2014-07-23

    Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search: 07 April 2014. Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of osteogenesis imperfecta. Two authors independently extracted data and assessed the risk of bias of the included trials. Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no statistically significant difference for the number of participants with at least one fracture, risk ratio 0.56 (95

  11. Bisphosphonate therapy for osteogenesis imperfecta.

    PubMed

    Dwan, Kerry; Phillipi, Carrie A; Steiner, Robert D; Basel, Donald

    2016-10-19

    Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta. This is an update of a previously published Cochrane Review. To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density, reducing fractures and improving clinical function in people with osteogenesis imperfecta. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We additionally searched PubMed and major conference proceedings.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Register: 28 April 2016. Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of osteogenesis imperfecta. Two authors independently extracted data and assessed the risk of bias of the included trials. Fourteen trials (819 participants) were included. Overall, the trials were mainly at a low risk of bias, although selective reporting was an issue in several of the trials. Data for oral bisphosphonates versus placebo could not be aggregated; a statistically significant difference favouring oral bisphosphonates in fracture risk reduction and number of fractures was noted in two trials. No differences were reported in the remaining three trials which commented on fracture incidence. Five trials reported data for spine bone mineral density; all found statistically significant increased lumbar spine density z scores for at least one time point studied. For intravenous bisphosphonates versus placebo

  12. Recent developments in osteogenesis imperfecta

    PubMed Central

    Shaker, Joseph L.; Albert, Carolyne; Fritz, Jessica; Harris, Gerald

    2015-01-01

    Osteogenesis imperfecta (OI) is an uncommon genetic bone disease associated with brittle bones and fractures in children and adults. Although OI is most commonly associated with mutations of the genes for type I collagen, many other genes (some associated with type I collagen processing) have now been identified. The genetics of OI and advances in our understanding of the biomechanical properties of OI bone are reviewed in this article. Treatment includes physiotherapy, fall prevention, and sometimes orthopedic procedures. In this brief review, we will also discuss current understanding of pharmacologic therapies for treatment of OI. PMID:26401268

  13. Intramedullary rodding in osteogenesis imperfecta.

    PubMed

    Mulpuri, K; Joseph, B

    2000-01-01

    The results of intramedullary rodding of long bones of 16 children with osteogenesis imperfecta, over a 10-year period, were analyzed. Sheffield elongating rods or non-elongating rods were used. The frequency of fractures was dramatically reduced after implantation of either type of rod, and the ambulatory status improved in all instances. The results were significantly better after Sheffield rodding with regard to the frequency of complications requiring reoperations and the longevity of the rods. Migration of the rods, encountered frequently, appears to be related to improper placement of the rods in the bone. It seems likely that if care is taken to ensure precise placement of a rod of appropriate size, several of these complications may be avoided.

  14. Experience with bisphosphonates in osteogenesis imperfecta.

    PubMed

    Glorieux, Francis H

    2007-03-01

    Until recently, medical management of osteogenesis imperfecta, a genetic disorder of reduced bone mass and frequent fractures, was elusive, and treatment was focused on maximizing mobility and function. The introduction of bisphosphonates for the treatment of osteogenesis imperfecta 14 years ago changed this paradigm. Cyclic intravenous pamidronate therapy leads to an increase in bone density and a decrease in fracture rate in patients with osteogenesis imperfecta. Pamidronate therapy has a positive impact on functional parameters including improved energy, decreased bone pain, and increased ambulation. Histomorphometric studies have shown that the reduced osteoclast activity results in gains in cortical thickness and trabecular bone volume. Potential negative effects may include prolonged time to heal after osteotomies and a decrease in the rate of bone remodeling. Overall, it seems clear that the benefits of pamidronate therapy outweigh its potential risks in moderate-to-severe osteogenesis imperfecta, and pamidronate therapy has become the standard of care for patients with this condition. Questions remain regarding when treatment should be stopped and the need for pamidronate therapy in patients with mild osteogenesis imperfecta.

  15. New Perspectives on Osteogenesis Imperfecta

    PubMed Central

    Forlino, Antonella; Cabral, Wayne A.; Barnes, Aileen M.; Marini, Joan C.

    2012-01-01

    A new paradigm has emerged for osteogenesis imperfecta (OI) as a collagen-related disorder. The more prevalent autosomal dominant forms of OI are caused by primary defects in type I collagen, while autosomal recessive forms are caused by deficiency of proteins which interact with type I procollagen for post-translational modification and/or folding. Factors contributing to the mechanism of dominant OI include intracellular stress, disruption of interactions between collagen and non-collagenous proteins, compromised matrix structure, abnormal cell-cell and cell-matrix interactions and tissue mineralization. Recessive OI is caused by deficiency of any of the three components of the collagen prolyl 3-hydroxylation complex; absence of 3-hydroxylation is associated with increased modification of the collagen helix, supporting delayed collagen folding. Other causes of recessive OI include deficiency of collagen chaperones, FKBP65 or HSP47. Murine models are crucial to uncovering the common pathways in dominant and recessive OI bone dysplasia. Clinical management of OI is multidiscipinary, encompassing substantial progress in physical rehabilitation and surgical procedures, managment of hearing, dental and pulmonary abnormalities, as well as drugs such as bisphosphonates and rGH. Novel treatments using cell therapy or new drug regimens hold promise for the future. PMID:21670757

  16. Suspect osteogenesis imperfecta in a male kitten.

    PubMed

    Evason, Michelle D; Taylor, Susan M; Bebchuk, Trevor N

    2007-03-01

    A 4.5-month-old, male domestic shorthair was presented with bilateral femoral fractures after falling from a low height. Radiographs revealed reduced radio-opacity and thin cortices of all long bones. A presumptive diagnosis of osteodystrophy, secondary to osteogenesis imperfecta, was made on postmortem examination.

  17. Structure of initial crystals formed during human amelogenesis

    NASA Astrophysics Data System (ADS)

    Cuisinier, F. J. G.; Voegel, J. C.; Yacaman, J.; Frank, R. M.

    1992-02-01

    X-ray diffraction analysis revealed only the existence of carbonated hydroxyapatite (c.HA) during amelogenesis, whereas conventional transmission electron microscopy investigations showed that developing enamel crystals have a ribbon-like habit. The described compositional changes could be an indication for the presence of minerals different from c.HA. However, the absence of identification of such a mineral shows the need of studies by high resolution electron microscopy (HREM) of initial formed human enamel crystals. We demonstrate the existence of two crystal families involved in the early stages of biomineralization: (a) nanometer-size particles which appeared as a precursor phase; (b) ribbon-like crystals, with a structure closely related to c.HA, which by a progressive thickening process tend to attain the mature enamel crystal habit.

  18. Behavior of scoliosis during growth in children with osteogenesis imperfecta.

    PubMed

    Anissipour, Alireza K; Hammerberg, Kim W; Caudill, Angela; Kostiuk, Theodore; Tarima, Sergey; Zhao, Heather Shi; Krzak, Joseph J; Smith, Peter A

    2014-02-05

    Spinal deformities are common in patients with osteogenesis imperfecta, a heritable disorder that causes bone fragility. The purpose of this study was to describe the behavior of spinal curvature during growth in patients with osteogenesis imperfecta and establish its relationship to disease severity and medical treatment with bisphosphonates. The medical records and radiographs of 316 patients with osteogenesis imperfecta were retrospectively reviewed. The severity of osteogenesis imperfecta was classified with the modified Sillence classification. Serial curve measurements were recorded throughout the follow-up period for each patient with scoliosis. Regression analysis was used to determine the effect of disease severity (Sillence type), patient age, and bisphosphonate treatment on the progression of scoliosis as measured with the Cobb method. Of the 316 patients with osteogenesis imperfecta, 157 had associated scoliosis, a prevalence of 50%. Scoliosis prevalence (68%) and mean progression rate (6° per year) were the highest in the group of patients with the most severe osteogenesis imperfecta (modified Sillence type III). A group with intermediate osteogenesis imperfecta severity, modified Sillence type IV, demonstrated intermediate scoliosis values (54%, 4° per year). The patient group with the mildest form of osteogenesis imperfecta, modified Sillence type I, had the lowest scoliosis prevalence (39%) and rate of progression (1° per year). Early treatment-before the patient reached the age of six years-of type-III osteogenesis imperfecta with bisphosphonate therapy decreased the curve progression rate by 3.8° per year, which was a significant decrease. Bisphosphonate treatment had no demonstrated beneficial effect on curve behavior in patients with other types of osteogenesis imperfecta or in patients of older age. The prevalence of scoliosis in association with osteogenesis imperfecta is high. Progression rates of scoliosis in children with osteogenesis

  19. Cardiovascular Involvement in Children with Osteogenesis Imperfecta

    PubMed Central

    Karamifar, Hamdollah; Ilkhanipoor, Homa; Ajami, Gholamhossein; Karamizadeh, Zohreh; Amirhakimi, Gholamhossein; Shakiba, Ali-Mohammad

    2013-01-01

    Objective Osteogenesis imperfecta is a hereditary disease resulting from mutation in type I procollagen genes. One of the extra skeletal manifestations of this disease is cardiac involvement. The prevalence of cardiac involvement is still unknown in the children with osteogenesis imperfecta. The present study aimed to investigate the prevalence of cardiovascular abnormalities in these patients. Methods 24 children with osteogenesis imperfecta and 24 normal children who were matched with the patients regarding sex and age were studied. In both groups, standard echocardiography was performed, and heart valves were investigated. Dimensions of left ventricle, aorta annulus, sinotubular junction, ascending and descending aorta were measured and compared between the two groups. Findings The results revealed no significant difference between the two groups regarding age, sex, ejection fraction, shortening fraction, mean of aorta annulus, sinotubular junction, ascending and descending aorta, but after correction based on the body surface area, dimensions of aorta annulus, sinotubular junction, ascending and descending aorta in the patients were significantly higher than those in the control group (P<0.05). Two (8.3%) patients had aortic insufficiency and five (20%) patients had tricuspid regurgitation, three of whom had gradient >25 mmHg and one patient had pulmonary insufficiency with indirect evidence of pulmonary hypertension. According to Z scores of aorta annulus, sinotubular junction and ascending aorta, 5, 3, and 1 out of 24 patients had Z scores >2 respectively. Conclusion The prevalence of valvular heart diseases and aortic root dilation was higher in children with osteogenesis imperfecta. In conclusion, cardiovascular investigation is recommended in these children. PMID:24800009

  20. Subdural hematoma as clinical presentation of osteogenesis imperfecta.

    PubMed

    Groninger, Anja; Schaper, Jörg; Messing-Juenger, Martina; Mayatepek, Ertan; Rosenbaum, Thorsten

    2005-02-01

    Osteogenesis imperfecta is an inherited collagenous disease. The mildest form may present with less severe findings, for example blue sclera, but can also lead to significant handicap such as deafness or multiple bone fractures. We describe an 11-month-old female in whom bilateral chronic subdural hematoma was the leading clinical presentation of osteogenesis imperfecta type I. She was hospitalized due to epileptic seizures caused by these bilateral subdural hematomas without preceding trauma. Osteogenesis imperfecta type I was diagnosed on the basis of clinical and radiologic findings. This case demonstrates that nontraumatic chronic subdural hematoma in patients with osteogenesis imperfecta type I may be caused by impaired bone calcification, vascular fragility, and permanent friction between multiple bone fragments of the skull. Osteogenesis imperfecta type I should be considered as an underlying disease in cases of nontraumatic subdural hematoma. A thorough clinical examination is recommended to exclude subtle characteristics of the disease.

  1. The Specific Role of FAM20C in Amelogenesis

    PubMed Central

    Wang, X.; Jung, J.; Liu, Y.; Yuan, B.; Lu, Y.; Feng, J.Q.; Qin, C.

    2013-01-01

    Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice in which Fam20C was ubiquitously inactivated had severe defects in dentin, enamel, and bone, along with hypophosphatemia. It remains to be determined if the enamel defects in the mice with universal inactivation of Family with sequence similarity 20-C (FAM20C) were associated with the dentin defects and whether hypophosphatemia in the knockout mice contributed to the enamel defects. In this study, we crossed Fam20Cfl/fl mice with keratin 14-Cre (K14-Cre) transgenic mice to specifically inactivate Fam20C in the epithelial cells, including the dental epithelial cells that are responsible for forming tooth enamel. X-ray, backscattered scanning electron microscopic, and histological analyses showed that the K14-Cre;Fam20Cfl/fl mice had severe enamel and ameloblast defects, while their dentin and alveolar bone were not significantly affected. Accordingly, serum biochemistry of the K14-Cre;Fam20Cfl/fl mice showed normal phosphate and FGF23 levels in the circulation. Analysis of these data indicates that, while FAM20C is a molecule essential to amelogenesis, its inactivation in the dental epithelium does not significantly affect dentinogenesis. Hypophosphatemia makes no significant contribution to the enamel defects in the mice with the ubiquitous deletion of Fam20C. PMID:24026952

  2. Bone properties by nanoindentation in mild and severe osteogenesis imperfecta.

    PubMed

    Albert, Carolyne; Jameson, John; Toth, Jeffrey M; Smith, Peter; Harris, Gerald

    2013-01-01

    Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone fragility. Previous research suggests that impaired collagen network and abnormal mineralization affect bone tissue properties, however, little data is yet available to describe bone material properties in individuals with this disorder. Bone material properties have not been characterized in individuals with the most common form of osteogenesis imperfecta, type I. Bone tissue elastic modulus and hardness were measured by nanoindentation in eleven osteotomy specimens that were harvested from children with osteogenesis imperfecta during routine surgeries. These properties were compared between osteogenesis imperfecta types I (mild, n=6) and III (severe, n=5), as well as between interstitial and osteonal microstructural regions using linear mixed model analysis. Disease severity type had a small but statistically significant effect on modulus (7%, P=0.02) and hardness (8%, P<0.01). Individuals with osteogenesis imperfecta type I had higher modulus and hardness than did those with type III. Overall, mean modulus and hardness values were 13% greater in interstitial lamellar bone regions than in osteonal regions (P<0.001). The current study presents the first dataset describing bone material properties in individuals with the most common form of osteogenesis imperfecta, i.e., type I. Results indicate that intrinsic bone tissue properties are affected by phenotype. Knowledge of the material properties of bones in osteogenesis imperfecta will contribute to the ability to develop models to assist in predicting fracture risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. [Prenatal diagnosis of type II osteogenesis imperfecta].

    PubMed

    Rodríguez-García, R; Salomé-Salomé, J; Mercado-García, A; Simg-Alor, C

    1998-02-01

    We present one case of a 23 week old fetus that was diagnosed with osteogenesis imperfecta type II via ultrasound, The principal ultrasonographic findings were; lack of mineralization in the calvaria, short, wide, and angulated femurs, with the presence of fractures, the length corresponds to a 17.5 week old gestation, more than two standard deviations below the mean for gestational age. The rest of the long bones show fractures and poor mineralization that was suggested by reduced acoustic shadowing. An elective cesarean was programmed at 39.4 weeks of gestation. The osseous lesions were confirmed postnatally by means of a conventional radiographs.

  4. Osteogenesis Imperfecta, Pseudoachalasia, and Gastric Cancer

    PubMed Central

    Mizrak, Dilsa; Alkan, Ali; Erdogdu, Batuhan; Utkan, Gungor

    2015-01-01

    Osteogenesis imperfecta (OI) is a rare, inherited skeletal disorder characterized by abnormalities of type 1 collagen. Malignancy is rarely reported in patients with OI and it was suggested that this disease can protect against cancer. Here, we report a 41-year-old woman with symptoms of achalasia where repeated treatment of pneumatic dilation and stent replacement was unsuccessful; therefore, surgery was performed. Pathology showed gastric adenocarcinoma unexpectedly. Chemotherapy was given after assessing dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can be deficient in OI patients. This is the first report of gastric cancer mimicking achalasia in a patient with OI. PMID:25874139

  5. Osteogenesis imperfecta with partial trisomy 15

    PubMed Central

    Prasad, Rajniti; Basu, Biswanath; Singh, Utpal Kant; Mishra, Om Prakash

    2009-01-01

    Osteogenesis imperfecta (OI) is the most common genetic cause of osteoporosis, which presents as multiple fractures of bone. Mutations in the loci COL1A1 on band 17q21 and COL1A2 on band 7q22 have been reported as the cause in most cases of OI, but partial trisomy 15 has not been reported previously as a possible cause. A 3-month-old child with OI with an unusual association of partial trisomy 15 is reported. PMID:21686500

  6. Basilar impression in osteogenesis imperfecta tarda. Case report.

    PubMed

    Kurimoto, M; Ohara, S; Takaku, A

    1991-01-01

    A case is presented of basilar impression secondary to osteogenesis imperfecta tarda, associated with hemifacial spasm and brain-stem compression syndrome. The symptoms improved with posterior fossa decompression and posterior fusion.

  7. How Do Health Care Providers Diagnose Osteogenesis Imperfecta?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose osteogenesis imperfecta (OI)? Skip sharing on ... Page Content If OI is moderate or severe, health care providers usually diagnose it during prenatal ultrasound at ...

  8. Challenges of Fracture Management for Adults With Osteogenesis Imperfecta.

    PubMed

    Gil, Joseph A; DeFroda, Steven F; Sindhu, Kunal; Cruz, Aristides I; Daniels, Alan H

    2017-01-01

    Osteogenesis imperfecta is caused by qualitative or quantitative defects in type I collagen. Although often considered a disease with primarily pediatric manifestations, more than 25% of lifetime fractures are reported to occur in adulthood. General care of adults with osteogenesis imperfecta involves measures to preserve bone density, regular monitoring of hearing and dentition, and maintenance of muscle strength through physical therapy. Surgical stabilization of fractures in these patients can be challenging because of low bone mineral density, preexisting skeletal deformities, or obstruction by instrumentation from previous surgeries. Additionally, unique perioperative considerations exist when operatively managing fractures in patients with osteogenesis imperfecta. To date, there is little high-quality literature to help guide the optimal treatment of fractures in adult patients with osteogenesis imperfecta. [Orthopedics. 2017; 40(1):e17-e22.]. Copyright 2016, SLACK Incorporated.

  9. Bone Material Properties in Osteogenesis Imperfecta.

    PubMed

    Bishop, Nick

    2016-04-01

    Osteogenesis imperfecta entrains changes at every level in bone tissue, from the disorganization of the collagen molecules and mineral platelets within and between collagen fibrils to the macroarchitecture of the whole skeleton. Investigations using an array of sophisticated instruments at multiple scale levels have now determined many aspects of the effect of the disease on the material properties of bone tissue. The brittle nature of bone in osteogenesis imperfecta reflects both increased bone mineralization density-the quantity of mineral in relation to the quantity of matrix within a specific bone volume-and altered matrix-matrix and matrix mineral interactions. Contributions to fracture resistance at multiple scale lengths are discussed, comparing normal and brittle bone. Integrating the available information provides both a better understanding of the effect of current approaches to treatment-largely improved architecture and possibly some macroscale toughening-and indicates potential opportunities for alternative strategies that can influence fracture resistance at longer-length scales. © 2016 American Society for Bone and Mineral Research.

  10. [Genetic heterogeneity of osteogenesis imperfecta. Study of 6 cases].

    PubMed

    Olivares, J L; Hernández, M C; Bueno, M

    1986-09-01

    Osteogenesis imperfecta one of the most common disorders of connective tissue, has been known for centuries. The most characteristic alterations which define it are: osteoporosis, osseous fragility with multiple fractures, blue sclerae, deafness and imperfect dentinogenesis. Important advances in the biochemical, anatomopathological, genetic, therapeutic and prophylactic fields have resulted in a great present-day interest in this disease. In this work we report six cases of osteogenesis imperfecta according to the current classification and we review the most outstanding aspects.

  11. Anesthesia for maxillary and mandibular osteotomies in osteogenesis imperfecta.

    PubMed Central

    Rodrigo, C.

    1995-01-01

    A 21-yr-old female suffering from osteogenesis imperfecta was anesthetized for correction of maxillary and mandibular deformities that had restricted her chewing. Preoperative assessment revealed a difficult intubation, restrictive lung disease secondary to bony deformities, and multiple repairs of fractures. Management of anesthesia for this operation--which is very rarely carried out in this disorder--is described along with a review of the problems of anesthesia associated with osteogenesis imperfecta. PMID:8934957

  12. Prevalence of Dentinogenesis Imperfecta in a French Population

    PubMed Central

    Cassia, Antoine; Aoun, Georges; El-Outa, Abbass; Pasquet, Gérard; Cavézian, Robert

    2017-01-01

    Background: Dentinogenesis imperfecta is a genetic disorder of the dentin occurring during the tooth development. It leads to many structural changes that can be identified clinically (brownish colored teeth, cracked enamel) and radiologically (globular crown, cervical constriction, short roots, and obliterated pulp chamber and/or root canals). The aim of this study was to determine by panoramic radiographs assessment the incidence of dentinogenesis imperfecta in a group of patients attending a specialized maxillofacial imaging center in Paris, France. Material and Methods: A retrospective observational study was conducted using panoramic radiographs of 8830 patients (3723 males and 5107 females), which were used to search the radiological criteria of dentinogenesis imperfecta. Results: In our sample, the prevalence of dentinogenesis imperfecta was 0.057%. Out of the 8830 subjects, 0.080% of the males presented the radiological signs of the dentinogenesis imperfecta against 0.039% of the females. Conclusion: In our study, we found that dentinogenesis imperfecta is a relatively rare dental anomaly in France, with a rate different from the rates reported in other studies and with no disparity in prevalence among genders. PMID:28462180

  13. Single Molecule Effects of Osteogenesis Imperfecta Mutations in Tropocollagen Protein Domains

    DTIC Science & Technology

    2008-12-02

    Single molecule effects of osteogenesis imperfecta mutations in tropocollagen protein domains Alfonso Gautieri,1,2 Simone Vesentini,2 Alberto...2008 proteinscience.org Abstract: Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones, skeletal deformities and, in severe...diagnosis and treatment, an effort referred to as materiomics. Keywords: steered molecular dynamics; osteogenesis imperfecta ; Young’s modulus; collagen

  14. [Osteogenesis imperfecta: quality of life in children].

    PubMed

    Fano, Virginia; del Pino, Mariana; Rodríguez Celin, Mercedes; Buceta, Susana; Obregón, M Gabriela

    2013-01-01

    The impact produced by osteogenesis imperfecta in childrens' quality of life almost has not been reported; 65 children, 38 males, were evaluated according to the questionnaire PedsQL 4.0 Argentinean Spanish version. Median age was 7.76 years; 35 children with OI type I were compared with 30 type III-IV (according to Sillence Classification) finding significant difference in the physical domain in both visions, children and parents, and only in parents' vision in the social area. Multivariate analysis showed an association between better PedQL scores and treatment compliance (coef. β= 19.41 p= 0.03) in children's vision. In parental report on the other hand, the association was found with greater pamidronate doses (coef. β 1.44 p=0.037), lower height compromise (coef. β= 3.8; p= 0.039) and less number of fractures (coef. β= 0.69; p= 0.003).

  15. [Treatment of osteogenesis imperfecta with bisphosphonates].

    PubMed

    Tau, Cristina

    2007-01-01

    Treatment with bisphosphonates (BP) improves the quality of life of patients with osteogenesis imperfecta (OI). Beneficial effects are the relief of bone pain, a reduction of fracture incidence, improvement of corporal mobility and recovery of normal vertebral form. Treatment is less effective after completion of growth [corrected] An update of the literature is here presented. A number of important unsolved questions have been pointed out: for how long should treatment be instituted? Is the oral route as effective as the intravenous one? Which is the best dose? When treatment should be stopped? How well preserved is the longterm integrity of the bones? Which are the phenomena occurring in bone tissue after interruption of therapy?

  16. [Orthotic management for patients with osteogenesis imperfecta].

    PubMed

    Alguacil Diego, I M; Molina Rueda, F; Gómez Conches, M

    2011-02-01

    Osteogenesis imperfecta (OI) is a disease caused by a genetic defect in the qualitative and quantitative synthesis of type I collagen. There is a wide variation in its clinical signs, characterized by bone fragility, resulting in a bone vulnerable to external and internal forces, determining the occurrence of frequent fractures with minimal or no trauma. The therapeutic objective is directed to improve the functional capacity of the child or adult concerned, adopting those compensatory strategies to optimise their independence. In this sense, the use of different orthoses and assistive technology are important for achieving these objectives. We reviewed the main contributions to this orthotic disease and the evolution of the different devices used in different databases over the last 25 years.

  17. Valvular and aortic diseases in osteogenesis imperfecta.

    PubMed

    Lamanna, Arvin; Fayers, Trevor; Clarke, Sophie; Parsonage, William

    2013-10-01

    Osteogenesis imperfecta (OI) is an inheritable connective tissue disorder caused by defective collagen synthesis with the principal manifestations of bone fragility. OI has been associated with left sided valvular regurgitation and aortic dilation. Valve and aortic surgery are technically feasible in patients with OI but are inherently high risk due to the underlying connective tissue defect. This report reviews the valvular and aortic pathology associated with OI and their management. We describe two cases of patients with OI who have significant aortic and mitral valve regurgitation, one of whom has been managed conservatively and the other who has undergone successful mitral valve repair and aortic valve replacement. The latter case represents the fifth case of mitral valve repair in a patient with OI reported in the medical literature. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  18. IFITM5 mutations and osteogenesis imperfecta.

    PubMed

    Hanagata, Nobutaka

    2016-03-01

    Interferon-induced transmembrane protein 5 (IFITM5) is an osteoblast-specific membrane protein that has been shown to be a positive regulatory factor for mineralization in vitro. However, Ifitm5 knockout mice do not exhibit serious bone abnormalities, and thus the function of IFITM5 in vivo remains unclear. Recently, a single point mutation (c.-14C>T) in the 5' untranslated region of IFITM5 was identified in patients with osteogenesis imperfecta type V (OI-V). Furthermore, a single point mutation (c.119C>T) in the coding region of IFITM5 was identified in OI patients with more severe symptoms than patients with OI-V. Although IFITM5 is not directly involved in the formation of bone in vivo, the reason why IFITM5 mutations cause OI remains a major mystery. In this review, the current state of knowledge of OI pathological mechanisms due to IFITM5 mutations will be reviewed.

  19. [Limb lengthening in children with osteogenesis imperfecta].

    PubMed

    Sułko, Jerzy; Radło, Wojciech

    2005-01-01

    The authors operated on 7 children (5 girls, 2 boys) suffering from osteogenesis imperfecta (oi) type I according to Sillence classification, with lower limbs discrepancy. We elongated 10 segments (7 femurs and 3 tibias). Mean age at operation time was 14.7 years (13-17 years). The mean leg length discrepancy was 9.3 cm (4-18 cm), and shortening of one bone was 6.5 cm (4-9 cm). We used Ilizarov technique twice in tibial lengthening. We used Wagner technique in one tibial elongation and in 7 femur elongation. Except for one tibia, in the remaining cases there was Rush rod inserted intramedullary in the bone being elongated. During tibial elongation we fixed lateral malleous by screw. The osteotomy was performed in proximal metaphysis of the 5 femurs and 3 tibias, and in distal femurs in two cases. The elongation was 1 mm for day, with frequency 4 x 1/4 mm. The mean bone lengthening achieved was 5.5 cm (2-9 cm); the mean lengthening of the limb was 7.9 cm (2-18 cm). The mean time of elongation was 2.8 months (2-5 months). Elongation index was 26 days for 1 cm of lengthening. The mean time of fixator removal was 9.2 months (4-13 months). Healing index was 58 day/1 cm (overall number of days for 1 cm lengthening). The complications occurred in all the patients. Although the risk of numerous complication is high, lower limbs lengthening in children with type I osteogeneis imperfecta is possible to perform and allows equalizing discrepant limbs or, at least reducing the difference.

  20. GEP, a local growth factor, is critical for odontogenesis and amelogenesis.

    PubMed

    Cao, Zhengguo; Jiang, Baichun; Xie, Yixia; Liu, Chuan-ju; Feng, Jian Q

    2010-11-25

    Granulin epithelin precursor (GEP) is a new growth factor that functions in brain development, chondrogenesis, tissue regeneration, tumorigenesis, and inflammation. The goal of this study was to study whether GEP was critical for odontogenesis and amelogenesis both in vivo and in vitro. The in situ hybridization and immunohistochemistry data showed that GEP was expressed in both odontoblast and ameloblast cells postnatally. Knockdown of GEP by crossing U6-ploxPneo-GEP and Sox2-Cre transgenic mice led to a reduction of dentin thickness, an increase in predentin thickness, and a reduction in mineral content in enamel. The in vitro application of recombinant GEP up-regulated molecular markers important for odontogenesis (DMP1, DSPP, and ALP) and amelogenesis (ameloblastin, amelogenin and enamelin). In conclusion, both the in vivo and the in vivo data support an important role of GEP in tooth formation during postnatal development.

  1. GEP, a Local Growth Factor, is Critical for Odontogenesis and Amelogenesis

    PubMed Central

    Cao, Zhengguo; Jiang, Baichun; Xie, Yixia; Liu, Chuan-ju; Feng, Jian Q.

    2010-01-01

    Granulin epithelin precursor (GEP) is a new growth factor that functions in brain development, chondrogenesis, tissue regeneration, tumorigenesis, and inflammation. The goal of this study was to study whether GEP was critical for odontogenesis and amelogenesis both in vivo and in vitro. The in situ hybridization and immunohistochemistry data showed that GEP was expressed in both odontoblast and ameloblast cells postnatally. Knockdown of GEP by crossing U6-ploxPneo-GEP and Sox2-Cre transgenic mice led to a reduction of dentin thickness, an increase in predentin thickness, and a reduction in mineral content in enamel. The in vitro application of recombinant GEP up-regulated molecular markers important for odontogenesis (DMP1, DSPP, and ALP) and amelogenesis (ameloblastin, amelogenin and enamelin). In conclusion, both the in vivo and the in vivo data support an important role of GEP in tooth formation during postnatal development. PMID:21152114

  2. Basilar impression and platybasia in osteogenesis imperfecta tarda.

    PubMed

    Frank, E; Berger, T; Tew, J M

    1982-02-01

    Osteogenesis imperfecta, a rare, genetically transmitted disorder of bone, is known to be associated with the development of basilar impression and platybasia. These deformities of the base of the skull may cause neurosurgical abnormalities secondary to compression of the brainstem and hydrocephalus. The case is presented of a young boy with a family history of osteogenesis imperfecta tarda who suffered respiratory arrest during hospitalization. Cranial nerves and pyramidal tract signs were demonstrated. Roentgenograms showed severe basilar impression and hydrocephalus. Decompression of the brainstem and shunting were performed with improvement in the patient's neurological status. This case represents a rare by significant central nervous system complication of osteogenesis imperfecta. Early recognition and implementation of aggressive treatment are important if irreversible neurological deficits are to be avoided.

  3. A rare combination of amniotic constriction band with osteogenesis imperfecta.

    PubMed

    Shah, Krupa Hitesh; Shah, Hitesh

    2015-11-11

    Amniotic constriction bands and osteogenesis imperfecta are disorders arising from a collagen defect. We report a rare association of amniotic bands with osteogenesis imperfecta in a child. The child was born with multiple amniotic bands involving the right leg, both hands and both feet. Multiple fractures of long bones of lower limbs occurred in childhood due to trivial trauma. Deformities of the femur and tibia due to malunion with osteopenia and blue sclerae were present. The patient was treated with z plasty of constriction band of the right tibia and bisphosphonate for osteogenesis imperfecta. This rare association of both collagen diseases may provide further insight for the pathogenesis of these diseases. 2015 BMJ Publishing Group Ltd.

  4. Novel WDR72 Mutation and Cytoplasmic Localization

    PubMed Central

    Lee, S.-K.; Seymen, F.; Lee, K.-E.; Kang, H.-Y.; Yildirim, M.; Bahar Tuna, E.; Gencay, K.; Hwang, Y.-H.; Nam, K.H.; De La Garza, R.J.; Hu, J.C.-C.; Simmer, J.P.; Kim, J.-W.

    2010-01-01

    The proven candidate genes for amelogenesis imperfecta (AI) are AMELX, ENAM, MMP20, KLK4, FAM83H, and WDR72. We performed mutation analyses on seven families with hypomaturation AI. A novel WDR72 dinucleotide deletion mutation (g.57,426_57,427delAT; c.1467_ 1468delAT; p.V491fsX497) was identified in both alleles of probands from Mexico and Turkey. Haplotype analyses showed that the mutations arose independently in the two families. The disease perfectly segregated with the genotype. Only persons with both copies of the mutant allele were affected. Their hypomineralized enamel suffered attrition and orange-brown staining following eruption. Expression of WDR72 fused to green fluorescent protein showed a cytoplasmic localization exclusively and was absent from the nucleus. We conclude that WDR72 is a cytoplasmic protein that is critical for dental enamel formation. PMID:20938048

  5. Orthotic treatment of positional brachycephaly associated with osteogenesis imperfecta.

    PubMed

    Matarazzo, Carolina G; Schreen, Gerd; Lago-Rizzardi, Camilla D do; Peccin, Maria Stella; Pinto, Fernando Cg

    2017-01-01

    Osteogenesis imperfecta is an inherited disorder of the connective tissue characterized primarily by fractures with no or small causal antecedents and extremely variable clinical presentation. The disorder requires a global and, therefore, multidisciplinary therapeutic approach that should aim, among other aspects, at the prevention and treatment of deformities resulting from osteogenesis imperfecta. Due to limitations related to bony deformities, it can be difficult to place these infants in a variety of positions that would help remediate skull deformities, so a cranial orthosis becomes the therapy of choice. The aim of this study was to demonstrate the results obtained during treatment with a cranial remolding orthosis (helmet) in babies with osteogenesis imperfecta. Case Description and Methods: For the first time in the scientific literature, this study describes the use of a cranial orthosis for the treatment of infants with osteogenesis imperfecta. Both children had severe asymmetrical brachycephaly documented by laser digital scanning and were submitted to treatment with a cranial remolding orthosis. Outcomes and Conclusion: The study showed that there was a significant improvement in cranial proportion and symmetry, with a reduction in the cephalic index at reevaluation. It is concluded that the orthotic therapy is an effective therapeutic modality to improve the proportion and minimize the asymmetry in children with osteogenesis imperfecta. Clinical relevance The clinical relevance of such a description is that children with osteogenesis imperfecta may have numerous deformities and minimizing them can be an important factor. This report showed a beneficial result as the orthotic therapy modality improved the proportions and minimized the asymmetry. This treatment offers too high levels of satisfaction to parents and brings these children closer to normal indices.

  6. Clinical manifestations and dental management of dentinogenesis imperfecta associated with osteogenesis imperfecta: Case report

    PubMed Central

    Abukabbos, Halima; Al-Sineedi, Faisal

    2013-01-01

    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. PMID:24371383

  7. An osteogenesis imperfecta case with breast cancer.

    PubMed

    Taira, Fumi; Shimizu, Hideo; Kosaka, Taijiro; Saito, Mitsue; Kasumi, Fujio

    2014-11-01

    Osteogenesis imperfecta (OI) is a rare connective tissue disease characterized by abnormalities of type 1 collagen and an increased risk of bone fractures. Several OI cases with malignancies have been reported. Herein, we describe an OI case with breast cancer. A 36-year-old premenopausal woman with OI was admitted to our hospital for evaluation of a right breast lump. We diagnosed right breast cancer with axillary and parasternal lymph node metastasis (T2N3M0 stage IIIC). The tumor had increased in size and tumor markers were elevated after 10 months of hormone therapy. We performed a right mastectomy and axillary dissection. She subsequently received adjuvant chemotherapy and radiotherapy. She is currently taking trastuzumab and tamoxifen. Anesthesia is challenging in OI patients because of difficulty with airway control and intubation. We performed the mastectomy in this case without difficulty by working in cooperation with experienced anesthesiologists, orthopedists, and other medical personnel. Some OI patients reportedly have severe 5-fluorouracil (5-FU) toxicity related to dihydropyrimidine dehydrogenase (DPD) deficiency. DPD is the main enzyme involved in the catabolism of 5-FU. Our present case also had low DPD activity and we thus chose epirubicin and cyclophosphamide for chemotherapy. Our search of the literature yielded only two OI cases with breast cancer as of April 2011. To our knowledge, this is the first case reported in Japan.

  8. Intravenous pamidronate in osteogenesis imperfecta type VII.

    PubMed

    Cheung, Moira S; Glorieux, Francis H; Rauch, Frank

    2009-03-01

    Cyclical intravenous treatment with pamidronate is widely used to treat osteogenesis imperfecta (OI) types I, III, and IV, which are due to dominant mutations affecting collagen type I alpha chains. There is no information about the effects of pamidronate in children with OI type VII, an autosomal-recessive form of OI caused by a mutation in the cartilage-associated protein gene. In this retrospective single-center study, we compared the effects of pamidronate in four girls with OI type VII (age range 3.9-12.7 years) to those in eight girls with OI types caused by collagen type I mutations who were matched for age and disease severity. During 3 years of pamidronate therapy, lumbar spine areal bone mineral density increased and lumbar vertebral bodies improved in shape in patients with OI type VII. Other outcomes such as fracture rates and mobility scores did not show statistically significant changes in this small study cohort. There were no significant side effects noted during the time of follow-up. Thus, intravenous treatment with pamidronate seems to be safe and of some benefit in patients with OI type VII.

  9. Dentinogenesis imperfecta: an early treatment strategy.

    PubMed

    Sapir, S; Shapira, J

    2001-01-01

    Dentinogenesis imperfecta (DI) type 2 is a disease inherited in a simple autosomal dominant mode. As soon as the teeth erupt the parents may notice the problem and look for a pediatric dentist's advice and treatment. Early diagnosis and treatment of DI is recommended, as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. The purpose of this article is to present the objectives, treatment options, and problems encountered in the treatment of DI in the early primary dentition. A two-stage treatment of a toddler under general anesthesia is described and discussed. This paper recommends for severe cases of DI two treatment stages performed under general anesthesia. Stage 1 is early (around age 18-20 months) and is directed to covering the incisors with composite restorations and the first primary molars with preformed crowns. Stage 2 (around age 28-30 months) seeks to protect the second primary molars with preformed crowns and cover the canines with composite restorations.

  10. Osteogenesis imperfecta: a case with hand deformities.

    PubMed

    Oz, Bengi; Olmez, Nese; Memis, Asuman

    2005-09-01

    In a 51-year-old woman with a history of fractures and dislocations after low intensity trauma in childhood, intensive blue sclera, short stature, and hearing loss, the diagnosis of osteogenesis imperfecta (OI) was suspected. She was referred to our clinic with hand deformities and left knee pain and stiffness. She had difficulty in walking and reported a history of immobilization for 6 months because of knee pain. She had bilateral flexion contracture of the elbows which occurred following dislocations of the elbows in childhood. She had Z deformity of the first phalanges, reducible swan-neck deformity of the third finger of the left and the second finger of the right hand, flexion contracture of the proximal interphalangeal joint of the fifth finger of the left hand, and syndactyly of the third and fourth fingers of the right hand. Flexion contractures of both knees were observed. Pes planus and short toes were the deformities of the feet. Acute phase reactants of the patient were normal. She had no history of arthritis or morning stiffness. Bone mineral density evaluated by dual-energy X-ray absorptiometry (DEXA) showed severe osteoporosis of the femur and lumbar vertebrae. She had radiographic evidence of healed fractures of the left fibula, the third metacarpal, and the fourth and fifth middle phalanges of the right hand. OI, affecting the type I collagen tissue of the sclera, skin, ligaments, and skeleton, presenting with ligament laxity resulting in subluxations and hand deformities may be misdiagnosed as hand deformities of rheumatoid arthritis.

  11. Skeletal muscle weakness in osteogeneis imperfecta mice

    PubMed Central

    Gentry, Bettina A; Ferreira, J. Andries; McCambridge, Amanda J.; Brown, Marybeth; Phillips, Charlotte L.

    2010-01-01

    Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (Po, Po/mg and Po/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased Po and an inability to sustain Po for the 300 ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology. PMID:20619344

  12. Osteogenesis Imperfecta: A Review with Clinical Examples

    PubMed Central

    van Dijk, F.S.; Cobben, J.M.; Kariminejad, A.; Maugeri, A.; Nikkels, P.G.J.; van Rijn, R.R.; Pals, G.

    2011-01-01

    Osteogenesis imperfecta (OI) is characterized by susceptibility to bone fractures, with a severity ranging from subtle increase in fracture frequency to prenatal fractures. The first scientific description of OI dates from 1788. Since then, important milestones in OI research and treatment have, among others, been the classification of OI into 4 types (the ‘Sillence classification’), the discovery of defects in collagen type I biosynthesis as a cause of most cases of OI and the use of bisphosphonate therapy. Furthermore, in the past 5 years, it has become clear that OI comprises a group of heterogeneous disorders, with an estimated 90% of cases due to a causative variant in the COL1A1 or COL1A2 genes and with the remaining 10% due to causative recessive variants in the 8 genes known so far, or in other currently unknown genes. This review aims to highlight the current knowledge around the history, epidemiology, pathogenesis, clinical/radiological features, management, and future prospects of OI. The text will be illustrated with clinical descriptions, including radiographs and, where possible, photographs of patients with OI. PMID:22570641

  13. Evaluation of stomatognathic problems in children with osteogenesis imperfecta (osteogenesis imperfecta - oi) - preliminary study.

    PubMed

    Smoląg, Danuta; Kulesa-Mrowiecka, Małgorzata; Sułko, Jerzy

    2017-01-01

    According to epidemiological data, muscular dysfunctions of the masticatory system occur in 15-23% of the population. Preventive examinations of functional disorders of the stomatognathic system are, therefore, of particular importance. A distinct group of patients exposed to dysfunctions in the area of the masticatory organ locomotor apparatus comprises those with genetic diseases characterised by disorders in collagen formation. One of such diseases is osteogenesis imperfecta (OI) and dentinogenesis imperfecta that usually goes together with the former. The objective of this work was to evaluate the frequency with which particular disorders of the masticatory organ locomotor apparatus occur within the group of patients with osteogenesis imperfecta. The study was performed on patients of the Orthopaedic Clinic of the Polish-American Paediatric Institute in Kraków. The mean age of the children was 7.9 years. In all the cases, a genetic diagnosis of OI has been confirmed. The research methods were based on an in-depth interview on family diseases, pregnancy, postnatal period, feeding, subjective assessment of dysfunctions in the stomatognathic system. An examination of the deformations in the stomatognathic system and the skeleton was conducted, as well as an examination of the trauma and tone of the jaw. The relationship between breastfeeding and swallowing and speech disorders was also evaluated. The impact of intubation on mandibular ranges was investigated. The results obtained were subjected to statistical analysis on the basis of which conclusions were drawn concerning disorders in the stomatognathic system which tend to occur in children with OI. The renunciation of breastfeeding significantly contributes to sucking and swallowing disorders, rumen disorders, as well as biomechanical disorders in the temporomandibular joint. A significant dependence between breastfeeding and swallowing problems was found, whereas there was no such dependence with respect to

  14. Musculoskeletal manifestations of mild osteogenesis imperfecta in the adult.

    PubMed

    McKiernan, Fergus E

    2005-12-01

    The musculoskeletal manifestations of mild forms of osteogenesis imperfecta are not well defined in the adult. The aim of this study was to characterize the musculoskeletal manifestations and resulting impairments reported by adults with mild osteogenesis imperfecta. For this task a survey of musculoskeletal symptoms and impairments was hosted on the Osteogenesis Imperfecta Foundation web site for 6 weeks. Survey responses are reported herein. There were 111 unduplicated, adult respondents (78 female). Mean age was 40.8 years. More than one-quarter of 3,410 lifetime fractures occurred in adulthood. Nearly half of respondents reported an established diagnosis of "arthritis" (usually osteoarthritis), and the majority of these reported some degree of impairment attributable to arthritis. Articular pain, stiffness and instability were dominant in the large, weight-bearing joints of the lower extremities. Back pain and scoliosis were common. Of the respondents, 15% required assistance with light physical tasks and personal care. Two-thirds reported joint hyper-mobility, and one-third reported a previous tendon rupture. Complex regional pain syndrome was rare. Respondents reported frequent use of medications known to have potential adverse skeletal effects. In spite of these concerns the majority rated their overall physical health as good or excellent. Adults with mild osteogenesis imperfecta continue to sustain fractures into adulthood, and the majority reports some functional impairment due to musculoskeletal issues. Significant impairment is not rare.

  15. A type IV osteogenesis imperfecta family and pregnancy: a case report and literature review.

    PubMed

    Feng, Zhao-yi; Chen, Qian; Shi, Chun-yan; Wen, Hong-wu; Ma, Ke; Yang, Hui-xia

    2012-04-01

    Osteogenesis imperfecta is a group of inherited connective-tissue disorders in which synthesis or structure of type I collagen is defective and causes osseous fragility. Type IV osteogenesis imperfecta is dominant inheritance. Here, we report a case of type IV osteogenesis imperfecta family and their female member's pregnancy. Abnormal sonographic findings (marked bowing and shortening of long bones) and family history made the diagnosis of fetus with osteogenesis imperfecta. The parents decided to give up rescuing the infant and a caesarean section at 27 weeks of gestation was implemented. In conclusion, it is possible to make a prenatal diagnosis of osteogenesis imperfecta by ultrasound. For the pregnant women with osteogenesis imperfecta, management decision should be made on an individual basis.

  16. A Guide to Education for Children with Osteogenesis Imperfecta. What Is OIF? Care of an Osteogenesis Imperfecta Baby and Child.

    ERIC Educational Resources Information Center

    Ostegenesis Imperfecta Foundation, Inc., Manchester, NH.

    Three pamphlets provide basic information on the care and education of children with osteogenesis imperfecta (OI) a lifelong liability to fractures due to imperfectly formed "brittle bones." The first brochure, a guide to education for children with OI, addresses the importance of attitudes, the value of early education, public school…

  17. A Guide to Education for Children with Osteogenesis Imperfecta. What Is OIF? Care of an Osteogenesis Imperfecta Baby and Child.

    ERIC Educational Resources Information Center

    Ostegenesis Imperfecta Foundation, Inc., Manchester, NH.

    Three pamphlets provide basic information on the care and education of children with osteogenesis imperfecta (OI) a lifelong liability to fractures due to imperfectly formed "brittle bones." The first brochure, a guide to education for children with OI, addresses the importance of attitudes, the value of early education, public school…

  18. [Shaken baby syndrome and osteogenesis imperfecta].

    PubMed

    Cabrerizo de Diago, R; Ureña-Hornos, T; Conde-Barreiro, S; Labarta-Aizpun, J; Peña-Segura, J L; López-Pisón, J

    Shaken baby syndrome (SBS) is a form of physical abuse that includes the presence of a subdural or subarachnoid haematoma or diffuse cerebral oedema, retinal haemorrhages and, in general, absence of other physical signs of traumatic injury. Osteogenesis imperfecta (OI) is a genetic disorder affecting the synthesis of type I collagen that leads to brittle bones with frequently occurring fractures, with presenting clinical symptoms taking a variety of forms. A differential diagnosis allowing it to be distinguished from physical abuse is known, due to the existence of bone fractures with no known traumatic injuries, but we do not understand the link between OI and SBS. We describe the case of an infant who, at the age of 3 months, suffered symptoms of acute encephalopathy with convulsions, subdural haematoma and retinal haemorrhages compatible with SBS, as well as bilateral rib fractures. The skeletal series of X-rays revealed alterations in bone structure and texture, which led to a diagnosis of OI that was confirmed by a study of the collagen in skin fibroblasts. The suspected existence of SBS is unpleasant both for the health care professional and for the patient's relatives. The existence of rib fractures in an obvious case of shaken baby syndrome suggested malicious abuse; however, the parents' attitude and the existence of OI made us think that no harm was intended. Shaking could have been secondary to bouts of crying due to microfissures related to the OI. The differential diagnosis of processes that can be mistaken for shaken baby or from favourable or predisposing medical factors must be taken into consideration.

  19. Collagen defects in lethal perinatal osteogenesis imperfecta.

    PubMed Central

    Bateman, J F; Chan, D; Mascara, T; Rogers, J G; Cole, W G

    1986-01-01

    Quantitative and qualitative abnormalities of collagen were observed in tissues and fibroblast cultures from 17 consecutive cases of lethal perinatal osteogenesis imperfecta (OI). The content of type I collagen was reduced in OI dermis and bone and the content of type III collagen was also reduced in the dermis. Normal bone contained 99.3% type I and 0.7% type V collagen whereas OI bone contained a lower proportion of type I, a greater proportion of type V and a significant amount of type III collagen. The type III and V collagens appeared to be structurally normal. In contrast, abnormal type I collagen chains, which migrated slowly on electrophoresis, were observed in all babies with OI. Cultured fibroblasts from five babies produced a mixture of normal and abnormal type I collagens; the abnormal collagen was not secreted in two cases and was slowly secreted in the others. Fibroblasts from 12 babies produced only abnormal type I collagens and they were also secreted slowly. The slower electrophoretic migration of the abnormal chains was due to enzymic overmodification of the lysine residues. The distribution of the cyanogen bromide peptides containing the overmodified residues was used to localize the underlying structural abnormalities to three regions of the type I procollagen chains. These regions included the carboxy-propeptide of the pro alpha 1(I)-chain, the helical alpha 1(I) CB7 peptide and the helical alpha 1(I) CB8 and CB3 peptides. In one baby a basic charge mutation was observed in the alpha 1(I) CB7 peptide and in another baby a basic charge mutation was observed in the alpha 1(I) CB8 peptide. The primary defects in lethal perinatal OI appear to reside in the type I collagen chains. Type III and V collagens did not appear to compensate for the deficiency of type I collagen in the tissues. Images Fig. 1. Fig. 2. Fig. 4. PMID:3827862

  20. Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors

    PubMed Central

    Houari, Sophia; Loiodice, Sophia; Jedeon, Katia; Berdal, Ariane; Babajko, Sylvie

    2016-01-01

    Endocrine disrupting chemicals (EDCs) play a part in the modern burst of diseases and interfere with the steroid hormone axis. Bisphenol A (BPA), one of the most active and widely used EDCs, affects ameloblast functions, leading to an enamel hypomineralization pattern similar to that of Molar Incisor Hypomineralization (MIH). In order to explore the molecular pathways stimulated by BPA during amelogenesis, we thoroughly investigated the receptors known to directly or indirectly mediate the effects of BPA. The expression patterns of high affinity BPA receptors (ERRγ, GPR30), of ketosteroid receptors (ERs, AR, PGR, GR, MR), of the retinoid receptor RXRα, and PPARγ were established using RT-qPCR analysis of RNAs extracted from microdissected enamel organ of adult rats. Their expression was dependent on the stage of ameloblast differentiation, except that of ERβ and PPARγ which remained undetectable. An additional large scale microarray analysis revealed three main groups of receptors according to their level of expression in maturation-stage ameloblasts. The expression level of RXRα was the highest, similar to the vitamin D receptor (VDR), whereas the others were 13 to 612-fold lower, with AR and GR being intermediate. Immunofluorescent analysis of VDR, ERα and AR confirmed their presence mainly in maturation- stage ameloblasts. These data provide further evidence that ameloblasts express a specific combination of hormonal receptors depending on their developmental stage. This study represents the first step toward understanding dental endocrinology as well as some of the effects of EDCs on the pathophysiology of amelogenesis. PMID:27853434

  1. Osteogenesis Imperfecta (Type IV) with Dental Findings in Siblings

    PubMed Central

    Shetty, Shishir Ram; Dsouza, Deepa; Babu, Subhas; Balan, Preethi

    2011-01-01

    Osteogenesis imperfecta (OI) is a hereditary disorder characterized by increased tendency for bone fractures due to high fragility. The clinical and radiological features of OI manifest in different age groups, although the disease is congenital in nature. Besides bone fragility, features like laxity of the ligaments, blue sclera, growth retardation, and scoliosis are also observed. In severe cases, respiratory distress and death have been reported. The most important oral finding in OI is the presence of yellowish-brown-coloured brittle teeth characteristic of dentinogenesis imperfecta. Genetic factors play a very important role in the pathogenesis of OI either as a dominant or recessive factor. When a child has OI, there is a 25% chance of the sibling to have the same disorder. We report two cases of OI in siblings born to parents with a history of consanguineous marriage. The clinical and radiological features of the two cases are described in detail. PMID:22567450

  2. Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification

    PubMed Central

    de La Dure-Molla, Muriel; Philippe Fournier, Benjamin; Berdal, Ariane

    2015-01-01

    Dentinogenesis imperfecta is an autosomal dominant disease characterized by severe hypomineralization of dentin and altered dentin structure. Dentin extra cellular matrix is composed of 90% of collagen type I and 10% of non-collagenous proteins among which dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP) are crucial in dentinogenesis. These proteins are encoded by a single gene: dentin sialophosphoprotein (DSPP) and undergo several post-translational modifications such as glycosylation and phosphorylation to contribute and to control mineralization. Human mutations of this DSPP gene are responsible for three isolated dentinal diseases classified by Shield in 1973: type II and III dentinogenesis imperfecta and type II dentin dysplasia. Shield classification was based on clinical phenotypes observed in patient. Genetics results show now that these three diseases are a severity variation of the same pathology. So this review aims to revise and to propose a new classification of the isolated forms of DI to simplify diagnosis for practitioners. PMID:25118030

  3. Multidisciplinary approach for a patient with dentinogenesis imperfecta and anterior trauma.

    PubMed

    Roh, Won-Jong; Kang, Seung-Goo; Kim, Su-Jung

    2010-09-01

    Dentinogenesis imperfecta is an inherited dentinal dysplasia involving several risks for orthodontic treatment. This case report describes the multidisciplinary treatment of a 17-year-old girl whose Class II Division 1 malocclusion was complicated by dentinogenesis imperfecta type II and maxillary anterior trauma. 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  4. Children with Osteogenesis Imperfecta and Their Life Situation. Report and Documentation.

    ERIC Educational Resources Information Center

    Brodin, Jane

    Children with osteogenesis imperfecta form a small and relatively unknown group, with 5 to 10 children diagnosed in Sweden each year and a total of around 200 people under the age of 17 having the condition. A questionnaire was completed by families of 24 Swedish children with osteogenesis imperfecta, and three families were interviewed. The…

  5. Anesthetic Management in a Gravida with Type IV Osteogenesis Imperfecta

    PubMed Central

    Vue, Elizabeth; Davila, Juan

    2016-01-01

    Osteogenesis imperfecta (OI) is an inherited disorder of the connective tissues caused by abnormalities in collagen formation. OI may present many challenges to the anesthesiologist. A literature review reveals a wide range of implications, from basic positioning to management of the difficult airway. We present the anesthetic management of a 25-year-old gravid woman with OI, fetal demise, and possible uterine rupture, admitted for an exploratory laparotomy. PMID:27433164

  6. Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta

    PubMed Central

    Åström, Eva; Jorulf, Håkan; Söderhäll, Stefan

    2007-01-01

    Objective Children with the severe forms of osteogenesis imperfecta have in several studies been treated with intravenous pamidronate, but there are only few reports of the effect of early treatment. Aim To evaluate the effect of treatment started in infancy. Methods In a prospective observational study, with a historic control group, intravenous disodium pamidronate (APD) was given as monthly infusions to 11 children with osteogenesis imperfecta aged 3–13 (median 3.6) months, who had severe osteogenesis imperfecta with congenital bowing of the femora and vertebral compression fractures. Results During treatment of children aged between 3 and 6 (median 4.5) years, dual‐energy x ray absorptiometry measurements of the lumbar spine showed a gradual increase in bone density. Bone metabolism parameters in serum (alkaline phosphatase, osteocalcin, procollagen 1 carboxy‐terminal peptide, collagen 1 teleopeptide) and in urine (deoxypyridinoline) indicated a decrease in bone turnover. An improvement of mobility was seen and at the latest recording, at the age of 3.3–6.5 (median 4.8) years, the children could all walk. Vertebral remodelling was seen, with increased vertebral height, and no child developed scoliosis, kyphosis or basilar impression. All children required femoral intramedullar rods for fractures, and five needed tibial rodding for extreme curvatures that prevented functional standing and walking. No adverse effects were seen on growth, fracture healing or blood chemistry. Conclusions APD is an efficient symptomatic treatment for infants with severe osteogenesis imperfecta, but additional orthopaedic surgery is often needed. Early treatment may prevent scoliosis and basilar impression. Long‐term follow‐up is important. PMID:17114205

  7. Osteogenesis imperfecta type I with unusual dental abnormalities.

    PubMed

    Levin, L S; Young, R J; Pyeritz, R E

    1988-12-01

    A large kindred with dominantly inherited osteogenesis imperfecta was evaluated. Affected individuals had bone fractures, blue sclerae, and hearing loss. In addition, all had dental abnormalities distinct from those previously described in other families with this syndrome. Deciduous teeth were normal in color or blue-grey. On radiographs of an early developing deciduous dentition, pulps were larger than normal. In patients with mixed dentitions, pulp chambers of deciduous teeth were partially obliterated. Increased constriction at the junctions of the crowns and roots was found in some deciduous teeth. One patient had large pulp stones in the pulp chambers of all maxillary deciduous molars. Permanent teeth were normal in color but had oval pulp chambers with apical extensions into the coronal portions of the roots, large coronal pulp stones, narrow root canals, and thin roots. Individuals in this family who did not have osteogenesis imperfecta had normal teeth. In addition, a well circumscribed radiolucency without a sclerotic periphery, involving the apices of all permanent mandibular incisors, was found in the anterior mandible in one patient. These findings support the hypothesis that this family has yet another type I osteogenesis imperfecta "syndrome".

  8. Bilateral papilledema in a child with osteogenesis imperfecta.

    PubMed

    Sendul, Selam Yekta; Atilgan, Cemile Ucgul; Tiryaki, Semra; Guven, Dilek

    2016-01-01

    To present a female child patient with osteogenesis imperfecta who had bilateral papilledema. A twelve-year-old girl with osteogenesis imperfecta was referred to our clinic. Bilateral best corrected visual acuity of the patient was 5/10 (corrected with +3.50 for right eye, +5.00 for left eye) with a standard Snellen scale at a distance of a 6 m. Anterior chamber, iris and lens examination of both of her eyes were unremarkable. In her fundus examination, bilateral stage 2 papilledema and the wrinkles in papillomacular area were noticed. Optical coherence tomography images revealed the macular pucker and thickening in the retinal nerve fibre layers of both eyes. Computed tomography images revealed that there were ossifications in the optic chiasma and occlusion in all periorbital sinus areas. Osteogenesis imperfecta is a rare, autosomal dominant connective tissue disorder characterised by bone fractures, deafness and blue sclera. We would like to draw attention to the clinical course of our patient with computed tomography, optical coherence tomography and visual field findings.

  9. Pamidronate treatment for osteogenesis imperfecta in black South Africans.

    PubMed

    Henderson, B D; Isaac, N; Mabele, O; Khiba, S; Nkayi, A; Mokoena, T

    2016-05-25

    Osteogenesis imperfecta is a heritable disorder of bone connective tissue. Type III has a high incidence in the black pop-ulation of South Africa. Affected people experience numerous fractures, bone pain and progressive disability. Until the introduction of bisphosphonates to reduce fracture incidence, treatment revolved around orthopaedic and supportive care. Objective. To assess the subjective attitude of patients towards pamidronate treatment. Thirty black patients with osteogenesis imperfecta type III treated at Universitas Hospital were approached and 26 were included in this study. Patients or their parents were interviewed using a standardised researcher-administered questionnaire, either in person or by telephone. Most patients reported a reduction in symptoms, a feeling of increased wellbeing, increased strength and rated the pamidronate treatment highly. The intravenous route of administration and the side-effects experienced were bearable. Overall all patients would recommend this treatment to other affected persons. This is first study to look at bisphosphonate treatment for osteogenesis imperfecta type III in black South Africans. The treatment is well tolerated and highly rated by the patients. Reported improvements and side-effects are similar to those reported in other populations. Using this form of treatment in this population is supported by these findings.

  10. Osteogenesis imperfecta: from diagnosis and multidisciplinary treatment to future perspectives.

    PubMed

    Bregou Bourgeois, Aline; Aubry-Rozier, Bérengère; Bonafé, Luisa; Laurent-Applegate, Lee; Pioletti, Dominique P; Zambelli, Pierre-Yves

    2016-01-01

    Osteogenesis imperfecta is an inherited connective tissue disorder with wide phenotypic and molecular heterogeneity. A common issue associated with the molecular abnormality is a disturbance in bone matrix synthesis and homeostasis inducing bone fragility. In very early life, this can lead to multiple fractures and progressive bone deformities, including long bone bowing and scoliosis. Multidisciplinary management improves quality of life for patients with osteogenesis imperfecta. It consists of physical therapy, medical treatment and orthopaedic surgery as necessary. Medical treatment consists of bone-remodelling drug therapy. Bisphosphonates are widely used in the treatment of moderate to severe osteogenesis imperfecta, from infancy to adulthood. Other more recent drug therapies include teriparatide and denosumab. All these therapies target the symptoms and have effects on the mechanical properties of bone due to modification of bone remodelling, therefore influencing skeletal outcome and orthopaedic surgery. Innovative therapies, such as progenitor and mesenchymal stem cell transplantation, targeting the specific altered pathway rather than the symptoms, are in the process of development.

  11. Basilar impression in osteogenesis imperfecta. A report of three cases in one family.

    PubMed

    Pozo, J L; Crockard, H A; Ransford, A O

    1984-03-01

    Basilar impression is a well-recognised though rare complication of osteogenesis imperfecta. Three patients, all members of the same family, with advanced basilar impression complicating osteogenesis imperfecta tarda, are described. The clinical features in these cases illustrate the natural history of this condition: from asymptomatic ventricular dilatation, through the foramen magnum compression syndrome, to death from brain-stem compression. The radiological criteria on which the diagnosis is based, are defined. Review of the literature reveals only seven previously documented cases, all in patients with mild forms of osteogenesis imperfecta. The unusually low incidence of basilar impression in osteogenesis imperfecta and its apparent restriction to patients with mild forms of the disease is discussed. The examination of close relatives of patients with basilar impression and osteogenesis imperfecta is emphasised in order to anticipate the onset of severe neurological complications.

  12. Immunocytochemical Detection of Dentin Matrix Proteins in Primary Teeth from Patients with Dentinogenesis Imperfecta Associated with Osteogenesis Imperfecta

    PubMed Central

    Orsini, G.; Majorana, A.; Mazzoni, A.; Putignano, A.; Falconi, M.; Polimeni, A.; Breschi, L.

    2014-01-01

    Dentinogenesis imperfecta determines structural alterations of the collagen structure still not completely elucidated. Immunohisto-chemical analysis was used to assay type I and VI collagen, various non-collagenous proteins distribution in human primary teeth from healthy patients or from patients affected by type I dentinogenesis imperfecta (DGI-I) associated with osteogenesis imperfecta (OI). In sound primary teeth, an organized well-known ordered pattern of the type I collagen fibrils was found, whereas atypical and disorganized fibrillar structures were observed in dentin of DGI-I affected patients. Expression of type I collagen was observed in both normal and affected primary teeth, although normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of type VI collagen was significantly lower in normal teeth than in dentin from DGI-I affected patients (P<0.05). Expressions of dentin matrix protein-1 (DMP1) and osteopontin (OPN) were observed in both normal dentin and dentin from DGI-I affected patients, without significant differences, being DMP1 generally more abundantly expressed. Immuno labeling for chondroitin sulfate (CS) and biglycan (BGN) was weaker in dentin from DGI-I-affected patients compared to normal dentin, this decrease being significant only for CS. This study shows ultra-structural alterations in dentin obtained from patients affected by DGI-I, supported by immunocytochemical assays of different collagenous and non-collagenous proteins. PMID:25578972

  13. Androgen Receptor Involvement in Rat Amelogenesis: An Additional Way for Endocrine-Disrupting Chemicals to Affect Enamel Synthesis.

    PubMed

    Jedeon, Katia; Loiodice, Sophia; Salhi, Khaled; Le Normand, Manon; Houari, Sophia; Chaloyard, Jessica; Berdal, Ariane; Babajko, Sylvie

    2016-11-01

    Endocrine-disrupting chemicals (EDCs) that interfere with the steroid axis can affect amelogenesis, leading to enamel hypomineralization similar to that of molar incisor hypomineralization, a recently described enamel disease. We investigated the sex steroid receptors that may mediate the effects of EDCs during rat amelogenesis. The expression of androgen receptor (AR), estrogen receptor (ER)-α, and progesterone receptor was dependent on the stage of ameloblast differentiation, whereas ERβ remained undetectable. AR was the only receptor selectively expressed in ameloblasts involved in final enamel mineralization. AR nuclear translocation and induction of androgen-responsive element-containing promoter activity upon T treatment, demonstrated ameloblast responsiveness to androgens. T regulated the expression of genes involved in enamel mineralization such as KLK4, amelotin, SLC26A4, and SLC5A8 but not the expression of genes encoding matrix proteins, which determine enamel thickness. Vinclozolin and to a lesser extent bisphenol A, two antiandrogenic EDCs that cause enamel defects, counteracted the actions of T. In conclusion, we show, for the first time, the following: 1) ameloblasts express AR; 2) the androgen signaling pathway is involved in the enamel mineralization process; and 3) EDCs with antiandrogenic effects inhibit AR activity and preferentially affect amelogenesis in male rats. Their action, through the AR pathway, may specifically and irreversibly affect enamel, potentially leading to the use of dental defects as a biomarker of exposure to environmental pollutants. These results are consistent with the steroid hormones affecting ameloblasts, raising the issue of the hormonal influence on amelogenesis and possible sexual dimorphism in enamel quality.

  14. Basilar impression complicating osteogenesis imperfecta type IV: the clinical and neuroradiological findings in four cases

    PubMed Central

    Hayes, M; Parker, G; Ell, J; Sillence, D

    1999-01-01

    OBJECTIVES—To describe the clinical and neuroradiological features of basilar impression in patients with osteogenesis imperfecta type IV.
METHODS—Four patients with basilar impression were ascertained in a population study of osteogenesis imperfecta. All four had detailed clinical and neuroradiological examination with both CT and MRI of the craniocervical junction andposterior fossa structures.
RESULTS—All four showed significant compression of the posterior fossa structures and surgical decompression was performed with relief of symptoms.
CONCLUSION—Symptoms of cough headache and trigeminal neuralgia occurring in patients with osteogenesis imperfecta are indications for detailed clinical and neuroradiological investigation to document basilar impression.

 PMID:10084535

  15. Osteogenesis imperfecta due to compound heterozygosity for the LEPRE1 gene.

    PubMed

    Moul, Adrienne; Alladin, Amanda; Navarrete, Cristina; Abdenour, George; Rodriguez, Maria M

    2013-10-01

    Osteogenesis imperfecta is a rare connective tissue disorder characterized by bone fragility and low bone density. Most cases are caused by an autosomal dominant mutation in either COL1A1 or COL1A2 gene encoding type I collagen. However, autosomal recessive forms have been identified. We present a patient with severe respiratory distress due to osteogenesis imperfecta simulating type II, born to a non-consanguineous couple with mixed African-American and African-Hispanic ethnicity. Cultured skin fibroblasts demonstrated compound heterozygosity for mutations in the LEPRE1 gene encoding prolyl 3-hydroxylase 1 confirming the diagnosis of autosomal recessive osteogenesis imperfecta type VIII, perinatal lethal type.

  16. The operative management of basilar impression in osteogenesis imperfecta.

    PubMed

    Harkey, H L; Crockard, H A; Stevens, J M; Smith, R; Ransford, A O

    1990-11-01

    Four patients with osteogenesis imperfecta and neurologically significant basilar impression have been treated over the past 8 years. The experience has resulted in changes in our therapeutic strategy for this particularly difficult problem. These cases are discussed with respect to the disease process, neurological involvement, radiological findings, and modes of surgical therapy. The errors in management as well as the success resulting from our learning experience are described. Currently, we recommend the extensive removal of the anterior bony compression by a transoral approach. This should be followed by a posterior rigid fixation that transfers the weight of the head to the thoracic spine, in an effort to prevent further basilar invagination.

  17. [PREPARATIONS OF PAMIDRONOVIC ACID IN COMPLEX TREATMENT ON OSTEOGENESIS IMPERFECTA].

    PubMed

    Zyma, A M; Guk, Yu M; Magomedov, O M; Gayko, O G; Kincha-Polishchuk, T A

    2015-07-01

    Modern view of drug therapy in the complex treatment of orthopedic manifestations of osteogenesis imperfecta (OI) was submitted. Developed and tested system of drug correction of structural and functional state of bone tissue (BT) using drugs pamidronovic acid, depending on osteoporosis severity and type of disease. Such therapy is appropriate to apply both independently and in conjunction with surgery to correct deformations of long bones of the lower extremities. Effectiveness and feasibility of the proposed methods of drug therapy was proved, most patients resume features walking and support.

  18. Adhesive Restorations as An Esthetic Solution in Dentinogenesis Imperfecta.

    PubMed

    Ubaldini, Adriana Lemos Mori; Giorgi, Maria Cecília Caldas; Carvalho, Ariany Borges; Pascon, Fernanda Miori; Lima, Débora Alves Nunes Leite; Baron, Gisele Maria Marchi; Paulillo, Luís Alexandre Maffei Sartini; Aguiar, Flávio Henrique Baggio

    2015-01-01

    Loss of tooth structure is the main sequela of dentinogenesis imperfecta (DI). Due to severe enamel attrition, patients with DI often present with esthetic, occlusal, endodontic, and speech complications. Therefore, an interdisciplinary approach, divided into separate clinical steps, should be developed to provide comprehensive dental rehabilitation. The purpose of this case report is to discuss the use of composite resin restorations as a transitional treatment step for the anterior teeth of an eight-year-old boy with DI until his bone and dental development permit orthodontic and orthognatic surgery.

  19. Genotype-Phenotype Correlations in Autosomal Dominant Osteogenesis Imperfecta

    PubMed Central

    Ben Amor, I. Mouna; Glorieux, Francis H.; Rauch, Frank

    2011-01-01

    Osteogenesis imperfecta, discussed in Baldridge et al. 2008 is an inherited bone fragility disorder with a wide range of clinical severity that in the majority of cases is caused by mutations in COL1A1 or COL1A2, the genes that encode the two collagen type I alpha chains. Here we describe genotype-phenotype correlations in OI patients who have mutations affecting collagen type I. This paper is based on findings in a large single-centre OI population and a review of the literature. PMID:21912751

  20. Osteogenesis Imperfecta: A Case Report and Review of Literature

    PubMed Central

    Edelu, BO; Ndu, IK; Asinobi, IN; Obu, HA; Adimora, GN

    2014-01-01

    Osteogenesis imperfecta (OI) is a group of rare inherited disorders of connective tissue with the common feature of excessive fragility of bones caused by mutations in collagen. Diagnosis is mainly based on the clinical features of the disorder. We report, the case of a male neonate delivered to a 33-year-old para 2 female at University of Nigeria Teaching Hospital, Enugu with no family history suggestive of OI. He had clinical features of a type II OI and severe birth asphyxia. Multidisciplinary management was instituted, but he died on the 7th day of life. PMID:25031897

  1. Prosthetic treatment of dentinogenesis imperfecta. A case report.

    PubMed

    Eerikäinen, E

    1981-03-01

    Prosthetic reconstruction was made on dentition affected by dentinogenesis imperfecta. The bite was first raised with fixed bite plates, and then with temporary acrylic bridges; finally full gold and veneer crowns were made in the posterior teeth. The crowns were retained on the severely attrited teeth with self-threading parapulpal screws (TMS, Whaledent International, New York, U.S.A.) and amalgam and composite resin (Consise, 3M Company, St Paul, U.S.A.) posts. The teeth seem to have enough strength to withstand the occlusal forces, and the dentine appears hard enough to retain parapulpal screws. The prosthetic construction is still functioning well today, 5 years after starting treatment.

  2. Perinatal lethal type II osteogenesis imperfecta: a case report.

    PubMed

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy termination; they felt that the diagnosis was late. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. Death occurred on day 25 of life related to respiratory failure.

  3. Clinical perspectives on osteogenesis imperfecta versus non-accidental injury.

    PubMed

    Pereira, Elaine Maria

    2015-12-01

    Although non-accidental injuries (NAI) are more common in cases of unexplained fractures than rare disorders such as osteogenesis imperfecta (OI), ruling out OI and other medical causes of fracture is always indicated. The majority of OI patients can be diagnosed with the help of family history, physical examination, and radiographic findings. In particular, there are a few radiological findings which are seen more commonly in NAI than in OI which may help guide clinician considerations regarding the probability of either of these diagnoses. At the same time, molecular testing still merits careful consideration in cases with unexplained fractures without obvious additional signs of abuse. © 2015 Wiley Periodicals, Inc.

  4. Update on the evaluation and treatment of osteogenesis imperfecta.

    PubMed

    Harrington, Jennifer; Sochett, Etienne; Howard, Andrew

    2014-12-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that presents with a wide clinical phenotype spectrum: from perinatal lethality and severe deformities to very mild forms without fractures. Most cases of OI are due to autosomal dominant mutations of the type I collagen genes. A multidisciplinary approach with rehabilitation, orthopedic surgery, and consideration of medical therapy with bisphosphonates underpins current management. Greater understanding of the pathogenesis of OI may lead to novel, therapeutic approaches to help improve clinical symptoms of children with OI in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Basilar impression and osteogenesis imperfecta in a three-year-old girl: CT and MRI.

    PubMed

    Rush, P J; Berbrayer, D; Reilly, B J

    1989-01-01

    A 3-year-old girl with osteogenesis imperfecta developed symptomatic basilar impression. Her neurological symptoms were treated by foramen magnum decompression and laminectomy. This is an unusually young patient to have this condition.

  6. Osteogenesis imperfecta types I-XI: implications for the neonatal nurse.

    PubMed

    Womack, Jody

    2014-10-01

    Osteogenesis imperfecta (OI), also called "brittle bone disease," is a rare heterozygous connective tissue disorder that is caused by mutations of genes that affect collagen. Osteogenesis imperfecta is characterized by decreased bone mass, bone fragility, and skin hyperlaxity. The phenotype present is determined according to the mutation on the affected gene as well as the type and location of the mutation. Osteogenesis imperfecta is neither preventable nor treatable. Osteogenesis imperfecta is classified into 11 types to date, on the basis of their clinical symptoms and genetic components. This article discusses the definition of the disease, the classifications on the basis of its clinical features, incidence, etiology, and pathogenesis. In addition, phenotype, natural history, diagnosis and management of this disease, recurrence risk, and, most importantly, the implications for the neonatal nurse and management for the family are discussed.

  7. Evaluation of the severity of malocclusions in children affected by osteogenesis imperfecta with the peer assessment rating and discrepancy indexes.

    PubMed

    Rizkallah, Jean; Schwartz, Stephane; Rauch, Frank; Glorieux, Francis; Vu, Duy-Dat; Muller, Katia; Retrouvey, Jean-Marc

    2013-03-01

    Osteogenesis imperfecta is a heritable disorder affecting bone and tooth development. Malocclusion is frequent in those affected by osteogenesis imperfecta, but this has not been studied in detail. The purpose of this study was to describe and quantify the severity of malocclusions in patients with osteogenesis imperfecta. Articulated dental casts were obtained from 49 patients diagnosed with osteogenesis imperfecta (ages 5-19 years; 28 female) and 49 age- and sex-matched control subjects who did not have osteogenesis imperfecta. Both groups were seeking orthodontic treatment. Malocclusions were scored by using the peer assessment rating (PAR) and the discrepancy index (DI). The average United Kingdom weighted PAR scores were 31.1 (SD, 14.5) for the osteogenesis imperfecta group and 22.7 (SD, 10.7) for the control group (P <0.05). The mean United States weighted PAR scores were 32.2 (SD, 15.0) for patients with osteogenesis imperfecta and 21.6 (SD, 9.6) for the controls (P <0.05). The average modified DI scores were 29.8 (SD, 20.2) for the osteogenesis imperfecta group and 12.4 (SD, 6.8) for the control group (P <0.05). Group differences were greatest for lateral open bite (osteogenesis imperfecta group, 7.1; control group, 0.3) for the DI parameters and anterior crossbite (osteogenesis imperfecta group, 13.0; control group, 3.8 [United Kingdom]) for the PAR. Both the PAR and the DI showed that malocclusions were significantly more severe in patients with osteogenesis imperfecta than in the control group. There was a higher incidence of Class III malocclusion associated with anterior and lateral open bites in patients affected by osteogenesis imperfecta. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  8. Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V

    PubMed Central

    Brizola, Evelise; Mattos, Eduardo P.; Ferrari, Jessica; Freire, Patricia O.A.; Germer, Raquel; Llerena Jr, Juan C.; Félix, Têmis M.

    2015-01-01

    Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5′UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity. PMID:26648832

  9. An atypical fracture in male patient with osteogenesis imperfecta

    PubMed Central

    Etxebarria-Foronda, Iñigo; Carpintero, Pedro

    2015-01-01

    Summary So-called atypical fractures have been related to prolonged treatment with bisphosphonates. Although there remain unanswered questions with respect to their etiology and physiopathology, it does appear to be a causal relationship. There are many references in the literature about this problem in patients in whom these drugs have been used to treat osteoporosis, but few reports in patients who have received this therapy for the management of osteogenesis imperfecta. The Authors describe a case of a young male patient with osteogenesis imperfecta with a number of historical fractures, and who received treatment with these drugs, initially parenterally and subsequently orally, presenting as a complication of the treatment, an atypical diaphyseal femoral fracture. The characteristics of the fracture are consistent with the updated diagnostic criteria of the American Society for Bone and Mineral Research. The clinical case, its treatment, both surgically and metabolically with teriparatide, and its development over a year, are analysed. The case is notable for, on the one hand, the significance of the presence of this type of fracture in a young patient with this disease, and on the other, because of the administration of teriparatide outside its established clinical indications, with twin objectives: to improve the bone structure of the patient’s underlying disease, and to counteract the harmful effects which bisphosphonates may have on this bone. PMID:26811713

  10. Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V.

    PubMed

    Brizola, Evelise; Mattos, Eduardo P; Ferrari, Jessica; Freire, Patricia O A; Germer, Raquel; Llerena, Juan C; Félix, Têmis M

    2015-10-01

    Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5'UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity.

  11. Advances in the Classification and Treatment of Osteogenesis Imperfecta.

    PubMed

    Thomas, Inas H; DiMeglio, Linda A

    2016-02-01

    Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.

  12. Orthopaedic Considerations for the Adult With Osteogenesis Imperfecta.

    PubMed

    Roberts, Timothy T; Cepela, Daniel J; Uhl, Richard L; Lozman, Jeffery

    2016-05-01

    Osteogenesis imperfecta is a heritable group of collagen-related disorders that affects up to 50,000 people in the United States. Although the disease is most symptomatic in childhood, adults with osteogenesis imperfecta also are affected by the sequelae of the disease. Orthopaedic manifestations include posttraumatic and accelerated degenerative joint disease, kyphoscoliosis, and spondylolisthesis. Other manifestations of abnormal collagen include brittle dentition, hearing loss, cardiac valve abnormalities, and basilar invagination. In general, nonsurgical treatment is preferred for management of acute fractures. High rates of malunion, nonunion, and subsequent deformity have been reported with both closed and open treatment. When surgery is necessary, surgeons should opt for load-sharing intramedullary devices that span the entire length of the bone; locking plates and excessively rigid fixation generally should be avoided. Arthroplasty may be considered for active patients, but the procedure frequently is associated with complications in this patient population. Underlying deformities, such as malunion, bowing, rotational malalignment, coxa vara, and acetabular protrusio, pose specific surgical challenges and underscore the importance of preoperative planning.

  13. Hearing Loss in Osteogenesis Imperfecta: Characteristics and Treatment Considerations

    PubMed Central

    Pillion, Joseph P.; Vernick, David; Shapiro, Jay

    2011-01-01

    Osteogenesis imperfecta (OI) is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed. PMID:22567374

  14. CLINICAL FEATURES AND PATTERN OF FRACTURES AT THE TIME OF DIAGNOSIS OF OSTEOGENESIS IMPERFECTA IN CHILDREN.

    PubMed

    Brizola, Evelise; Zambrano, Marina Bauer; Pinheiro, Bruna de Souza; Vanz, Ana Paula; Félix, Têmis Maria

    2017-01-01

    To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. Seventy-six patients (42 females) were included in the study. Individuals' age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures.

  15. CLINICAL FEATURES AND PATTERN OF FRACTURES AT THE TIME OF DIAGNOSIS OF OSTEOGENESIS IMPERFECTA IN CHILDREN

    PubMed Central

    Brizola, Evelise; Zambrano, Marina Bauer; Pinheiro, Bruna de Souza; Vanz, Ana Paula; Félix, Têmis Maria

    2017-01-01

    ABSTRACT Objective: To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. Methods: In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. Results: Seventy-six patients (42 females) were included in the study. Individuals’ age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. Conclusions: Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures. PMID:28977334

  16. Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta

    PubMed Central

    2011-01-01

    Background Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis. Methods The patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures. Results Homozygosity mapping identified FKBP10 as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene. Conclusions Our study demonstrates that FKBP10 mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with FKBP10 mutations. PMID:22107750

  17. End-stage posttraumatic osteoarthritis treated with THA in osteogenesis imperfecta.

    PubMed

    Chaus, George W; Heare, Travis

    2012-06-01

    Osteogenesis imperfecta is an incurable genetic disorder manifested with altered bone quality that predisposes patients to a multitude of fractures throughout their lives, including acetabular fractures. The management of acetabular fractures in patients with osteogenesis imperfecta remains a challenging clinical problem, with a paucity of literature supporting treatments and their outcomes. Limited reports in the literature validate the use of total hip arthroplasty (THA) in patients with osteogenesis imperfecta, and they describe the adult population only.This article describes a case of delayed diagnosis of a transverse acetabular fracture and femoral head impaction fracture that led to posttraumatic end-stage hip osteoarthritis in a 16-year-old boy with osteogenesis imperfecta (Sillence Type I) that was sustained after minimal trauma. Clinical examination 3 months postinjury revealed a significant pelvic obliquity, severe pain with hip range of motion, and limited hip range of motion. Imaging studies revealed a complete loss of articular cartilage and significant joint effusion.The patient underwent THA. No postoperative complications occurred. Two-year follow-up showed an excellent clinical result. The patient's hip was pain free, and he was able to walk with no limp.The authors are unaware of any reported cases of children with osteogenesis imperfecta undergoing THA. Based on the reported literature and the authors' experience, THA can be a reliable surgical option for patients with osteogenesis imperfecta. Copyright 2012, SLACK Incorporated.

  18. Fatal intraoperative hemorrhage during spinal fusion surgery for osteogenesis imperfecta.

    PubMed

    Sperry, K

    1989-03-01

    Osteogenesis imperfecta (OI) is an uncommon inherited systemic disorder of the connective tissues characterized primarily by varying degrees of bony fragility. Consequently, individuals affected by this condition frequently suffer severe skeletal injuries from otherwise innocuous traumatic events. This syndrome has other associated abnormalities, including hydrocephalus and brain stem compression on the basis of cranial developmental defects (platybasia), cardiac and vascular problems, respiratory disease from spinal deformities, vascular fragility, a bleeding disorder caused by an apparent platelet function abnormality, and anesthesia-related hyperpyrexia. A case is presented here of a young girl with advanced OI in whom intraoperative death occurred as a consequence of inadvertent rib fractures, with subsequent uncontrollable hemorrhage. OI may also potentially be mistaken for child abuse by an inexperienced examiner.

  19. Potential implications of cell therapy for osteogenesis imperfecta

    PubMed Central

    Niyibizi, Christopher; Li, Feng

    2009-01-01

    Osteogenesis imperfecta (OI) is a brittle-bone disease whose hallmark is bone fragility. Since the disease is genetic, there is currently no available cure. Several pharmacological agents have been tried with not much success, except the recent use of bisphosphonates. Stem cells have been suggested as an alternative OI treatment, but many hurdles remain before this technology can be applied for treating patients with OI. This review summarizes what is known at present regarding the application of stem cells to treat OI using animal models, clinical trials using mesenchymal stem cells to treat patients with OI and the knowledge gained from the clinical trials. Application of gene therapy in combination with stem cells is also discussed. The hurdles to be overcome to bring stem cells close to the clinic and future perspectives are discussed. PMID:20490372

  20. Prenatal transplantation of mesenchymal stem cells to treat osteogenesis imperfecta

    PubMed Central

    Chan, Jerry K. Y.; Götherström, Cecilia

    2014-01-01

    Osteogenesis imperfecta (OI) can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC) has the potential to improve the bone structure, growth, and fracture healing. In this review, we give an introduction to OI and MSC, and the basis for pre- and postnatal transplantation in OI. We also summarize the two patients with OI who have received pre- and postnatal transplantation of MSC. The findings suggest that prenatal transplantation of allogeneic MSC in OI is safe. The cell therapy is of likely clinical benefit with improved linear growth, mobility, and reduced fracture incidence. Unfortunately, the effect is transient. For this reason, postnatal booster infusions using same-donor MSC have been performed with clinical benefit, and without any adverse events. So far there is limited experience in this specific field and proper studies are required to accurately conclude on clinical benefits of MSC transplantation to treat OI. PMID:25346689

  1. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach

    PubMed Central

    Marr, Caroline; Seasman, Alison; Bishop, Nick

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder characterized by low bone density. The type and severity of OI are variable. The primary manifestations are fractures, bone deformity, and bone pain, resulting in reduced mobility and function to complete everyday tasks. OI affects not only the physical but also the social and emotional well-being of children, young people, and their families. As such, medical, surgical, and allied health professionals’ assessments all play a role in the management of these children. The multidisciplinary approach to the treatment of children and young people living with OI seeks to provide well-coordinated, comprehensive assessments, and interventions that place the child and family at the very center of their care. The coordinated efforts of a multidisciplinary team can support children with OI to fulfill their potential, maximizing function, independence, and well-being. PMID:28435282

  2. [Osteogenesis imperfecta. Clinical, functional and multidisciplinary evaluation of 65 patients].

    PubMed

    Fano, V; Rodríguez Celin, M; Del Pino, M; Buceta, S; Obregón, M G; Primomo, C; García, H; Miscione, H; Lejarraga, H

    2010-05-01

    Osteogenesis Imperfecta (OI) is a genetic disease, in which the main clinical features are increased bone fragility, pathological fractures, blue sclera, dentinogenesis imperfecta and conductive or mixed hearing loss. Clinical variability is wide. Although there is no curative treatment, there are several therapeutic tools capable of improving the course of the condition and patient quality of life. Sixty-five children seen in a Paediatric Hospital during six months in 2007 were evaluated. Thirty-five were type I OI, and thirty were types III-IV. Median age was 7.8 years (range 1.9-19.2); mean length of follow up was 4.7 years. The majority of children attended regular school for their corresponding age. Mean height was -1.4 sDS and -5.64 sDS in types I and III-IV respectively. Nineteen percent of patients were overweight and 11% were obese. Mean age at first orthopaedic surgery inserting telescopic rods was 6.5 years. Scoliosis was present in 44.6% of patients and was directly related to severity. Bleck's motor scale showed that 93% of patients with mild forms and 29% of severe forms had a sustainable walking ability. A wheelchair was used by 25% of patients. Family inheritance was confirmed in 65% of cases. Integral care using a multidisciplinary approach is required due to the complexity and clinical variability of the condition. Copyright 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  3. Initial report of the osteogenesis imperfecta adult natural history initiative.

    PubMed

    Tosi, Laura L; Oetgen, Matthew E; Floor, Marianne K; Huber, Mary Beth; Kennelly, Ann M; McCarter, Robert J; Rak, Melanie F; Simmonds, Barbara J; Simpson, Melissa D; Tucker, Carole A; McKiernan, Fergus E

    2015-11-14

    A better understanding of the natural history of osteogenesis imperfecta (OI) in adulthood should improve health care for patients with this rare condition. The Osteogenesis Imperfecta Foundation established the Adult Natural History Initiative (ANHI) in 2010 to give voice to the health concerns of the adult OI community and to begin to address existing knowledge gaps for this condition. Using a web-based platform, 959 adults with self-reported OI, representing a wide range of self-reported disease severity, reported symptoms and health conditions, estimated the impact of these concerns on present and future health-related quality of life (QoL) and completed a Patient-Reported Outcomes Measurement Information System (PROMIS®) survey of health issues. Adults with OI report lower general physical health status (p < .0001), exhibit a higher prevalence of auditory (58% of sample versus 2-16% of normalized population) and musculoskeletal (64% of sample versus 1-3% of normalized population) concerns than the general population, but report generally similar mental health status. Musculoskeletal, auditory, pulmonary, endocrine, and gastrointestinal issues are particular future health-related QoL concerns for these adults. Numerous other statistically significant differences exist among adults with OI as well as between adults with OI and the referent PROMIS® population, but the clinical significance of these differences is uncertain. Adults with OI report lower general health status but are otherwise more similar to the general population than might have been expected. While reassuring, further analysis of the extensive OI-ANHI databank should help identify areas of unique clinical concern and for future research. The OI-ANHI survey experience supports an internet-based strategy for successful patient-centered outcomes research in rare disease populations.

  4. Impact of three genetic musculoskeletal diseases: a comparative synthesis of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

    PubMed

    Dogba, Maman Joyce; Rauch, Frank; Douglas, Erin; Bedos, Christophe

    2014-10-25

    Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

  5. Respiratory failure during infusion of pamidronate in a 3 year-old male with osteogenesis imperfecta: a case report.

    PubMed

    Olson, Jennifer Ann

    2014-01-01

    Bisphosphonates are being used more frequently as part of the multi-disciplinary management of moderate to severe Osteogenesis Imperfecta (OI). This report details the development of respiratory failure during the second infusion of pamidronate in a 3.5 year-old male with osteogenesis imperfecta type 1 and no prior history of respiratory disease.

  6. [Postoperative radiation therapy for a patient with osteogenesis imperfecta: case report].

    PubMed

    Ducournau, A; Lagarde, P; Henriques de Figueiredo, B; Antoine, M; Breton-Callu, C; Petit, A; Dallaudière, B; Sargos, P

    2014-03-01

    Osteogenesis imperfecta is an unusual disease also called Lobstein disease. Characterized by abnormalities of collagen biosynthesis, a possible mutation on 17th chromosome is described. On the other hand, 29% of breast cancers present a mutation on the same chromosome. Nevertheless, the association of osteogenesis imperfecta and breast cancer is at the moment unknown. Therapeutic management is very difficult because of a loss in dihydropyrimidine dehydrogenase for patients having osteogenesis imperfecta, generating some toxicity by default in catabolism of 5-fluorouracil. We report the case of a 49-year-old woman with a breast cancer in the context of osteogenesis imperfecta. Dosimetric considerations permitting to reduce chess dose level have been performed for this patient. With a follow-up of 6 months, no imaging fracture has been revealed after radiotherapy. No evident conclusion about radiation injury from a case report could be described in case of osteogenesis imperfecta. To our knowledge, this is the first case which take into account potential radiation induced toxicities. Copyright © 2014. Published by Elsevier SAS.

  7. Transcatheter mitral valve repair in osteogenesis imperfecta associated mitral valve regurgitation.

    PubMed

    van der Kley, Frank; Delgado, Victoria; Ajmone Marsan, Nina; Schalij, Martin J

    2014-08-01

    Osteogenesis imperfecta is associated with increased prevalence of significant mitral valve regurgitation. Surgical mitral valve repair and replacement are feasible but are associated with increased risk of bleeding and dehiscence of implanted valves may occur more frequently. The present case report describes the outcomes of transcatheter mitral valve repair in a patient with osteogenesis imperfecta. A 60 year-old patient with osteogenesis imperfecta and associated symptomatic moderate to severe mitral regurgitation underwent transthoracic echocardiography which showed a nondilated left ventricle with preserved systolic function and moderate to severe mitral regurgitation. On transoesophageal echocardiography the regurgitant jet originated between the anterolateral scallops of the anterior and posterior leaflets (A1-P1). Considering the comorbidities associated with osteogenesis imperfecta the patient was accepted for transcatheter mitral valve repair using the Mitraclip device (Abbott vascular, Menlo, CA). Under fluoroscopy and 3D transoesophageal echocardiography guidance, a Mitraclip device was implanted between the anterolateral and central scallops with significant reduction of mitral regurgitation. The postoperative evolution was uneventful. At one month follow-up, transthoracic echocardiography showed a stable position of the Mitraclip device with no mitral regurgitation. Transcatheter mitral valve repair is feasible and safe in patients with osteogenesis imperfecta and associated symptomatic significant mitral regurgitation. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  8. Dentinogenesis imperfecta type II: A case report with 17 years of follow-up

    PubMed Central

    Gama, Francisco José Reis; Corrêa, Isabella Sousa; Valerio, Claudia Scigliano; Ferreira, Emanuelle de Fátima

    2017-01-01

    Dentinogenesis imperfecta is a dominant autosomal hereditary disorder of dentin formation that affects the deciduous and permanent teeth. Its etiology is characterized by inadequate cell differentiation during odontogenesis. The clinical characteristics of dentinogenesis imperfecta are discolored teeth with a translucency that varies from gray to brown or amber. Radiographically, the teeth exhibit pulp obliteration, thin and short roots, bell-shaped crowns, and periapical bone rarefaction. The aim of this report was to present a case of dentinogenesis imperfecta type II that was followed up over a 17-year period. This report also presents scanning electron microscopy images of the enamel and dentin, showing that both were altered in the affected teeth. The disease characteristics and the treatments that were administered are reported in this study to guide dentists with respect to the need for early diagnosis and adequate follow-up to avoid major sequelae. PMID:28680850

  9. Dentinogenesis imperfecta type II: A case report with 17 years of follow-up.

    PubMed

    Gama, Francisco José Reis; Corrêa, Isabella Sousa; Valerio, Claudia Scigliano; Ferreira, Emanuelle de Fátima; Manzi, Flávio Ricardo

    2017-06-01

    Dentinogenesis imperfecta is a dominant autosomal hereditary disorder of dentin formation that affects the deciduous and permanent teeth. Its etiology is characterized by inadequate cell differentiation during odontogenesis. The clinical characteristics of dentinogenesis imperfecta are discolored teeth with a translucency that varies from gray to brown or amber. Radiographically, the teeth exhibit pulp obliteration, thin and short roots, bell-shaped crowns, and periapical bone rarefaction. The aim of this report was to present a case of dentinogenesis imperfecta type II that was followed up over a 17-year period. This report also presents scanning electron microscopy images of the enamel and dentin, showing that both were altered in the affected teeth. The disease characteristics and the treatments that were administered are reported in this study to guide dentists with respect to the need for early diagnosis and adequate follow-up to avoid major sequelae.

  10. Custom hemiarthroplasties for retention of existing hardware associated with osteogenesis imperfecta.

    PubMed

    Nishida, Kevin; Choi, Daniel; Bostrom, Mathias

    2017-06-01

    Osteogenesis imperfecta is a rare genetic disorder that presents with heterogeneous phenotypes ranging from brittle bones to impaired hearing. Because of the decreased bone mineral density frequently observed in this patient population, many patients experience recurring and long-term fractures, which often require orthopaedic management. With the advancement of nonsurgical and surgical management and increased longevity of patients with osteogenesis imperfecta, the incidence of osteoarthritis has risen, presenting new orthopaedic challenges. However, compromised bone integrity and size combined with frequent existing hardware render traditional surgical therapies for osteoarthritis technically challenging in this patient population. In this report, we present a case in which we retained a portion of the patient's existing hardware, while performing staged bilateral custom hemiarthroplasties in a patient with osteogenesis imperfecta.

  11. Clinical application of antenatal genetic diagnosis of osteogenesis imperfecta type IV.

    PubMed

    Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

    2015-04-02

    Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families.

  12. Successful bone-anchored hearing aid implantation in a patient with osteogenesis imperfecta.

    PubMed

    Coutinho, M B; Marques, C; Mendes, G J; Gonçalves, C

    2015-11-01

    To report a case of successful bone-anchored hearing aid implantation in an adult patient with type III osteogenesis imperfecta, which is commonly regarded as a contraindication to this procedure. A 45-year-old man with type III osteogenesis imperfecta presented with mixed hearing loss. There was a mild sensorineural component in both ears, with an air-bone gap between 45 and 50 dB HL. He was implanted with a bone-anchored hearing aid. The audiological outcome was good, with no complications and good implant stability (as measured by resonance frequency analysis). To our knowledge, this is the first recorded case of bone-anchored hearing aid implantation in a patient with osteogenesis imperfecta.

  13. [Oral cavity features in patients suffering from osteogenesis imperfecta].

    PubMed

    Alania, K N; Iverieli, M B; Abashidze, N O; Gogishvili, Kh B; Chigladze, T T

    2011-04-01

    Osteogenesis Imperfecta (OI) is a rare hereditary connective tissue disorder. This pathology is characterized by disruption of biosynthesis of Type I collagen, and production of limited amount of defective and imperfect collagens. This causes decrease in bone mass of human body, bones become fragile and brittle, resulting in unreasonable multiple fractures. Reportedly, number of patients with OI ranges between 32-38 in Georgia. However, exact number of patients, including children and their parents, is unknown. Dentinogenesis Imperfecta (DI; DGI) and skeletal malocclusion occupy special place in varied spectrum of OI clinical symptoms. We studied 14 patients: 9 women (64.3%), 5 men (35.7%) and divided them in three age groups: I - 2.5-6 years - period of primary dentition (28.6%), II - 6-14 years - period of changing teeth dentition (35.7%) and III - above 14 years - period of permanent dentition (35.7%). 28.5% of screened patients had one of the symptoms of DI, such as tooth discoloration. Discoloration of primary teeth was revealed in 4 patients (primary dentition). Another symptom of DI, such as early abrasion, was detected in 5 patients i.e. 35.71%. This was divided in the following manner: I age group - 3 cases, II and III age groups - 1-1 cases. It was also observed that early abrasion of primary teeth prevails over permanent. One of DI's radiographic symptoms, such as peculiar form of teeth crown and root, was revealed in 21.4% or in 3 patients, 2 of whom had bulbous crown, and the third one deformed (curved) root. Peculiar characteristics of DI, such as increased constriction of the coronal-radicular junction, obliterated pulp chamber, short and narrow roots, were not observed in the patients examined. Interesting characteristic of DI, such as periapical destruction of intact tooth root, was revealed in the form of bone defect in 7.1% of those examined (1 patient). Therefore, out of examined 14 patients with OI - DI had 6 patients or 42.85% of cases. Also

  14. Evaluation of teriparatide treatment in adults with osteogenesis imperfecta

    PubMed Central

    Orwoll, Eric S.; Shapiro, Jay; Veith, Sandra; Wang, Ying; Lapidus, Jodi; Vanek, Chaim; Reeder, Jan L.; Keaveny, Tony M.; Lee, David C.; Mullins, Mary A.; Nagamani, Sandesh C.S.; Lee, Brendan

    2014-01-01

    Background. Adults with osteogenesis imperfecta (OI) have a high risk of fracture. Currently, few treatment options are available, and bone anabolic therapies have not been tested in clinical trials for OI treatment. Methods. 79 adults with OI were randomized to receive 20 μg recombinant human parathyroid hormone (teriparatide) or placebo for 18 months in a double-blind, placebo-controlled trial. The primary endpoint was the percent change in areal bone mineral density (aBMD) of the lumbar spine (LS), as determined by dual-energy X-ray absorptiometry. Secondary endpoints included percent change in bone remodeling markers and vertebral volumetric BMD (vBMD) by quantitative computed tomography, estimated vertebral strength by finite element analysis, and self-reported fractures. Results. Compared with the placebo group, the teriparatide group showed increased LS aBMD (6.1% ± 1.0% vs. 2.8% ± 1.0% change from baseline; P < 0.05) and total hip aBMD (2.6% ± 1.0% vs. –2.4% ± 1.0% change; P < 0.001). Vertebral vBMD and strength improved with teriparatide therapy (18% ± 6% and 15% ± 3% change, respectively), but declined with placebo (–5.0% ± 6% and –2.0% ± 3% change; P < 0.05 for both comparisons). Serum procollagen type 1 N-terminal propeptide (P1NP) and urine collagen N-telopeptide (NTx) levels increased with teriparatide therapy (135% ± 14% and 64% ± 10% change, respectively). Teriparatide-induced elevation of P1NP levels was less pronounced in severe forms of OI (type III/IV) compared with the milder form (type I). Type I OI patients exhibited robust BMD increases with teriparatide; however, there was no observed benefit for those with type III/IV OI. There was no difference in self-reported fractures between the 2 groups. Conclusions. Adults with OI, particularly those with less severe disease (type I), displayed a teriparatide-induced anabolic response, as well as increased hip and spine aBMD, vertebral vBMD, and estimated vertebral strength. Trial

  15. Bent Telescopic Rods in Patients With Osteogenesis Imperfecta.

    PubMed

    Lee, R Jay; Paloski, Michael D; Sponseller, Paul D; Leet, Arabella I

    2016-09-01

    Telescopic rods require alignment of 2 rods to enable lengthening. A telescopic rod converts functionally into a solid rod if either rod bends, preventing proper engagement. Our goal was to characterize implant bending as a mode of failure of telescopic rods used in the treatment of osteogenesis imperfecta in children. We conducted a retrospective review of our osteogenesis imperfecta database for patients treated with intramedullary telescopic rods at our institution from 1992 through 2010 and identified 12 patients with bent rods. The 6 boys and 6 girls had an average age at the time of initial surgery of 3.1 years (range, 1.8 to 8.3 y) and a total of 51 telescoping rods. Clinic notes, operative reports, and radiographs were reviewed. The rods were analyzed for amount of lengthening, characteristics of bending, presence of cut out, or disengagement from an anchor point. Bends in the rods were characterized by their location on the implant component. The bent and straight rods were compared. Data were analyzed with the Mann-Whitney test (statistical significance set at P≤0.05). Of the 51 telescoping rods, 17 constructs (33%) bent. The average interval between surgery and rod bending was 4.0 years (range, 0.9 to 8.2 y). Before bending, 11 of 17 telescoping rods had routine follow-up radiographs for review. In 10 of the rods, bending was present when early signs of rod failure were first detected. Rod bending did not seem to be related to rod size. There was no area on the rod itself that seemed more susceptible to bending. Rod bending can be an early sign of impending rod failure. When rod bending is first noted, it may predispose the rod to other subsequent failures such as loss of proximal and distal fixation and cut out. Rod bending should be viewed as an indicator for closer monitoring of the patient and discussions regarding future need for rod exchange. Level III-retrospective review.

  16. Osteogenesis imperfecta associated with basilar impression and cerebral atrophy: a case report.

    PubMed

    Brooks, M L; Gall, C; Wang, A M; Schick, R; Rumbaugh, C L

    1989-01-01

    Osteogenesis imperfecta is a disease of bone formation subdivided into two types, congenita and tarda. It is associated with bony fragility, blue sclerae and abnormality of tooth dentin. Rarely the tarda form is associated with basilar invagination or infolding of the foramen magnum and upper cervical segments into the posterior fossa. This results in hydrocephalus and a spectrum of neurologic dysfunction known as the foramen magnum compression syndrome. Many radiologic methods have been used to evaluate basilar invagination including plain film and CT. We describe a patient with osteogenesis imperfecta tarda examined with CT, with a unique finding of diffuse cerebral atrophy associated with basilar invagination.

  17. Successful operative rib fixation of traumatic flail chest in a patient with osteogenesis imperfecta.

    PubMed

    Kulaylat, Afif N; Chesnut, Charles H; Santos, Ariel P; Armen, Scott B

    2014-09-01

    Increasing attention has been directed towards operative rib fixation of traumatic flail chest; reported benefits include more rapid weaning from the ventilator, decreased intensive care unit stays, decreased complications and improved functional results. The outcomes of this surgical intervention in patients with osteogenesis imperfecta, a rare condition characterized by low bone density and bone fragility, are unknown. This case demonstrates that, in the management of traumatic flail chest in a patient with osteogenesis imperfecta, surgical fixation can be successful and should be considered early.

  18. Anatomic and dynamic aspects of stomatognathic structures in osteogenesis imperfecta: a case report.

    PubMed

    Ortega, Adriana de Oliveira L; Rosa, Vera L M; Zwir, Liete M L Figueiredo; Ciamponi, Ana L; Guimarães, Antonio S; Alonso, Luis G

    2007-04-01

    The osteogenesis imperfecta congenita (OMIM 166210) type II phenotype can be caused by mutation in either the COL1A1 gene or the COL1A2 gene that encode the chains of type I procollagen, the major protein in bones. Patients can therefore present a combination of features, including multiple long bone fractures and deformities, growth deficiency, joint laxity, hearing loss, blue sclera, and dentinogenesis imperfecta. The purpose of this study is to describe a clinical case of this syndrome, focusing on the anatomy of the temporomandibular joint (TMJ) that was assessed using computed tomography (CT) method. Clinical examination included evaluation of mandibular dynamics and investigation of temporomandibular dysfunction (TMD).

  19. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation.

    PubMed

    Marini, Joan C; Reich, Adi; Smith, Simone M

    2014-08-01

    Osteogenesis imperfecta or 'brittle bone disease' has mainly been considered a bone disorder caused by collagen mutations. Within the last decade, however, a surge of genetic discoveries has created a new paradigm for osteogenesis imperfecta as a collagen-related disorder, where most cases are due to autosomal dominant type I collagen defects, while rare, mostly recessive, forms are due to defects in genes whose protein products interact with collagen protein. This review is both timely and relevant in outlining the genesis, development, and future of this paradigm shift in the understanding of osteogenesis imperfecta. Bone-restricted interferon-induced transmembrane (IFITM)-like protein (BRIL) and pigment epithelium-derived factor (PEDF) defects cause types V and VI osteogenesis imperfecta via defective bone mineralization, while defects in cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1), and cyclophilin B (CYPB) cause types VII-IX osteogenesis imperfecta via defective collagen post-translational modification. Heat shock protein 47 (HSP47) and FK506-binding protein-65 (FKBP65) defects cause types X and XI osteogenesis imperfecta via aberrant collagen crosslinking, folding, and chaperoning, while defects in SP7 transcription factor, wingless-type MMTV integration site family member 1 (WNT1), trimeric intracellular cation channel type b (TRIC-B), and old astrocyte specifically induced substance (OASIS) disrupt osteoblast development. Finally, absence of the type I collagen C-propeptidase bone morphogenetic protein 1 (BMP1) causes type XII osteogenesis imperfecta due to altered collagen maturation/processing. Identification of these multiple causative defects has provided crucial information for accurate genetic counseling, inspired a recently proposed functional grouping of osteogenesis imperfecta types by shared mechanism to simplify current nosology, and has prodded investigations into common pathways in osteogenesis imperfecta. Such

  20. Roentgenographic Evaluation of the Spine in Patients With Osteogenesis Imperfecta.

    PubMed

    de Lima, Marcos Vaz; de Lima, Fabiana Vaz; Akkari, Miguel; Resende, Vanessa Ribeiro de; Santili, Claudio

    2015-11-01

    Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder that leads to bone weakness and deformities, especially in the spine, which can lead to poor outcomes.The aim of this study was to find patterns and risk factors in spinal deformities in patients with OI.In a retrospective study, 70 patients with OI were selected. Radiographs of the spine were evaluated. We observed the presence or absence of the following changes: biconcave vertebrae, chest and vertebral deformities, unilateral rib, and thoracolumbar kyphosis. The greater curve was considered the primary one, and the secondary curve considered compensatory.In the study sample, we observed that the patients' ages ranged between 7 and 50 years, with a mean equal to 13 years, and 76% had scoliosis. In 68% of cases the main curve in the thoracic region was observed with the convexity to the right.The following was found in patients with OI: scoliosis, biconcave vertebrae, vertebral and chest deformity, unilateral rib, and thoracolumbar kyphosis. The thoracolumbar kyphosis is highly associated with thoracic hypokyphosis in patients with OI.

  1. An unusual presentation of osteogenesis imperfecta type I

    PubMed Central

    Rebelo, Marta; Lima, Jandira; Vieira, José Diniz; Costa, José Nascimento

    2011-01-01

    Osteogenesis imperfecta (OI) is a rare inherited disorder with a broad spectrum of clinical and genetic variability. The genetic diversity involves, in the majority of the cases, mutations in one of the genes that encodes the type 1 collagen protein (COL1 A1 and COL1 A2), but it is not a requirement for the diagnosis. The most benign form is OI type I. The authors present a case report of a 25-year-old woman who had severe low back pain associated with incapacity to walk and breast-feed post-partum. Symptoms developed 2 weeks after delivery. The radiological examination revealed severe osteoporosis with no abnormalities in the laboratory findings. The clinical signs and a positive personal and family history of multiple fractures in childhood suggested OI type I, although other diagnosis, such as pregnancy-associated osteoporosis, was also considered. The atypical presentation of this rare disorder in adulthood calls attention to the need for early diagnosis for prompt treatment. Treatment of OI is never curative, but it improves the quality of the patient’s life. PMID:23754901

  2. Recessive Osteogenesis Imperfecta Caused by Missense Mutations in SPARC

    PubMed Central

    Mendoza-Londono, Roberto; Fahiminiya, Somayyeh; Majewski, Jacek; Tétreault, Martine; Nadaf, Javad; Kannu, Peter; Sochett, Etienne; Howard, Andrew; Stimec, Jennifer; Dupuis, Lucie; Roschger, Paul; Klaushofer, Klaus; Palomo, Telma; Ouellet, Jean; Al-Jallad, Hadil; Mort, John S.; Moffatt, Pierre; Boudko, Sergei; Bächinger, Hans-Peter; Rauch, Frank

    2015-01-01

    Secreted protein, acidic, cysteine-rich (SPARC) is a glycoprotein that binds to collagen type I and other proteins in the extracellular matrix. Using whole-exome sequencing to identify the molecular defect in two unrelated girls with severe bone fragility and a clinical diagnosis of osteogenesis imperfecta type IV, we identified two homozygous variants in SPARC (GenBank: NM_003118.3; c.497G>A [p.Arg166His] in individual 1; c.787G>A [p.Glu263Lys] in individual 2). Published modeling and site-directed mutagenesis studies had previously shown that the residues substituted by these mutations form an intramolecular salt bridge in SPARC and are essential for the binding of SPARC to collagen type I. The amount of SPARC secreted by skin fibroblasts was reduced in individual 1 but appeared normal in individual 2. The migration of collagen type I alpha chains produced by these fibroblasts was mildly delayed on SDS-PAGE gel, suggesting some overmodification of collagen during triple helical formation. Pulse-chase experiments showed that collagen type I secretion was mildly delayed in skin fibroblasts from both individuals. Analysis of an iliac bone sample from individual 2 showed that trabecular bone was hypermineralized on the material level. In conclusion, these observations show that homozygous mutations in SPARC can give rise to severe bone fragility in humans. PMID:26027498

  3. Physical activity in youth with osteogenesis imperfecta type I

    PubMed Central

    Pouliot-Laforte, A.; Veilleux, L-N.; Rauch, F.; Lemay, M.

    2015-01-01

    Introduction: Individuals with Osteogenesis Imperfecta (OI) type I often show muscular weakness. However, it is unclear whether muscular weakness is a consequence of physical inactivity or a result of the disease itself. The aim was to assess muscle function in youth with OI type I and evaluate physical activity (PA). Methods: Fourteen children with OI type I (mean age [SD]: 12.75 [4.62] years) were compared to 14 age- and gender-matched controls (mean age [SD]: 12.75 [4.59] years). Muscle force and power were determined through mechanography. PA and daily energy expenditure were measured with an accelerometer and a questionnaire. Results: Compared to controls, children with OI type I had lower muscle force and power. OI type I children were as active as their healthy counterparts. Conclusions: Children and adolescents with OI type I and their healthy counterparts did not reached daily recommendations of PA. Given their muscle function deficit, youth with OI type I would benefit to reach these recommendations to prevent precocious effect of aging on muscles. PMID:26032209

  4. Therapy with pamidronate in children with osteogenesis imperfecta

    PubMed Central

    Marginean, Otilia; Tamasanu, Raluca Corina; Mang, Niculina; Mozos, Ioana; Brad, Giorgiana Flavia

    2017-01-01

    Osteogenesis imperfecta (OI) is a genetic disease characterized by excessive bone fragility with fractures consecutive to minor trauma. Considering lack of standardization of therapy with pamidronate in children, it was our aim to present our experience over a period of 10 years regarding evolution and treatment in patients diagnosed with osteoporosis and OI. Nine patients diagnosed with OI were admitted to the First Pediatric Clinic, Timisoara. They were investigated (clinical, biomarkers of bone metabolism and imaging studies), and a quality-of-life questionnaire was used to evaluate the impact of OI. Treatment was performed with pamidronate 1 mg/kg/cycle, every 3 months. The patients were evaluated every 3 months. The most frequent was type III (three patients), and two patients were diagnosed with type II, while the other patients were diagnosed with other forms such as types IV, V, VI and VIII. The clinical expression was polymorphic, and the number of fractures was variable. Bone pain ameliorated just after the first cycle of pamidronate, while the activity and mobility increased quickly. Osteodensitometry in children over 12 years showed a decreased bone mineral density (BMD) with a significant improvement after treatment. The values of the bone alkaline phosphatase and osteocalcin changed after the antiresorptive treatment, and the quality of life of the children and their family improved. Treatment with pamidronate is beneficial for the patient, family and society, increases mobility and bone density, improves quality of life and reduces family dependence in children with OI. PMID:28894358

  5. Osteogenesis imperfecta: an x ray fibre diffraction study.

    PubMed Central

    Bradshaw, J P; Miller, A

    1986-01-01

    The use of x ray fibre diffraction to study the molecular architecture of healthy and diseased human tendon is described. The three dimensional structure of human (finger) tendon is derived to high resolution and is shown to be very similar to that reported for rat tail tendon. In particular the presence of the 38 A row line in the diffraction pattern suggests that a high degree of lateral order within the collagen fibrils is a more widespread feature of tendon tissue than was formerly realised. Axially projected electron density maps of the 670 A unit repeat of the collagen fibrils of this tissue, and of tendon tissue from three cases of osteogenesis imperfecta (OI), are calculated and compared. The results are in agreement with recent biochemical studies in suggesting that type I (Sillence) OI is principally a quantitative, rather than a qualitative, defect of type I collagen biosynthesis. The features by which a molecular lesion may be recognised and characterised from diffraction data are discussed. Images PMID:3767461

  6. Mutations in SERPINF1 cause osteogenesis imperfecta type VI.

    PubMed

    Homan, Erica P; Rauch, Frank; Grafe, Ingo; Lietman, Caressa; Doll, Jennifer A; Dawson, Brian; Bertin, Terry; Napierala, Dobrawa; Morello, Roy; Gibbs, Richard; White, Lisa; Miki, Rika; Cohn, Daniel H; Crawford, Susan; Travers, Rose; Glorieux, Francis H; Lee, Brendan

    2011-12-01

    Osteogenesis imperfecta (OI) is a spectrum of genetic disorders characterized by bone fragility. It is caused by dominant mutations affecting the synthesis and/or structure of type I procollagen or by recessively inherited mutations in genes responsible for the posttranslational processing/trafficking of type I procollagen. Recessive OI type VI is unique among OI types in that it is characterized by an increased amount of unmineralized osteoid, thereby suggesting a distinct disease mechanism. In a large consanguineous family with OI type VI, we performed homozygosity mapping and next-generation sequencing of the candidate gene region to isolate and identify the causative gene. We describe loss of function mutations in serpin peptidase inhibitor, clade F, member 1 (SERPINF1) in two affected members of this family and in an additional unrelated patient with OI type VI. SERPINF1 encodes pigment epithelium-derived factor. Hence, loss of pigment epithelium-derived factor function constitutes a novel mechanism for OI and shows its involvement in bone mineralization.

  7. Osteogenesis imperfecta: Clinical diagnosis, nomenclature and severity assessment

    PubMed Central

    Van Dijk, FS; Sillence, DO

    2014-01-01

    Recently, the genetic heterogeneity in osteogenesis imperfecta (OI), proposed in 1979 by Sillence et al., has been confirmed with molecular genetic studies. At present, 17 genetic causes of OI and closely related disorders have been identified and it is expected that more will follow. Unlike most reviews that have been published in the last decade on the genetic causes and biochemical processes leading to OI, this review focuses on the clinical classification of OI and elaborates on the newly proposed OI classification from 2010, which returned to a descriptive and numerical grouping of five OI syndromic groups. The new OI nomenclature and the pre-and postnatal severity assessment introduced in this review, emphasize the importance of phenotyping in order to diagnose, classify, and assess severity of OI. This will provide patients and their families with insight into the probable course of the disorder and it will allow physicians to evaluate the effect of therapy. A careful clinical description in combination with knowledge of the specific molecular genetic cause is the starting point for development and assessment of therapy in patients with heritable disorders including OI. © 2014 The Authors. American Journal of Medical Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution–NonCommercial–NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. PMID:24715559

  8. Osteogenesis Imperfecta Type VI in Individuals from Northern Canada.

    PubMed

    Ward, Leanne; Bardai, Ghalib; Moffatt, Pierre; Al-Jallad, Hadil; Trejo, Pamela; Glorieux, Francis H; Rauch, Frank

    2016-06-01

    Osteogenesis imperfecta (OI) type VI is a recessively inherited form of OI that is caused by mutations in SERPINF1, the gene coding for pigment-epithelium derived factor (PEDF). Here, we report on two apparently unrelated children with OI type VI who had the same unusual homozygous variant in intron 6 of SERPINF1 (c.787-10C>G). This variant created a novel splice site that led to the in-frame addition of three amino acids to PEDF (p.Lys262_Ile263insLeuSerGln). Western blotting showed that skin fibroblasts with this mutation produced PEDF but failed to secrete it. Both children were treated with intravenous bisphosphonates, but the treatment of Individual 1 was switched to subcutaneous injections of denosumab (dose 1 mg per kg body weight, repeated every 3 months). An iliac bone sample obtained after 5 denosumab injections (and 3 months after the last injection) showed no change in the increased osteoid parameters that are typical of OI type VI, but the number of osteoclasts in trabecular bone was markedly increased. This suggests that the effect of denosumab on osteoclast suppression is of shorter duration in children with OI type VI than what has previously been reported on adults with osteoporosis.

  9. Current and emerging treatments for the management of osteogenesis imperfecta

    PubMed Central

    Monti, Elena; Mottes, Monica; Fraschini, Paolo; Brunelli, PierCarlo; Forlino, Antonella; Venturi, Giacomo; Doro, Francesco; Perlini, Silvia; Cavarzere, Paolo; Antoniazzi, Franco

    2010-01-01

    Osteogenesis imperfecta (OI) is the most common bone genetic disorder and it is characterized by bone brittleness and various degrees of growth disorder. Clinical severity varies widely; nowadays eight types are distinguished and two new forms have been recently described although not yet classified. The approach to such a variable and heterogeneous disease should be global and therefore multidisciplinary. For simplicity, the objectives of treatment can be reduced to three typical situations: the lethal perinatal form (type II), in which the problem is survival at birth; the severe and moderate forms (types III–IX), in which the objective is ‘autonomy’; and the mild form (type I), in which the aim is to reach ‘normal life’. Three types of treatment are available: non-surgical management (physical therapy, rehabilitation, bracing and splinting), surgical management (intramedullary rod positioning, spinal and basilar impression surgery) and medical-pharmacological management (drugs to increase the strength of bone and decrease the number of fractures as bisphosphonates or growth hormone, depending on the type of OI). Suggestions and guidelines for a therapeutic approach are indicated and updated with the most recent findings in OI diagnosis and treatment. PMID:20856683

  10. Fracture of mandible during yawning in a patient with osteogenesis imperfecta.

    PubMed

    Ram, Hari; Shadab, Mohammad; Vardaan, Ajay; Aga, Pallavi

    2014-08-07

    Osteogenesis imperfecta is a genetic disorder characterised by fragility and multiple fractures of bones. Clinical signs and symptoms vary depending on the type of disease. Fractures of facial bones are rare compared with load-bearing long bones. We report a case of fracture of the mandible during yawning which was managed by open reduction and internal fixation.

  11. Anesthetic management in a patient with osteogenesis imperfecta for rush nail removal in femur

    PubMed Central

    Gupta, Divanshu; Purohit, Alaka

    2016-01-01

    Osteogenesis imperfecta (OI) is a rare genetically inherited syndrome involving connective tissues, resulting in anatomic and physiologic abnormalities, which results in any form of anesthesia, a challenging task. We hereby report a case of OI type I presented with distinctively blue sclera, hearing loss, kyphoscoliosis, and mild pulmonary restrictive disease who underwent rush nail removal in the femur. PMID:27746572

  12. Three Preschool Children with Osteogenesis Imperfecta--Interviews with Parents. Handicap Research Group Report No. 5.

    ERIC Educational Resources Information Center

    Brodin, Jane; Millde, Kristina

    The report describes three preschool Swedish children with osteogenesis imperfecta (brittle bones) and the psychosocial support families require from society. Introductory sections explain the condition, review international research on brittle bones, consider the life situation of children with brittle bones, and examine societal support for…

  13. Children with Osteogenesis Imperfecta and Their Daily Living. Handicap Research Group Report No. 4.

    ERIC Educational Resources Information Center

    Brodin, Jane

    The study examined aspects of daily living of Swedish children with osteogenesis imperfecta, a mineral deficiency in the skeleton which results in stunted growth and frequent fractures. A questionnaire was administered to 24 families with children under the age of 18 and 3 families were interviewed. The study found the families in great need of…

  14. Unilateral spinal anaesthesia in a patient with Osteogenesis Imperfecta with a lower leg fracture: a case report.

    PubMed

    Baranovic, Senka; Lubina, Ivan Zvonimir; Vlahovic, Tomislav; Bakota, Bore; Maldini, Branka

    2013-09-01

    Osteogenesis Imperfecta is a rare, genetically determined disease with several possible complications in anaesthesia. Anaesthesiologists therefore pay special attention to the treatment of patients suffering from Osteogenesis Imperfecta since they commonly suffer from a difficult airway and intraoperative positioning difficulties. We report here the case of unilateral spinal anaesthesia in a patient suffering from Osteogenesis Imperfecta type I. A 28-year-old patient diagnosed with Osteogenesis Imperfecta type I was admitted to the hospital due to lower leg fracture requiring surgical treatment. The patient had blue sclerae, triangular-shaped face, macroglossia, scoliosis of thoracic and lumbar parts of the spine, pectus carinatum and thrombocytopenia. Upon the correction of thrombocytopenia, unilateral spinal anaesthesia with hyperbaric levobupivacain was chosen in order to avoid possible complications typical for general anaesthesia. Consequently, unilateral spinal anaesthesia with a customized local anesthetic could be consdered as a safe anesthetic method for such patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Serum microRNA is a promising biomarker for osteogenesis imperfecta.

    PubMed

    Wang, Ziqiang; Lu, Yanqin; Zhang, Xiumei; Ren, Xiuzhi; Wang, Yanzhou; Li, Zhiliang; Xu, Chao; Han, Jinxiang

    2012-05-01

    The purpose of our study was to screen preliminary differential expression bone-related microRNAs (miRNAs) in serum of patients with osteogenesis imperfacta and to clarify whether serum microRNA is a promising biomarker for osteogenesis imperfecta. geNorm and several other programes were performed to select suitable reference genes for quantitative detection of serum miRNAs from 6 candidate control genes. With geometric averaging of selected reference genes as a normalization factor, fluorescence-based quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect expression levels of more than 100 bone-related miRNAs obtained by means of miRanda, Targetscan and Pictar software calculations and reading the literature. Through analysis of expression stability and pairwise variations, all 6 candidate reference genes had a stable expression level in serum of 8 healthy controls and 8 patients with different characrteristics, and the optimal number of reference genes for normalization was 4 (snRNAU6, miR-92a, miR-16, and Let-7a). For further validation, the expression stability of 4 reference genes remained steady in serum of another 8 healthy controls and 16 patients with osteogenesis imperfecta (M < 1.5). When normalized using multiple control genes, 11 bone-related miRNAs showed differential expression in serum of 8 osteogenesis imperfecta patients compared with 8 healthy controls. In conclusion, we identified snRNAU6, miR-92a, miR-16, and Let-7a as an internal reference gene group for qRT-PCR normalization and screening results revealed that there existed many differential expression bone-related miRNAs in serum of patients with osteogenesis imperfecta compared with healthy controls, and that these miRNAs had potential to be biomarkers for serologic tests and diagnosis of osteogenesis imperfecta with analysis of bioinformation.

  16. Developmental charts for children with osteogenesis imperfecta, type I (body height, body weight and BMI).

    PubMed

    Graff, Krzysztof; Syczewska, Malgorzata

    2017-03-01

    Osteogenesis imperfecta (OI) is a rare genetic disorder of type I collagen. Type I is the most common, which is called a non-deforming type of OI, as in this condition, there are no major bone deformities. This type is characterised by blue sclera and vertebral fractures, leading to mild scoliosis. The body height of these patients is regarded as normal, or only slightly reduced, but there are no data proving this in the literature. The aim of this study is the preparation of the developmental charts of children with OI type I. The anthropometric data of 117 patients with osteogenesis imperfecta were used in this study (61 boys and 56 girls). All measurements were pooled together into one database (823 measurements in total). To overcome the problem of the limited number of data being available in certain age classes and gender groups, the method called reverse transformation was used. The body height of the youngest children, aged 2 and 3 years, is less than that of their healthy peers. Children between 4 and 7 years old catch up slightly, but at later ages, development slows down, and in adults, the median body height shows an SDS of -2.7. These results show that children with type I OI are smaller from the beginning than their healthy counterparts, their development slows down from 8 years old, and, ultimately, their body height is impaired. What is Known: • The body height of patients with osteogenesis imperfecta type I is regarded as normal, or only slightly reduced, but in the known literature, there is no measurement data supporting this opinion. What is New: • Children with type I osteogenesis imperfecta are smaller from the beginning than their healthy counterparts, their development slows down from 8 years old and, ultimately, their final body height is impaired. • The developmental charts for the body height, body weight and BMI of children with type I osteogenesis imperfecta are shown.

  17. Femoral neck fractures in osteogenesis imperfecta treated with bisphosphonates

    PubMed Central

    Papanna, M. C.; Tafazal, S.; Bell, M. J.; Giles, S. N.; Fernandes, J. A.

    2017-01-01

    Abstract Purpose Osteogenesis imperfecta (OI) is a condition characterised by bone fragility and multiple fractures, which cause considerable morbidity in the affected patients. Most cases are associated with mutations in one of the type I collagen genes. Recently, bisphosponates have been used widely to reduce pain and the incidence of fragility fractures in OI in children, even though there have been concerns raised regarding the long-term complications of it due to their effect on the bone. The fragility fractures involving the neck of the femur in children with intramedullary rods in the femoral shaft are very difficult to treat. Although these fractures are frequently un-displaced, they require optimal internal fixation to achieve fracture union. The aim of this study was to assess the clinical and radiological outcomes of OI patients with intracapsular femoral neck fracture treated with headless compression screws. Method and results At our institute, we identified seven patients (11 hips) with OI who underwent internal fixation with headless compression screws for a neck of femur fracture between June 2010 and Dec 2012. The time to fractures healing was on average 14 weeks (12 to 16). All patients gained their pre-injury ambulatory status. Conclusion It is very challenging and technically demanding for orthopaedic surgeons when treating the fragility fracture of the neck of femur in patients with intramedullary rod in the femoral shaft. The published data regarding the management of these complex conditions are very limited. We describe our experience with the technique of percutaneous headless compression screw fixation for treating the femoral neck fractures in OI patients. PMID:28828062

  18. Intramedullary fixation using Kirschner wires in children with osteogenesis imperfecta.

    PubMed

    Imajima, Yukari; Kitano, Motohiro; Ueda, Takafumi

    2015-06-01

    Surgical treatment for osteogenesis imperfecta (OI) remains controversial. The use of elongating rods has become a mainstay in this treatment, and there have been many reports of the results of this procedure. In contrast, using nonelongating rods is considered to be the classic method. This older method is still used by surgeons who are concerned about the possibility of trauma on the articular surface due to arthrotomy at the insertion of the elongating rod or who are working in developing countries with fewer resources. We are among those who prefer the use of nonelongating rods to elongating rods. This article presents the results of intramedullary fixation using nonelongating rods such as Kirschner wires (K-wires) in children with OI and the proper timing of wire exchange to prevent further fracture. We treated 29 femora in 17 patients with OI by means of stabilization using K-wires. For these patients we calculated revision-free survival and analyzed the details of any fractures that occurred after the primary surgery. We also investigated the relations between the wire length ratio, which was defined as the ratio of the intramedullary wire length divided by the femoral length, and the fracture type. The revision-free survival for the 29 primary procedures was 63% at 3 years, and 36% at 5 years. All fractures that occurred at the wire tip required additional surgery, whereas only 51% of fractures at other sites required additional surgery. The wire length ratio of wire-tip fractures was significantly lower than that of fractures at other sites. There is a significant difference in the incidence of wire-tip fractures and other fractures between ratios of 65% and 75%. Wire exchange surgeries should be performed before the wire length ratio drops to <70%. This information could be useful for preventing further fractures that require surgery when OI patients are treated by intramedullary fixation with nonelongating rods. Level IV.

  19. [Zoledronic acid (zoledronate) in children with osteogenesis imperfecta].

    PubMed

    Sánchez-Sánchez, Luz María; Cabrera-Pedroza, Alfredo Uriel; Palacios-Saucedo, Gerardo; de la Fuente-Cortez, Beatriz

    2015-01-01

    Zoledronic acid or zo/edronate is a potent bisphosphonate that recently has been used in children with osteoporosis and osteogenesis imperfecta (01), so it could be an option in the treatment of children with this terrible disease that virtually condemns them to a life of pain and prostration. The aim of this study was to evaluate the clinical and biochemical conditions of pediatric patients with 01 before and after treatment with zo /edronate. We included 14 patients, median age six years (6 months to 14 years), eight (57.1 %) males and six (42 .9%) females, weight 19 kg (5.8-45 kg). According to the type of 01, six (42.9%) were type I, six (42.9%) type Ill, and two (14.2%) type IV The functional score (Bleck) previous to treatment was 4 (1-9) and 6 (2-9) after treatment (p = 0.001). Pain intensity prior to zo/edronate was 2 (1-9) and 0 (0-2) after (p = 0.008). Previous fractures five (1-15) and post-treatment one (0-2) (p = 0.001 ). There were no significant differences in calcium, phosphorus, alkaline phosphatase, and parathyroid hormone. Zoledronic acid decreases the number of bone fractures and pain in children with osteogenesis imperfect and improves functional status. The most common side effects were fever and bone pain within five days after the infusion,which disappear paracetamol. No adverse long-term effects such as hypocalcemia or hypoparathyroidism were reported.

  20. Pamidronate affects the mandibular cortex of children with osteogenesis imperfecta.

    PubMed

    Apolinário, A C; Figueiredo, P T; Guimarães, A T; Acevedo, A C; Castro, L C; Paula, A P; Paula, L M; Melo, N S; Leite, A F

    2015-03-01

    We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI. © International & American Associations for Dental Research.

  1. Large osteoclasts in pediatric osteogenesis imperfecta patients receiving intravenous pamidronate.

    PubMed

    Cheung, Moira S; Glorieux, Francis H; Rauch, Frank

    2009-04-01

    Intravenous pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). Changes in the appearance of osteoclasts have previously been noted in children receiving pamidronate and have been interpreted as signs of toxicity. In this study, we analyzed osteoclast parameters in paired iliac bone specimens before and after 2-4 yr of cyclical intravenous pamidronate therapy in 44 pediatric OI patients (age range: 1.4-17.5 yr; 21 girls). During pamidronate treatment, average osteoclast diameter and the mean number of nuclei present per osteoclast increased by 18% (p = 0.02) and 43% (p < 0.001), respectively. The number of samples containing large osteoclasts (LOcs, diameter > 50 mum) increased from 6 (14%) before treatment to 23 (52%) after pamidronate therapy (p < 0.001 by chi(2) test). Post-treatment samples containing LOcs had a greater core width (p = 0.04) and a higher cancellous bone volume per tissue volume (p < 0.001), because cancellous bone volume had increased more during pamidronate treatment (p < 0.001). Osteoclast number and surface were higher in samples with LOcs, but there was no difference in cancellous bone formation parameters. The presence of LOcs was independent of OI type, type of collagen type I mutation, lumbar spine BMD, and other clinical or biochemical measures. In conclusion, this study did not show any indication that LOcs during pamidronate treatment are indicative of toxicity. It seems more likely that the observed abnormalities in osteoclast morphology are part of the mechanism of action of this drug.

  2. Fractures at Diagnosis in Infants and Children with Osteogenesis Imperfecta

    PubMed Central

    Greeley, Christopher Spencer; Donaruma-Kwoh, Marcella; Vettimattam, Melanie; Lobo, Christine; Williard, Coco; Mazur, Lynnette

    2012-01-01

    Background In infants and children with fractures from an unclear cause, Osteogenesis Imperfecta (OI) is often included as a potential etiology. In infants and children with OI there exists a gap in the published literature regarding the fracture pattern seen at the time of diagnosis. As an additional aid to the diagnosis of OI, we sought to characterize the fracture patterns in infants and children at the time of their diagnosis. Methods We performed a retrospective chart review of a series of infants and children under 18 years of age who have the diagnosis of OI (any type) from a single institution. Results We identified 68 infants and children with OI: 23 (34%) type 1, 1(2%) type 2, 17(25%) type 3, 24(35%) type 4 and 3(4%) unknown type. A family history of OI is present in 46% of children. Forty-nine (72.0%) patients were diagnosed solely on clinical characteristics, without genetic or fibroblast confirmation. Rib fractures were noted in 21% of the subjects with none being identified during infancy. The number of fractures identified at diagnosis ranged from 1 to >37 with 7 (10%) having more than 2 fractures. All subjects with more than 2 fractures were diagnosed prenatally or in the immediate newborn period. Seventeen (25%) infants were diagnosed after 1 week of age but prior to 12 months of age. None of these infants had either rib fractures or more than 1 fracture at the time of diagnosis. Conclusion The majority of children diagnosed with OI are diagnosed by clinical features alone. The fracture pattern at the time of diagnosis in OI is variable with 10% having more than 2 fractures. The diagnosis of OI was made in utero or at delivery in 43% of children. Multiple rib fractures in an infant would be an unexpected finding in OI. Level Of Evidence Level III PMID:23232376

  3. Static Postural Control in Youth With Osteogenesis Imperfecta Type I.

    PubMed

    Pouliot-Laforte, Annie; Lemay, Martin; Rauch, Frank; Veilleux, Louis-Nicolas

    2017-04-19

    To assess static postural control in eyes-open and eyes-closed conditions in individuals with osteogenesis imperfecta (OI) type I as compared with typically developing (TD) individuals and to explore the relation between postural control and lower limb muscle function. Cross-sectional study. Outpatient department of a pediatric orthopedic hospital. A convenience sample (N=38) of individuals with OI type I (n=22; mean age, 13.1y; range, 6-21y) and TD individuals (n=16; mean age, 13.1y; range, 6-20y) was selected. Participants were eligible if they were between 6 and 21 years and if they did not have any fracture or surgery in the lower limb in the 12 months before testing. Not applicable. Postural control was assessed through static balance tests and muscle function through mechanographic tests on a force platform. Selected postural parameters were path length, velocity, 90% confidence ellipse area, and the ellipse's length of the mediolateral and anteroposterior axes. Mechanographic parameters were peak force and peak power as measured using the multiple two-legged hopping and the single two-legged jump test, respectively. Individuals with OI type I had poorer postural control than did TD individuals as indicated by longer and faster displacements and a larger ellipse area. Muscle function was unrelated to postural control in the OI group. Removing visual information resulted in a larger increase in postural control parameters in the OI group than in the TD group. A proprioceptive deficit could explain poorer postural control in individuals with OI type I. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  4. Popcorn calcification in osteogenesis imperfecta: incidence, progression, and molecular correlation.

    PubMed

    Obafemi, Abimbola A; Bulas, Dorothy I; Troendle, James; Marini, Joan C

    2008-11-01

    Osteogenesis imperfecta (OI) is a heritable disorder characterized by osteoporosis and increased susceptibility to fracture. All children with severe OI have extreme short stature and some have "popcorn" calcifications, areas of disorganized hyperdense lines in the metaphysis and epiphysis around the growth plate on lower limb radiographs. Popcorn calcifications were noted on radiographs of two children with non-lethal type VIII OI, a recessive form caused by P3H1 deficiency. To determine the incidence, progression, and molecular correlations of popcorn calcifications, we retrospectively examined serial lower limb radiographs of 45 children with type III or IV OI and known dominant mutations in type I collagen. Popcorn calcifications were present in 13 of 25 type III (52%), but only 2 of 20 type IV (10%), OI children. The mean age of onset was 7.0 years, with a range of 4-14 years. All children with popcorn calcifications had this finding in their distal femora, and most also had calcifications in proximal tibiae. While unilateral popcorn calcification contributes to femoral growth deficiency and leg length discrepancy, severe linear growth deficiency, and metaphyseal flare do not differ significantly between type III OI patients with and without popcorn calcifications. The type I collagen mutations associated with popcorn calcifications occur equally in both COL1A1 and COL1A2, and have no preferential location along the chains. These data demonstrate that popcorn calcifications are a frequent feature of severe OI, but do not distinguish cases with defects in collagen structure (primarily dominant type III OI) or modification (recessive type VIII OI). Copyright 2008 Wiley-Liss, Inc.

  5. Pamidronate Affects the Mandibular Cortex of Children with Osteogenesis Imperfecta

    PubMed Central

    Apolinário, A.C.; Figueiredo, P.T.; Guimarães, A.T.; Acevedo, A.C.; Castro, L.C.; Paula, A.P.; Paula, L.M.; Melo, N.S.; Leite, A.F.

    2015-01-01

    We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI. PMID:25608973

  6. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment.

    PubMed

    Van Dijk, F S; Sillence, D O

    2014-06-01

    Recently, the genetic heterogeneity in osteogenesis imperfecta (OI), proposed in 1979 by Sillence et al., has been confirmed with molecular genetic studies. At present, 17 genetic causes of OI and closely related disorders have been identified and it is expected that more will follow. Unlike most reviews that have been published in the last decade on the genetic causes and biochemical processes leading to OI, this review focuses on the clinical classification of OI and elaborates on the newly proposed OI classification from 2010, which returned to a descriptive and numerical grouping of five OI syndromic groups. The new OI nomenclature and the pre-and postnatal severity assessment introduced in this review, emphasize the importance of phenotyping in order to diagnose, classify, and assess severity of OI. This will provide patients and their families with insight into the probable course of the disorder and it will allow physicians to evaluate the effect of therapy. A careful clinical description in combination with knowledge of the specific molecular genetic cause is the starting point for development and assessment of therapy in patients with heritable disorders including OI. © 2014 The Authors. American Journal of Medical Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2014 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

  7. Exclusion of the alpha 1(II) cartilage collagen gene as the mutant locus in type IA osteogenesis imperfecta.

    PubMed Central

    Sykes, B; Smith, R; Vipond, S; Paterson, C; Cheah, K; Solomon, E

    1985-01-01

    Using two restriction site polymorphisms within the structural gene coding for human type II collagen we have examined the segregation of this gene in three pedigrees with dominantly inherited osteogenesis imperfecta (Sillence type IA). We have demonstrated that the gene does not segregate with clinical expression of the disease and cannot, therefore, contain the mutation responsible for osteogenesis imperfecta in these families. Images PMID:2989526

  8. Ruptured intracranial aneurysm in patients with osteogenesis imperfecta: 2 familial cases and a systematic review of the literature.

    PubMed

    Gaberel, T; Rochey, A; di Palma, C; Lucas, F; Touze, E; Emery, E

    2016-12-01

    Osteogenesis imperfecta is an inherited connective tissue disorder that causes bone fragility. Vascular complications have been described, but only few cases of ruptured intracranial aneurysm have been reported. We first described 2 familial cases of ruptured intracranial aneurysm and then conducted a systematic review of the literature. A mother and her daughter with a typical history of osteogenesis imperfecta presented with subarachnoid hemorrhage, which was related to a posterior communicating artery aneurysm in both cases. The mother had early rebleeding and died. The aneurysm was excluded by coiling in the daughter. Despite occurrence of hydrocephalus and delayed cerebral ischemia, she had an excellent functional outcome. A systematic review of the literature identified seven additional cases. None of the cases were in fact familial. All patients had a previous medical history of multiple fractures. Seven aneurysms were resolved, three by surgical clipping and four by endovascular procedure. No periprocedural complication was reported. One patient died prematurely and 6 experienced good functional outcome. We report the first familial cases of aneurysmal subarachnoid hemorrhage in osteogenesis imperfecta patients. Intracranial aneurysms are probably linked to a collagen pathology, which is at the origin of osteogenesis imperfecta. In cases of aneurysmal subarachnoid hemorrhage in an osteogenesis imperfecta family, intracranial aneurysm screenings in the relatives showing osteogenesis imperfecta should be considered. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Impaired osteoblastogenesis in a murine model of dominant osteogenesis imperfecta: a new target for osteogenesis imperfecta pharmacological therapy.

    PubMed

    Gioia, Roberta; Panaroni, Cristina; Besio, Roberta; Palladini, Giovanni; Merlini, Giampaolo; Giansanti, Vincenzo; Scovassi, Ivana A; Villani, Simona; Villa, Isabella; Villa, Anna; Vezzoni, Paolo; Tenni, Ruggero; Rossi, Antonio; Marini, Joan C; Forlino, Antonella

    2012-07-01

    The molecular basis underlying the clinical phenotype in bone diseases is customarily associated with abnormal extracellular matrix structure and/or properties. More recently, cellular malfunction has been identified as a concomitant causative factor and increased attention has focused on stem cells differentiation. Classic osteogenesis imperfecta (OI) is a prototype for heritable bone dysplasias: it has dominant genetic transmission and is caused by mutations in the genes coding for collagen I, the most abundant protein in bone. Using the Brtl mouse, a well-characterized knockin model for moderately severe dominant OI, we demonstrated an impairment in the differentiation of bone marrow progenitor cells toward osteoblasts. In mutant mesenchymal stem cells (MSCs), the expression of early (Runx2 and Sp7) and late (Col1a1 and Ibsp) osteoblastic markers was significantly reduced with respect to wild type (WT). Conversely, mutant MSCs generated more colony-forming unit-adipocytes compared to WT, with more adipocytes per colony, and increased number and size of triglyceride drops per cell. Autophagy upregulation was also demonstrated in mutant adult MSCs differentiating toward osteogenic lineage as consequence of endoplasmic reticulum stress due to mutant collagen retention. Treatment of the Brtl mice with the proteasome inhibitor Bortezomib ameliorated both osteoblast differentiation in vitro and bone properties in vivo as demonstrated by colony-forming unit-osteoblasts assay and peripheral quantitative computed tomography analysis on long bones, respectively. This is the first report of impaired MSC differentiation to osteoblasts in OI, and it identifies a new potential target for the pharmacological treatment of the disorder. Copyright © 2012 AlphaMed Press.

  10. Osteogenesis imperfecta and clubfoot—a rare combination

    PubMed Central

    Persiani, Pietro; Ranaldi, Filippo Maria; Martini, Lorena; Zambrano, Anna; Celli, Mauro; D’Eufemia, Patrizia; Villani, Ciro

    2016-01-01

    Abstract Background: Osteogenesis imperfecta (OI) is a rare congenital genetic osteodystrophy, which has a prevalence of 1:20,000. OI is caused by the mutation of the COL1A1/COL1A2 genes, leading to a deficit of quality and/or quantity in the synthesis of procollagen-α type 1. Seven different forms of diverse clinical entity have been classified by Sillence and Glorieux, although, recently, up to 11 forms characterized by different genetic mutations have been recognized. Patients with OI suffer from extreme bone fragility and osteoporosis, which often predisposes them to frequent fractures. This paper presents the case of a child with OI type IV who, at birth, was also diagnosed with a severe clubfoot (congenital talipes equinovarus) grade III. Patient's mother also suffers from OI type IV. Methods: The treatment was started by placing femoro-podalic corrective casts, according to the Ponseti method, but some unexpected problems occurred during this treatment. When the patient was 3 months of age, we decided to correct the clubfoot before the time limit planned, performing a bilateral posteromedial surgical release. Results: Three weeks after surgery the casts were removed and replaced with bilateral Spica cast-like braces. On the 6th postoperative week, the patient began wearing Bebax corrective shoes, after 1 year ambidextrous orthopedic shoes. Now, he is 2 years old and has started to walk properly without any orthesis. Conclusion: In the presence of an orthopedic pathology associated with OI, it is recommended to manage the patient according to the underlying pathology, always considering the bone fragility associated with OI. The final surgical treatment to correct the clubfoot can be done earlier, if necessary. In our opinion, this uncommon association between OI and clubfoot is non-syndromic. This means that the two congenital diseases are not necessarily included in a singular uncommon genetic syndrome, but the clubfoot was caused by multifactorial causes

  11. Severe Osteogenesis Imperfecta in Cyclophilin B–Deficient Mice

    PubMed Central

    Choi, Jae Won; Sutor, Shari L.; Lindquist, Lonn; Evans, Glenda L.; Madden, Benjamin J.; Bergen, H. Robert; Hefferan, Theresa E.; Yaszemski, Michael J.; Bram, Richard J.

    2009-01-01

    Osteogenesis Imperfecta (OI) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in Prolyl-3-Hydroxylase-1 (LEPRE1). Although P3H1 is known to hydroxylate a single residue (pro-986) in type I collagen chains, it is unclear how this modification acts to facilitate collagen fibril formation. P3H1 exists in a complex with CRTAP and the peptidyl-prolyl isomerase cyclophilin B (CypB), encoded by the Ppib gene. Mutations in CRTAP cause OI in mice and humans, through an unknown mechanism, while the role of CypB in this complex has been a complete mystery. To study the role of mammalian CypB, we generated mice lacking this protein. Early in life, Ppib-/- mice developed kyphosis and severe osteoporosis. Collagen fibrils in Ppib-/- mice had abnormal morphology, further consistent with an OI phenotype. In vitro studies revealed that in CypB–deficient fibroblasts, procollagen did not localize properly to the golgi. We found that levels of P3H1 were substantially reduced in Ppib-/- cells, while CRTAP was unaffected by loss of CypB. Conversely, knockdown of either P3H1 or CRTAP did not affect cellular levels of CypB, but prevented its interaction with collagen in vitro. Furthermore, knockdown of CRTAP also caused depletion of cellular P3H1. Consistent with these changes, post translational prolyl-3-hydroxylation of type I collagen by P3H1 was essentially absent in CypB–deficient cells and tissues from CypB–knockout mice. These data provide significant new mechanistic insight into the pathophysiology of OI and reveal how the members of the P3H1/CRTAP/CypB complex interact to direct proper formation of collagen and bone. PMID:19997487

  12. Severe osteogenesis imperfecta in cyclophilin B-deficient mice.

    PubMed

    Choi, Jae Won; Sutor, Shari L; Lindquist, Lonn; Evans, Glenda L; Madden, Benjamin J; Bergen, H Robert; Hefferan, Theresa E; Yaszemski, Michael J; Bram, Richard J

    2009-12-01

    Osteogenesis Imperfecta (OI) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in Prolyl-3-Hydroxylase-1 (LEPRE1). Although P3H1 is known to hydroxylate a single residue (pro-986) in type I collagen chains, it is unclear how this modification acts to facilitate collagen fibril formation. P3H1 exists in a complex with CRTAP and the peptidyl-prolyl isomerase cyclophilin B (CypB), encoded by the Ppib gene. Mutations in CRTAP cause OI in mice and humans, through an unknown mechanism, while the role of CypB in this complex has been a complete mystery. To study the role of mammalian CypB, we generated mice lacking this protein. Early in life, Ppib-/- mice developed kyphosis and severe osteoporosis. Collagen fibrils in Ppib-/- mice had abnormal morphology, further consistent with an OI phenotype. In vitro studies revealed that in CypB-deficient fibroblasts, procollagen did not localize properly to the golgi. We found that levels of P3H1 were substantially reduced in Ppib-/- cells, while CRTAP was unaffected by loss of CypB. Conversely, knockdown of either P3H1 or CRTAP did not affect cellular levels of CypB, but prevented its interaction with collagen in vitro. Furthermore, knockdown of CRTAP also caused depletion of cellular P3H1. Consistent with these changes, post translational prolyl-3-hydroxylation of type I collagen by P3H1 was essentially absent in CypB-deficient cells and tissues from CypB-knockout mice. These data provide significant new mechanistic insight into the pathophysiology of OI and reveal how the members of the P3H1/CRTAP/CypB complex interact to direct proper formation of collagen and bone.

  13. Cranial base abnormalities in osteogenesis imperfecta: phenotypic and genotypic determinants.

    PubMed

    Cheung, Moira S; Arponen, Heidi; Roughley, Peter; Azouz, Michel E; Glorieux, Francis H; Waltimo-Sirén, Janna; Rauch, Frank

    2011-02-01

    Cranial base abnormalities are an important complication of osteogenesis imperfecta (OI), a hereditary bone fragility disorder that in most patients is caused by mutations affecting collagen type I. To elucidate which clinical characteristics are associated with the occurrence of cranial base abnormalities in OI, we compared cephalometric results of 187 OI patients (median age 12.0 years, range 3.4 to 47 years; 96 female) with those of 191 healthy subjects and related findings to clinical descriptors of the disease. Overall, 41 patients (22%) had at least one unambiguously abnormal skull base measure. Multivariate logistic regression analysis in patients with OI types I, III, and IV (n = 169) revealed that height Z-score [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.43-0.66, p < .001]--but not age, gender, scleral hue, lumbar spine areal bone mineral density, or a history of bisphosphonate treatment--was a significant independent determinant of skull base abnormalities. Among patients with a height Z-score below -3, 48% had a skull base abnormality regardless of whether they had received bisphosphonate treatment in the first year of life or not. Genotype-phenotype correlations were evaluated in patients with detectable mutations in COL1A1 or COL1A2, the genes coding for collagen type I (n = 140). Skull base abnormalities were present in 6% of patients with haploinsufficiency (frameshift or nonsense) mutations, in 43% of patients with helical glycine substitutions caused by COL1A1 mutations, in 32% of patients with helical glycine substitutions owing to COL1A2 mutations, and in 17% of patients with splice-site mutations affecting either COL1A1 or COL1A2. However, multivariate logistic regression analysis showed that height Z-score but not the type of collagen type I mutation was independently associated with the prevalence of skull base abnormalities. In conclusion, this study shows that clinical severity of OI, as expressed by the height Z-score, was

  14. Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype

    PubMed Central

    2011-01-01

    Background Osteogenesis Imperfecta (OI) is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of life as a conductive hearing loss, frequently evolving to mixed hearing loss thereafter. A minority of patients develop pure sensorineural hearing loss. The interindividual variability in the audiological characteristics of the hearing loss is unexplained. Methods With the purpose of evaluating inter- and intrafamilial variability, hearing was thorougly examined in 184 OI patients (type I: 154; type III: 4; type IV: 26), aged 3-89 years, with a mutation in either COL1A1 or COL1A2 and originating from 89 different families. Due to the adult onset of hearing loss in OI, correlations between the presence and/or characteristics of the hearing loss and the underlying mutation were investigated in a subsample of 114 OI patients from 64 different families who were older than 40 years of age or had developed hearing loss before the age of 40. Results Hearing loss was diagnosed in 48.4% of the total sample of OI ears with increasing prevalence in the older age groups. The predominant type was a mixed hearing loss (27.5%). A minority presented a pure conductive (8.4%) or pure sensorineural (12.5%) loss. In the subsample of 114 OI subjects, no association was found between the nature of the mutation in COL1A1 or COL1A2 genes and the occurrence, type or severity of hearing loss. Relatives originating from the same family differed in audiological features, which may partially be attributed to their dissimilar age. Conclusions Our study confirms that hearing loss in OI shows a strong intrafamilial variability. Additional modifications in other genes are assumed to be responsible for the expression of hearing loss in OI. PMID:22206639

  15. Chronic ventilator use in osteogenesis imperfecta congenita with basilar impression: a case report.

    PubMed

    Wang, T G; Yang, G F; Alba, A

    1994-06-01

    Osteogenesis imperfecta, a rare connective tissue disorder, is known to be associated sometimes with the invagination of the basilar skull. This deformity may disturb respiratory function secondary to brain stem compression and hydrocephalus. In addition, the deformed thoracic cage and fragile ribs make pulmonary care more complicated. A case of 24-year-old man is presented with brain stem compression syndrome secondary to osteogenesis imperfecta congenita with basilar impression. He developed respiratory failure and became tracheostomy positive-pressure ventilator dependent at the age of 21 years. He also suffered multiple skeletal abnormalities and mental retardation, and following the brain stem compression, severe quadriparesis. The patient's condition is stable since he has been using the ventilator and he is currently living in the community.

  16. Dentinogenesis imperfecta type I: A case report with literature review on nomenclature system

    PubMed Central

    Devaraju, D; Devi, BK Yashoda; Vasudevan, Vijeev; Manjunath, V

    2014-01-01

    Dentinogenesis imperfecta (DI) is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. Mutation in dentin sialophosphoprotein (DSPP) has been found to cause the dentin disorders DI - I and II (shields II and III). Early diagnosis and treatment of DI is recommended as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. Here, we report a case with characteristic clinical, radiological and histological features of DI-I. The etiology and classification followed in literature is confusing since dentinoenamel junction (DEJ) in DI seems to be structurally and functionally normal and DI is clearly a disorder distinct from osteogenesis imperfecta (OI), but we still relate etiology of DI to DEJ and follow Shields classification. Therefore, we have briefly reviewed etiology and nomenclature system of DI. PMID:25364163

  17. Swellings over the Limbs as the Earliest Feature in a Patient with Osteogenesis Imperfecta Type V

    PubMed Central

    Ganger, Rudolf; Klaushofer, Klaus; Grill, Franz

    2014-01-01

    Swellings over the upper and lower limbs were encountered in a one-year-old child. Skeletal survey showed a constellation of distinctive radiographic abnormalities of osteoporosis, hyperplastic callus and ossification of the interosseous membrane of the forearm, femora, and to lesser extent the tibiae. Neither wormian bones of the skull nor dentinogenesis imperfecta was present. Genetic tests revealed absence of mutation in COL1A1 or COL1A2 genes, respectively. The overall phenotypic features were consistent with the diagnosis of osteogenesis imperfecta type V (OI-V). The aim of this paper is to distinguish between swellings because of intrinsic bone disorders and these due to child physical abuse. PMID:24772361

  18. Dentinogenesis imperfecta type I: A case report with literature review on nomenclature system.

    PubMed

    Devaraju, D; Devi, Bk Yashoda; Vasudevan, Vijeev; Manjunath, V

    2014-09-01

    Dentinogenesis imperfecta (DI) is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. Mutation in dentin sialophosphoprotein (DSPP) has been found to cause the dentin disorders DI - I and II (shields II and III). Early diagnosis and treatment of DI is recommended as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. Here, we report a case with characteristic clinical, radiological and histological features of DI-I. The etiology and classification followed in literature is confusing since dentinoenamel junction (DEJ) in DI seems to be structurally and functionally normal and DI is clearly a disorder distinct from osteogenesis imperfecta (OI), but we still relate etiology of DI to DEJ and follow Shields classification. Therefore, we have briefly reviewed etiology and nomenclature system of DI.

  19. Early Rehabilitation of Incisors with Dentinogenesis Imperfecta Type II - Case Report.

    PubMed

    Beltrame, Ana Paula Ca; Rosa, Maíra Mery; Noschang, Ricardo At; Almeida, Izabel Cs

    Dentinogenesis imperfecta is an phenotypic alteration in the formation of the organic matrix. It causes the rapid and progressive wear of tooth structure, which may compromise tooth function and aesthetics. This is a case of a 1y, 8m-old child with dentinogenesis imperfecta. All teeth presented with an opalescent appearance and grayish color hue. Compromised structural integrity was noted as excessive wear and fracturing of the enamel from the dentin layer. With low doses of midazolam (oral) and chloral hydrate (rectal) administration, in a hospital environment, sedation was used to aid full mouth rehabilitation. Direct bonded restorations were performed on primary maxillary incisors and indirect restorations, pre-made on a plaster model using composite resin, were performed on primary mandibular incisors. After 32 months, we observed that diagnosis and early treatment allowed preventive maintenance of the patient's primary dentition, maintaining tooth function and esthetics.

  20. Management of osteogenesis imperfecta type I in pregnancy; a review of literature applied to clinical practice.

    PubMed

    Cozzolino, Mauro; Perelli, Federica; Maggio, Luana; Coccia, Maria Elisabetta; Quaranta, Michela; Gizzo, Salvatore; Mecacci, Federico

    2016-06-01

    Osteogenesis imperfecta (OI) is a rare heritable heterogenous disorder characterized by bone fragility and susceptibility to fractures with a wide spectrum of clinical expression due to defects in collagen type I biosynthesis. The purpose of the review is to highlight the practical norms in pregnancies with osteogenesis imperfecta. We carried out a literature review in MEDLINE on OI during pregnancy, focusing on diagnosis, therapy and delivery. We reviewed 28 articles (case reports, original articles and reviews). Pregnant women affected by type I OI should be closely monitored to assess fetal well-being and detect pregnancy-related complications associated with an increased risk for osteoporosis, restrictive pulmonary disease, cephalopelvic disproportion and other problems related to connective tissue disorders. Mode of delivery remains controversial and should be determined on an individual basis. In conclusion, women affected by type I OI represent a subset of patients whose pregnancies should be considered high risk and warrant a multidisciplinary approach in a referral center.

  1. Dentinogenesis imperfecta: a case report of comprehensive treatment for a teenager.

    PubMed

    Biethman, Rick; Capati, Laura Richards; Eldger, Nicole

    2014-01-01

    Improving a smile can change a person's self-image. This case report describes treatment for an adolescent boy with dentinogenesis imperfecta. Soon to begin high school, the 14-year-old patient was severely obese and disliked his stained teeth. A combination of surgical periodontal treatment, endodontic treatment, and veneers improved both his smile and self-perception-which may have played a role in achieving his weight loss goal of 125 lb at 12 months post-treatment.

  2. A rare presentation of a child with osteogenesis imperfecta and congenital laryngomalacia for herniotomy

    PubMed Central

    Chandran, Roshith; Dave, Nandini; Padvi, Amit; Garasia, Madhu

    2011-01-01

    Sometimes anaesthesiologists come across rare congenital anomalies in their practice. The inherent complications associated with the disorder necessitate tailor-made approaches for providing anaesthesia to even seemingly simple surgical interventions. Here, we share our experience of anaesthesia management of an infant with congenital laryngomalacia and recently diagnosed osteogenesis imperfecta type 1 who had presented to us with an acute abdomen for a semi-emergency herniotomy. PMID:22174477

  3. Osteogenesis imperfecta and hearing loss--description of three case reports.

    PubMed

    Pereira da Silva, Ana; Feliciano, Telma; Figueirinhas, Rosário; Almeida E Sousa, Cecília

    2013-01-01

    Osteogenesis imperfecta is the commonest connective tissue hereditary disease. Its clinical presentation has a wide spectrum of characteristics, which includes skeletal deformities and hearing loss. We describe three case reports of individuals carriers of this disease presenting with different patterns of hearing loss. Hearing loss prevalence and patterns are variable and have no clear relation with genotype. Its assessment at initial evaluation and posterior monitoring is essential to provide the best therapeutic alternatives.

  4. Diagnostic features and pedodontic-orthodontic management in dentinogenesis imperfecta type II: a case report.

    PubMed

    Huth, K Ch; Paschos, E; Sagner, T; Hickel, R

    2002-09-01

    Dentinogenesis imperfecta type II, also known as hereditary opalescent dentin, is an isolated inherited condition transmitted as an autosomal dominant trait affecting the primary and permanent dentition. The combined pedodontic-orthodontic management of a 4-year-old child is described. Following orthodontic analysis to encourage a favourable growth outcome, treatment comprised restoration of the primary teeth with stainless steel crowns and composite crowns. Differential diagnosis and alternative therapies, including orthodontic considerations, are discussed.

  5. Dentinogenesis imperfecta: a review and case report of a family over four generations.

    PubMed

    Bhandari, Sudhir; Pannu, Karneev

    2008-01-01

    Dentinogenesis imperfecta (DGI) is one of the most common hereditary disorders of dentin formation. It follows an autosomal dominant pattern of transmission, affecting both the formation and mineralization of dentin. Either or both primary and permanent dentition is affected by it. This paper briefly reviews the manifestations of DGI Type II (DGI1) and presents a case report of a family affected with DGI1 over four generations.

  6. Sandwich allografts for long-bone nonunions in patients with osteogenesis imperfecta: a retrospective study.

    PubMed

    Puvanesarajah, Varun; Shapiro, Jay R; Sponseller, Paul D

    2015-02-18

    Patients with osteogenesis imperfecta often develop nonunions, as internal fixation has limited applicability in this condition. We report the outcomes of a modified "sandwich technique" in the treatment of long-bone nonunions in patients with osteogenesis imperfecta; this technique brings circumferential stabilization and normal collagen to the nonunion site. From May 2003 through February 2012, twelve patients (eight females, four males; median age, 39.0 years; range, eleven to seventy-eight years) who had osteogenesis imperfecta (Sillence type I [three], type III [eight], and type IV [one]) and a combined total of thirteen nonunions (two humeral, two radial, three femoral, four tibial, and two ulnar; median duration, 15.0 months; range, six to 204 months) were treated at our institution with compressed sandwich allograft cortical struts. The struts were fashioned to be wide enough to allow for increased osteoconductive surface area and to approximate a hemicylindrical shape. Treatment history and demographics data were acquired through retrospective chart review. Follow-up radiographs were analyzed by two attending orthopaedic surgeons to determine radiographic findings. The median follow-up time was 4.6 years (range, 2.1 to 10.3 years). All thirteen nonunions, including one requiring a second graft procedure, healed with abundant, smooth allograft incorporation, resulting in an initial healing rate of 92% because of a refracture in one patient. This patient's nonunion ultimately healed with additional allograft struts and a new intramedullary rod. One patient required removal of prominent screws. The final follow-up examinations revealed no pain or refracture at the original nonunion site. All patients regained their prefracture level of function. Sandwich allograft struts constitute a durable, safe method for the stabilization and healing of persistent long-bone nonunions in patients with osteogenesis imperfecta. All patients showed incorporation of the

  7. A cephalometric method to diagnosis the craniovertebral junction abnormalities in osteogenesis imperfecta patients.

    PubMed

    Ríos-Rodenas, Mercedes; de Nova, Joaquín; Gutiérrez-Díez, María-Pilar; Feijóo, Gonzalo; Mourelle, Maria-Rosa; Garcilazo, Mario; Ortega-Aranegui, Ricardo

    2015-02-01

    Osteogenesis imperfecta (OI) is a hereditary bone fragility disorder that in most patients is caused by mutations affecting collagen type I. Their typical oral and craneofacial characteristics (Dentinogenesis imperfecta type I and class III malocclusion), involve the dentist in the multidisciplinary team that treat these patients. It is usual to perform lateral skull radiographs for the orthodontic diagnosis. In addition, this radiograph is useful to analyse the junctional area between skull base and spine, that could be damaged in OI. Pathology in the craneovertebral junction (CVJ) is a serious complication of OI with a prevalence ranging from rare to 37%. To diagnosis early skull base anomalies in these patients, previously the neurological symptoms have been appear, we make a simple cephalometric analysis of the CVJ. This method has four measurements and one angle. Once we calculate the values of the OI patient, we compare the result with the mean and the standard deviations of an age-appropriate average in healthy controls. If the patient has a result more than 2,5 SDs above the age-appropriate average in healthy controls, we should to refer the patient to his/her pediatrician or neurologist. These doctors have to consider acquiring another diagnostic images to be used to determine cranial base measurements with more reliability. Thereby, dentists who treat these patients, must be aware of the normal radiological anatomy of the cervical spine on the lateral cephalogram. Key words:Osteogenesis imperfecta, craniovertebral junction, cephalometric.

  8. Osteogenesis imperfecta: Level of independence and of social, recreational and sports participation among adolescents and youth.

    PubMed

    Rodríguez Celin, Mercedes; Fano, Virginia

    2016-06-01

    Osteogenesis imperfecta is a group of hereditary connective tissue disorders that cause bone fragility, with a wide clinical variability resulting in varying degrees of motor disability. To describe the level of independence and of social, recreational and sports participation among adolescents with osteogenesis imperfecta. Descriptive, analytical and crosssectional study conducted in patients with osteogenesis imperfecta older than 15 years old attending the Skeletal Dysplasia Office of Hospital "Prof. Dr. Juan P. Garrahan" (May 2013 through December 2014). Self-administered survey. Short stature was an outcome measure that indicated severity. There were 18 patients; age: 19.17 (±3.4 sDE); 83% had moderate-severe forms of OI; median height: -7.9 sDE; 50% used a wheelchair. Average education years: 12.2; 56% participated in sporting activities; and 78% were involved in recreational and social activities. A high level of independence was observed. We found a correlation between short stature and use of wheelchair (r: -0.77) and between short stature and participation in sporting activities (r: 0.66). No correlation was observed with years of education (r: -0.15), participation in social activities (r: -0.22) or recreational activities (r: 0.35). Sociedad Argentina de Pediatría.

  9. Identification of a Frameshift Mutation in Osterix in a Patient with Recessive Osteogenesis Imperfecta

    PubMed Central

    Lapunzina, Pablo; Aglan, Mona; Temtamy, Samia; Caparrós-Martín, José A.; Valencia, Maria; Letón, Rocío; Martínez-Glez, Victor; Elhossini, Rasha; Amr, Khalda; Vilaboa, Nuria; Ruiz-Perez, Victor L.

    2010-01-01

    Osteogenesis imperfecta, or “brittle bone disease,” is a type I collagen-related condition associated with osteoporosis and increased risk of bone fractures. Using a combination of homozygosity mapping and candidate gene approach, we have identified a homozygous single base pair deletion (c.1052delA) in SP7/Osterix (OSX) in an Egyptian child with recessive osteogenesis imperfecta. The clinical findings from this patient include recurrent fractures, mild bone deformities, delayed tooth eruption, normal hearing, and white sclera. OSX encodes a transcription factor containing three Cys2-His2 zinc-finger DNA-binding domains at its C terminus, which, in mice, has been shown to be essential for bone formation. The frameshift caused by the c.1052delA deletion removes the last 81 amino acids of the protein, including the third zinc-finger motif. This finding adds another locus to the spectrum of genes associated with osteogenesis imperfecta and reveals that SP7/OSX also plays a key role in human bone development. PMID:20579626

  10. New trends in the treatment of osteogenesis imperfecta type III - own experience.

    PubMed

    Jakubowska-Pietkiewicz, Elzbieta; Chlebna-Sokół, Danuta

    2008-01-01

    Osteogenesis imperfecta (OI) is a genetic disorder caused by a mutation in the genes that encode the chains of type I collagen. Clinical manifestations include increased bone fragility and blue sclerae. OI type III is the most severe form with fractures occurring already in utero. Fracture immobilisation and orthopaedic surgery are the mainstay of treatment for patients with OI, and are combined with rehabilitation and bisphosphonate therapy. The study involved 8 children with osteogenesis imperfecta type III, aged 1 month to 6 years. All of them were treated with cyclic intravenous infusions of pamidronate. Laboratory studies conducted before and after each 3-day cycle of pamidronate therapy included complete blood count, serum calcium, phosphorus, magnesium, osteocalcin, and calcium/creatinine index in morning urine and collagen type I cross-linked N-telopeptide (NTx). Infant total body densitometric scans were obtained in 5/8 patients. Patients were treated for periods of 3-58 months. Fracture rates decreased with treatment in all patients compared to the prenatal period. Pamidronate also slowed down bone turnover, and particularly the resorption rate. The most common side effects during treatment included hypocalcaemia (7/8 patients) and fever (up to 39 degrees C) after the first cycle of treatment. Symptomatic bisphosphonate therapy in children with osteogenesis imperfecta ameliorated the clinical course (decreased bone pain and reduced incidence of fractures). Pamidronate therapy had a positive impact on functional parameters such as independence in everyday activities and better mobility. The treatment was safe.

  11. Osteonectin, bone proteoglycan, and phosphophoryn defects in a form of bovine osteogenesis imperfecta.

    PubMed Central

    Termine, J D; Robey, P G; Fisher, L W; Shimokawa, H; Drum, M A; Conn, K M; Hawkins, G R; Cruz, J B; Thompson, K G

    1984-01-01

    Bovine osteogenesis imperfecta is a congenital disease in Holstein cattle having several characteristics in common with human osteogenesis imperfecta syndromes. In particular, affected calves have multiple bone fractures and friable teeth. Bone collagen isolated from the affected animals (Texas variant) showed slightly decreased alpha 1(I) and alpha 2(I) chain electrophoretic mobility and increased hydroxylysine content. Overall collagen was present in the affected bones at 80-90% of normal values. However, osteonectin, a 32,000 Mr bone-specific protein found previously to promote collagen mineralization in vitro and present in abundance (approximately equal to 3% of total protein) in normal calf bone, was severely depleted (less than 2% of normal levels) in the osteogenesis imperfecta bone and dentin. The bone proteoglycan was similarly depleted. In contrast, the bone sialoprotein was not as severely affected. Further, the diseased teeth lacked (less than 10% of normal values) phosphophoryn, a dentin-specific protein normally present as 4-5% of the total calf dentin matrix. The data suggest multiple hard tissue matrix protein deletions, perhaps due to impaired cell development. Images PMID:6585794

  12. A cephalometric method to diagnosis the craniovertebral junction abnormalities in osteogenesis imperfecta patients

    PubMed Central

    Ríos-Rodenas, Mercedes; Gutiérrez-Díez, María-Pilar; Feijóo, Gonzalo; Mourelle, Maria-Rosa; Garcilazo, Mario; Ortega-Aranegui, Ricardo

    2015-01-01

    Osteogenesis imperfecta (OI) is a hereditary bone fragility disorder that in most patients is caused by mutations affecting collagen type I. Their typical oral and craneofacial characteristics (Dentinogenesis imperfecta type I and class III malocclusion), involve the dentist in the multidisciplinary team that treat these patients. It is usual to perform lateral skull radiographs for the orthodontic diagnosis. In addition, this radiograph is useful to analyse the junctional area between skull base and spine, that could be damaged in OI. Pathology in the craneovertebral junction (CVJ) is a serious complication of OI with a prevalence ranging from rare to 37%. To diagnosis early skull base anomalies in these patients, previously the neurological symptoms have been appear, we make a simple cephalometric analysis of the CVJ. This method has four measurements and one angle. Once we calculate the values of the OI patient, we compare the result with the mean and the standard deviations of an age-appropriate average in healthy controls. If the patient has a result more than 2,5 SDs above the age-appropriate average in healthy controls, we should to refer the patient to his/her pediatrician or neurologist. These doctors have to consider acquiring another diagnostic images to be used to determine cranial base measurements with more reliability. Thereby, dentists who treat these patients, must be aware of the normal radiological anatomy of the cervical spine on the lateral cephalogram. Key words:Osteogenesis imperfecta, craniovertebral junction, cephalometric. PMID:25810828

  13. Two novel mutations in the PPIB gene cause a rare pedigree of osteogenesis imperfecta type IX.

    PubMed

    Jiang, Yu; Pan, Jingxin; Guo, Dongwei; Zhang, Wei; Xie, Jie; Fang, Zishui; Guo, Chunmiao; Fang, Qun; Jiang, Weiying; Guo, Yibin

    2017-06-01

    Osteogenesis imperfecta (OI) is a rare genetic skeletal disorder characterized by increased bone fragility and vulnerability to fractures. PPIB is identified as a candidate gene for OI-IX, here we detect two pathogenic mutations in PPIB and analyze the genotype-phenotype correlation in a Chinese family with OI. Next-generation sequencing (NGS) was used to screen the whole exome of the parents of proband. Screening of variation frequency, evolutionary conservation comparisons, pathogenicity evaluation, and protein structure prediction were conducted to assess the pathogenicity of the novel mutations. Sanger sequencing was used to confirm the candidate variants. RTQ-PCR was used to analyze the PPIB gene expression. All mutant genes screened out by NGS were excluded except PPIB. Two novel heterozygous PPIB mutations (father, c.25A>G; mother, c.509G>A) were identified in relation to osteogenesis imperfecta type IX. Both mutations were predicted to be pathogenic by bioinformatics analysis and RTQ-PCR analysis revealed downregulated PPIB expression in the two carriers. We report a rare pedigree with an autosomal recessive osteogenesis imperfecta type IX (OI-IX) caused by two novel PPIB mutations identified for the first time in China. The current study expands our knowledge of PPIB mutations and their associated phenotypes, and provides new information on the genetic defects associated with this disease for clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. DLX3 mutation in a new family and its phenotypic variations.

    PubMed

    Lee, S-K; Lee, Z H; Lee, S-J; Ahn, B-D; Kim, Y-J; Lee, S-H; Kim, J-W

    2008-04-01

    Tricho-dento-osseous syndrome (TDO) is an autosomal-dominant disease characterized by curly hair at birth, enamel hypoplasia, taurodontism, and a thick cortical bone. A common DLX3 gene mutation (c.571_574delGGGG) has been identified in multiple families with variable clinical phenotypes. Recently, another DLX3 gene mutation (c.561_562delCT) was reported to cause amelogenesis imperfecta with taurodontism (AIHHT). We identified a Korean family with overlapping phenotypes of TDO and AIHHT. We performed mutational analysis to discover its genetic etiology. The identified mutation was c.561_562delCT mutation in the DLX3 gene. The enamel was hypomature and hypoplastic. The characteristic taurodontic features were not identified. Increased bone density or thickness could not be revealed by cephalometric, hand-wrist, and panoramic radiographs. Affected individuals reported that their nails were brittle, and they had curly hair at birth. This study clearly showed that the c.561_562delCT mutation had not only enamel defects, but also other clinical phenotypes resembling those of TDO syndrome.

  15. Transcription Factor FoxO1 Is Essential for Enamel Biomineralization

    PubMed Central

    Poché, Ross A.; Sharma, Ramaswamy; Garcia, Monica D.; Wada, Aya M.; Nolte, Mark J.; Udan, Ryan S.; Paik, Ji-Hye; DePinho, Ronald A.; Bartlett, John D.; Dickinson, Mary E.

    2012-01-01

    The Transforming growth factor β (Tgf-β) pathway, by signaling via the activation of Smad transcription factors, induces the expression of many diverse downstream target genes thereby regulating a vast array of cellular events essential for proper development and homeostasis. In order for a specific cell type to properly interpret the Tgf-β signal and elicit a specific cellular response, cell-specific transcriptional co-factors often cooperate with the Smads to activate a discrete set of genes in the appropriate temporal and spatial manner. Here, via a conditional knockout approach, we show that mice mutant for Forkhead Box O transcription factor FoxO1 exhibit an enamel hypomaturation defect which phenocopies that of the Smad3 mutant mice. Furthermore, we determined that both the FoxO1 and Smad3 mutant teeth exhibit changes in the expression of similar cohort of genes encoding enamel matrix proteins required for proper enamel development. These data raise the possibility that FoxO1 and Smad3 act in concert to regulate a common repertoire of genes necessary for complete enamel maturation. This study is the first to define an essential role for the FoxO family of transcription factors in tooth development and provides a new molecular entry point which will allow researchers to delineate novel genetic pathways regulating the process of biomineralization which may also have significance for studies of human tooth diseases such as amelogenesis imperfecta. PMID:22291941

  16. Shear bond strength of dentin and deproteinized enamel of AI mouse incisors

    PubMed Central

    Pugach, M.K.; Ozer, F.; Mulmadgi, R.; Li, Y.; Suggs, C.; Wright, J.T.; Bartlett, J.D.; Gibson, C.W.; Lindemeyer, R.G.

    2014-01-01

    Purpose To investigate the adhesion through shear bond strength (SBS) testing of a resin composite bonded with a self-etching bonding system (SEB) to amelogenesis imperfecta (AI)-affected deproteinized mouse enamel or dentin; and to compare wild-type (WT), amelogenin null (AmelxKO) and matrix metalloproteinase-20 null (Mmp20KO) enamel and dentin phenotypes using microCT and nanoindentation. Methods Enamel incisor surfaces of WT, AmelxKO and Mmp20KO mice were treated with SEB with and without NaOCl and tested for SBS. Incisor dentin was also treated with SEB and tested for SBS. These surfaces were further examined by SEM. MicroCT and nanoindentation analyses were performed on mouse dentin and enamel. Data were analyzed for significance by ANOVA. Results Deproteinization did not improve SBS of SEB to these AI-affected enamel surfaces. SBS of AmelxKO teeth was similar in dentin and enamel; however, it was higher in Mmp20KO dentin. The nanohardness of knockout enamel was significantly lower than WT, while knockout dentin nanohardness was not different from WT. Conclusions Using animal AI models, it was demonstrated that enamel NaOCl deproteinization of hypoplastic and hypoplastic-hypomaturation enamel did not increase shear bond strength while removal of the defective enamel allowed optimal dentin bonding. PMID:25303500

  17. Evolution of Klk4 and enamel maturation in eutherians

    PubMed Central

    Kawasaki, Kazuhiko; Hu, Jan C.-C; Simmer, James P.

    2014-01-01

    Kallikrein-related peptidase 4 (KLK4) is a secreted serine protease that degrades residual enamel proteins to facilitate their removal by ameloblasts, which increases mineralization and hardens the enamel. Mutations in human KLK4 cause hypomaturation amelogenesis imperfecta. Enamel formed by Klk4 null mice is normal in thickness and prism structure, but the enamel layer retains proteins, is hypomineralized, and undergoes rapid attrition following tooth eruption. We searched multiple databases, retrieved Klk4 and Klk5 from various mammalian genomes, and identified Klk4 in 47 boreoeutherian genomes. In non-Boreoeutheria, Klk4 was detected in only one afrotherian genome (as a pseudogene), and not in the other six afrotherian, two xenarthran, or three marsupial genomes. In contrast, Klk5 was detected in both marsupial and eutherian mammals. Our phylogenetic and mutation rate analyses support the hypothesis that Klk4 arose from Klk5 by gene duplication near the divergence of Afrotheria, Xenarthra and Boreoeutheria, and that functionally- differentiated Klk4 survived only in Boreoeutheria. Afrotherian mammals share the feature of delayed dental eruption relative to boreoeutherian mammals. KLK4 shortens the time required for enamel maturation and could have alleviated negative selection following mutations that resulted in thicker enamel or earlier tooth eruption, without reducing enamel hardness or causing dental attrition. PMID:25153384

  18. Transcription factor FoxO1 is essential for enamel biomineralization.

    PubMed

    Poché, Ross A; Sharma, Ramaswamy; Garcia, Monica D; Wada, Aya M; Nolte, Mark J; Udan, Ryan S; Paik, Ji-Hye; DePinho, Ronald A; Bartlett, John D; Dickinson, Mary E

    2012-01-01

    The Transforming growth factor β (Tgf-β) pathway, by signaling via the activation of Smad transcription factors, induces the expression of many diverse downstream target genes thereby regulating a vast array of cellular events essential for proper development and homeostasis. In order for a specific cell type to properly interpret the Tgf-β signal and elicit a specific cellular response, cell-specific transcriptional co-factors often cooperate with the Smads to activate a discrete set of genes in the appropriate temporal and spatial manner. Here, via a conditional knockout approach, we show that mice mutant for Forkhead Box O transcription factor FoxO1 exhibit an enamel hypomaturation defect which phenocopies that of the Smad3 mutant mice. Furthermore, we determined that both the FoxO1 and Smad3 mutant teeth exhibit changes in the expression of similar cohort of genes encoding enamel matrix proteins required for proper enamel development. These data raise the possibility that FoxO1 and Smad3 act in concert to regulate a common repertoire of genes necessary for complete enamel maturation. This study is the first to define an essential role for the FoxO family of transcription factors in tooth development and provides a new molecular entry point which will allow researchers to delineate novel genetic pathways regulating the process of biomineralization which may also have significance for studies of human tooth diseases such as amelogenesis imperfecta.

  19. Phase angle and World Health Organization criteria for the assessment of nutritional status in children with osteogenesis imperfecta

    PubMed Central

    Pileggi, Vicky Nogueira; Scalize, Antonio Rodolpho Hakime; Camelo, José Simon

    2016-01-01

    Abstract Objective: To compare the phase angle of patients with osteogenesis imperfecta treated at a tertiary university hospital with patients in a control group of healthy children, and to assess the nutritional status of these patients through the body mass index proposed by the World Health Organization. Methods: Cross-sectional study carried out in a university hospital that included seven patients with osteogenesis imperfecta and a control group of 17 healthy children of the same gender and age. Weight and height were measured and bioelectrical impedance was performed. Subsequently, the phase angle was calculated based on resistance and reactance values. Results: The phase angle of the group of children with osteogenesis imperfecta was significantly lower than that of the control group (p<0.05). The body mass index criterion for age of the World Health Organization showed no difference between groups. Conclusions: Children with osteogenesis imperfecta have a nutritional risk detected by the phase angle, which is a useful tool for nutritional screening. The calculation result could help in the diet therapy of patients with osteogenesis imperfecta. PMID:27102998

  20. Systematic Review on the Incidence of Bisphosphonate Related Osteonecrosis of the Jaw in Children Diagnosed with Osteogenesis Imperfecta

    PubMed Central

    Jayasinghe, Jap; Khajeh, Janette; Macfarlane, Tatiana V.

    2013-01-01

    ABSTRACT Objectives To conduct a systematic review of epidemiological literature to determine the incidence of bisphosphonate related osteonecrosis of the jaw occurring either spontaneously or after dental surgery, in children and adolescents diagnosed with osteogenesis imperfecta. Material and Methods MEDLINE, HMIC and EMBASE were used to search for English-language articles published from 1946 - 2013. Inclusion criteria consisted of population based studies of children and adolescents (24 years and younger) diagnosed with osteogenesis imperfecta, only studies which included a dental examination, and patients treated with intravenous bisphosphonates were included. Articles were excluded if patients had any other co-morbidity which could affect osteonecrosis of the jaw, and those which treated patients with oral bisphosphonates only. Results Five studies consisting of four retrospective cohort studies and one case series were identified. Study populations ranged from 15 to 278 patients and number of subjects with osteogenesis imperfecta ranged from 15 to 221. Mean duration of intravenous bisphosphonate use ranged from 4.5 to 6.8 years. All patients were clinically examined and no patients were found to have osteonecrosis of the jaw. Conclusions There is no evidence to support hypothesis of causal relationship between bisphosphonates and osteonecrosis of the jaw in children and adolescents with osteogenesis imperfecta. More prospective studies on bisphosphonate use in osteogenesis imperfecta needs to be carried out. PMID:24478911

  1. Systematic review on the incidence of bisphosphonate related osteonecrosis of the jaw in children diagnosed with osteogenesis imperfecta.

    PubMed

    Hennedige, Anusha Adeline; Jayasinghe, Jap; Khajeh, Janette; Macfarlane, Tatiana V

    2013-10-01

    To conduct a systematic review of epidemiological literature to determine the incidence of bisphosphonate related osteonecrosis of the jaw occurring either spontaneously or after dental surgery, in children and adolescents diagnosed with osteogenesis imperfecta. MEDLINE, HMIC and EMBASE were used to search for English-language articles published from 1946 - 2013. Inclusion criteria consisted of population based studies of children and adolescents (24 years and younger) diagnosed with osteogenesis imperfecta, only studies which included a dental examination, and patients treated with intravenous bisphosphonates were included. Articles were excluded if patients had any other co-morbidity which could affect osteonecrosis of the jaw, and those which treated patients with oral bisphosphonates only. Five studies consisting of four retrospective cohort studies and one case series were identified. Study populations ranged from 15 to 278 patients and number of subjects with osteogenesis imperfecta ranged from 15 to 221. Mean duration of intravenous bisphosphonate use ranged from 4.5 to 6.8 years. All patients were clinically examined and no patients were found to have osteonecrosis of the jaw. There is no evidence to support hypothesis of causal relationship between bisphosphonates and osteonecrosis of the jaw in children and adolescents with osteogenesis imperfecta. More prospective studies on bisphosphonate use in osteogenesis imperfecta needs to be carried out.

  2. Phase angle and World Health Organization criteria for the assessment of nutritional status in children with osteogenesis imperfecta.

    PubMed

    Pileggi, Vicky Nogueira; Scalize, Antonio Rodolpho Hakime; Camelo Junior, José Simon

    2016-12-01

    To compare the phase angle of patients with osteogenesis imperfecta treated at a tertiary university hospital with patients in a control group of healthy children, and to assess the nutritional status of these patients through the body mass index proposed by the World Health Organization. Cross-sectional study carried out in a university hospital that included seven patients with osteogenesis imperfecta and a control group of 17 healthy children of the same gender and age. Weight and height were measured and bioelectrical impedance was performed. Subsequently, the phase angle was calculated based on resistance and reactance values. The phase angle of the group of children with osteogenesis imperfecta was significantly lower than that of the control group (p<0.05). The body mass index criterion for age of the World Health Organization showed no difference between groups. Children with osteogenesis imperfecta have a nutritional risk detected by the phase angle, which is a useful tool for nutritional screening. The calculation result could help in the diet therapy of patients with osteogenesis imperfecta. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  3. Ultrastructural and immunocytochemical characterization of ameloblast-enamel adhesion at maturation stage in amelogenesis in Macaca fuscata tooth germ.

    PubMed

    Sawada, Takashi

    2015-12-01

    Maturation-stage ameloblasts are firmly bound to the tooth enamel by a basal lamina-like structure. The mechanism underlying this adhesion, however, remains to be fully clarified. The goal of this study was to investigate the mechanism underlying adhesion between the basal lamina-like structure and the enamel in monkey tooth germ. High-resolution immunogold labeling was performed to localize amelotin and laminin 332 at the interface between ameloblasts and tooth enamel. Minute, electron-dense strands were observed on the enamel side of the lamina densa, extending into the degrading enamel matrix to produce a well-developed fibrous layer (lamina fibroreticularis). In un-demineralized tissue sections, mineral crystals smaller than those in the bulk of the enamel were observed adhering to these strands where they protruded into the surface enamel. Immunogold particles reactive for amelotin were preferentially localized on these strands in the fibrous layer. On the other hand, those for laminin 332 were localized solely in the lamina densa; none were observed in the fibrous layer. These results suggest that the fibrous layer of the basal lamina-like structure is partly composed of amelotin molecules, and that these molecules facilitate ameloblast-enamel adhesion by promoting mineralization of the fibrous layer during the maturation stage of amelogenesis.

  4. Immunohistochemical localization of carbonic anhydrase isozyme II in rat incisor epithelial cells at various stages of amelogenesis.

    PubMed

    Toyosawa, S; Ogawa, Y; Inagaki, T; Ijuhin, N

    1996-08-01

    Carbonic anhydrase II (CAII) was purified from erythrocytes of male Sprague-Dawley rats, and its localization in rat maxillary incisor epithelial cells at various stages of amelogenesis was studied by means of immunoperoxidase staining using a rat CAII-specific monoclonal antibody. In the most apical portion of the incisor, some CAII immunoreactivity was localized in the outer or inner dental epithelium near the apical loop (i.e., the multiple layer of the outer dental epithelium and the posterior portion of ameloblasts facing the pulp). Immunoreactivity disappeared largely during the presecretory and secretory stages. CAII immunoreactivity appeared suddenly in ameloblasts during the transitional stage between enamel secretion and maturation. Immunoreactivity became intense in both ameloblasts and papillary cells during enamel maturation; the intracellular distribution of CAII was in the cytosol. The CAII signal in these cells was constant until the end of the maturation stage. These findings support the notion that the ameloblasts and papillary cells change into ion transport epithelial cells from the secretory to the maturation stage and that CAII in these cells plays an important role in the regulation of pH.

  5. Surgical treatment in Osteogenesis Imperfecta – 10 years experience

    PubMed Central

    Georgescu, I; Vlad, C; Gavriliu, TȘ; Dan, S; Pârvan, AA

    2013-01-01

    Introduction. Osteogenesis imperfecta (OI) is a very rare disease compared to other afflictions, running the risk of social isolation for children and their parents, due to the problems specific to the disease. All the social, psychological and physical disadvantages must be removed or at least mitigated, all within the society’s limited resources. In Romania, this situation has led in the last couple of years to the selection of a number of extremely severe cases, which could not be solved by orthopedic and classic surgical treatment methods. These patients exhibit gracile long bones, which are distorted, often with cystic degeneration at the level of the extremities, pseudarthroses, limb length discrepancies, most of them being unable to walk, being condemned to sitting in a wheelchair. Aim. This paper deals with the experience of the Orthopedics Department of "Maria Sklodowska Curie" Clinical Emergency Hospital for Children, in Bucharest, in the field of surgical treatment for moderate and severe forms of OI, within the time frame of May 2002-May 2012. For the first time in Romania, on May 20, 2002, the team led by Professor Gh. Burnei, MD, has implanted telescopic rods in the femur and tibia of a patient with OI. One of the most important themes, of great interest in the orthopedic surgery, is the osteoarticular regularization and reconstruction in severe forms of OI, which should allow the patients to stand and walk. These cases are a challenge for the surgeon, who is in the position of applying new, complex procedures, or perfecting, modifying and adapting techniques that have already been established. The aim of the surgical treatment is the increase of the quality of life of these children and adolescents and of their social integration. Methods and results. In the above-mentioned period, from the OI patients who are in the evidence of our clinic, 32 were operated on, totaling 81 surgeries. Out of these, 28 patients, aged 2-27 years, have benefited from

  6. Burnei's technique of femoral neck variation and valgisation by using the intramedullary rod in Osteogenesis imperfecta.

    PubMed

    Georgescu, I; Gavriliu, Șt; Nepaliuc, I; Munteanu, L; Țiripa, I; Ghiță, R; Japie, E; Hamei, S; Dughilă, C; Macadon, M

    2014-01-01

    Varus or valgus deviations of the femoral neck in osteogenesis imperfecta have been an ignored chapter because the classic correction procedures were applied in medical practice with unsatisfying results. Until the use of telescopic rods, coronal deviations remained unsolved and the distal configuration of the proximal femoral extremity remained uncorrected or partially corrected, which required an extensive use of the wheel chair or bed immobilization of the patient. The concomitant correction of the complex deformities, coxa vara/valga and femoral integrated configuration, have been a progress which allowed the patients to walk with or without support. The purpose of this study is to present the Burnei's technique, a therapeutic alternative in deformity corrections of the varus or valgus hip in children with osteogenesis imperfecta. The paper is about a retrospective study done in a single center, which analyses Burnei technique and other procedures described in literature. The content of the article is based on a 12 years experience on a batch of 51 patients with osteogenesis imperfecta from which 10 patients (13 hips) presented frontal plane deviations of the femoral neck. All the patients with osteogenesis imperfecta who presented coxa vara or valga were submitted to investigations with the purpose of measuring blood loss, the possibility of extending the surgical intervention to the leg, the association of severe deformities of the proximal extremity of the femur and the necessity of postoperative intensive care. Burnei's technique: The operation was first performed in 2002. A subtrochanteric osteotomy was made in an oblique cut, from the internal side to the external side and from proximal to distal for coxa vara, or by using a cuneiform resection associated with muscular disinsertions. Only telescopic rods were used for osteosynthesis. There are a few articles in literature, which approach corrections of vara or valgus deviations in osteogenesis imperfecta

  7. Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation

    PubMed Central

    Wang, Shih-Kai; Hu, Yuanyuan; Yang, Jie; Smith, Charles E; Nunez, Stephanie M; Richardson, Amelia S; Pal, Soumya; Samann, Andrew C; Hu, Jan C-C; Simmer, James P

    2015-01-01

    Defects in WDR72 (WD repeat-containing protein 72) cause autosomal recessive hypomaturation amelogenesis imperfecta. We generated and characterized Wdr72-knockout/lacZ-knockin mice to investigate the role of WDR72 in enamel formation. In all analyses, enamel formed by Wdr72 heterozygous mice was indistinguishable from wild-type enamel. Without WDR72, enamel mineral density increased early during the maturation stage but soon arrested. The null enamel layer was only a tenth as hard as wild-type enamel and underwent rapid attrition following eruption. Despite the failure to further mineralize enamel deposited during the secretory stage, ectopic mineral formed on the enamel surface and penetrated into the overlying soft tissue. While the proteins in the enamel matrix were successfully degraded, the digestion products remained inside the enamel. Interactome analysis of WDR72 protein revealed potential interactions with clathrin-associated proteins and involvement in ameloblastic endocytosis. The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle-ended ameloblasts. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Fewer blood vessels were observed in the papillary layer supporting ameloblasts. Specific WDR72 expression by maturation stage ameloblasts explained the observation that enamel thickness and rod decussation (established during the secretory stage) are normal in the Wdr72 null mice. We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization. PMID:26247047

  8. Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance?

    PubMed

    Cauwels, R G E C; De Coster, P J; Mortier, G R; Marks, L A M; Martens, L C

    2005-08-01

    The follow-up history and oral findings in two brothers from consanguineous parents suggest that the association of dentinogenesis imperfecta (DI), delayed tooth eruption, mild mental retardation, proportionate short stature, sensorineural hearing loss and dysmorphic facies may represent a new syndrome with autosomal recessive inheritance. Histological examination of the dentin matrix of a permanent molar from one of the siblings reveals morphological similarities with defective dentinogenesis as presenting in patients affected with Osteogenesis Imperfecta (OI), a condition caused by deficiency of type I collagen. A number of radiographic and histological characteristics, however, are inconsistent with classical features of DI. These findings suggest that DI may imply greater genetical heterogeneity than currently assumed.

  9. Two years' experience with denosumab for children with osteogenesis imperfecta type VI.

    PubMed

    Hoyer-Kuhn, Heike; Netzer, Christian; Koerber, Friederike; Schoenau, Eckhard; Semler, Oliver

    2014-09-26

    Osteogenesis imperfecta (OI) is a hereditary disease causing reduced bone mass, increased fracture rate, long bone deformities and vertebral compressions. Additional non skeletal findings are caused by impaired collagen function and include hyperlaxity of joints and blue sclera. Most OI cases are caused by dominant mutations in COL1A1/2 affecting bone formation. During the last years, recessive forms of OI have been identified, mostly affecting posttranslational modification of collagen. In 2011, mutations in SERPINF1 were identified as the molecular cause of OI type VI, and thereby a novel pathophysiology of the disease was elucidated. The subgroup of patients with OI type VI are affected by an increased bone resorption, leading to the same symptoms as observed in patients with an impaired bone formation. Severely affected children are currently treated with intravenous bisphosphonates regardless of the underlying mutation and pathophysiology. Patients with OI type VI are known to have a poor response to such a bisphosphonate treatment. Deciphering the genetic cause of OI type VI in our 4 patients (three children and one adolescent) led to an immediate translational approach in the form of a treatment with the monoclonal RANKL antibody Denosumab (1 mg/kg body weight every 12 weeks). Short-term biochemical response to this treatment was reported previously. We now present the results after 2 years of treatment and demonstrate a long term benefit as well as an increase of bone mineral density, a normalization of vertebral shape, an increase of mobility, and a reduced fracture rate. This report presents the first two-year data of denosumab treatment in patients with Osteogenesis imperfecta type VI and in Osteogenesis imperfecta in general as an effective and apparently safe treatment option.

  10. Gene expression profiling of bone marrow mesenchymal stem cells from Osteogenesis Imperfecta patients during osteoblast differentiation.

    PubMed

    Kaneto, Carla Martins; Pereira Lima, Patrícia S; Prata, Karen Lima; Dos Santos, Jane Lima; de Pina Neto, João Monteiro; Panepucci, Rodrigo Alexandre; Noushmehr, Houtan; Covas, Dimas Tadeu; de Paula, Francisco José Alburquerque; Silva, Wilson Araújo

    2017-06-01

    Mesenchymal stem cells (MSCs) are precursors present in adult bone marrow that are able to differentiate into osteoblasts, adipocytes and chondroblasts that have gained great importance as a source for cell therapy. Recently, a number of studies involving the analysis of gene expression of undifferentiated MSCs and of MSCs in the differentiation into multiple lineage processes were observed but there is no information concerning the gene expression of MSCs from Osteogenesis Imperfecta (OI) patients. Osteogenesis Imperfecta is characterized as a genetic disorder in which a generalized osteopenia leads to excessive bone fragility and severe bone deformities. The aim of this study was to analyze gene expression profile during osteogenic differentiation from BMMSCs (Bone Marrow Mesenchymal Stem Cells) obtained from patients with Osteogenesis Imperfecta and from control subjects. Bone marrow samples were collected from three normal subjects and five patients with OI. Mononuclear cells were isolated for obtaining mesenchymal cells that had been expanded until osteogenic differentiation was induced. RNA was harvested at seven time points during the osteogenic differentiation period (D0, D+1, D+2, D+7, D+12, D+17 and D+21). Gene expression analysis was performed by the microarray technique and identified several differentially expressed genes. Some important genes for osteoblast differentiation had lower expression in OI patients, suggesting a smaller commitment of these patient's MSCs with the osteogenic lineage. Other genes also had their differential expression confirmed by RT-qPCR. An increase in the expression of genes related to adipocytes was observed, suggesting an increase of adipogenic differentiation at the expense osteogenic differentiation. Copyright © 2017. Published by Elsevier Masson SAS.

  11. Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

    PubMed

    Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

    2016-01-01

    Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

  12. Surgical technique of double valve replacement in a patient with osteogenesis imperfecta.

    PubMed

    Sumi, Mizuki; Ariyoshi, Tsuneo; Matsukuma, Seiji; Nakaji, Shun; Hashizume, Koji; Kinoshita, Naoe; Eishi, Kiyoyuki

    2016-04-01

    Osteogenesis imperfecta (OI) is an inherited connective tissue disorder. Left ventricle dilation and valve insufficiency are complications in patients with OI and such patients are at high risk of mortality and complications related to bleeding and tissue friability during cardiac surgery. Valve dehiscence due to extreme friability of the annulus is a major complication of cardiac valve replacement with OI. We describe OI in a male patient who underwent double valve replacement with mechanical valves using a tissue protective method to prevent valve dehiscence.

  13. Endoscopic transnasal decompression for management of basilar invagination in osteogenesis imperfecta.

    PubMed

    Hansen, Mitchell A; da Cruz, Melville J; Owler, Brian K

    2008-10-01

    Osteogenesis imperfecta (OI) is a disorder of bone development caused by a genetic dysfunction of collagen synthesis. Basilar invagination (BI) is an uncommon but serious complication of OI. Brainstem decompression in OI is undertaken in certain circumstances. Transoral-transpalatopharyngeal ventral decompression with posterior occipitocervical fusion has become the treatment of choice when required. This technical note outlines a novel endoscopic transnasal approach for ventral decompression. The literature is reviewed and a strategy for the management of BI in patients with OI is outlined.

  14. Comparative study of dentinogenesis imperfecta in different families of the same topographical region.

    PubMed

    Jindal, Mk; Maheshwari, Sandhya; Verma, Radhika; Khan, Mohd Toseef

    2009-09-01

    Dental hard tissue is subject to variety of disorders. Dentinogenesis Imperfecta is one such disorder attributed to heredity. It is known to be an autosomal dominant trait. Teeth with such 'imperfect' dentin are liable to be weak and discolored. The disease has variable penetration and therefore can be expressed as a range of phenotypic manifestations from mild discoloration and chipping to frank attrition and multiple pulp canal exposures. Here we present a comparative study of a series of cases from different families of one topographical region with widely different presentation and histories that are characteristic of this disease.

  15. Dentinogenesis Imperfecta : A Family which was Affected for Over Three Generations

    PubMed Central

    Surendra, Poornima; Shah, Rohan; N.M., Roshan; Reddy, V.V. Subba

    2013-01-01

    Dentinogenesis Imperfecta (DI) or hereditary opalescent dentin is inherited in a simple autosomal dominant mode with high penetrance and low mutation rates. It generally affects both the deciduous and the permanent dentitions. DI corresponds to a localized form of mesodermal dysplasia which is observed in the histo-differentiation. An early diagnosis and treatment are therefore fundamental, which aim at obtaining a favourable prognosis, since at late intervention makes the treatment more complex. We are presenting here a case of DI in which the disease affected the three generations of a family in India. PMID:24086922

  16. Dental Management of a Child with Dentinogenesis Imperfecta: A Case Report

    PubMed Central

    Akhlaghi, Najmeh; Eshghi, Ali-Reza; Mohamadpour, Mehrnaz

    2016-01-01

    Dentinogenesis imperfecta (DI) is a hereditary dentin defect caused by an autosomal dominant mutation in dentin sialophosphoprotein gene. Defective dentin development results in discolored teeth that are prone to wear and fracture. Early diagnosis and proper treatment are necessary to achieve better functional and esthetic results and minimize nutritional deficiencies and psychosocial distress. In order to prevent excessive loss of tooth structure, placement of stainless steel crowns (SSCs) on deciduous and young permanent posterior teeth is recommended as soon as such teeth erupt. This clinical report presents the clinical manifestations and management of a 3.5-year-old child diagnosed with DI type II. PMID:27928242

  17. Comparative Study of Dentinogenesis Imperfecta in Different Families of the Same Topographical Region

    PubMed Central

    Jindal, MK; Maheshwari, Sandhya; Verma, Radhika; Khan, Mohd Toseef

    2009-01-01

    Dental hard tissue is subject to variety of disorders. Dentinogenesis Imperfecta is one such disorder attributed to heredity. It is known to be an autosomal dominant trait. Teeth with such ‘imperfect’ dentin are liable to be weak and discolored. The disease has variable penetration and therefore can be expressed as a range of phenotypic manifestations from mild discoloration and chipping to frank attrition and multiple pulp canal exposures. Here we present a comparative study of a series of cases from different families of one topographical region with widely different presentation and histories that are characteristic of this disease. PMID:25206119

  18. Dental Management of a Child with Dentinogenesis Imperfecta: A Case Report.

    PubMed

    Akhlaghi, Najmeh; Eshghi, Ali-Reza; Mohamadpour, Mehrnaz

    2016-03-01

    Dentinogenesis imperfecta (DI) is a hereditary dentin defect caused by an autosomal dominant mutation in dentin sialophosphoprotein gene. Defective dentin development results in discolored teeth that are prone to wear and fracture. Early diagnosis and proper treatment are necessary to achieve better functional and esthetic results and minimize nutritional deficiencies and psychosocial distress. In order to prevent excessive loss of tooth structure, placement of stainless steel crowns (SSCs) on deciduous and young permanent posterior teeth is recommended as soon as such teeth erupt. This clinical report presents the clinical manifestations and management of a 3.5-year-old child diagnosed with DI type II.

  19. An integrated treatment approach: a case report for dentinogenesis imperfecta type II.

    PubMed

    Shetty, N; Joseph, M; Basnet, P; Dixit, S

    2007-01-01

    Dentinogenesis imperfecta type II or hereditary opalscent dentin is one of the most common autosomal dominant anomaly of dentin that occurs in both sex affecting approximately 1:8000 persons. Clinically this disorder is characterized by variable blue gray to yellow brown teeth, with fracture of enamel and excessive wear. The treatment strategy is focused towards protecting teeth from further wear and tear and total oral rehabilitation of patient with paramount importance to aesthetics, obtaining an appropriate vertical dimension and providing soft tissue support which will help to return the facial profile to a more normal appearance. A multidisciplinary treatment planning is required for treatment of these individuals.

  20. Effect of osteogenesis imperfecta mutations in tropocollagen molecule on strength of biomimetic tropocollagen-hydroxyapatite nanocomposites

    NASA Astrophysics Data System (ADS)

    Dubey, Devendra K.; Tomar, Vikas

    2010-01-01

    Osteogenesis Imperfecta (OI) is a genetic disorder that affects cellular synthesis of Type-I collagen fibrils and causes extreme bone fragility. This study reports the effects of OI mutations in Tropocollagen (TC) molecules on strength of model Tropocollagen-Hydroxyapatite biomaterials with two different mineral [hydroxyapatite (HAP)] distributions using three dimensional atomistic simulations. Results show that the effect of TC mutations on the strength of TC-HAP biomaterials is insignificant. Instead, change in mineral distribution showed significant impact on the overall strength of TC-HAP biomaterials. Study suggests that TC mutations manifest themselves by changing the mineral distribution during hydroxyapatite growth and nucleation period.

  1. Investigation of the Human Disease Osteogenesis Imperfecta: A Research-Based Introduction to Concepts and Skills in Biomolecular Analysis

    ERIC Educational Resources Information Center

    Mate, Karen; Sim, Alistair; Weidenhofer, Judith; Milward, Liz; Scott, Judith

    2013-01-01

    A blended approach encompassing problem-based learning (PBL) and structured inquiry was used in this laboratory exercise based on the congenital disease Osteogenesis imperfecta (OI), to introduce commonly used techniques in biomolecular analysis within a clinical context. During a series of PBL sessions students were presented with several…

  2. Investigation of the Human Disease Osteogenesis Imperfecta: A Research-Based Introduction to Concepts and Skills in Biomolecular Analysis

    ERIC Educational Resources Information Center

    Mate, Karen; Sim, Alistair; Weidenhofer, Judith; Milward, Liz; Scott, Judith

    2013-01-01

    A blended approach encompassing problem-based learning (PBL) and structured inquiry was used in this laboratory exercise based on the congenital disease Osteogenesis imperfecta (OI), to introduce commonly used techniques in biomolecular analysis within a clinical context. During a series of PBL sessions students were presented with several…

  3. Femoral geometric parameters and BMD measurements by DXA in adult patients with different types of osteogenesis imperfecta.

    PubMed

    Kocijan, Roland; Muschitz, Christian; Fratzl-Zelman, Nadja; Haschka, Judith; Dimai, Hans-Peter; Trubrich, Angela; Bittighofer, Christina; Resch, Heinrich

    2013-02-01

    Osteogenesis imperfecta (OI) is an inherited disorder characterized by increased bone fragility with recurrent fractures that leads to skeletal deformities in severe cases. Consequently, in most OI patients, the hip is the only reliable measuring site for estimating future fracture risk. The aim of the study was to assess the applicability of hip structure analysis (HSA) by DXA in adult patients with osteogenesis imperfecta. We evaluated bone mineral density (BMD) and hip structure analysis (HSA) by DXA, including cross-sectional area (CSA), cross-sectional moment of inertia (CSMI) and femoral strength index (FSI) in 30 adult patients with different types of OI and 30 age-matched healthy controls (CO). The OI total group (OI-tot) was divided into two subgroups: the mild OI I group (OI-I) and the more severe OI III and IV group (OI-III-IV). The mean neck BMD of OI-I and OI-III-IV were significantly lower compared to CO (-15.9 %, p < 0.005 and -37.5 %, p < 0.001 respectively). Similar results were observed at trochanter and total hip. CSA and the CSMI value were significantly lower for OI-I (-23.2 %, p < 0.001) and OI-III-IV (-45.9 %, p < 0.001) in comparison to CO. In addition, significant differences were found between the mild OI-I and the severe OI-III-IV group (-29.6 %, p < 0.05). FSI was significantly decreased in the OI-III-IV (25.7 %, p < 0.05) in comparison to the CO. Furthermore, significant correlations between BMD and HSA and between HSA and height and weight were found in osteogenesis imperfecta and controls. BMD measurement in osteogenesis imperfecta patients is very critical. The combination of BMD and geometric structural measurements at the hip in osteogenesis imperfecta patients may represent an additional helpful means in estimating bone strength and fracture risk.

  4. Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice

    PubMed Central

    Árvai, Kristóf; Horváth, Péter; Balla, Bernadett; Tobiás, Bálint; Kató, Karina; Kirschner, Gyöngyi; Klujber, Valéria; Lakatos, Péter; Kósa, János P.

    2016-01-01

    Next generation sequencing (NGS) is a rapidly developing area in genetics. Utilizing this technology in the management of disorders with complex genetic background and not recurrent mutation hot spots can be extremely useful. In this study, we applied NGS, namely semiconductor sequencing to determine the most significant osteogenesis imperfecta-related genetic variants in the clinical practice. We selected genes coding collagen type I alpha-1 and-2 (COL1A1, COL1A2) which are responsible for more than 90% of all cases. CRTAP and LEPRE1/P3H1 genes involved in the background of the recessive forms with relatively high frequency (type VII and VIII) represent less than 10% of the disease. In our six patients (1–41 years), we identified 23 different variants. We found a total of 14 single nucleotide variants (SNV) in COL1A1 and COL1A2, 5 in CRTAP and 4 in LEPRE1. Two novel and two already well-established pathogenic SNVs have been identified. Among the newly recognized mutations, one results in an amino acid change and one of them is a stop codon. We have shown that a new full-scale cost-effective NGS method can be developed and utilized to supplement diagnostic process of osteogenesis imperfecta with molecular genetic data in clinical practice. PMID:27335225

  5. A Case Report for a Complex Denture Case on a Special Care Patient with Osteogenesis Imperfecta.

    PubMed

    Sawyer, Colin; Drysdale, David

    2015-05-01

    This case report presents a patient with Dentogenesis Imperfecta (DI) associated with Osteogenesis Imperfecta (OI) and its subsequent dental manifestations. The patient in this report (see Figure 1) has spent his life living with his disability type III OI (also known as brittle bone disease) and its degenerative affects. The patient is independent and enjoys his social life but felt his existing dentures were having an adverse effect on the quality of his life. The patient attended Dorset County Hospitals Special Care Dentistry and on clinical examination it was noted the patient was partially dentate with a class III malocclusion and brownish discoloration of the remaining teeth caused by enamel hypoplasia. Treatment for this patient would entail making a maxillary complete denture and a mandibular partial chrome denture, normally quite simple tasks but due to the DI and its dental manifestations, the treatment would be complicated. This case demonstrates how a complex case treated by a collaborative dental team using their different skills and knowledge can lead to a successful and rewarding treatment for both patient and team.

  6. Combined treatment with laser sintering and zirconium: a case report of dentinogenesis imperfecta.

    PubMed

    Ayyildiz, Simel; Sahin, Cem; Akgün, Ozlem Marti; Basak, Feridun

    2013-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS) technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics.

  7. Three-dimensional ultrasound in the prenatal diagnosis of osteogenesis imperfecta.

    PubMed

    Tsai, Pei-Yin; Chang, Chiung-Hsin; Yu, Chen-Hsiang; Cheng, Yueh-Chin; Chang, Fong-Ming

    2012-09-01

    Fetal osteogenesis imperfecta (OI) is a heterogeneous group of collagen disorders characterized by bone fragility, blue sclerae, deafness, and dentinogenesis imperfecta. Ultrasonography is acknowledged as a reliable diagnostic modality for the prenatal diagnosis of OI, especially type II. In the past, two-dimensional (2D) ultrasound (US) has been applied as the mainstay of prenatal diagnosis of OI. In this series, we report our work of detecting OI using three-dimensional (3D) US. We reviewed our computer database of prenatal diagnosis of OI at the National Cheng Kung University Hospital from April 1996 to July 2010. All the cases were scanned by 2D and 3D US. In total, six cases of fetal OI were diagnosed. Compared with 2D US, 3D US can detect fetal OI precisely, and provide additional vivid illustration after various modes of reconstruction that 2D US cannot. In conclusion, 3D US may contribute significantly to the detection of OI in utero and provide a novel visual depiction of this defect after reconstruction. The technique may thus substantially assist in prenatal diagnosis as well as consultations for fetal OI. Copyright © 2012. Published by Elsevier B.V.

  8. Bisphosphonate therapy and osteogenesis imperfecta: The lived experience of children and their mothers.

    PubMed

    Wiggins, Shirley; Kreikemeier, Rose

    2017-09-06

    Osteogenesis imperfecta (OI) is a chronic, genetic condition frequently described as "brittle bones." This condition is expressed by low bone density and characterized by frequent fractures with and without trauma. Additional symptoms include pain, altered growth, and challenges with mobility. This experience has a great impact on the daily life of the child diagnosed with OI and their family. With the introduction of bisphosphonate therapy children diagnosed with OI experienced an increase in bone density that included a change in symptoms and improvement in daily functioning. The purpose of this study was to describe the lived experience of children receiving bisphosphonate therapy for osteogenesis imperfecta (OI) and their mothers. A phenomenological study was conducted using interviews with a purposive sample of six children diagnosed with OI and their six mothers (N = 12). Children ranged in age from 6 to 18 years. The Giorgi (2009) methodology was used to discover the meaning of living day to day since initiating the bisphosphonate infusion therapy. Four themes emerged from the synthesis of the meaning units that reflected the experience that bisphosphonate therapy had on daily life with OI. These four themes explicitly described the phenomena being studied and included living daily life in stride; normalcy is living with uncertainty; renewal with infusions; and making choices and living with the consequences. Nurses must take an active role in developing and promoting family-centered interventions for transition and support. © 2017 Wiley Periodicals, Inc.

  9. Osteogenesis imperfecta type V: clinical and radiographic manifestations in mutation confirmed patients.

    PubMed

    Kim, Ok-Hwa; Jin, Dong-Kyu; Kosaki, Keisuke; Kim, Jung-Wook; Cho, Sung Yoon; Yoo, Won Joon; Choi, In Ho; Nishimura, Gen; Ikegawa, Shiro; Cho, Tae-Joon

    2013-08-01

    Osteogenesis imperfecta (OI) type V is a specific OI phenotype with interosseous membrane calcification of the forearm and hyperplastic callus formation as typical features. The causative gene mutation for OI type V has been recently discovered. The purpose of this report is to review the clinical and radiographic characteristics of mutation confirmed OI type V in detail. Sixteen (nine familial and seven sporadic) patients were enrolled in the study. Blue sclera and dentinogenesis imperfecta were not evident in any patient. However, hypodontia in the permanent teeth, ectopic eruption, and short roots in molars were additionally observed in 11 patients. Of the radiographic abnormalities, cortical thickening and bony excrescence of interosseous margin of the ulna was the most common finding, followed by overgrowth of the olecranon and/or coronoid process of the ulna. Slender ribs and sloping of the posterior ribs with or without fractures were also a consistent finding. Hyperplastic callus was detected in 75% of patients and was commonly encountered at the femur. Heterotopic ossification in the muscles and tendon insertion sites were noted in four patients, which resulted in bony ankylosis or contracture of joints. The current study confirms common clinical and radiographic findings of OI type V and reports additional phenotypic information. These observations provide clues to recognize OI type V more promptly and guide to direct targeted molecular study. © 2013 Wiley Periodicals, Inc.

  10. Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta.

    PubMed

    Brizola, Evelise; McCarthy, Edward; Shapiro, Jay Robert

    2015-01-01

    Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes. We clinically and radiologically describes an adult male with type III osteogenesis imperfecta who presents a rare bone dysplasia termed bulbous epiphyseal deformity in association with popcorn calcifications. Popcorn calcifications may occur with bulbous epiphyseal deformity or independently. Molecular analysis was performed for COL1A1, COL1A2, LEPRE1 and WNT1 genes. An uncommon COL1A1 mutation was identified. Clinical and radiological exams confirmed a distinctive bulbous epiphyseal deformity with popcorn calcifications in distal femurs. We have identified four additional OI patients reported in current literature, whose X-rays show bulbous epiphyseal deformity related to mutations in CR-TAP, LEPRE1 and WNT1 genes. The mutation identified here had been previously described twice in OI patients and no previous correlation with bulbous epiphyseal deformity was described. The occurrence of this bone dysplasia focuses attention on alterations in normal growth plate differentiation and the subsequent effect on endochondral bone formation in OI.

  11. Combined Treatment with Laser Sintering and Zirconium: A Case Report of Dentinogenesis Imperfecta

    PubMed Central

    Sahin, Cem; Akgün, Özlem Marti; Basak, Feridun

    2013-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS) technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics. PMID:23533828

  12. Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice.

    PubMed

    Árvai, Kristóf; Horváth, Péter; Balla, Bernadett; Tobiás, Bálint; Kató, Karina; Kirschner, Gyöngyi; Klujber, Valéria; Lakatos, Péter; Kósa, János P

    2016-06-23

    Next generation sequencing (NGS) is a rapidly developing area in genetics. Utilizing this technology in the management of disorders with complex genetic background and not recurrent mutation hot spots can be extremely useful. In this study, we applied NGS, namely semiconductor sequencing to determine the most significant osteogenesis imperfecta-related genetic variants in the clinical practice. We selected genes coding collagen type I alpha-1 and-2 (COL1A1, COL1A2) which are responsible for more than 90% of all cases. CRTAP and LEPRE1/P3H1 genes involved in the background of the recessive forms with relatively high frequency (type VII and VIII) represent less than 10% of the disease. In our six patients (1-41 years), we identified 23 different variants. We found a total of 14 single nucleotide variants (SNV) in COL1A1 and COL1A2, 5 in CRTAP and 4 in LEPRE1. Two novel and two already well-established pathogenic SNVs have been identified. Among the newly recognized mutations, one results in an amino acid change and one of them is a stop codon. We have shown that a new full-scale cost-effective NGS method can be developed and utilized to supplement diagnostic process of osteogenesis imperfecta with molecular genetic data in clinical practice.

  13. Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen type I genes.

    PubMed

    Malmgren, B; Andersson, K; Lindahl, K; Kindmark, A; Grigelioniene, G; Zachariadis, V; Dahllöf, G; Åström, E

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2). Tooth agenesis is a common feature of OI. We investigated the association between tooth agenesis and collagen type I mutations in individuals with OI. In this cohort study, 128 unrelated individuals with OI were included. Panoramic radiographs were analyzed regarding dentinogenesis imperfecta (DGI) and congenitally missing teeth. The collagen I genes were sequenced in all individuals, and in 25, multiplex ligation-dependent probe amplification was performed. Mutations in the COL1A1 and COL1A2 genes were found in 104 of 128 individuals. Tooth agenesis was diagnosed in 17% (hypodontia 11%, oligodontia 6%) and was more frequent in those with DGI (P = 0.016), and in those with OI type III, 47%, compared to those with OI types I, 12% (P = 0.003), and IV, 13% (P = 0.017). Seventy-five percent of the individuals with oligodontia (≥6 missing teeth) had qualitative mutations, but there was no association with OI type, gender, or presence of DGI. The prevalence of tooth agenesis is high (17%) in individuals with OI, and OI caused by a qualitative collagen I mutation is associated with oligodontia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. How tough is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone††

    PubMed Central

    Carriero, A.; Zimmermann, E. A.; Paluszny, A.; Tang, S. Y.; Bale, H.; Busse, B.; Alliston, T.; Kazakia, G.

    2015-01-01

    The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level we attribute the loss in toughness to a decrease in the stabilizing enzymatic crosslinks and an increase in non-enzymatic crosslinks, which may break prematurely inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales. PMID:24420672

  15. Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta

    PubMed Central

    Brizola, Evelise; McCarthy, Edward; Shapiro, Jay Robert

    2015-01-01

    Summary Background Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes. We clinically and radiologically describes an adult male with type III osteogenesis imperfecta who presents a rare bone dysplasia termed bulbous epiphyseal deformity in association with popcorn calcifications. Popcorn calcifications may occur with bulbous epiphyseal deformity or independently. Methods Molecular analysis was performed for COL1A1, COL1A2, LEPRE1 and WNT1 genes. Results An uncommon COL1A1 mutation was identified. Clinical and radiological exams confirmed a distinctive bulbous epiphyseal deformity with popcorn calcifications in distal femurs. We have identified four additional OI patients reported in current literature, whose X-rays show bulbous epiphyseal deformity related to mutations in CR-TAP, LEPRE1 and WNT1 genes. Conclusion The mutation identified here had been previously described twice in OI patients and no previous correlation with bulbous epiphyseal deformity was described. The occurrence of this bone dysplasia focuses attention on alterations in normal growth plate differentiation and the subsequent effect on endochondral bone formation in OI. PMID:26604951

  16. Aortic valve replacement in a patient with ostegenesis imperfecta A case report.

    PubMed

    Concistrè, Giovanni; Casali, Giovanni; Della Monica, Paola Lilla; Montalto, Andrea; Ranocchi, Federeico; Fiorani, Brenno; Musumeci, Francesco

    2014-01-01

    L’Osteogenesi Imperfecta (OI) è un’alterazione ereditaria del tessuto connettivo in cui l’estrema fragilità ossea causa fratture. La dilatazione aneurismatica della radice aortica, l’insufficienza valvolare aortica ed il prolasso mitralico sono rare manifestazioni cardiovascolari di OI. L’intervento cardiochirurgico in questi pazienti può presentare importanti complicanze legate alla incrementata fragilità tissutale e capillare. Noi riportiamo un caso di chirurgia a cuore aperto in una donna con insufficienza valvolare aortica isolata secondaria ad OI. Il decorso postoperatorio è stato privo di complicanze maggiori e la paziente è stata dimessa presso propria abitazione in ottava giornata postoperatoria. È stata seguita con controlli frequenti per un anno. Nonostante la fragilità tissutale non abbia avuto impatto sul decorso postoperatorio, bisogna sempre tenere in considerazione la possibilità di eventi avversi nei pazienti con tale disordine connettivale. È necessario pertanto una meticolosa tecnica chirurgica che possa anticipare possibili complicanze postoperatorie.

  17. Identification and in vivo functional characterization of novel compound heterozygous BMP1 variants in osteogenesis imperfecta.

    PubMed

    Cho, Sung Yoon; Asharani, P V; Kim, Ok-Hwa; Iida, Aritoshi; Miyake, Noriko; Matsumoto, Naomichi; Nishimura, Gen; Ki, Chang-Seok; Hong, Geehay; Kim, Su Jin; Sohn, Young Bae; Park, Sung Won; Lee, Jieun; Kwun, Younghee; Carney, Thomas J; Huh, Rimm; Ikegawa, Shiro; Jin, Dong-Kyu

    2015-02-01

    Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal-dominant inheritance, but many autosomal-recessive genes have been reported. We applied whole-exome sequencing to identify mutations in a Korean OI patient who had an umbilical hernia, frequent fractures, a markedly short stature, delayed motor development, scoliosis, and dislocation of the radial head, with a bowed radius and ulna. We identified two novel variants in the BMP1 gene: c.808A>G and c.1297G>T. The former variant caused a missense change p.(Met270Val) and the latter variant caused the skipping of exon 10. The hypofunctional nature of the two variants was demonstrated in a zebrafish assay.

  18. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta.

    PubMed

    Lindert, Uschi; Cabral, Wayne A; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N; Janecke, Andreas R; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C; Shotelersuk, Vorasuk

    2016-07-06

    Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development.

  19. Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta

    PubMed Central

    Astrom, E; Soderhall, S

    2002-01-01

    Aim: To find an effective symptomatic treatment for osteogenesis imperfecta (OI). Methods: In a prospective observational study disodium pamidronate (APD) was given as monthly intravenous infusions to 28 children and adolescents (aged 0.6–18 years) with severe OI or a milder form of the disease, but with spinal compression fractures. Results: During treatment for 2–9 years, dual energy x ray absorptiometry measurements of the total body and of the lumbar spine showed a gradual increase in bone density. All bone metabolism variables in serum (alkaline phosphatase, osteocalcin, procollagen 1 C-terminal peptide, collagen 1 teleopeptide) and urine (deoxypyridinoline) indicated that there was a decrease in bone turnover. All patients experienced beneficial effects and the younger patients reported a major improvement in wellbeing, pain, and mobility without significant side effects. Vertebral remodelling was also seen. Conclusions: APD seems to be an efficient symptomatic treatment for children and adolescents with OI. PMID:11970931

  20. In utero stem cell transplantation for radical treatment of osteogenesis imperfecta: perspectives and controversies.

    PubMed

    Amin, Mariam Taher Mohamed; Shazly, Sherif Abd-Elkarim Mohammed

    2014-11-01

    Osteogenesis imperfecta (OI) is a lethal hereditary connective tissue disease that affects the synthesis of type I collagen. Current treatment options including surgical, physical, and medical treatment help to reduce pain, deformities, and rate of bone fracture. However, these choices are insufficient and are associated with many adverse effects. The development of stem cell therapy allows scientists to consider this option for radical treatment of many genetic diseases including OI. In utero stem cell transplantation provides a better opportunity for early prenatal intervention while the fetus is preimmune and before any permanent damage occurs. Few animal and human trials for treatment of OI have been published, and the results were promising but still controversial. Our objective is to review the available evidence and discuss the points of controversy including the parameters of treatment success and postnatal predictors of long-term treatment outcome.

  1. Osteogenesis imperfecta lethal in infancy: case report and scanning electron microscopic studies of the deciduous teeth.

    PubMed

    Levin, L S; Rosenbaum, K N; Brady, J M; Dorst, J P

    1982-12-01

    Radiologic evaluation of the skeleton and scanning electron microscopic studies of the teeth were performed on an infant boy with a lethal osteogenesis imperfecta (OI) syndrome who died at 10 mo of pneumonia. The skeletal findings included ribs that were focally expanded by fracture calluses, flat vertebral bodies, and wide limb bones. On fractured tooth surfaces, the enamel and dentin were normal as was the dentin calcification front. Although microscopic abnormalities have been noted in teeth from previously reported infants with lethal OI, a few studies also report infants with normal teeth. These differences in dental findings may indicate heterogeneity in OI lethal in infancy. Results of our study indicate that, until the primary biochemical defects in the OI syndromes are elucidated, examination of teeth from other infants with lethal OI and detailed evaluation of other clinical and skeletal features will aid in delineating heterogeneity and variation in expression in lethal OI.

  2. Basilar impression in osteogenesis imperfecta: can it be treated with halo traction and posterior fusion?

    PubMed

    Noske, D P; van Royen, B J; Bron, J L; Vandertop, W P

    2006-12-01

    Basilar impression (BI) and hydrocephalus complicating osteogenesis imperfecta (OI) is usually treated by anterior transoral decompression and posterior fixation. Nevertheless, it may be questioned if posterior fusion following axial halo traction is adequate in patients with symptomatic BI complicating OI. We report on a case with progressive symptomatic hydrocephalus and BI complicating OI that was successfully treated by halo traction followed by posterior occipitocervical fusion. However, after a symptom free interval of 2 years the patient suffered from recurrence of symptomatic hydrocephalus needing additional ventriculoperitoneal (VP) shunt placement. In conclusion, posterior fusion without additional VP shunt placement may not be effective in the long term for ameliorating symptoms and signs and halting progressive hydrocephalus in BI complicating OI.

  3. Osteogenesis imperfecta presenting as aneurysmal subarachnoid haemorrhage in a 53-year-old man

    PubMed Central

    Kaliaperumal, Chandrasekaran; Walsh, Tom; Balasubramanian, Chandramouli; Wyse, Gerry; Fanning, Noel; Kaar, George

    2011-01-01

    The authors describe a case of aneurysmal subarachnoid haemorrhage in a 53-year-old man with background of osteogenesis imperfecta (OI). CT brain revealed diffuse subarachnoid haemorrhage (SAH) and cerebral angiogram subsequently confirmed vertebral artery aneurysm rupture leading to SAH. To the authors knowledge this is the first case of vertebral artery aneurysmal SAH described in OI. A previously undiagnosed OI was confirmed by genetic analysis (COL1A1 gene mutation). This aneurysm was successfully treated by endovascular route. Post interventional treatment patient developed stroke secondary to vasospasm. Communicating hydrocephalus, which developed in the process of management, was successfully treated with ventriculo-peritoneal shunt. The aetio-pathogenesis and management of this condition is described. The authors have reviewed the literature and genetic basis of this disease. PMID:22674700

  4. Phenotype Characterization and DSPP Mutational Analysis of Three Brazilian Dentinogenesis Imperfecta Type II Families

    PubMed Central

    Acevedo, A.C.; Santos, L.J.S.; Paula, L.M.; Dong, J.; MacDougall, M.

    2008-01-01

    The aim of this study was to perform phenotype analysis and dentin sialophosphoprotein (DSPP) mutational analysis on 3 Brazilian families diagnosed with dentinogenesis imperfecta type II (DGI-II) attending the Dental Anomalies Clinic in Brasilia, Brazil. Physical and oral examinations, as well as radiographic and histopathological analyses, were performed on 28 affected and unaffected individuals. Clinical, radiographic and histopathological analyses confirmed the diagnosis of DGI-II in 19 individuals. Pulp stones were observed in ground sections of several teeth in 2 families, suggesting that obliteration of pulp chambers and root canals results from the growth of these nodular structures. Mutational DSPP gene analysis of representative affected family members revealed 7 various non-disease-causing alterations in exons 1–4 within the dentin sialoprotein domain. Further longitudinal studies are necessary to elucidate the progression of pulpal obliteration in the DGI-II patients studied as well as the molecular basis of their disease. PMID:18797159

  5. Diagnosis of fetal osteogenesis imperfecta by multidisciplinary assessment: a retrospective study of 10 cases.

    PubMed

    Wu, Qichang; Wang, Wenbo; Cao, Lin; Sun, Li; Xu, Yasong; Zhong, Xiaohong

    2015-02-01

    To describe our 2 year experience in diagnosing prenatal-onset osteogenesis imperfecta (OI) by multidisciplinary assessment. We retrospectively analyzed 10 cases of fetal OI by using prenatal ultrasound evaluation, postnatal radiographic diagnosis, and molecular genetic testing of COL1A1/2. By postnatal radiographic examination, five patients were diagnosed with type II OI and five were diagnosed with type III OI. A causative variant in the COL1A1 gene was found in four cases of type II and one case of type III OI; a causative variant in the COL1A2 gene was found in two cases of type III OI. The definitive diagnosis of fetal OI should be accomplished using a multidisciplinary assessment, which is paramount for proper genetic counseling. With the discovery of COL1A1/2 gene variants as a cause of OI, sequence analysis of these genes will add to the diagnostic process.

  6. Bone tissue ultrastructural defects in a mouse model for osteogenesis imperfecta: a Raman spectroscopy study

    NASA Astrophysics Data System (ADS)

    Chen, Tsoching; Kozloff, Kenneth M.; Goldstein, Steven A.; Morris, Michael D.

    2004-07-01

    Osteogenesis imperfecta (OI) is genetic defect in which the genes that code for the α1(I) or α2(I) chains of type I collagen are defective. The defects often result in substitution of a bulky amino acid for glycine, causing formation of collagen that can not form the normal triple helix. Depending on the details of the defects, the outcomes range from controllable to lethal. This study focuses on OI type IV, a more common and moderately severe form of the disease. People with the disease have a substantial increase in the risk and rate of fracture. We examine the spectroscopic consequences of these defects, using a mouse model (BRTL) that mimics OI type IV. We compare Raman images from tibial cortical tissue of wild-type mice and BRTL mice with single copy of mutation and show that both mineral to matrix ratios and collagen inter-fibril cross-links are different in wild-type and mutant mice.

  7. Progressive Bilateral Vertebral Artery Dissection in a Case of Osteogenesis Imperfecta.

    PubMed

    Kato, Yuji; Nagoya, Harumitsu; Abe, Tetsuya; Hayashi, Takeshi; Yasuda, Masanori; Uchino, Akira; Tanahashi, Norio; Takao, Masaki

    2017-03-01

    A 32-year-old woman with osteogenesis imperfecta (OI) was admitted to the hospital because of a right-sided occipital headache and facial paresthesia. She was diagnosed with lateral medullary syndrome due to right vertebral artery (VA) dissection. She was treated conservatively without antithrombotic therapy. She developed subarachnoid hemorrhage because of contralateral VA dissection 18 days later. This clinical course may reflect the underlying weakness of the vessel wall in OI. In patients with OI, occlusion of a unilateral VA could cause dissection and subsequent rupture of the contralateral VA. Early surgical treatment for lesions of the VA is required in such cases. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

    PubMed Central

    Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

    2016-01-01

    Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

  9. Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta.

    PubMed

    Lindahl, Katarina; Åström, Eva; Rubin, Carl-Johan; Grigelioniene, Giedre; Malmgren, Barbro; Ljunggren, Östen; Kindmark, Andreas

    2015-08-01

    Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the α1-chain were associated with blue sclera (P=0.0110). Comparing glycine with serine substitutions, α1-alterations were associated with more severe phenotype (P=0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P<0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population.

  10. Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

    PubMed Central

    Oestreich, Arin K.; Kamp, William M.; McCray, Marcus G.; Carleton, Stephanie M.; Karasseva, Natalia; Lenz, Kristin L.; Jeong, Youngjae; Daghlas, Salah A.; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M.; Ellersieck, Mark R.; Schulz, Laura C.; Phillips, Charlotte L.

    2016-01-01

    During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstntm1Sjl/+) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstntm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2oim), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2oim/+ offspring from natural mating of Mstntm1Sjl/+ dams to Col1a2oim/+sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2oim/+ dams to Col1a2oim/+ sires. Finally, increased bone biomechanical strength of Col1a2oim/+ offspring that had been transferred into Mstntm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta. PMID:27821779

  11. Mutations in FKBP10 Cause Recessive Osteogenesis Imperfecta and Bruck Syndrome

    PubMed Central

    Kelley, Brian P; Malfait, Fransiska; Bonafe, Luisa; Baldridge, Dustin; Homan, Erica; Symoens, Sofie; Willaert, Andy; Elcioglu, Nursel; Van Maldergem, Lionel; Verellen-Dumoulin, Christine; Gillerot, Yves; Napierala, Dobrawa; Krakow, Deborah; Beighton, Peter; Superti-Furga, Andrea; De Paepe, Anne; Lee, Brendan

    2011-01-01

    Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue characterized by bone fragility and alteration in synthesis and posttranslational modification of type I collagen. Autosomal dominant OI is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen. Bruck syndrome is a recessive disorder featuring congenital contractures in addition to bone fragility; Bruck syndrome type 2 is caused by mutations in PLOD2 encoding collagen lysyl hydroxylase, whereas Bruck syndrome type 1 has been mapped to chromosome 17, with evidence suggesting region 17p12, but the gene has remained elusive so far. Recently, the molecular spectrum of OI has been expanded with the description of the basis of a unique posttranslational modification of type I procollagen, that is, 3-prolyl-hydroxylation. Three proteins, cartilage-associated protein (CRTAP), prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene), and the prolyl cis-trans isomerase cyclophilin-B (PPIB), form a complex that is required for fibrillar collagen 3-prolyl-hydroxylation, and mutations in each gene have been shown to cause recessive forms of OI. Since then, an additional putative collagen chaperone complex, composed of FKBP10 (also known as FKBP65) and SERPINH1 (also known as HSP47), also has been shown to be mutated in recessive OI. Here we describe five families with OI-like bone fragility in association with congenital contractures who all had FKBP10 mutations. Therefore, we conclude that FKBP10 mutations are a cause of recessive osteogenesis imperfecta and Bruck syndrome, possibly Bruck syndrome Type 1 since the location on chromosome 17 has not been definitely localized. © 2011 American Society for Bone and Mineral Research. PMID:20839288

  12. Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation.

    PubMed

    Lacomb, Ronald; Nadiarnykh, Oleg; Campagnola, Paul J

    2008-06-01

    We report the integrated use of 3D second harmonic generation (SHG) imaging microscopy and Monte Carlo simulation as a combined metric to quantifiably differentiate normal and diseased tissues based on the physical properties of the respective extracellular matrix. To achieve this, we have identified a set of parameters comprised of the SHG creation attributes and the bulk optical parameters, which are used collectively via comparative analysis. Monte Carlo simulations of the SHG axial directional and attenuation responses allow their decomposition into the underlying factors that are not readily obtainable through experimental techniques. Specifically, this approach allows for estimation of the SHG creation attributes (directionality and relative conversion efficiency) and separation of primary and secondary filter effects, collectively that form the observed SHG contrast. The quantitative metric is shown for the connective tissue disorder Osteogenesis Imperfecta (characterized by abnormal assembly of type I collagen) using a murine model that expresses the disease in the dermis layer of skin. Structural dissimilarities between the osteogenesis imperfecta mouse and wild-type tissues lead to significant differences in the SHG depth-dependent directionality and signal attenuation. The Monte Carlo simulations of these responses using measured bulk optical parameters reproduce the experimental data trends, and the extracted emission directionality and conversion efficiencies are consistent with independent determinations. The simulations also illustrate the dominance of primary filter affects on overall SHG generation and attenuation. Thus, the combined method of 3D SHG imaging and modeling forms an essential foundation for parametric description of the matrix properties that are not distinguishable by sole consideration of either bulk optical parameters or SHG alone. Moreover, due to the quasi-coherence of the SHG process in tissues, we submit that this approach

  13. What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases.

    PubMed

    Pepin, Melanie G; Byers, Peter H

    2015-12-01

    Non-accidental injury (NAI) is a major medical concern in the United States. One of the challenges in evaluation of children with unexplained fractures is that genetic forms of bone fragility are one of the differential diagnoses. Infants who present with fractures with mild forms of osteogenesis imperfecta (OI) (OI type I or OI type IV), the most common genetic form of bone disease leading to fractures might be missed if clinical evaluation alone is used to make the diagnosis. Diagnostic clinical features (blue sclera, dentinogenesis imperfecta, Wormian bones on X-rays or positive family history) may not be present or apparent at the age of evaluation. The evaluating clinician faces the decision about whether genetic testing is necessary in certain NAI cases. In this review, we outline clinical presentations of mild OI and review the history of genetic testing for OI in the NAI versus OI setting. We summarize our data of molecular testing in the Collagen Diagnostic Laboratory (CDL) from 2008 to 2014 where NAI was noted on the request for DNA sequencing of COL1A1 and COL1A2. We provide recommendations for molecular testing in the NAI versus OI setting. First, DNA sequencing of COL1A1, COL1A2, and IFITM5 simultaneously and duplication/deletion testing is recommended. If a causative variant is not identified, in the absence of a pathologic clinical phenotype, no additional gene testing is indicated. If a VUS is found, parental segregation studies are recommended. © 2015 Wiley Periodicals, Inc.

  14. Increased intra-cortical porosity reduces bone stiffness and strength in pediatric patients with osteogenesis imperfecta.

    PubMed

    Vardakastani, V; Saletti, D; Skalli, W; Marry, P; Allain, J M; Adam, C

    2014-12-01

    Osteogenesis imperfecta (OI) is a heritable disease occurring in one out of every 20,000 births. Although it is known that Type I collagen mutation in OI leads to increased bone fragility, the mechanism of this increased susceptibility to fracture is not clear. The aim of this study was to assess the microstructure of cortical bone fragments from patients with osteogenesis imperfecta (OI) using polarized light microscopy, and to correlate microstructural observations with the results of previously performed mechanical compression tests on bone from the same source. Specimens of cortical bone were harvested from the lower limbs of three (3) OI patients at the time of surgery, and were divided into two groups. Group 1 had been subjected to previous micro-mechanical compression testing, while Group 2 had not been subjected to any prior testing. Polarized light microscopy revealed disorganized bone collagen architecture as has been previously observed, as well as a large increase in the areal porosity of the bone compared to typical values for healthy cortical bone, with large (several hundred micron sized), asymmetrical pores. Importantly, the areal porosity of the OI bone samples in Group 1 appears to correlate strongly with their previously measured apparent Young's modulus and compressive strength. Taken together with prior nanoindentation studies on OI bone tissue, the results of this study suggest that increased intra-cortical porosity is responsible for the reduction in macroscopic mechanical properties of OI cortical bone, and therefore that in vivo imaging modalities with resolutions of ~100 μm or less could potentially be used to non-invasively assess bone strength in OI patients. Although the number of subjects in this study is small, these results highlight the importance of further studies in OI bone by groups with access to human OI tissue in order to clarify the relationship between increased porosity and reduced macroscopic mechanical integrity

  15. Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

    PubMed Central

    Lindahl, Katarina; Åström, Eva; Rubin, Carl-Johan; Grigelioniene, Giedre; Malmgren, Barbro; Ljunggren, Östen; Kindmark, Andreas

    2015-01-01

    Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype–phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the α1-chain were associated with blue sclera (P=0.0110). Comparing glycine with serine substitutions, α1-alterations were associated with more severe phenotype (P=0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P<0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population. PMID:25944380

  16. Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with Osteogenesis Imperfecta

    PubMed Central

    Jameson, John; Smith, Peter; Harris, Gerald

    2015-01-01

    Osteogenesis Imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64–68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3–42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (p≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight towards understanding bone fragility and the role of intracortical porosity on the strength of bone

  17. Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I

    PubMed Central

    Rauch, Frank; Lalic, Liljana; Roughley, Peter; Glorieux, Francis H

    2010-01-01

    Osteogenesis imperfecta (OI) is a heritable disorder with bone fragility that is often associated with short stature, tooth abnormalities (dentinogenesis imperfecta), and blue sclera. The most common mutations associated with OI result from the substitution for glycine by another amino acid in the triple helical domain of either the α1 or the α2 chain of collagen type I. In this study, we compared the results of genotype analysis and clinical examination in 161 OI patients (median age: 13 years) who had glycine mutations in the triple helical domain of α1(I) (n=67) or α2(I) (n=94). Serine substitutions were the most frequently encountered type of mutation in both chains. Compared with patients with serine substitutions in α2(I) (n=40), patients with serine substitutions in α1(I) (n=42) on average were shorter (median height z-score −6.0 vs −3.4; P=0.005), indicating that α1(I) mutations cause a more severe phenotype. Height correlated with the location of the mutation in the α2(I) chain but not in the α1(I) chain. Patients with mutations affecting the first 120 amino acids at the amino-terminal end of the collagen type I triple helix had blue sclera but did not have dentinogenesis imperfecta. Among patients from different families sharing the same mutation, about 90 and 75% were concordant for dentinogenesis imperfecta and blue sclera, respectively. These data should be useful to predict disease phenotype in newly diagnosed OI patients. PMID:20087402

  18. Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta.

    PubMed

    Albert, Carolyne; Jameson, John; Smith, Peter; Harris, Gerald

    2014-09-01

    Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3 and 42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (P≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone

  19. Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials.

    PubMed

    Hald, Jannie D; Evangelou, Evangelos; Langdahl, Bente L; Ralston, Stuart H

    2015-05-01

    Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2  = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2  = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2  = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition. © 2014 American Society for

  20. The sagittal balance of the spine in children and adolescents with osteogenesis imperfecta

    PubMed Central

    Abelin, Karimane; Lenoir, Thibault; Thévenin-Lemoine, Camille; Damsin, Jean-Paul; Forin, Véronique

    2008-01-01

    In severe forms of osteogenesis imperfecta, multiple compression fractures of the spine, as well as vertebral height shortening could be responsible for an increased thoracic kyphosis or a diminished lumbar lordosis. Theses progressive changes in sagittal shapes of the trunk could be responsible for a global sagittal trunk imbalance. We compare the parameters of sagittal spinopelvic balance in young patients with OI to those parameters in a control group of healthy volunteers. Eighteen patients with osteogenesis imperfecta were compared to a cohort of 300 healthy volunteers. A standing lateral radiograph of the spine was obtained in a standardized fashion. The sacral slope, pelvic tilt, pelvic incidence, lumbar lordosis, thoracic kyphosis, T1 and T9 sagittal offset were measured using a computer-assisted method. The variations and reciprocal correlations of all parameters in both groups according to each other were studied. Comparison of angular parameters between OI patients and control group showed an increased T1T12 kyphosis in OI patients. T1 and T9 sagittal offset was positive in OI patients and negative in control group. This statistically significant difference among sagittal offsets in both groups indicated that OI patients had a global sagittal balance of the trunk displaced anteriorly when compared to the normal population. Reciprocal correlations between angular parameters in OI patients showed a strong correlation between lumbar lordosis (L1L5 and L1S1) and sacral slope. The T9 sagittal offset was also strongly correlated with pelvic tilt. Pelvic incidence was correlated with L1S1 lordosis, T1 sagittal offset and pelvic tilt. In OI patients, the T1T12 thoracic kyphosis was statistically higher than in control group and was not correlated with other shape (LL) or pelvic (SS, PT or PI) parameters. Because isolated T1T12 kyphosis increase without T4T12 significant modification, we suggest that vertebral deformations worsen in OI patients at the upper part

  1. The sagittal balance of the spine in children and adolescents with osteogenesis imperfecta.

    PubMed

    Abelin, Karimane; Vialle, Raphaël; Lenoir, Thibault; Thévenin-Lemoine, Camille; Damsin, Jean-Paul; Forin, Véronique

    2008-12-01

    In severe forms of osteogenesis imperfecta, multiple compression fractures of the spine, as well as vertebral height shortening could be responsible for an increased thoracic kyphosis or a diminished lumbar lordosis. Theses progressive changes in sagittal shapes of the trunk could be responsible for a global sagittal trunk imbalance. We compare the parameters of sagittal spinopelvic balance in young patients with OI to those parameters in a control group of healthy volunteers. Eighteen patients with osteogenesis imperfecta were compared to a cohort of 300 healthy volunteers. A standing lateral radiograph of the spine was obtained in a standardized fashion. The sacral slope, pelvic tilt, pelvic incidence, lumbar lordosis, thoracic kyphosis, T1 and T9 sagittal offset were measured using a computer-assisted method. The variations and reciprocal correlations of all parameters in both groups according to each other were studied. Comparison of angular parameters between OI patients and control group showed an increased T1T12 kyphosis in OI patients. T1 and T9 sagittal offset was positive in OI patients and negative in control group. This statistically significant difference among sagittal offsets in both groups indicated that OI patients had a global sagittal balance of the trunk displaced anteriorly when compared to the normal population. Reciprocal correlations between angular parameters in OI patients showed a strong correlation between lumbar lordosis (L1L5 and L1S1) and sacral slope. The T9 sagittal offset was also strongly correlated with pelvic tilt. Pelvic incidence was correlated with L1S1 lordosis, T1 sagittal offset and pelvic tilt. In OI patients, the T1T12 thoracic kyphosis was statistically higher than in control group and was not correlated with other shape (LL) or pelvic (SS, PT or PI) parameters. Because isolated T1T12 kyphosis increase without T4T12 significant modification, we suggest that vertebral deformations worsen in OI patients at the upper part

  2. Quality of life in children and adolescents with Osteogenesis Imperfecta: a qualitative interview based study

    PubMed Central

    2014-01-01

    Background Osteogenesis Imperfecta (OI) is a disease with varying severity affecting physical, social and emotional well-being of the child and their family. There is no existing evidence on how the OI population regard their quality of life (QoL). The main aim of this study was to determine how OI impacts on the quality of life and well-being of children and their family. It is the first stage of a larger project to develop a disease specific quality of life measure for children with OI. Methods Purposive sampling was used to cover the diversity of the OI population. Twenty-five qualitative interviews were undertaken with children (n = 10), parents (n = 10) and health professionals (n = 5). Interviews were digitally recorded and transcribed verbatim. Significant themes were identified, extracted and organised, undergoing framework analysis. Results Six main themes were identified; being safe and careful, reduced function, pain, fear, isolation, independence. There was a large amount of agreement between the three groups of interviewees, although discrepancies did occur between parents and children, with regard to the themes independence and fear. Conclusions This data presents the first step in developing items for a disease specific QoL measure for children with OI. Several of the themes uncovered showed similarity to other QoL measures, but the addition of being safe and careful, particularly in relation to fractures, demonstrated the need for a disease specific measure for children with OI. PMID:24742068

  3. Safety enhancement of a specialized power assisted tricycle for a child with osteogenesis imperfecta type III.

    PubMed

    Geu, Matthew J; Tuffner, Francis F; Madsen, Robert O; Harman, William M; Barrett, Steven F

    2005-01-01

    A child in the community of Laramie, Wyoming was born with Osteogenesis Imperfecta which is a genetic disorder that limits the physical abilities, size, and strength of the child. A customized power assisted tricycle was developed, which offered a unique opportunity to serve multiple purposes in his childhood development. This tricycle will ultimately provide him with the opportunity to gain muscle mass, strength, coordination, and confidence. The tricycle was completed as a senior design project in 2002, funded by the National Science Foundation, Biomedical Engineering Program and research to Aid Persons with Disabilities Program and University of Wyoming, College of Engineering Undergraduate Design Project to Aid Wyoming Persons with Disabilities. Unfortunately, the tricycle did not provide the necessary features to allow him to ride the tricycle safely. For this reason the tricycle was redesigned to include many different redundant safety systems which allows the tricycle to be safe for the child's use. Being funded by the same grant, new systems were added to the tricycle. A panic kill switch, automatic brakes, numerous redundant velocity sensors, tip over prevention circuitry, a redesigned operating system, a battery recharge port, and other systems were added, allowing for the tricycle to provide a high level of safety. A great deal of testing and sound design practices have been taken into consideration throughout the addition of these systems. Without these improvements, the child would not have the opportunity to use the tricycle to help with his development.

  4. Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

    PubMed Central

    Jones, Gemma N.; Moschidou, Dafni; Abdulrazzak, Hassan; Kalirai, Bhalraj Singh; Vanleene, Maximilien; Osatis, Suchaya; Shefelbine, Sandra J.; Horwood, Nicole J.; Marenzana, Massimo; De Coppi, Paolo; Bassett, J.H. Duncan; Williams, Graham R.; Fisk, Nicholas M.

    2014-01-01

    Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oim mice) improved the phenotype. However, the clinical use of fetal MSC is constrained by their limited number and low availability. In contrast, human fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions and isolated in high numbers from the placenta during ongoing pregnancy. Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. Exogenous cells preferentially homed to long bone epiphyses, expressed osteoblast genes, and produced collagen COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. In conclusion, the placenta is a practical source of stem cells for the treatment of OI. PMID:24028330

  5. Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium

    PubMed Central

    Barron, Melissa L; Rybchyn, Mark S; Ramesh, Sutharshani; Mason, Rebecca S; Fiona Bonar, S; Stalley, Paul; Khosla, Sundeep; Hudson, Bernie; Arthur, Christopher; Kim, Edward; Clifton-Bligh, Roderick J; Clifton-Bligh, Phillip B

    2017-01-01

    Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient’s osteoblasts in culture. When normal osteoblasts were cultured with the patient’s serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function. PMID:28326223

  6. Fibrogenesis Imperfecta Ossium and Response to Human Growth Hormone: A Potential Therapy.

    PubMed

    Bhadada, Sanjay Kumar; Dhiman, Vandana; Mukherjee, Soham; Aggarwal, Sameer; Bal, Amanjit; Sukumar, Suja P; Sood, Ashwani; Sharma, Dinesh Chandra; Khandelwal, Niranjan; Bhansali, Anil; Van Hul, Wim; Rao, Sudhaker D

    2017-05-01

    Fibrogenesis imperfecta ossium (FIO) is a rare bone disease manifested by generalized bone pain, fragility fractures, progressive disability, and extensive mineralization defect seen in bone biopsy specimens. The pathogenesis of the disease is unknown and currently there is no effective treatment. To report on the effect of recombinant human growth hormone (rhGH) therapy in FIO. An observational study in two patients. Endocrinology clinic in an academic institution. Two siblings with FIO. rhGH was administered subcutaneously at a dose of 1 U daily for 1 year. Changes in clinical, biochemical, radiological, and bone histological (i.e., light and transmission electron microscopy, and histomorphometry) investigations. Except for an elevated serum alkaline phosphatase level, results of routine biochemical, hematological, and hormonal investigations were normal in both patients. Radiographs showed pseudofractures and bone scans revealed a "beheaded" tracer activity pattern (i.e., superscan without uptake in the skull). Bone biopsy specimens showed severe mineralization defect simulating osteomalacia with disorganized collagen fibril alignment. Treatment with rhGH was followed by clinical, biochemical, and radiological improvement in both the patients, with substantial improvement in the mineralization defect, most likely due to rhGH-induced improvement in collagen fibril arrangement. We report on two brothers with FIO and demonstrate clinical improvement and restoration of normal bone pathology with rhGH therapy. We suggest that rhGH is a potential therapy for FIO for which no effective therapy currently exists.

  7. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    PubMed

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Two mutations in IFITM5 causing distinct forms of osteogenesis imperfecta.

    PubMed

    Guillén-Navarro, Encarna; Ballesta-Martínez, María Juliana; Valencia, María; Bueno, Ana María; Martinez-Glez, Victor; López-González, Vanesa; Burnyte, Birute; Utkus, Algirdas; Lapunzina, Pablo; Ruiz-Perez, Victor L

    2014-05-01

    The IFITM5 gene has recently been found to be mutated in patients with autosomal dominant osteogenesis imperfecta (OI) type V. This form of OI is characterized by distinctive clinical manifestations, including hyperplastic callus formation at the site of fractures, calcification of the interosseous membrane of the forearm, and dislocation of the head of the radius. Notably, in spite of the fact that a considerable number of patients with IFITM5 mutations have been identified, to date all of them have been shown to have the same heterozygous mutation (c.-14C>T). Herein, we describe one patient with a de novo c.119C>T heterozygous mutation in IFITM5, which predicts p.Ser40Leu, and another with the recurrent c.-14C>T transition that was also apparently de novo. While the patient with the p.Ser40Leu mutation had none of the typical signs of OI type V and was diagnosed with limb shortening at prenatal stages, the patient with the c.-14C>T mutation developed hyperplastic calluses and had calcification of the forearm interosseous membrane. This study challenges the lack of allelic and clinical heterogeneity in IFITM5 mutations. © 2014 Wiley Periodicals, Inc.

  9. Limb lengthening and correction of deformity in the lower limbs of children with osteogenesis imperfecta.

    PubMed

    Saldanha, K A N; Saleh, M; Bell, M J; Fernandes, J A

    2004-03-01

    We performed limb lengthening and correction of deformity of nine long bones of the lower limb in six children (mean age, 14.7 years) with osteogenesis imperfecta (OI). All had femoral lengthening and three also had ipsilateral tibial lengthening. Angular deformities were corrected simultaneously. Five limb segments were treated using a monolateral external fixator and four with the Ilizarov frame. In three children, lengthening was done over previously inserted femoral intramedullary rods. The mean lengthening achieved was 6.26 cm (mean healing index, 33.25 days/cm). Significant complications included one deep infection, one fracture of the femur and one anterior angulation deformity of the tibia. The abnormal bone of OI tolerated the external fixators throughout the period of lengthening without any episodes of migration of wires or pins through the soft bone. The regenerate bone formed within the time which is normally expected in limb-lengthening procedures performed for other conditions. We conclude that despite the abnormal bone characteristics, distraction osteogenesis to correct limb-length discrepancy and angular deformity can be performed safely in children with OI.

  10. Structure–mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model

    PubMed Central

    Andriotis, O. G.; Chang, S. W.; Vanleene, M.; Howarth, P. H.; Davies, D. E.; Shefelbine, S. J.; Buehler, M. J.; Thurner, P. J.

    2015-01-01

    The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry. PMID:26468064

  11. Full-mouth rehabilitation for a patient with dentinogenesis imperfecta: a clinical report.

    PubMed

    Bencharit, Sompop; Border, Michael B; Mack, C Russell; Byrd, Warren C; Wright, John T

    2014-10-01

    Dentinogenesis imperfecta (DI) is a genetic disorder affecting the structural integrity of the dentin that can result in weakened dentin. The affected teeth, especially posterior teeth, often need to be extracted due to severe wear or fracture. This frequently yields a loss of posterior occlusion and occlusal vertical dimension. Besides wear and fracture, anterior teeth often have an unesthetic appearance because of discoloration. Current treatments of choice, including composite bonding restorations and, more recently, all-ceramic restorations, are typically suggested to preserve the remaining teeth and tooth structure. However, there are a limited number of studies on dental implants in patients with DI. The effectiveness of dentin bonding and dental implants in patients with DI is not known. This clinical report describes a 32-year-old Asian woman with DI who underwent full-mouth rehabilitation. The posterior occlusion, mostly in the molar areas, was restored with dental implants and ceramometal restorations. The anterior teeth and premolars were restored with bonded lithium disilicate glass-ceramic pressed veneers and crowns made with computer-aided design/computer-aided manufacturing. This case demonstrates that restoring functional occlusion and esthetics for a patient with DI can be completed successfully using contemporary implant therapy and adhesive dentistry.

  12. Multiparametric Classification of Skin from Osteogenesis Imperfecta Patients and Controls by Quantitative Magnetic Resonance Microimaging.

    PubMed

    Ashinsky, Beth G; Fishbein, Kenneth W; Carter, Erin M; Lin, Ping-Chang; Pleshko, Nancy; Raggio, Cathleen L; Spencer, Richard G

    2016-01-01

    The purpose of this study is to evaluate the ability of quantitative magnetic resonance imaging (MRI) to discriminate between skin biopsies from individuals with osteogenesis imperfecta (OI) and skin biopsies from individuals without OI. Skin biopsies from nine controls (unaffected) and nine OI patients were imaged to generate maps of five separate MR parameters, T1, T2, km, MTR and ADC. Parameter values were calculated over the dermal region and used for univariate and multiparametric classification analysis. A substantial degree of overlap of individual MR parameters was observed between control and OI groups, which limited the sensitivity and specificity of univariate classification. Classification accuracies ranging between 39% and 67% were found depending on the variable of investigation, with T2 yielding the best accuracy of 67%. When several MR parameters were considered simultaneously in a multivariate analysis, the classification accuracies improved up to 89% for specific combinations, including the combination of T2 and km. These results indicate that multiparametric classification by quantitative MRI is able to detect differences between the skin of OI patients and of unaffected individuals, which motivates further study of quantitative MRI for the clinical diagnosis of OI.

  13. Dental panoramic indices and fractal dimension measurements in osteogenesis imperfecta children under pamidronate treatment.

    PubMed

    Apolinário, Ana C; Sindeaux, Rafael; de Souza Figueiredo, Paulo T; Guimarães, Ana T B; Acevedo, Ana C; Castro, Luiz C; de Paula, Ana P; de Paula, Lilian M; de Melo, Nilce S; Leite, André F

    2016-01-01

    To verify radiomorphometric indices and fractal dimension (FD) in dental panoramic radiographs (DPRs) of children with different types of osteogenesis imperfecta (OI) and also to verify the effect of pamidronate (PAM) treatment in such panoramic analyses. In this retrospective study, 197 DPRs of 62 children with OI Types I, III and IV who were in treatment with a comparable dosage of intravenous PAM were selected. The mandibular cortical width (MCW), mandibular cortical index, visual estimation of the cortical width and FD of three standardized trabecular and cortical mandibular regions of interest were obtained from the radiographs. Factorial analysis of variance and Fisher test were used to compare FD and MCW measurements in children with different types of OI for different PAM cycles. Children with all types of OI have thinner and more porous mandibular cortices at the beginning of treatment. There were significant differences between MCW and FD of the cortical bone, regarding different types of OI and number of PAM cycles (p = 0.037 and p = 0.044, respectively). FD measurements of the trabecular bone were not statistically different among OI types nor were PAM cycles (p > 0.05). Children with OI presented cortical bone alterations after PAM treatment. Both MCW and the FD of the cortical bone were higher in children with OI after PAM treatment. It is argued that cortical bone should be considered for analyzing patients with OI, as well as to monitor the progress of PAM treatment.

  14. Osteogenesis imperfecta in children and adolescents-new developments in diagnosis and treatment.

    PubMed

    Trejo, P; Rauch, F

    2016-12-01

    Osteogenesis imperfecta (OI) is the most prevalent heritable bone fragility disorder in children. It has been known for three decades that the majority of individuals with OI have mutations in COL1A1 or COL1A2, the two genes coding for collagen type I alpha chains, but in the past 10 years defects in at least 17 other genes have been linked to OI. Almost all individuals with a typical OI phenotype have a mutation in one of the currently known genes. Regarding medical treatment, intravenous bisphosphonate therapy is the most widely used medical approach. This has a marked effect on vertebra in growing children and can lead to vertebral reshaping after compression fractures, but there is little effect of bisphosphonate therapy on the development of scoliosis. Bisphosphonate treatment decreases long-bone fracture rates, but such fractures are still frequent. Newer medications with anti-resorptive and bone anabolic action are being investigated in an attempt to improve on the efficacy of bisphosphonates but the safety and efficacy of these new approaches in children with OI is not yet established.

  15. Childhood Osteoporosis and Presentation of Two Cases with Osteogenesis Imperfecta Type V

    PubMed Central

    BRATANIC, Nina; DZODAN, Bojana; TREBUSAK PODKRAJSEK, Katarina; BERTOK, Sara; OSTANEK, Barbara; MARC, Janja; BATTELINO, Tadej; AVBELJ STEFANIJA, Magdalena

    2015-01-01

    Introduction Osteogenesis imperfecta (OI) is etiologically heterogeneous disorder characterized by childhood osteoporosis. A subtype OI type V is caused by the same c.-14C>T mutation in the IFITM5 gene. Nevertheless, there is a marked interindividual phenotypic variability in clinical presentation; however, response to bisphosphonates is reported to be good. Methods Two individuals with OI type V had multiple recurrent fractures with hypertrophic calluses, scoliosis and ossifications of the forearm interosseous membranes. Sequencing of IFITM5, genotyping of variants rs2297480 in farnesyl diphosphate synthase gene (FDPS), and rs3840452 in geranylgeranyl diphosphate synthase 1 gene (GGPS1), both involved in bisphosphonate metabolism, was performed. Results In patient 1 BMD reached normal values during bisphosphonate treatment and remained normal four years after the treatment discontinuation. In patient 2 no increase in BMD after five years of bisphosphonate treatment was observed and callus formation continued. The c.-14C>T IFITM5 mutation in heterozygous state was detected in both individuals. Additionally, both patients carried FDPS variant rs2297480 in homozygous state, and were heterozygous for GGPS 1 variant rs3840452. Conclusions The paper presents a short overview of childhood osteoporosis with a special emphasis on OI type V by presenting two cases. Both OI type V patients had identical disease-causing mutation, but marked interindividual phenotypic variability. The striking failure in response to bisphosphonate treatment in one of the patients could not be explained by the variants in genes involved in bisphosphonate metabolism. PMID:27646918

  16. Testing for osteogenesis imperfecta in cases of suspected non-accidental injury

    PubMed Central

    Marlowe, A; Pepin, M; Byers, P

    2002-01-01

    To evaluate if laboratory testing for osteogenesis imperfecta (OI) identifies children unrecognised by clinical examination in instances where non-accidental injury (NAI) is suspected as the likely cause of fracture, we carried out a retrospective review of available medical records and biochemical test results from 262 patients. Cultured fibroblasts were received for biochemical testing for OI from children in whom the diagnosis of NAI was suspected. Eleven of the samples had alterations in the amount or structure of type I collagen synthesised, consistent with the diagnosis of OI, and in 11 others we could not exclude OI. Referring physicians correctly identified children with OI in six of the 11 instances established by biochemical studies, did not identify OI by clinical examination in three, and there was inadequate clinical information to know in two others. Biochemical testing was inconclusive in 11 infants in whom the diagnosis of OI could not be excluded, none of whom were thought to be affected by the referring clinicians. Four children believed to have OI by clinical examination had normal biochemical studies, a false positive clinical diagnosis attributed, in large part, to the use of scleral hue (a feature that is age dependent) as a major diagnostic criterion. Given the inability to identify all children with OI by clinical examination in situations of suspected NAI, laboratory testing for OI (and other genetic predispositions for fractures) is a valuable adjunct in discerning the basis for fractures and may identify a small group of children with previously undiagnosed OI. PMID:12070242

  17. Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families

    PubMed Central

    Moldenhauer Minillo, Renata; Sobreira, Nara; de Fatima de Faria Soares, Maria; Jurgens, Julie; Ling, Hua; Hetrick, Kurt N.; Doheny, Kimberly F.; Valle, David; Brunoni, Decio; Alvarez Perez, Ana B.

    2014-01-01

    Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed. PMID:25565926

  18. Child abuse and osteogenesis imperfecta: how can they be still misdiagnosed? A case report

    PubMed Central

    D’Eufemia, Patrizia; Palombaro, Marta; Lodato, Valentina; Zambrano, Anna; Celli, Mauro; Persiani, Pietro; De Bari, Maria Pia; Sangiorgi, Luca

    2012-01-01

    Summary Osteogenesis imperfecta (OI) is a rare hereditary disease caused by mutations in genes coding for type I collagen, resulting in bone fragility. In literature are described forms lethal in perinatal period, forms which are moderate and slight forms where the only sign of disease is osteopenia. Child abuse is an important social and medical problem. Fractures are the second most common presentation after skin lesions and may present specific patterns. The differential diagnosis between slight-moderate forms of OI and child abuse could be very challenging especially when other signs typical of abuse are absent, since both could present with multiple fractures without reasonable explanations. We report a 20 months-old female with a history of 4 fractures occurred between the age of three and eighteen months, brought to authorities’ attention as a suspected child abuse. However when she came to our department physical examination, biochemical tests, total body X-ray and a molecular analysis of DNA led the diagnosis of OI. Thus, a treatment with bisphosphonate and a physical rehabilitation process, according to Vojta method, were started with improvement in bony mineralization, gross motor skills and absence of new fracture. In conclusion our case demonstrates how in any child presenting fractures efforts should be made to consider, besides child abuse, all the other hypothesis even the rarest as OI. PMID:23289038

  19. Phenotypic Variation in Dentinogenesis Imperfecta/Dentin Dysplasia Linked to 4q21

    PubMed Central

    Beattie, M.L.; Kim, J.-W.; Gong, S.-G.; Murdoch-Kinch, C.A.; Simmer, J.P.; Hu, J.C.-C.

    2008-01-01

    Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders that primarily affect the formation of tooth dentin. Both conditions are autosomal-dominant and can be caused by mutations in the dentin sialophospho-protein gene (DSPP, 4q21.3). We recruited 23 members of a four-generation kindred, including ten persons with dentin defects, and tested the hypothesis that these defects are linked to DSPP. The primary dentition showed amber discoloration, pulp obliteration, and severe attrition. The secondary dentition showed either pulp obliteration with bulbous crowns and gray discoloration or thistle-tube pulp configurations, normal crowns, and mild gray discoloration. Haplotype analyses showed no recombination between three 4q21-q24 markers and the disease locus. Mutational analyses identified no coding or intron junction sequence variations associated with affection status in DMP1, MEPE, or the DSP portion of DSPP. The defects in the permanent dentition were typically mild and consistent with a diagnosis of DD-II, but some dental features associated with DGI-II were also present. We conclude that DD-II and DGI-II are milder and more severe forms, respectively, of the same disease. PMID:16567553

  20. Phenotype and genotype analyses in seven families with dentinogenesis imperfecta or dentin dysplasia.

    PubMed

    Li, F; Liu, Y; Liu, H; Yang, J; Zhang, F; Feng, H

    2017-04-01

    Hereditary dentin defects can be categorised into two classes according to their clinical manifestations: dentinogenesis imperfecta (DGI), which includes three types (DGI-I, DGI-II and DGI-III), and dentin dysplasia (DD), which includes two types (DD-I and DD-II). This study investigated the phenotypic characteristics and genetic causes of hereditary dentin defects in seven Chinese families. Seven families affected with DGI-II, DGI-III or DD-II were enrolled. Clinical examinations were performed to determine the phenotypic characteristics, and DNA samples were collected for Sanger sequencing. Clinical diagnoses revealed DGI-II in five families, DGI-III in one family and DD-II in one family. Variants of the dentin sialophosphoprotein (DSPP) gene were found in six of the seven families. Of these, c.52G>T was identified in two families. Each of the remaining four families had a different variant: c.2684delG, c.52-2A>G, c.1874-1877delACAG and c.3509-3521del13bp; the last three variants were novel. This is the first study to analyse all three important types of hereditary dentin defect and include comprehensive genetic analyses of both dentin sialoprotein and dentin phosphoprotein in Chinese families. This study expands the spectrum of DSPP variants, highlighting their associated phenotypic continuum. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Potential of human fetal chorionic stem cells for the treatment of osteogenesis imperfecta.

    PubMed

    Jones, Gemma N; Moschidou, Dafni; Abdulrazzak, Hassan; Kalirai, Bhalraj Singh; Vanleene, Maximilien; Osatis, Suchaya; Shefelbine, Sandra J; Horwood, Nicole J; Marenzana, Massimo; De Coppi, Paolo; Bassett, J H Duncan; Williams, Graham R; Fisk, Nicholas M; Guillot, Pascale V

    2014-02-01

    Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oim mice) improved the phenotype. However, the clinical use of fetal MSC is constrained by their limited number and low availability. In contrast, human fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions and isolated in high numbers from the placenta during ongoing pregnancy. Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. Exogenous cells preferentially homed to long bone epiphyses, expressed osteoblast genes, and produced collagen COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. In conclusion, the placenta is a practical source of stem cells for the treatment of OI.

  2. Anthropometry, nutritional status, and dietary intake in pediatric patients with osteogenesis imperfecta.

    PubMed

    Zambrano, Marina B; Brizola, Evelise S; Refosco, Lilia; Giugliani, Roberto; Félix, Têmis M

    2014-01-01

    The aim of the present study was to assess anthropometric measurements, nutritional status, dietary intake, and body fat percentage of pediatric patients with osteogenesis imperfecta (OI). A cross-sectional study evaluated 63 OI patients from 0 to 19 years of age. We analyzed anthropometric measurements, mobility, bisphosphonate treatment, body fat percentage (by dual-energy x-ray absorptiometry [DEXA] and sum of skinfold thickness), nutritional status, and dietary intake (using World Health Organization [WHO] and dietary reference intake recommendations for macronutrients and calcium intake, respectively). Participants' energy requirements were calculated using both kilocalorie per centimeter measurements and WHO methods. Patients with different types of OI had different anthropometric measurements (p < 0.05), where OI type III had severely limited stature and poor mobility. Nutritional status was correlated with measurements of arm circumference and body fat. We also found a strong correlation between the 2 methods used to calculate percentage of body fat (r = 0.803). OI type III had a higher percentage of energy intake. We observed that 75% of subjects had a calcium intake below 95% of recommended daily value and there was an inverse correlation between age and calcium intake. This study showed that stature was compromised mainly in OI type III. Skinfold thickness and arm circumference correlated to nutritional status and also to body fat calculated by DEXA. Daily calcium intake was below the recommended levels in pediatric patients with OI. These findings are important for the management of OI subjects.

  3. Muscle force sensitivity of a finite element fracture risk assessment model in osteogenesis imperfecta - biomed 2009.

    PubMed

    Fritz, Jessica M; Guan, Yabo; Wang, Mei; Smith, Peter A; Harris, Geald F

    2009-01-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder characterized by skeletal deformities and increased bone fragility. There is currently no established clinical method for quantifying fracture risk in OI patients. A method for developing a finite element model of the femur to assist in fracture risk assessment of a selected patient with OI type I was created. The material properties were based on nanoindentation testing of OI bone specimens collected during routine surgery. Dynamic data from clinical gait analysis was used to prescribe joint reaction forces and moments in a quasi-static model. Muscle forces were prescribed according to current literature. Von Mises stresses were analyzed across all seven phases of the gait cycle and analyzed for sensitivity to changes in muscle forces. The model showed that the patient with OI was not at current risk for fracture during normal gait. The highest stress levels occurred during mid stance and loading response. Maximum von Mises stresses were most sensitive to the gluteal muscles. Insight provided by the model may be useful for similar clinical applications, more refined model development and an improved ability for fracture prediction.

  4. A fracture risk assessment model of the femur in children with osteogenesis imperfecta (OI) during gait.

    PubMed

    Fritz, Jessica M; Guan, Yabo; Wang, Mei; Smith, Peter A; Harris, Gerald F

    2009-11-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder characterized by skeletal deformities and increased bone fragility. There is currently no established clinical method for quantifying fracture risk in OI patients. This study begins the development of a patient-specific model for femur fracture risk assessment and prediction based on individuals' gait analysis data, bone geometry from imaging and material properties from nanoindentation (Young's modulus=19 GPa, Poisson's ratio=0.3). Finite element models of the femur were developed to assess fracture risk of the femur in a pediatric patient with OI type I. Kinetic data from clinical gait analysis was used to prescribe loading conditions on the femoral head and condyles along with muscle forces on the bone's surface. von Mises stresses were analyzed against a fracture strength of 115 MPa. The patient with OI whose femur was modeled showed no risk of femoral fracture during normal gait. The highest stress levels occurred during the mid-stance and loading responses phases of gait. The location of high stress migrated throughout the femoral diaphysis across the gait cycle. Maximum femoral stress levels occurred during the gait cycle phases associated with the highest loading. The fracture risk (fracture strength/von Mises stress), however, was low. This study provides a relevant method for combining functional activity, material property and analytical methods to improve patient monitoring.

  5. Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice☆

    PubMed Central

    Vanleene, Maximilien; Porter, Alexandra; Guillot, Pascale-Valerie; Boyde, Alan; Oyen, Michelle; Shefelbine, Sandra

    2012-01-01

    Bone is a complex material with a hierarchical multi-scale organization from the molecule to the organ scale. The genetic bone disease, osteogenesis imperfecta, is primarily caused by mutations in the collagen type I genes, resulting in bone fragility. Because the basis of the disease is molecular with ramifications at the whole bone level, it provides a platform for investigating the relationship between structure, composition, and mechanics throughout the hierarchy. Prior studies have individually shown that OI leads to: 1. increased bone mineralization, 2. decreased elastic modulus, and 3. smaller apatite crystal size. However, these have not been studied together and the mechanism for how mineral structure influences tissue mechanics has not been identified. This lack of understanding inhibits the development of more accurate models and therapies. To address this research gap, we used a mouse model of the disease (oim) to measure these outcomes together in order to propose an underlying mechanism for the changes in properties. Our main finding was that despite increased mineralization, oim bones have lower stiffness that may result from the poorly organized mineral matrix with significantly smaller, highly packed and disoriented apatite crystals. Using a composite framework, we interpret the lower oim bone matrix elasticity observed as the result of a change in the aspect ratio of apatite crystals and a disruption of the crystal connectivity. PMID:22449447

  6. Minimally invasive orthodontics: elastodontic therapy in a growing patient affected by Dentinogenesis Imperfecta

    PubMed Central

    Ierardo, Gaetano; Luzzi, Valeria; Nardacci, Giuliana; Vozza, Iole; Polimeni, Antonella

    2017-01-01

    Summary Aim The aim of the study was to report the use of an elastodontic therapy in a growing patient affected by Dentinogenesis Imperfecta, second class malocclusion, deep bite and lower arch crowding from the deciduous dentition to permanent one. Case report At first, the 5-year-old patient was treated with an elastodontic device known as “Nite-Guide”. When the patient was 7 years old, during her first permanent molars and incisors eruption and after optimal house-practices, an Occlus-o-Guide Series G was placed at night and on daylight (two hours a day) performing exercises aimed to activate facial muscles and facilitate the deep bite reopening. At 9 years of age, with totally deep bite resolution, she used the Occluso-Guide only at night to hold down previous results and follow patient’s dental growth. At 11 years of age, after successful teeth switching, we prescribed an Occlus-o-Guide Series N, which is functional for permanent dentition and guaranteed an eruptive guide for last dental elements. Conclusions This clinic case could be considered an example of approach for all those patients with systemic and/or dental diseases that do not allow adequate dental retention, which is necessary for most orthodontic appliances; elastodontic devices do not require adequate dental retention and define a minimum intervention on the surfaces of the teeth. PMID:28736605

  7. Case report: Clinical, histological and ultrastructural characterization of type II dentinogenesis imperfecta.

    PubMed

    Leal, C T; Martins, L D; Verli, F D; de Souza, M A L; Ramos-Jorge, M L

    2010-12-01

    Type II dentinogenesis imperfecta (DGIII) is an autosomal dominant dental development anomaly that affects both the primary and permanent dentition. This case report describes the clinical, radiographic and morphological characteristics of the teeth of a seven-year-old child with DGI-II determined by optical microscopy and scanning electron microscopy. This consisted of extraction of the primary teeth with periapical lesions due to the advanced state of tooth resorption. Aesthetic restorations were performed on the mandibular anterior teeth and occlusal fissure sealants were applied to erupting teeth. A removable partial upper denture was made in order to return anterior aesthetic function and to aid mastication and speech. The child was examined at 3 month intervals. Over the following 3 years the prosthesis was replaced due to facial growth and fluoride was applied at each follow-up visit to all teeth. The patient remains in follow up and management. Individuals with DGI-II must not neglect their dental health. Early diagnosis, professional advice and treatment with periodic follow-up can help improve the quality of life of such patients.

  8. Quantitative changes in human epithelial cancers and osteogenesis imperfecta disease detected using nonlinear multicontrast microscopy.

    PubMed

    Adur, Javier; Pelegati, Vitor B; de Thomaz, Andre A; D'Souza-Li, Lilia; Assunção, Maria do Carmo; Bottcher-Luiz, Fátima; Andrade, Liliana A L A; Cesar, Carlos L

    2012-08-01

    We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for different types of human breast cancer, mucinous ovarian tumors, and skin dermis of patients with OI. Using a set of scoring methods (anisotropy, correlation, uniformity, entropy, and lifetime components), we found significant differences in the content, distribution and organization of collagen fibrils in the stroma of breast and ovary as well as in the dermis of skin. We suggest that our results provide a framework for using NLO techniques as a clinical diagnostic tool for human cancer and OI. We further suggest that the SHG and FLIM metrics described could be applied to other connective or epithelial tissue disorders that are characterized by abnormal cells proliferation and collagen assembly.

  9. Analysis of cyanogen bromide peptides of type I collagen from a patient with lethal osteogenesis imperfecta.

    PubMed Central

    Kirsch, E; Glanville, R W; Krieg, T; Müller, P

    1983-01-01

    The CNBr peptides of type I collagen from bone of a patient with lethal osteogenesis imperfecta and age-matched controls were isolated by molecular-sieve chromatography and their amino acid compositions were determined. No differences were found between the compositions of the peptides from the patient and those from the controls, except for an increase in the degree of hydroxylation of lysine in all peptides from the patient. Type I collagen CNBr peptides from chick-embryo skin [Barnes, Constable Morton & Kodicek (1971) Biochem. J. 125, 925--928] and guinea-pig scar tissue [Shuttleworth, Forrest & Jackson (1975) Biochim. Biophys. Acta 379, 207--216] also have an increased degree of hydroxylation of lysine with an otherwise normal amino acid composition, and it was believed that this could be an embryonic form of collagen. As a similar collagen was present in the bones of the patient studied, it seems possible that the same 'embryonic' collagen is synthesized during development, in repair process and also in genetic disorders of collagen metabolism. Images Fig. 3. Fig. 4. PMID:6411063

  10. Monoallelic and biallelic CREB3L1 variant causes mild and severe osteogenesis imperfecta, respectively.

    PubMed

    Keller, Rachel B; Tran, Thao T; Pyott, Shawna M; Pepin, Melanie G; Savarirayan, Ravi; McGillivray, George; Nickerson, Deborah A; Bamshad, Michael J; Byers, Peter H

    2017-08-17

    PurposeOsteogenesis imperfecta (OI) is a heritable skeletal dysplasia. Dominant pathogenic variants in COL1A1 and COL1A2 explain the majority of OI cases. At least 15 additional genes have been identified, but those still do not account for all OI phenotypes that present. We sought the genetic cause of mild and lethal OI phenotypes in an unsolved family.MethodsWe performed exome sequencing on seven members of the family, both affected and unaffected.ResultsWe identified a variant in cyclic AMP responsive element binding protein 3-like 1 (CREB3L1) in a consanguineous family. The variant caused a prenatal/perinatal lethal OI in homozygotes, similar to that seen in OI type II as a result of mutations in type I collagen genes, and a mild phenotype (fractures, blue sclerae) in multiple heterozygous family members. CREB3L1 encodes old astrocyte specifically induced substance (OASIS), an endoplasmic reticulum stress transducer. The variant disrupts a DNA-binding site and prevents OASIS from acting on its transcriptional targets including SEC24D, which encodes a component of the coat protein II complex.ConclusionThis report confirms that CREB3L1 is an OI-related gene and suggests the pathogenic mechanism of CREB3L1-associated OI involves the altered regulation of proteins involved in cellular secretion.GENETICS in MEDICINE advance online publication, 17 August 2017; doi:10.1038/gim.2017.115.

  11. Power stapes: an alternative method for treating hearing loss in osteogenesis imperfecta?

    PubMed

    Kontorinis, Georgios; Lenarz, Thomas; Mojallal, Hamidreza; Hinze, Anna-Lena; Schwab, Burkard

    2011-06-01

    To present power stapes, stapedotomy, and middle ear implantation with Vibrant SoundBridge (VSB) performed in a one-step surgery as an alternative option for hearing rehabilitation in patients with osteogenesis imperfecta (OI). Retrospective case series. Tertiary referral ear center. A family with genetically proven OI Type I. Two patients, mother and son, with severe to profound mixed hearing loss underwent 3 power stapes, 1 unilateral and 1 bilateral sequential. Thorough audiological diagnostic batteries including aided and unaided pure-tone and free-field audiometry and Freiburg monosyllabic word test were used to assess the preoperative status and the postoperative hearing outcome. High-resolution computed tomography of the temporal bones was performed as well. Surgical procedure and any special considerations were analyzed in detail. The hearing outcome was favorable in all cases, showing in comparison to the preoperative values an average improvement of 36.8 dB. Severe intraoperative bleeding of the middle ear mucosa was the only complication and could be easily controlled by allowing short time intervals. Inner ear trauma did not occur in any case. Power stapes represents a safe and promising procedure for treating hearing loss in selected patients with OI. Furthermore, it introduces a new, advantageous VSB application in cases of mixed hearing loss with severe otosclerosis and increased bone-conduction thresholds.

  12. Multiparametric Classification of Skin from Osteogenesis Imperfecta Patients and Controls by Quantitative Magnetic Resonance Microimaging

    PubMed Central

    Carter, Erin M.; Lin, Ping-Chang; Pleshko, Nancy; Raggio, Cathleen L.; Spencer, Richard G.

    2016-01-01

    The purpose of this study is to evaluate the ability of quantitative magnetic resonance imaging (MRI) to discriminate between skin biopsies from individuals with osteogenesis imperfecta (OI) and skin biopsies from individuals without OI. Skin biopsies from nine controls (unaffected) and nine OI patients were imaged to generate maps of five separate MR parameters, T1, T2, km, MTR and ADC. Parameter values were calculated over the dermal region and used for univariate and multiparametric classification analysis. A substantial degree of overlap of individual MR parameters was observed between control and OI groups, which limited the sensitivity and specificity of univariate classification. Classification accuracies ranging between 39% and 67% were found depending on the variable of investigation, with T2 yielding the best accuracy of 67%. When several MR parameters were considered simultaneously in a multivariate analysis, the classification accuracies improved up to 89% for specific combinations, including the combination of T2 and km. These results indicate that multiparametric classification by quantitative MRI is able to detect differences between the skin of OI patients and of unaffected individuals, which motivates further study of quantitative MRI for the clinical diagnosis of OI. PMID:27416032

  13. Structure-mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model.

    PubMed

    Andriotis, O G; Chang, S W; Vanleene, M; Howarth, P H; Davies, D E; Shefelbine, S J; Buehler, M J; Thurner, P J

    2015-10-06

    The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry.

  14. Gender-dependence of bone structure and properties in adult osteogenesis imperfecta murine model.

    PubMed

    Yao, Xiaomei; Carleton, Stephanie M; Kettle, Arin D; Melander, Jennifer; Phillips, Charlotte L; Wang, Yong

    2013-06-01

    Osteogenesis imperfecta (OI) is a dominant skeletal disorder characterized by bone fragility and deformities. Though the oim mouse model has been the most widely studied of the OI models, it has only recently been suggested to exhibit gender-dependent differences in bone mineralization. To characterize the impact of gender on the morphometry/ultra-structure, mechanical properties, and biochemical composition of oim bone on the congenic C57BL/J6 background, 4-month-old oim/oim, +/oim, and wild-type (wt) female and male tibiae were evaluated using micro-computed tomography, three-point bending, and Raman spectroscopy. Dramatic gender differences were evident in both cortical and trabecular bone morphological and geometric parameters. Male mice had inherently more bone and increased moment of inertia than genotype-matched female counterparts with corresponding increases in bone biomechanical strength. The primary influence of gender was structure/geometry in bone growth and mechanical properties, whereas the mineral/matrix composition and hydroxyproline content of bone were influenced primarily by the oim collagen mutation. This study provides evidence of the importance of gender in the evaluation and interpretation of potential therapeutic strategies when using mouse models of OI.

  15. Osteogenesis imperfecta type V: Genetic and clinical findings in eleven Chinese patients.

    PubMed

    Liu, Yi; Wang, Jiawei; Ma, Doudou; Lv, Fang; Xu, Xiaojie; Xia, Weibo; Jiang, Yan; Wang, Ou; Xing, Xiaoping; Zhou, Peiran; Wang, Jianyi; Yu, Wei; Li, Mei

    2016-11-01

    Osteogenesis imperfecta (OI) type V is a rare inherited disease characterized by multiple fractures, intraosseous membrane calcification, and hypercallus formation. We investigate the causative gene, phenotype and also observe the effects of zoledronic acid in Chinese OI type V patients. The clinical phenotype and causative gene mutation was investigated in eleven patients with type V OI. Patients were given a dose of zoledronic acid 5mg intravenously. Fracture incidence and Z-score of bone mineral density (BMD) were evaluated. Serum levels of biomarkers such as cross linked C-telopeptide of type I collagen (β-CTX) and safety parameters were assessed. The c.-14C>T mutation in the 5' untranslated region of IFITM5 was detected in all patients. The phenotype was largely variable, and no significant correlation of genotype and phenotype was found. After one dose of zoledronic acid infusion, fracture incidence significantly dropped from 2fractures/year before treatment to 0fracture/year after treatment (P=0.01). Z score of lumbar spine BMD elevated from -2.6 to -1.3 (P<0.001). Serum β-CTX level decreased by 50% (P<0.05). No serious adverse event was found. No obvious correlation was found between the genotype and phenotype. Zoledronic acid had significantly skeletal protective effects in OI of type V. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Micro-CT characterization of human trabecular bone in osteogenesis imperfecta

    NASA Astrophysics Data System (ADS)

    Jameson, John; Albert, Carolyne; Smith, Peter; Molthen, Robert; Harris, Gerald

    2011-03-01

    Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling possibilities for the future of OI bone assessment.

  17. Quantitative changes in human epithelial cancers and osteogenesis imperfecta disease detected using nonlinear multicontrast microscopy

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; D'Souza-Li, Lilia; Assunção, Maria do Carmo; Bottcher-Luiz, Fátima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

    2012-08-01

    We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for different types of human breast cancer, mucinous ovarian tumors, and skin dermis of patients with OI. Using a set of scoring methods (anisotropy, correlation, uniformity, entropy, and lifetime components), we found significant differences in the content, distribution and organization of collagen fibrils in the stroma of breast and ovary as well as in the dermis of skin. We suggest that our results provide a framework for using NLO techniques as a clinical diagnostic tool for human cancer and OI. We further suggest that the SHG and FLIM metrics described could be applied to other connective or epithelial tissue disorders that are characterized by abnormal cells proliferation and collagen assembly.

  18. Phenotypic Variability of Osteogenesis Imperfecta Type V Caused by an IFITM5 Mutation

    PubMed Central

    Shapiro, Jay R; Lietman, Caressa; Grover, Monica; Lu, James T; Nagamani, Sandesh CS; Dawson, Brian C; Baldridge, Dustin M; Bainbridge, Matthew N; Cohn, Dan H; Blazo, Maria; Roberts, Timothy T; Brennen, Feng-Shu; Wu, Yimei; Gibbs, Richard A; Melvin, Pamela; Campeau, Philippe M; Lee, Brendan H

    2013-01-01

    In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5′ untranslated region (5′UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.–14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation. PMID:23408678

  19. Quantitative second-harmonic generation imaging to detect osteogenesis imperfecta in human skin samples

    NASA Astrophysics Data System (ADS)

    Adur, J.; Ferreira, A. E.; D'Souza-Li, L.; Pelegati, V. B.; de Thomaz, A. A.; Almeida, D. B.; Baratti, M. O.; Carvalho, H. F.; Cesar, C. L.

    2012-03-01

    Osteogenesis Imperfecta (OI) is a genetic disorder that leads to bone fractures due to mutations in the Col1A1 or Col1A2 genes that affect the primary structure of the collagen I chain with the ultimate outcome in collagen I fibrils that are either reduced in quantity or abnormally organized in the whole body. A quick test screening of the patients would largely reduce the sample number to be studied by the time consuming molecular genetics techniques. For this reason an assessment of the human skin collagen structure by Second Harmonic Generation (SHG) can be used as a screening technique to speed up the correlation of genetics/phenotype/OI types understanding. In the present work we have used quantitative second harmonic generation (SHG) imaging microscopy to investigate the collagen matrix organization of the OI human skin samples comparing with normal control patients. By comparing fibril collagen distribution and spatial organization, we calculated the anisotropy and texture patterns of this structural protein. The analysis of the anisotropy was performed by means of the two-dimensional Discrete Fourier Transform and image pattern analysis with Gray-Level Co-occurrence Matrix (GLCM). From these results, we show that statistically different results are obtained for the normal and disease states of OI.

  20. Normal Collagen and Bone Production by Gene-targeted Human Osteogenesis Imperfecta iPSCs

    PubMed Central

    Deyle, David R; Khan, Iram F; Ren, Gaoying; Wang, Pei-Rong; Kho, Jordan; Schwarze, Ulrike; Russell, David W

    2012-01-01

    Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease. PMID:22031238

  1. Health outcomes of neonates with osteogenesis imperfecta: a cross-sectional study.

    PubMed

    Yimgang, Doris P; Brizola, Evelise; Shapiro, Jay R

    2016-12-01

    To assess at-birth health outcomes of neonates with osteogenesis imperfecta (OI). A total of 53 women who self-reported having had at least one child with OI completed the survey. We evaluated pregnancy length, neonatal intensive care unit (NICU) usage, at-birth complications, and the child's clinical information including OI type, height and weight. Information was gathered on a total of 77 children (60 type I, 4 type III and 13 type IV). Health conditions reported at birth included breech presentation (24%), prematurity (27%), fracture (18%), bone deformity (18%) and respiratory problems (22%). Approximately 31% (n = 24) received NICU care. There was a significant association between younger maternal age, preterm delivery and NICU admission. Our findings suggest that newborns with OI appear to be at high risk of skeletal disorders, preterm delivery and breech presentation. Younger maternal age and preterm delivery seem to be strong predictors of the need for NICU care. Our data suggest that pregnant women with OI younger than 20 years of age may benefit from added clinical supervision in anticipation of adverse effects on their child.

  2. Microstructural and Photoacoustic Infrared Spectroscopic Studies of Human Cortical Bone with Osteogenesis Imperfecta

    NASA Astrophysics Data System (ADS)

    Gu, Chunju; Katti, Dinesh R.; Katti, Kalpana S.

    2016-04-01

    The molecular basis of bone disease osteogenesis imperfecta (OI) and the mineralization of hydroxyapatite in OI bone have been of significant research interest. To further investigate the mechanism of OI disease and bone mineralization, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, and x-ray diffraction (XRD) are used in the present study to describe the structural and compositional differences between OI and healthy bone. OI bone exhibits more porous, fibrous features, abnormal collagen fibrils, and abnormal mineral deposits. Likewise, photoacoustic-FTIR experiments indicate an aberrant collagen structure and an altered mineral structure in OI. In contrast, there is neither significant difference in the non-collagenous proteins (NCPs) composition observed nor apparent change in the crystal structure between OI and healthy bone minerals as shown in XRD and energy-dispersive x-ray spectroscopy (EDS) results. This observation indicates that the biomineralization process is more controlled by the bone cells and non-collagenous phosphorylated proteins. The present study also confirms that there is an orientational influence on the stoichiometry of the mineral in OI bone. Also, a larger volume of the hydrated layer in the transverse plane than the longitudinal plane of the mineral crystal structure is proposed. The appearance of a new C-S band in the FTIR spectra in OI bone suggests the substitution of glycine by cysteine in collagen molecules or/and an increased amount of cysteine-rich osteonectin that relates to mineral nucleation and mineral crystal formation.

  3. Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta.

    PubMed

    Sinder, Benjamin P; Eddy, Mary M; Ominsky, Michael S; Caird, Michelle S; Marini, Joan C; Kozloff, Kenneth M

    2013-01-01

    Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly→Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in a knock-in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. Copyright © 2013 American Society for Bone and Mineral Research.

  4. Two novel compound heterozygous BMP1 mutations in a patient with osteogenesis imperfecta: a case report.

    PubMed

    Sangsin, Apiruk; Kuptanon, Chulaluck; Srichomthong, Chalurmpon; Pongpanich, Monnat; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

    2017-03-04

    Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia leading to a susceptibility to fractures. OI can be caused by mutations in several genes including BMP1. It encodes two isoforms, bone morphogenetic protein 1 (BMP1) and mammalian tolloid (mTLD); both have proteolytic activity to remove the C-propeptide from procollagen. We report a Thai OI patient who had his first fracture at the age of three months. Using next generation sequencing, we successfully identified two novel compound heterozygous BMP1 mutations. One mutation, c.796_797delTT (p.Phe266Argfs*25) affects both BMP1 and mTLD isoforms, while the other, c.2108-2A > G, affects only the BMP1 isoform. Preservation of the mTLD may explain the relatively less severe clinical phenotype in this patient. Intravenous bisphosphonate was given from the age of 8 months to 5 years. He was free from fractures for 9 months before discontinuation. This case expands the mutation spectrum of BMP1, strengthens the correlation between genotype and phenotype, and supports the benefits of bisphosphonate in OI patients with BMP1 mutations.

  5. Salubrinal improves mechanical properties of the femur in osteogenesis imperfecta mice.

    PubMed

    Takigawa, Shinya; Frondorf, Brian; Liu, Shengzhi; Liu, Yang; Li, Baiyan; Sudo, Akihiro; Wallace, Joseph M; Yokota, Hiroki; Hamamura, Kazunori

    2016-10-01

    Salubrinal is an agent that reduces the stress to the endoplasmic reticulum by inhibiting de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). We and others have previously shown that the elevated phosphorylation of eIF2α stimulates bone formation and attenuates bone resorption. In this study, we applied salubrinal to a mouse model of osteogenesis imperfecta (Oim), and examined whether it would improve Oim's mechanical property. We conducted in vitro experiments using RAW264.7 pre-osteoclasts and bone marrow derived cells (BMDCs), and performed in vivo administration of salubrinal to Oim (+/-) mice. The animal study included two control groups (wildtype and Oim placebo). The result revealed that salubrinal decreased expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) and suppressed osteoclast maturation, and it stimulated mineralization of mesenchymal stem cells from BMDCs. Furthermore, daily injection of salubrinal at 2 mg/kg for 2 months made stiffness (N/mm) and elastic module (GPa) of the femur undistinguishable to those of the wildtype control. Collectively, this study supported salubrinal's beneficial role to Oim's femora. Unlike bisphosphonates, salubrinal stimulates bone formation. For juvenile OI patients who may favor strengthening bone without inactivating bone remodeling, salubrinal may present a novel therapeutic option. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  6. Pregnancy- and lactation-associated transient osteoporosis of both hips in a 32 year old patient with osteogenesis imperfecta.

    PubMed

    Pabinger, C; Heu, C; Frohner, A; Dimai, H P

    2012-07-01

    Combination of osteogenesis imperfecta (OI), pregnancy, and transient osteoporosis (TO) of the hip is rare, only a few cases have been published so far. We report a 32 year old woman with OI, with TO on the right hip in her late third trimester. Non-pharmacological measures such as non-weight-bearing resulted in complete remission. Shortly after weaning, TO of the contralateral hip developed and non-pharmacological measures remained ineffective this time. Under treatment with a prostaglandin I(2) analog (iloprost), i.v. bisphosphonate (pamidronate), calcium and vitamin D supplementation rapid improvement of pain and complete remission was achieved. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. [Early use of BiPAP in the management of respiratory failure in an infant with osteogenesis imperfecta: case report].

    PubMed

    Vega-Briceño, Luis; Contreras, Ilse; Sánchez, Ignacio; Bertrand, Pablo

    2004-07-01

    Osteogenesis imperfecta (OI) is an heterogeneous group of genetic disorders that affect connective tissue integrity. Severe forms cause chest deformities, sometimes associated to alveolar hypoventilation. We report a 4 months old infant with OI type III, who developed respiratory failure (RF) due to a bronchiolitis and required mechanical ventilation. Weaning progressed successfully to a nasal bi-level Positive Airway Pressure (n-BiPAP) device. Clinical follow up showed a normal cognitive development and growth. Respiratory condition, blood gases and ventilation status were in normal ranges. Non invasive ventilation, associated to careful monitoring may avoid tracheostomy and its complications in infants with OI.

  8. Unusual Femur Stress Fractures in Children With Osteogenesis Imperfecta and Intramedullary Rods on Long-term Intravenous Pamidronate Therapy.

    PubMed

    Hegazy, Abdelsalam; Kenawey, Mohamed; Sochett, Etienne; Tile, Lianne; Cheung, Angela M; Howard, Andrew W

    2016-01-01

    In this report, we describe 6 children with osteogenesis imperfecta with unusual stress femoral fractures. All children were on long-term cyclic pamidronate treatment. All fractures occurred without trauma or with minimal trauma and were located in the subtrochanteric or the diaphyseal regions of the femur over preexisting intramedullary rods. These fractures have very similar features to the reported minimal trauma atypical femoral fractures in adults on long-term bisphosphonate treatment. These fractures raise concerns about the role of prolonged remodeling suppression and microdamage accumulation and the risk of increased bone fragility.

  9. A novel COL1A1 mutation in a family with osteogenesis imperfecta associated with phenotypic variabilities

    PubMed Central

    Seto, Toshiyuki; Yamamoto, Toshiyuki; Shimojima, Keiko; Shintaku, Haruo

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous disorder that is characterized by bone fragility and systemic complications, and is mainly caused by gene mutations in COL1A1 or COL1A2. A novel COL1A1 splicing mutation, c.750+2T>A, was identified in a Japanese OI family. Only the proband in this family showed various complications, such as heart valve diseases and severe scoliosis. The clinical heterogeneity in the family is discussed in this study. PMID:28326186

  10. Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta

    NASA Astrophysics Data System (ADS)

    Tehrani, Kayvan F.; Pendleton, Emily G.; Lin, Charles P.; Mortensen, Luke J.

    2016-04-01

    Osteogenesis imperfecta (OI) is a currently uncurable disease where a mutation in collagen type I yields brittle bones. One potential therapy is transplantation of mesenchymal stem cells (MSCs), but controlling and enhancing transplanted cell survival has proven challenging. Therefore, we use a 2- photon imaging system to study individual transplanted cells in the living bone marrow. We ablated cells deep in the bone marrow and observed minimal collateral damage to surrounding tissue. Future work will evaluate the local impact of transplanted MSCs on bone deposition in vivo.

  11. Clinical Aspects, Imaging Features, and Considerations on Bisphosphonate-Related Osteonecrosis Risk in a Pediatric Patient with Osteogenesis Imperfecta

    PubMed Central

    Costa, Fábio Wildson Gurgel; Nogueira, Alexandre Simões; Rodrigues Carvalho, Francisco Samuel; Pereira, Karuza Maria Alves; Kurita, Lúcio Mitsuo; Rodrigues, Rodrigo Rodrigues; Fonteles, Cristiane Sá Roriz

    2014-01-01

    Osteogenesis imperfecta (OI) is a rare hereditary condition caused by changes in collagen metabolism. It is classified into four types according to clinical, genetic, and radiological criteria. Clinically, bone fragility, short stature, blue sclerae, and locomotion difficulties may be observed in this disease. OI is often associated to severe dental problems, such as dentinogenesis imperfecta (DI) and malocclusions. Radiographically, affected teeth may have crowns with bulbous appearance, accentuated constriction in the cementoenamel junction, narrowed roots, large root canals due to defective dentin formation, and taurodontism (enlarged pulp chambers). There is no definitive cure, but bisphosphonate therapy is reported to improve bone quality; however, there is a potential risk of bisphosphonate-related osteonecrosis of the jaw. In this study we report a case of OI in a male pediatric patient with no family history of OI who was receiving ongoing treatment with intravenous perfusion of bisphosphonate and who required dental surgery. In addition, we discussed the clinical and imaging findings and briefly reviewed the literature. PMID:25215248

  12. Specific entities affecting the craniocervical region: osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management of basilar impression.

    PubMed

    Menezes, Arnold H

    2008-10-01

    Osteogenesis imperfecta (OI) is an inheritable disorder of bone development caused by defective collagen synthesis. The attendant basilar impression or secondary basilar invagination is uncommon but can be devastating. Fifty-two patients with osteochondrodysplasia (28 with OI, six with Hajdu-Cheney syndrome, six with Paget's disease, and 12 with spondyloepiphyseal dysplasia) with basilar impression were evaluated between 1985 and 2005. The male/female ratio in this cohort was 1:1. The mean age at presentation was 12.2 years. Symptoms and signs included headache, lower cranial nerve dysfunction, dysphagia, respiratory embarrassment, weakness, and ataxia. In the earlier part of the series (1985-1995), all patients with hydrocephalus were shunted and a ventral transoral decompression made for ventral compression of the pontomedullary junction followed by a dorsal occipitocervical fusion. As a result of this evaluation, it was felt that most patients would benefit by early bracing after the hydrocephalus was shunted if it existed. However, 20% of patients still required an anterior ventral decompression and the occipitocervical fusion. The results showed that the fusions were stable but over a period of time, there was progressive forward bending with osteogenesis imperfecta as well as with the Hajdu-Cheney syndrome. All patients with spondyloepiphyseal dysplasia had a good strong stable fusion which stood the test of time. In conclusion, we feel that early intervention with occipitocervical bracing can prevent the progressive march of significant basilar impression which leads to mortality.

  13. [Mutation analysis and prenatal diagnosis of COL1A1 gene in a Chinese family with type I osteogenesis imperfecta].

    PubMed

    Zhang, Hui; Wu, Dong; Hou, Qiaofang; Liu, Zhiyou; Qin, Litao; Liao, Shixiu

    2014-12-01

    To detect mutation of COL1A1 gene in a Chinese family affected with type I osteogenesis imperfecta (OI) and to provide prenatal diagnosis for a fetus at 17th gestational week. Polymerase chain reaction, DNA sequencing and restriction endonuclease analysis were used to verify the detected mutation among other members of the family and 100 healthy controls. No mutation has been detected in the COL1A2 gene in all of the subjects. A heterozygous mutation c.104-1G>C was identified in the COL1A1 gene among all patients from this family. The same mutation was not found in other members from the family and the 100 healthy controls. The mutation was not found in the fetus, and was verified to be a new mutation according to the type I collagen mutation database. The c.104-1G>C mutation of the COL1A1 gene probably underlies the type I osteogenesis imperfecta in this family. Under the premise of a clear genetic diagnosis, prenatal diagnosis may be provided to reduce the risk for the disease.

  14. Osteogenesis imperfecta Type VI with severe bony deformities caused by novel compound heterozygous mutations in SERPINF1.

    PubMed

    Cho, Sung Yoon; Ki, Chang-Seok; Sohn, Young Bae; Kim, Su Jin; Maeng, Se Hyun; Jin, Dong-Kyu

    2013-07-01

    Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

  15. Osteogenesis Imperfecta Type VI with Severe Bony Deformities Caused by Novel Compound Heterozygous Mutations in SERPINF1

    PubMed Central

    Cho, Sung Yoon; Ki, Chang-Seok; Sohn, Young Bae; Kim, Su Jin; Maeng, Se Hyun

    2013-01-01

    Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1. PMID:23853499

  16. Fluoroscopy-guided Sacroiliac Joint Steroid Injection for Low Back Pain in a Patient with Osteogenesis Imperfecta

    PubMed Central

    Dawson, PUA; Rose, REC; Wade, NA

    2015-01-01

    ABSTRACT Background: Osteogenesis imperfecta, also known as ‘brittle bone disease’, is a genetic connective tissue disease. It is characterized by bone fragility and osteopenia (low bone density). In this case, a 57-year old female presented to the University Hospital of the West Indies (UHWI), Physical Medicine and Rehabilitation Clinic with left low back pain rated 6/10 on the numeric rating scale (NRS). Clinically, the patient had sacroiliac joint-mediated pain although X-rays did not show the sacroiliac joint changes. Fluoroscopy-guided left sacroiliac joint steroid injection was done. Methods: Numeric rating scale and Oswestry Disability Index (ODI) questionnaire were used to evaluate outcome. This was completed at baseline, one week follow-up and at eight weeks post fluoroscopy-guided sacroiliac joint steroid injection. Results: Numeric rating scale improved from 6/10 before the procedure to 0/10 post procedure, and ODI questionnaire score improved from a moderate disability score of 40% to a minimal disability score of 13%. Up to eight weeks, the NRS was 0/10 and ODI remained at minimal disability of 15%. Conclusion: Fluoroscopy-guided sacroiliac joint injection is a known diagnostic and treatment method for sacroiliac joint mediated pain. To our knowledge, this is the first case published on the use of fluoroscopy-guided sacroiliac joint steroid injection in the treatment of sacroiliac joint mediated low back pain in a patient with osteogenesis imperfecta. PMID:26624601

  17. An unusual pattern of peptide-bound lysine metabolism in collagen from an infant with lethal perinatal osteogenesis imperfecta.

    PubMed Central

    Petrovic, O M; Miller, E J

    1984-01-01

    Collagens extracted from bones, cartilage, dermis, and dura mater of an infant with type II (lethal perinatal) osteogenesis imperfecta were evaluated with respect to chain composition and chemical characteristics of their constituent chains. The results indicated that the various types of collagen were present in the indicated tissues in proportions that approximated normal tissues. Nevertheless, the constituent chains of collagens extracted from dermis, i.e., alpha 1(I), alpha 2(I), alpha 1(III), alpha 1(V), and alpha 2(V), chromatographed on carboxymethyl cellulose as though they possessed substantially lower overall positive charge than the homologous chains of normal tissues. Amino acid analyses of the chains confirmed this observation and showed that the chains lacked five to seven residues of lysine (plus hydroxylysine). It was subsequently shown that the apparent deficiency in lysyl residues was due, at least in part, to the presence of unusually high levels of allysine , a cross-link precursor formed from peptide-bound lysine under the catalytic action of lysyl oxidase. These results, in conjunction with previous results obtained on collagens from type II osteogenesis imperfecta tissues, suggest that aberrant fibril formation in this syndrome allows increased lysyl oxidase activity. Images PMID:6427276

  18. A Cross-sectional Multicenter Study of Osteogenesis Imperfecta in North America – Results from the Linked Clinical Research Centers

    PubMed Central

    Patel, Ronak M; Nagamani, Sandesh CS; Cuthbertson, David; Campeau, Philippe M; Krischer, Jeffrey P; Shapiro, Jay R; Steiner, Robert D; Smith, Peter A; Bober, Michael B; Byers, Peter H; Pepin, Melanie; Durigova, Michaela; Glorieux, Francis H; Rauch, Frank; Lee, Brendan H; Smith, Tracy; Sutton, V. Reid

    2017-01-01

    Osteogenesis Imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n=544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean LS aBMD was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answer questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of “phenotypic expansion” driven by next-generation sequencing. PMID:24754836

  19. WHOLE-BODY VIBRATION EXERCISE IMPROVES FUNCTIONAL PARAMETERS IN PATIENTS WITH OSTEOGENESIS IMPERFECTA: A SYSTEMATIC REVIEW WITH A SUITABLE APPROACH.

    PubMed

    Sá-Caputo, Danubia C; Dionello, Carla da F; Frederico, Éric Heleno F F; Paineiras-Domingos, Laisa L; Sousa-Gonçalves, Cintia Renata; Morel, Danielle S; Moreira-Marconi, Eloá; Unger, Marianne; Bernardo-Filho, Mario

    2017-01-01

    Patients with osteogenesis imperfecta (OI) have abnormal bone modelling and resorption. The bone tissue adaptation and responsivity to dynamic and mechanical loading may be of therapeutic use under controlled circumstances. Improvements due to the wholebody vibration (WBV) exercises have been reported in strength, motion, gait, balance, posture and bone density in several osteopenic individuals, as in post-menopausal women or children with disabling conditions, as patients with OI. The aim of this investigation was to systematically analyse the current available literature to determine the effect of WBV exercises on functional parameters of OI patients. Three reviewers independently accessed bibliographical databases. Searches were performed in the PubMed, Scopus, Science Direct and PEDro databases using keywords related to possible interventions (including WBV) used in the management of patients with osteogenesis imperfecta. Three eligible studies were identified by searches in the analysed databases. It was concluded that WBV exercises could be an important option in the management of OI patients improving the mobility and functional parameters. However, further studies are necessary for establishing suitable protocols for these patients.

  20. A novel homozygous variant in SERPINH1 associated with a severe, lethal presentation of osteogenesis imperfecta with hydranencephaly.

    PubMed

    Marshall, Charlotte; Lopez, Jaime; Crookes, Laura; Pollitt, Rebecca C; Balasubramanian, Meena

    2016-12-20

    Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance. However, within the last two decades, there have been growing number of variants identified in genes that follow an autosomal recessive pattern of inheritance. Our proband is a child born in Mexico with multiple fractures of ribs, minimal calvarial mineralisation, platyspondyly, marked compression and deformed long bones. He also presented with significant hydranencephaly, requiring ventilatory support from birth, and died at 8days of age. A homozygous c.338_357delins22 variant in exon 2 of SERPINH1 was identified. This gene encodes heat shock protein 47, a collagen-specific chaperone which binds to the procollagen triple helix and is responsible for collagen stabilisation in the endoplasmic reticulum. There is minimal literature on the mechanism of action for variants in SERPINH1 resulting in osteogenesis imperfecta. Here we discuss this rare, previously unreported variant, and expand on the phenotypic presentation of this novel variant resulting in a severe, lethal phenotype of OI in association with hydranencephaly. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

    PubMed

    Patel, R M; Nagamani, S C S; Cuthbertson, D; Campeau, P M; Krischer, J P; Shapiro, J R; Steiner, R D; Smith, P A; Bober, M B; Byers, P H; Pepin, M; Durigova, M; Glorieux, F H; Rauch, F; Lee, B H; Hart, T; Sutton, V R

    2015-02-01

    Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Evaluation of a Modified Pamidronate Protocol for the Treatment of Osteogenesis Imperfecta.

    PubMed

    Palomo, Telma; Andrade, Maria C; Peters, Barbara S E; Reis, Fernanda A; Carvalhaes, João Tomás A; Glorieux, Francis H; Rauch, Frank; Lazaretti-Castro, Marise

    2016-01-01

    Intravenous pamidronate is widely used to treat children with osteogenesis imperfecta (OI). In a well-studied protocol ('standard protocol'), pamidronate is given at a daily dose of 1 mg per kg body weight over 4 h on 3 successive days; infusion cycles are repeated every 4 months. Here, we evaluated renal safety of a simpler protocol for intravenous pamidronate infusions (2 mg per kg body weight given in a single infusion over 2 h, repeated every 4 months; 'modified protocol'). Results of 18 patients with OI types I, III, or IV treated with the modified protocol for 12 months were compared to 18 historic controls, treated with standard protocol. In the modified protocol, mild transient post-infusion increases in serum creatinine were found during each infusion but after 12 months serum creatinine remained similar from baseline [0.40 mg/dl (SD: 0.13)] to the end of the study [0.41 mg/dl (SD: 0.11)] (P = 0.79). The two protocols led to similar changes in serum creatinine during the first pamidronate infusion [modified protocol: +2% (SD: 21%); standard protocol: -3% (SD: 8%); P = 0.32]. Areal lumbar spine bone mineral density Z-scores increased from -2.7 (SD: 1.5) to -1.8 (SD: 1.4) with the modified protocol, and from -4.1 (SD: 1.4) to -3.1 (SD: 1.1) with standard protocol (P = 0.68 for group differences in bone density Z-score changes). The modified pamidronate protocol is safe and may have similar effects on bone density as the standard pamidronate protocol. More studies are needed with longer follow-up to prove anti-fracture efficacy.

  3. Association between spondylolisthesis and L5 fracture in patients with Osteogenesis Imperfecta.

    PubMed

    Persiani, Pietro; Graci, Jole; de Cristo, Claudia; Noia, Giovanni; Villani, Ciro; Celli, Mauro

    2015-01-01

    To investigate if an association between spondylolisthesis and L5 fracture occurs in patients affected by Osteogenesis Imperfecta (O.I.). Anteroposterior and lateral radiograms were performed on the sample (38 O.I. patients, of whom 19 presenting listhesis); on imaging studies spondylolisthesis was quantified according to the Meyerding classification. Genant's semiquantitative classification was applied on lateral view to evaluate the L5 fractures; skeleton spinal morphometry (MXA) was carried out on the same images to collect quantitative data comparable and superimposable to Genant's classification. The gathered information were analyzed through statistical tests (O.R., χ (2) test, Fisher's test, Pearson's correlation coefficient). The prevalence of L5 fractures is 73.7 % in O.I. patients with spondylolisthesis and their risk of experiencing such a fracture is twice than O.I. patients without listhesis (OR 2.04). Pearson's χ (2) test demonstrates an association between L5 spondylolisthesis and L5 fracture, especially with moderate, posterior fractures (p = 0.017) and primarily in patients affected by type IV O.I. Spondylolisthesis represents a risk factor for the development of more severe and biconcave/posterior type fractures of L5 in patients suffering from O.I., especially in type IV. This fits the hypothesis that the anterior sliding of the soma of L5 alters the dynamics of action of the load forces, localizing them on the central and posterior heights that become the focus of the stress due to movement of flexion-extension and twisting of the spine. As a result, there is greater probability of developing an important subsidence of the central and posterior walls of the soma.

  4. Surgical Treatment With Pedicle Screws of Scoliosis Associated With Osteogenesis Imperfecta in Children.

    PubMed

    Piantoni, Lucas; Noel, Mariano A; Francheri Wilson, Ida A; Tello, Carlos A; Galaretto, Eduardo; Remondino, Rodrigo G; Bersusky, Ernesto S

    2017-09-01

    Retrospective study. To assess results of posterior instrumented fusion using pedicle screws in 12 children with osteogenesis imperfecta (OI) with spinal deformity at a single institution from 2001 to 2012. This is the first case series of OI patients who underwent non-cement augmented screw-rod instrumented fusion published in the literature. Of a total of 54 children with spinal deformity associated with OI, 12 (22.2%) were submitted to posterior spinal fusion with pedicle screws (80% density) because of severe spinal deformity. Here we reported the results in seven females and five males. Five thoracic (41.7%), five double (thoracic and lumbar 41.7%), and two lumbar (16.7%) curves were considered. The mean number of fused levels was 11.8 (range: 5 to 16). Mean age at surgery was 13 years 8 months. Mean follow-up was 7 years 11 months (range: 3 years 7 months to 16 years 1 month). The mean preoperative scoliosis angle was 75.6°, whereas the postoperative angle was 31.4° (58.5% correction rate). The mean preoperative kyphosis angle was 57.4° and the postoperative angle was 42.3°. We observed one superficial infection, one dural tear, and three cases of proximal junctional kyphosis; two patients required one revision surgery each (2 years and 4 months postoperatively on average). To our knowledge, this is the first case series published in the literature regarding OI with instrumented fusion with non-cement augmented pedicle screws exclusively in children with spinal deformity. We found that posterior spinal fusion with the screw-rod system in OI deformity in children is feasible and reliable, and has acceptable clinical and imaging results in the long-term follow-up. Level IV. Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  5. Molecular spectrum and differential diagnosis in patients referred with sporadic or autosomal recessive osteogenesis imperfecta.

    PubMed

    Caparros-Martin, Jose A; Aglan, Mona S; Temtamy, Samia; Otaify, Ghada A; Valencia, Maria; Nevado, Julián; Vallespin, Elena; Del Pozo, Angela; Prior de Castro, Carmen; Calatrava-Ferreras, Lucia; Gutierrez, Pilar; Bueno, Ana M; Sagastizabal, Belen; Guillen-Navarro, Encarna; Ballesta-Martinez, Maria; Gonzalez, Vanesa; Basaran, Sarenur Y; Buyukoglan, Ruksan; Sarikepe, Bilge; Espinoza-Valdez, Cecilia; Cammarata-Scalisi, Francisco; Martinez-Glez, Victor; Heath, Karen E; Lapunzina, Pablo; Ruiz-Perez, Victor L

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations in COL1A1 or COL1A2 and show autosomal dominant inheritance, during the last years there has been an explosion in the number of genes responsible for both recessive and dominant forms of this condition. Herein, we have analyzed a cohort of patients with OI, all offspring of unaffected parents, to determine the spectrum of variants accounting for these cases. Twenty patients had nonrelated parents and were sporadic, and 21 were born to consanguineous relationships. Mutation analysis was performed using a next-generation sequencing gene panel, homozygosity mapping, and whole exome sequencing (WES). Patients offspring of nonconsanguineous parents were mostly identified with COL1A1 or COL1A2 heterozygous changes, although there were also a few cases with IFITM5 and WNT1 heterozygous mutations. Only one sporadic patient was a compound heterozygote for two recessive mutations. Patients offspring of consanguineous parents showed homozygous changes in a variety of genes including CRTAP,FKBP10,LEPRE1,PLOD2,PPIB,SERPINF1,TMEM38B, and WNT1. In addition, two patients born to consanguineous parents were found to have de novo COL1A1 heterozygous mutations demonstrating that causative variants in the collagen I structural genes cannot be overlooked in affected children from consanguineous couples. Further to this, WES analysis in probands lacking mutations in OI genes revealed deleterious variants in SCN9A,NTRK1, and SLC2A2, which are associated with congenital indifference to pain (CIP) and Fanconi-Bickel syndrome (FBS). This work provides useful information for clinical and genetic diagnosis of OI patients with no positive family history of this disease. Our data also indicate that CIP and FBS are conditions to be considered in the differential diagnosis of OI and suggest a positive role of SCN9A and NTRK1 in bone development.

  6. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta

    SciTech Connect

    Orioli, I.M.; Castilla, E.E.; Scarano, G.; Mastroiacovo, P.

    1995-11-06

    The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite (IPIMC) and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congenitas (ECLAMC) series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 {plus_minus} 6.74 years in the IPIMC, and 37.19 {plus_minus} 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 {plus_minus} 7.08 years in the IPIMC, and 36.41 {plus_minus} 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 {plus_minus} 9.25 years, but not in the IPIMC, 32.26 {plus_minus} 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area. 28 refs., 1 fig., 6 tabs.

  7. Decrease in serum FGF23 levels after intravenous infusion of pamidronate in patients with osteogenesis imperfecta.

    PubMed

    Kitaoka, Taichi; Namba, Noriyuki; Miura, Kohji; Kubota, Takuo; Ohata, Yasuhisa; Fujiwara, Makoto; Hirai, Haruhiko; Yamamoto, Takehisa; Ozono, Keiichi

    2011-09-01

    Fibroblast growth factor 23 (FGF23) plays a central role in phosphate (P) homeostasis. However, the precise mechanism of how FGF23 secretion is regulated remains to be elucidated. In the present study, we examined the effect of intravenous pamidronate administration on serum levels of FGF23. Thirteen patients with osteogenesis imperfecta were treated with two cycles of 3-day pamidronate infusion. Blood samples at pre- and post-drip pamidronate infusion were evaluated for serum calcium, P, intact PTH (iPTH), 1,25(OH)(2)D, intact FGF23 (FGF23), type I collagen cross-linked N-telopeptides (NTx), bone-specific alkaline phosphatase (BAP), and TmP/GFR. During the two cycles, FGF23 levels decreased significantly preceding the decline in P levels. Although the change in P levels became less apparent during the second cycle, the reduction in FGF23 levels was similar during both cycles. Moreover, absence of correlation between FGF23 and P indicates that FGF23 attenuation is independent of the decrease in P levels during pamidronate infusion. Significant correlation between NTx suppression and the decrease in FGF23 levels during the 1st cycle (r = 0.665, P = 0.013) suggests that inhibition of osteoclast function may have some role in suppressing FGF23 levels. Because pamidronate dose was most associated with the decrease in FGF23 levels during the second cycle, pamidronate may directly attenuate osteocyte/osteoblast-mediated FGF23 production. This is the first evidence of a rapid fall in FGF23 levels following pamidronate infusion, raising the possibility that inhibition of bone resorption and/or direct effects of pamidronate may suppress secretion of FGF23.

  8. Pamidronate alters the growth plate in the oim mouse model for osteogenesis imperfecta.

    PubMed

    Evans, K D; Sheppard, L E; Rao, S H; Martin, R B; Oberbauer, A M

    2009-12-01

    Bisphosphonates alleviate bone pain and fractures associated with osteogenesis imperfecta (OI). Using the oim mouse model to simulate variations in OI severity, the effect of pamidronate on bone growth was assessed. Homozygous (oim/oim) and heterozygous (oim/wt) mice from 4 to 12 weeks of age were given pamidronate at 0 mg/kg/wk (control), 1.25 mg/kg/wk (low) and 2.5 mg/kg/wk (high). Humerus and ulna lengths were reduced in oim/oim mice relative to those of the oim/wt. Further, the oim/oim genotype exhibited a 23.5% prevalence of fractures in these bones as compared to the 2.8% prevalence observed in the oim/wt mice. Pamidronate tended to reduce fracture prevalence in a dose dependent manner for the oim/oim genotype (p<0.08) but had no effect on the low fracture prevalence in oim/wtmice. The high dose of pamidronate reduced bone length in females of both genotypes but not males when compared to control (p<0.01). Pamidronate increased growth plate area (p<0.05) by increasing growth plate height, particularly the proliferative and hypertrophic zones, in both genotypes indicating reduced growth plate cell turnover. The increased area coincided with increased osteoclast numbers in the metaphyseal region (p<0.05) though when corrected for the greater mineralized surface area that accompanies bisphosphonate treatment, osteoclasts per surface area were reduced indicating reduced resorptive capacity. This study demonstrated that the effects of pamidronate were independent of the degree of collagen deficit and fracture prevalence was improved in the most severe OI model, the oim/oim genotype.

  9. Prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta associated with unaffected parents and paternal gonadal mosaicism.

    PubMed

    Chen, Chih-Ping; Lin, Shuan-Pei; Su, Yi-Ning; Chern, Schu-Rern; Su, Jun-Wei; Wang, Wayseen

    2013-03-01

    To present the prenatal diagnosis of recurrent autosomal dominant osteogenesis imperfecta (OI) associated with unaffected parents and paternal gonadal mosaicism. A 37-year-old woman was referred for genetic counseling at 18 weeks of gestation because of advanced maternal age and a family history of OI. The woman had a daughter who was affected with OI type III and carried an insertion frameshift mutation of c.4308_4309insA in exon 52 of the COL1A1 gene. The woman and her husband were non-consanguineous and healthy. Amniocentesis was performed at 18 weeks of gestation. Cytogenetic analysis revealed a karyotype of 46,XX. Molecular analysis of the amniocytes revealed a recurrent mutation of c.4308_4309insA in exon 52 of the COL1A1 gene. Mutational analysis of the family revealed no mutation of the COL1A1 gene in the parental bloods. However, mosaicism for the COL1A1 mutation was found in the paternal sperms. Level II ultrasound examination showed a curved right tibia, a narrow chest with irregular ribs and mild frontal bossing in the fetus. The parents decided to terminate the pregnancy, and a female fetus was delivered at 23 weeks of gestation with curved long bones. Recurrent autosomal dominant OI may occur in the offspring of unaffected parents with parental gonadal mosaicism. Genetic counseling of recurrent autosomal dominant OI should include a thorough mutational analysis of the family members, and mutational analysis of the sperm may detect paternal gonadal mosaicism for the mutation. Copyright © 2013. Published by Elsevier B.V.

  10. COL1 C-propeptide Cleavage Site Mutations Cause High Bone Mass Osteogenesis Imperfecta

    PubMed Central

    Lindahl, Katarina; Barnes, Aileen M.; Fratzl-Zelman, Nadja; Whyte, Michael P.; Hefferan, Theresa E.; Makareeva, Elena; Brusel, Marina; Yaszemski, Michael J.; Rubin, Carl-Johan; Kindmark, Andreas; Roschger, Paul; Klaushofer, Klaus; McAlister, William H.; Mumm, Steven; Leikin, Sergey; Kessler, Efrat; Boskey, Adele L.; Ljunggren, Östen; Marini, Joan C.

    2011-01-01

    Osteogenesis imperfecta (OI) is most often caused by mutations in the type I procollagen genes (COL1A1/COL1A2). We identified two children with substitutions in the type I procollagen C-propeptide cleavage site, which disrupt a unique processing step in collagen maturation and define a novel phenotype within OI. The patients have mild OI caused by mutations in COL1A1 (Patient 1: p.Asp1219Asn) or COL1A2 (Patient 2: p.Ala1119Thr), respectively. Patient 1 L1-L4 DXA z-score was +3.9 and pQCT vBMD was +3.1; Patient 2 had L1-L4 DXA z-score of 0.0 and pQCT vBMD of −1.8. Patient BMD contrasts with radiographic osteopenia and histomorphometry without osteosclerosis. Mutant procollagen processing is impaired in pericellular and in vitro assays. Patient dermal collagen fibrils have irregular borders. Incorporation of pC-collagen into matrix leads to increased bone mineralization. FT-IR imaging confirms elevated mineral/matrix ratios in both patients, along with increased collagen maturation in trabecular bone, compared to normal or OI controls. Bone mineralization density distribution revealed a marked shift toward increased mineralization density for both patients. Patient 1 has areas of higher and lower bone mineralization than controls; Patient 2’s bone matrix has a mineral content exceeding even classical OI bone. These patients define a new phenotype of high BMD OI and demonstrate that procollagen C-propeptide cleavage is crucial to normal bone mineralization. PMID:21344539

  11. Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta.

    PubMed

    Balasubramanian, Meena; Cartwright, Ashley; Smith, Kath; Arundel, Paul; Bishop, Nicholas J

    2016-02-01

    We report a sibling-pair and a 4-year old child from two families with an atypical presentation in Osteogenesis imperfecta (OI). In the sib-pair, the older sibling initially came to medical attention due to a fracture history (Patient 1) and she was shown to have a COL1A2 mutation. In addition, she also had developmental delay, facial dysmorphism, and a history of frequent infections which led to a search for an alternate diagnosis. ArrayCGH revealed a 4.3 Mb duplication on chromosome 19q13.42q13.43, which was confirmed by FISH analysis. On further familial analysis, the younger sibling who had no previous fracture history was also found to have the COL1A2 mutation and tested positive for the 19q13.42q13.43 duplication (Patient 2). The 19q13 duplication appears to be the cause of intellectual disability in these siblings but given that this is a chromosomal duplication, it is still possible that there is an as yet unidentified cause that may account for the combined phenotype in this family. Patient 3 was a 4-year old child presenting with a femoral fracture, blue sclerae, developmental delay, and joint hypermobility. Genetic analyses confirmed a COL1A2 mutation but also revealed an 8.8 Mb deletion of 11q24.2q25, confirmed by G-band chromosome analysis. We discuss the differing phenotypes in patients presenting with atypical OI and stress the need to consider ancillary investigations in individuals presenting with heterogeneous phenotypic symptoms, not entirely attributable to OI.

  12. Null mutations in LEPRE1 and CRTAP cause severe recessive osteogenesis imperfecta.

    PubMed

    Marini, Joan C; Cabral, Wayne A; Barnes, Aileen M

    2010-01-01

    Classical osteogenesis imperfecta (OI) is a dominant genetic disorder of connective tissue caused by mutations in either of the two genes encoding type I collagen, COL1A1 and COL1A2. Recent investigations, however, have generated a new paradigm for OI incorporating many of the prototypical features that distinguish dominant and recessive conditions, within a type I collagen framework. We and others have shown that the long-sought cause of the recessive form of OI, first postulated in the Sillence classification, lies in defects in the genes encoding cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1 (P3H1/LEPRE1). Together with cyclophilin B (PPIB), CRTAP and P3H1 comprise the collagen prolyl 3-hydroxylation complex, which catalyzes a specific posttranslational modification of types I, II, and V collagen, and may act as a general chaperone. Patients with mutations in CRTAP or LEPRE1 have a lethal to severe osteochondrodystrophy that overlaps with Sillence types II and III OI but has distinctive features. Infants with recessive OI have white sclerae, undertubulation of the long bones, gracile ribs without beading, and a small to normal head circumference. Those who survive to childhood or the teen years have severe growth deficiency and extreme bone fragility. Most causative mutations result in null alleles, with the absence or severe reduction of gene transcripts and proteins. As expected, 3-hydroxylation of the Pro986 residue is absent or severly reduced, but bone severity and survival length do not correlate with the extent of residual hydroxylation. Surprisingly, the collagen produced by cells with an absence of Pro986 hydroxylation has helical overmodification by lysyl hydroxylase and prolyl 4-hydroxylase, indicating that the folding of the collagen helix has been substantially delayed.

  13. Tracing the pathway between mutation and phenotype in osteogenesis imperfecta: Isolation of mineralization-specific genes

    SciTech Connect

    Culbert, A.A.; Wallis, G.A.; Kadler, K.E.

    1996-05-03

    The brittleness of bone in people with lethal (type II) osteogenesis imperfecta, a heritable disorder caused by mutations in the type I collagen genes, arises from the deposition of abnormal collagen in the bone matrix. The inability of the abnormal collagen to participate in mineralization may be caused by its failure to interact with other bone proteins. Here, we have designed a strategy to isolate the genes important for mineralization of collagen during bone formation. Cells isolated from 16-day embryonic chick calvaria and seeded post-confluence in culture deposited a mineralized matrix over a period of 2 weeks. Chick skin fibroblasts seeded and cultured under the same conditions did not mineralize. Using RT-PCR, we prepared short cDNAs ({approximately}300 bp) corresponding to the 3{prime} ends of mRNA from fibroblasts and separately from the mineralizing calvarial cells. Subtractive cDNA hybridization generated a pool of cDNAs that were specific to mineralizing calvarial cells but not to fibroblasts. Screening of 100,000 plaques of a chick bone ZAP Express cDNA library with this pool of mineralizing-specific cDNAs identified ten clones which comprised full-length cDNAs for the bone proteins osteopontin (eight of the ten positives), bone sialoprotein II (one of the ten positives), and cystatin (one of the ten positives). cDNAs for type I collagen, fibronectin, alkaline phosphatase, house-keeping genes, and other genes expressed in fibroblasts were not identified in this preliminary screen. The pool of short cDNAs is likely to comprise cDNAs for further bone-specific genes and will be used to screen the entire bone cDNA library of 4.2 million clones. 30 refs., 4 figs.

  14. Induced ablation of Bmp1 and Tll1 produces osteogenesis imperfecta in mice

    PubMed Central

    Muir, Alison M.; Ren, Yinshi; Butz, Delana Hopkins; Davis, Nicholas A.; Blank, Robert D.; Birk, David E.; Lee, Se-Jin; Rowe, David; Feng, Jian Q.; Greenspan, Daniel S.

    2014-01-01

    Osteogenesis imperfecta (OI), or brittle bone disease, is most often caused by dominant mutations in the collagen I genes COL1A1/COL1A2, whereas rarer recessive OI is often caused by mutations in genes encoding collagen I-interacting proteins. Recently, mutations in the gene for the proteinase bone morphogenetic 1 (BMP1) were reported in two recessive OI families. BMP1 and the closely related proteinase mammalian tolloid-like 1 (mTLL1) are co-expressed in various tissues, including bone, and have overlapping activities that include biosynthetic processing of procollagen precursors into mature collagen monomers. However, early lethality of Bmp1- and Tll1-null mice has precluded use of such models for careful study of in vivo roles of their protein products. Here we employ novel mouse strains with floxed Bmp1 and Tll1 alleles to induce postnatal, simultaneous ablation of the two genes, thus avoiding barriers of Bmp1−/− and Tll1−/− lethality and issues of functional redundancy. Bones of the conditionally null mice are dramatically weakened and brittle, with spontaneous fractures—defining features of OI. Additional skeletal features include osteomalacia, thinned/porous cortical bone, reduced processing of procollagen and dentin matrix protein 1, remarkably high bone turnover and defective osteocyte maturation that is accompanied by decreased expression of the osteocyte marker and Wnt-signaling inhibitor sclerostin, and by marked induction of canonical Wnt signaling. The novel animal model presented here provides new opportunities for in-depth analyses of in vivo roles of BMP1-like proteinases in bone and other tissues, and for their roles, and for possible therapeutic interventions, in OI. PMID:24419319

  15. Abnormal type I collagen metabolism by cultured fibroblasts in lethal perinatal osteogenesis imperfecta.

    PubMed Central

    Bateman, J F; Mascara, T; Chan, D; Cole, W G

    1984-01-01

    Cultured skin fibroblasts from seven consecutive cases of lethal perinatal osteogenesis imperfecta (OI) expressed defects of type I collagen metabolism. The secretion of [14C]proline-labelled collagen by the OI cells was specifically reduced (51-79% of control), and collagen degradation was increased to twice that of control cells in five cases and increased by approx. 30% in the other two cases. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed that four of the OI cell lines produced two forms of type I collagen consisting of both normally and slowly migrating forms of the alpha 1(I)- and alpha 2(I)-chains. In the other three OI cell lines only the 'slow' alpha (I)'- and alpha 2(I)'-chains were detected. In both groups inhibition of the post-translational modifications of proline and lysine resulted in the production of a single species of type I collagen with normal electrophoretic migration. Proline hydroxylation was normal, but the hydroxylysine contents of alpha 1(I)'- and alpha 2(I)'-chains purified by h.p.l.c. were greater than in control alpha-chains. The glucosylgalactosylhydroxylysine content was increased approx. 3-fold while the galactosylhydroxylysine content was only slightly increased in the alpha 1(I)'-chains relative to control alpha 1(I)-chains. Peptide mapping of the CNBr-cleavage peptides provided evidence that the increased post-translational modifications were distributed throughout the alpha 1(I)'- and alpha 2(I)'-chains. It is postulated that the greater modification of these chains was due to structural defects of the alpha-chains leading to delayed helix formation. The abnormal charge heterogeneity observed in the alpha 1 CB8 peptide of one patient may reflect such a structural defect in the type I collagen molecule. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:6421277

  16. Intrafibrillar Mineral May be Absent in Dentinogenesis Imperfecta Type II (DI-II)

    SciTech Connect

    Pople, John A.

    2001-03-29

    High-resolution synchrotron radiation computed tomography (SRCT) and small angle x-ray scattering (SAXS) were performed on normal and dentinogenesis imperfecta type II (DI-II) teeth. Three normal and three DI-II human third molars were used in this study. The normal molars were unerupted and had intact enamel; donors were female and ranged in age from 18-21y. The DI-II specimens, which were also unerupted with intact enamel, came from a single female donor age 20y. SRCT showed that the mineral concentration was 33% lower on average in the DI-II dentin with respect to normal dentin. The SAXS spectra from normal dentin exhibited low-angle diffraction peaks at harmonics of 67.6 nm, consistent with nucleation and growth of the apatite phase within gaps in the collagen fibrils (intrafibrillar mineralization). In contrast, the low-angle peaks were almost nonexistent in the DI-II dentin. Crystallite thickness was independent of location in both DI-II and normal dentin, although the crystallites were significantly thicker in DI-II dentin (6.8 nm (s.d. = 0.5) vs 5.1 nm (s.d. = 0.6)). The shape factor of the crystallites, as determined by SAXS, showed a continuous progression in normal dentin from roughly one-dimensional (needle-like) near the pulp to two-dimensional (plate-like) near the dentin-enamel junction. The crystallites in DI-II dentin, on the other hand, remained needle-like throughout. The above observations are consistent with an absence of intrafibrillar mineral in DI-II dentin.

  17. Local transplantation is an effective method for cell delivery in the osteogenesis imperfecta murine model.

    PubMed

    Pauley, Penelope; Matthews, Brya G; Wang, Liping; Dyment, Nathaniel A; Matic, Igor; Rowe, David W; Kalajzic, Ivo

    2014-09-01

    Osteogenesis imperfecta is a serious genetic disorder that results from improper type I collagen production. We aimed to evaluate whether bone marrow stromal cells (BMSC) delivered locally into femurs were able to engraft, differentiate into osteoblasts, and contribute to formation of normal bone matrix in the osteogenesis imperfect murine (oim) model. Donor BMSCs from bone-specific reporter mice (Col2.3GFP) were expanded in vitro and transplanted into the femoral intramedullary cavity of oim mice. Engraftment was evaluated after four weeks. We detected differentiation of donor BMSCs into Col2.3GFP+ osteoblasts and osteocytes in cortical and trabecular bone of transplanted oim femurs. New bone formation was detected by deposition of dynamic label in the proximity to the Col2.3GFP+ osteoblasts, and new bone showed more organized collagen structure and expression of type I α2 collagen. Col2.3GFP cells were not found in the contralateral femur indicating that transplanted osteogenic cells did not disseminate by circulation. No osteogenic engraftment was observed following intravenous transplantation of BMSCs. BMSC cultures derived from transplanted femurs showed numerous Col2.3GFP+ colonies, indicating the presence of donor progenitor cells. Secondary transplantation of cells recovered from recipient femurs and expanded in vitro also showed Col2.3GFP+ osteoblasts and osteocytes confirming the persistence of donor stem/progenitor cells. We show that BMSCs delivered locally in oim femurs are able to engraft, differentiate into osteoblasts and osteocytes and maintain their progenitor potential in vivo. This suggests that local delivery is a promising approach for introduction of autologous MSC in which mutations have been corrected.

  18. Multidisciplinary Treatment of Severe Osteogenesis Imperfecta: Functional Outcomes at Skeletal Maturity.

    PubMed

    Montpetit, Kathleen; Palomo, Telma; Glorieux, Francis H; Fassier, François; Rauch, Frank

    2015-10-01

    To determine the functional outcomes associated with long-term multidisciplinary treatment, intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI types III or IV). Retrospective study where outcomes were measured prospectively. Pediatric orthopedic hospital. Adolescents (N=41; age range, 15-21y) with severe OI (OI type III: n=17; OI type IV: n=24) who had started therapy before the age of 6 years, had received treatment for at least 10 years, and had achieved final height. Intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation. Pediatric Evaluation of Disability Inventory. At the time of the last available follow-up examination, none of the individuals diagnosed with OI type III (most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV were able to ambulate without ambulation aids. Regarding self-care, we specifically assessed 8 skills that we deemed essential for living independently (grooming; dressing; toileting; bed, chair, toilet, tub, and car transfers). Only 6 (35%) of the youths with OI type III were able to complete all 8 items, whereas 23 (96%) individuals with OI type IV managed to perform all tasks. Teens with OI type III often needed assistance for the transfer to toilet, tub, and car and for personal hygiene and clothing management associated with toileting, usually because of limitations in upper-extremity function. These observations suggest that further improvements in the functional status of the most severely affected children with OI are contingent on advances in the clinical management of upper-extremity issues. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  19. Targeting the LRP5 pathway improves bone properties in a mouse model of Osteogenesis Imperfecta

    PubMed Central

    Jacobsen, Christina M.; Barber, Lauren A.; Ayturk, Ugur M.; Roberts, Heather J.; Deal, Lauren E.; Schwartz, Marissa A.; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G.; Warman, Matthew L.

    2014-01-01

    The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5p.A214V) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis Imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5+/p.A214V mice to Col1a2+/p.G610C mice, which model human type IV OI. We found that Col1a2+/p.G610C;Lrp5+/p.A214V offspring had significantly increased bone mass and strength compared to Col1a2+/p.G610C;Lrp5+/+ littermates. The improved bone properties were not due to altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2+/p.G610C mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody treated mice had significantly increased bone mass and strength compared to vehicle treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. PMID:24677211

  20. Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta.

    PubMed

    Roschger, Andreas; Roschger, Paul; Keplingter, Petra; Klaushofer, Klaus; Abdullah, Sami; Kneissel, Michaela; Rauch, Frank

    2014-09-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4weeks in male Col1a1(Jrt)/+mice, a model of severe dominant OI, starting either at 4weeks (growing mice) or at 20weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1(Jrt)/+mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. The effect of SERPINF1 in-frame mutations in osteogenesis imperfecta type VI.

    PubMed

    Al-Jallad, Hadil; Palomo, Telma; Roughley, Peter; Glorieux, Francis H; McKee, Marc D; Moffatt, Pierre; Rauch, Frank

    2015-07-01

    Osteogenesis imperfecta type VI is caused by mutations in SERPINF1, which codes for pigment-epithelium derived factor (PEDF). Most of the reported SERPINF1 mutations lead to premature termination codons, but three in-frame insertion or deletion mutations have also been reported. It is not clear how such in-frame mutations lead to OI type VI. In the present study we therefore investigated how SERPINF1 in-frame mutations affect the intracellular localization and secretion of PEDF. Skin fibroblasts affected by SERPINF1 in-frame mutations transcribed SERPINF1 at slightly reduced levels but secretion of PEDF was markedly diminished. Two deletions (p.F277del and the deletion of SERPINF1 exon 5) were associated with retention of PEDF in the endoplasmic reticulum and a stress response in osteoblastic cells. A recurrent in-frame duplication of three amino acids (p.Ala91_Ser93dup) appeared to lead to intracellular degradation but no retention in the endoplasmic reticulum or stress response. Immunofluorescence imaging in transiently transfected osteoblastic MC3T3-E1 cells suggested that PEDF affected by in-frame mutations was not transported along the secretory pathway. MC3T3-E1 osteoblasts stably overexpressing SERPINF1 with the p.Ala91_Ser93dup mutation had decreased collagen type I deposition and mineralization. Thus, the assessed homozygous in-frame deletions or insertions lead to retention or degradation within cellular compartments and thereby interfere with PEDF secretion. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.

    PubMed

    Arponen, Heidi; Vuorimies, Ilkka; Haukka, Jari; Valta, Helena; Waltimo-Sirén, Janna; Mäkitie, Outi

    2015-03-01

    Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology

  3. Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

    PubMed

    Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2014-10-01

    The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. © 2014 American Society for Bone and Mineral Research.

  4. Bone Collagen: New Clues to its Mineralization Mechanism From Recessive Osteogenesis Imperfecta

    PubMed Central

    Eyre, David R.; Ann Weis, Mary

    2013-01-01

    Until 2006 the only mutations known to cause osteogenesis imperfecta (OI) were in the two genes coding for type I collagen chains. These dominant mutations affecting the expression or primary sequence of collagen α1(I) and α2(I) chains account for over 90% of OI cases. Since then a growing list of mutant genes causing the 5–10% of recessive cases has rapidly emerged. They include CRTAP, LEPRE1 and PPIB, which encode three proteins forming the prolyl 3-hydroxylase complex; PLOD2 and FKBP10, which encode respectively lysyl hydroxylase 2 and a foldase required for its activity in forming mature cross-links in bone collagen; SERPIN H1, which encodes the collagen chaperone HSP47; SERPIN F1, which encodes pigment epithelium-derived factor required for osteoid mineralization; and BMP1, which encodes the type I procollagen C-propeptidase. All cause fragile bone in infancy, which can include over-mineralization or under-mineralization defects as well as abnormal collagen post-translational modifications. Consistently both dominant and recessive variants lead to abnormal cross-linking chemistry in bone collagen. These recent discoveries strengthen the potential for a common pathogenic mechanism of misassembled collagen fibrils. Of the new genes identified, eight encode proteins required for collagen post-translational modification, chaperoning of newly synthesized collagen chains into native molecules or transport through the endoplasmic reticulum and Golgi for polymerization, cross-linking and mineralization. In reviewing these findings, we conclude that a common theme is emerging in the pathogenesis of brittle bone disease of mishandled collagen assembly with important insights on post-translational features of bone collagen that have evolved to optimize it as a biomineral template. PMID:23508630

  5. Dental panoramic indices and fractal dimension measurements in osteogenesis imperfecta children under pamidronate treatment

    PubMed Central

    Apolinário, Ana C; Sindeaux, Rafael; de Souza Figueiredo, Paulo T; Guimarães, Ana T B; Acevedo, Ana C; Castro, Luiz C; de Paula, Ana P; de Paula, Lilian M; de Melo, Nilce S

    2016-01-01

    Objectives: To verify radiomorphometric indices and fractal dimension (FD) in dental panoramic radiographs (DPRs) of children with different types of osteogenesis imperfecta (OI) and also to verify the effect of pamidronate (PAM) treatment in such panoramic analyses. Methods: In this retrospective study, 197 DPRs of 62 children with OI Types I, III and IV who were in treatment with a comparable dosage of intravenous PAM were selected. The mandibular cortical width (MCW), mandibular cortical index, visual estimation of the cortical width and FD of three standardized trabecular and cortical mandibular regions of interest were obtained from the radiographs. Factorial analysis of variance and Fisher test were used to compare FD and MCW measurements in children with different types of OI for different PAM cycles. Results: Children with all types of OI have thinner and more porous mandibular cortices at the beginning of treatment. There were significant differences between MCW and FD of the cortical bone, regarding different types of OI and number of PAM cycles (p = 0.037 and p = 0.044, respectively). FD measurements of the trabecular bone were not statistically different among OI types nor were PAM cycles (p > 0.05). Conclusions: Children with OI presented cortical bone alterations after PAM treatment. Both MCW and the FD of the cortical bone were higher in children with OI after PAM treatment. It is argued that cortical bone should be considered for analyzing patients with OI, as well as to monitor the progress of PAM treatment. PMID:26954289

  6. X-ray micro-analysis of the mineralization patterns in developing enamel in hamster tooth germs exposed to fluoride in vitro during the secretory phase of amelogenesis

    SciTech Connect

    Lyaruu, D.M.; Blijleven, N.; Hoeben-Schornagel, K.; Bronckers, A.L.; Woeltgens, J.H.

    1989-09-01

    The developing enamel from three-day-old hamster first maxillary (M1) molar tooth germs exposed to fluoride (F-) in vitro was analyzed for its mineral content by means of the energy-dispersive x-ray microanalysis technique. The aim of this study was to obtain semi-quantitative data on the F(-)-induced hypermineralization patterns in the enamel and to confirm that the increase in electron density observed in micrographs of F(-)-treated enamel is indeed due to an increase in mineral content in the fluorotic enamel. The tooth germs were explanted during the early stages of secretory amelogenesis and initially cultured for 24 hr in the presence of 10 ppm F- in the culture medium. The germs were then cultured for another 24 hr without F-. In order to compare the ultrastructural results directly with the microprobe data, we used the same specimens for both investigations. The net calcium counts (measurement minus background counts) in the analyses were used as a measure of the mineral content in the enamel. The aprismatic pre-exposure enamel, deposited in vivo before the onset of culture, was the most hypermineralized region in the fluorotic enamel, i.e., it contained the highest amount of calcium measured. The degree of the F(-)-induced hypermineralization gradually decreased (but was not abolished) in the more mature regions of the enamel. The unmineralized enamel matrix secreted during the initial F- treatment in vitro mineralized during the subsequent culture without F-. The calcium content in this enamel layer was in the same order of magnitude as that recorded for the newly deposited enamel in control tooth germs cultured without F-.

  7. What type of valve is most appropriate for osteogenesis imperfecta patients?

    PubMed

    Dimitrakakis, Georgios; Challoumas, Dimitrios; von Oppell, Ulrich Otto

    2014-09-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was in osteogenesis imperfecta (OI) patients with valve disease undergoing valve replacement which type of valve (bioprosthetic or mechanical) is most appropriate in terms of safety, complications and survival. Altogether more than 77 papers were found as a result of the reported search, of which 43 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Previous review articles have presented case reports up to 2009. As all published data are based on case reports, we conducted a more detailed analysis that included the aforementioned series, reports that were missed prior to 2009 and all published data from 2009 to October 2013. Our analysis identified 43 OI patients. Mechanical valves were used in the majority of cases (31 patients), bioprosthetic valves in 10 patients and homografts in 2 patients. We conclude that based on the best available evidence, it appears that bioprosthetic valves have had better outcomes (mortality rate 10%) and a lower valve-related complication rate (0%) compared with mechanical valves (mortality rate 16.1%, complication rate 16.1%), even though differences were not statistically significant. Although the existing evidence is solely based on case reports of a relatively small number, we would suggest the use of bioprosthetic valves in OI patients with valve disease, as they appear to be safer according to our analysis. Moreover, considering the surgical difficulties related to the friability and weakness of the tissues in terms of suture lines and implantation of the valve as well as the high risk of perioperative bleeding which can be related to tissue friability, capillary fragility and platelet dysfunction followed by the risk of major traumatic fractures and a

  8. Assessment of quality of life of parents of children with osteogenesis imperfecta.

    PubMed

    Szczepaniak-Kubat, Anna; Kurnatowska, Olga; Jakubowska-Pietkiewicz, Elzbieta; Chlebna-Sokół, Danuta

    2012-01-01

    The aim of the work was an objective assessment of the quality of life of parents of children with osteogenesis imperfecta (OI) and of its determinant factors. The survey answers of 25 parents were analyzed and contained demographic parameters, socioeconomic status information, quality of life of responses and type of support they have been receiving. In order to assess the effects of this children's disease on the quality of life of the parents, families were divided into two groups depending on the OI severity: group M--mild (type I and IV OI), group S--severe (type III OI). The objective of the work was carried out based on the WHOQOL-BREF quality of life questionnaire and measures of family status: education degree based on the International Standard Classification of Education (ISCED), a subjective assessment of the family's wealth (Perceived Family Wealth, PFW), and the family's financial resources (Family Affluence Scale, FAS). 56% of respondents assessed their global quality of life (Quality of Life, QL) as good, whereas 8% answered poor. Perception of general health status was similar. Life domains assessed in the WHOQOL-BREF questionnaire received the following mean values on a scale from 4 to 20 points: physical--12.2 +/- 1.2, psychological--15.04 +/- 2.2, environmental--13.32 +/- 2, social relationships--14.28 +/- 1.5. In the severe OI group, the environmental domain was assessed as worse than in the mild OI group and this assessment was statistically significant, despite the fact that the group of families with severe cases of OI received more support from the appropriate institutions. Indicators of socioeconomic status did not affect the respondents' assessment of their global quality of life. In the tested group of families, the child's disease did not affect either the global quality of life assessment or health of the respondents or their quality of life in terms of physical and mental status and social relationships. The parents of children with

  9. [Osteogenesis imperfecta--experience of Dona Estefânia's Hospital orthopedics' department].

    PubMed

    Escobar, Carlos; Malveiro, Duarte; Salgado, António; Santos, Maria Inês; Lameirão Campagnolo, João; Cassiano Neves, Manuel

    2013-01-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and osteopenia. Treatment involves a multidisciplinary approach and aims to improve the quality of life. The authors aimed to describe the characteristics of a sample of children with OI, to evaluate the treatment and clinical outcome before and after therapy. An observational, longitudinal, retrospective and analytic study based on data obtained from the analisys of the clinical files of all patients with OI included in the pamidronate treatment protocol in Dona Estefânia's Hospital. The studied variables were: gender, age at diagnosis, familiar history of OI, age at fracture, fracture location, number of fractures, medical/surgical therapy, age at onset of treatment, number of courses of medical therapy, age at surgical treatment and its complications. A five percent statistics significance level was adopted. in 21 patients, 61.9% were male and 11 had its OI type registered (five type I, three type III, three type IV). The average age of diagnosis was 20.6 months and there were two diagnostic peaks: the first month - 37%, and 24 months - 26%. On average patients had 0.62 fractures/patient/year, of which 17.4% in the perinatal period and 62% before age three. Most of the fractures occurred in the lower limbs (55.6%). All patients underwent medical treatment, starting at an average of 4.3 years. In follow-up sample (n=14) there was a decrease in the number of fractures after starting treatment with pamidronate (0.76 to 0.35 fractures/patient/year). Intramedullary rods were placed in nine patients (64.3%). In eight patients they were placed in the femur, four unilateral and four bilateral, with no prior history of fracture in three cases. There were no new fractures in the surgically treated bones. OI is a disease with a wide clinical variability that mainly depends on its type. Despite no cure has been found, medical treatment with biphosphonates and surgical treatment, with

  10. Osteogenesis imperfecta in childhood: perceived competence in relation to impairment and disability.

    PubMed

    Engelbert, R H; Gulmans, V A; Uiterwaal, C S; Helders, P J

    2001-07-01

    To examine the perceived competence of children with different types of osteogenesis imperfecta (OI) and to investigate the possible relationships between their perceived competence and impairment parameters. Cross-sectional study. National referral center (hospital) for the treatment of children with OI. Forty children with OI (type I = 17; type III = 11; type IV = 12) with a mean age +/- standard deviation of 12.6 +/- 3.2 years. Measured joint range of motion (ROM) in the upper extremities (UEs), and lower extremities (LEs), muscle strength, functional skills, ambulation, and perceived competence. Joint ROM in UE and LE; muscle strength (using the manual muscle testing criteria of the Medical Research Council); functional skills using the Pediatric Evaluation of Disability Inventory in 3 domains (self-care, mobility, social function). Ambulation (according to Bleck and classified as nonwalking, therapy walking, household walking, neighborhood walking, community walking with or without the use of crutches), and perceived competence (using the Harter Self-Perception Profile for Children, which was cross-culturally validated for Dutch children). In children with type I, joint ROM and muscle strength were almost comparable to the healthy population. In children with type III, a severe decrease in joint ROM was measured, especially in the LEs, and muscle strength was severely decreased in the UEs and LEs. In children with type IV, joint ROM and muscle strength decreased, especially in the LEs. In all types, fairly to strongly positive perceived competence was measured except for fairly negative perceived competence in the athletic performance subscale in type I and a fairly negative perceived competence in the romance subscale in type III. No correlations were found between (1) joint ROM and athletic performance and physical appearance, (2) muscle strength and athletic performance or physical appearance, or (3) the functional skills, concerning self-care and mobility

  11. From pediatric to adult care: strategic evaluation of a transition program for patients with osteogenesis imperfecta.

    PubMed

    Dogba, Maman Joyce; Rauch, Frank; Wong, Trudy; Ruck, Joanne; Glorieux, Francis H; Bedos, Christophe

    2014-10-31

    Achieving a successful transition from pediatric to adult care for young adults with special needs, especially rare genetic diseases such as osteogenesis imperfecta (OI), is a prominent issue in healthcare research. This transition represents a challenge for patients with OI, their families, clinicians and healthcare managers because of the complex nature of the process and the lack of evaluation of existing transition programs. We evaluated a transition program for adolescents and young adults with OI from a pediatric orthopedic hospital to adult care. Data were collected by interview, observation, and document review from April 2013 to October 2013. Participants included six patients with OI, four parents, and 15 staff, including administrators, coordinators, social workers, nurses, pediatricians, surgeons, occupational therapists and physiotherapists. A SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis was performed. The strengths of the transition program included a solid theoretical approach based on a partnership with parents, and a comprehensive transition model based on fostering independent living and professional integration. The program's main weaknesses were the successive organizational changes and discontinuation of certain transition activities, and the potential conflict between the transition program and participation in research protocols. Further opportunities include the implementation of a multi-site transition model with cross-site personnel and user evaluations, with the inclusion of second-generation patients. Dissatisfaction reported by some care-team members at the adult care hospital could threaten collaboration among institutions involved in the transition process, whereas dissatisfaction of some former patients may reduce their perceptions of quality of care received during the transition. This study confirmed that a "one-size-fits-all" transition model for patients with OI would be inappropriate across, or even within

  12. Therapeutic impact of low amplitude high frequency whole body vibrations on the osteogenesis imperfecta mouse bone.

    PubMed

    Vanleene, Maximilien; Shefelbine, Sandra J

    2013-04-01

    Osteogenesis imperfecta (OI) is characterized by extremely brittle bone. Currently, bisphosphonate drugs allow a decrease of fracture by inhibiting bone resorption and increasing bone mass but with possible long term side effects. Whole body mechanical vibrations (WBV) treatment may offer a promising route to stimulate bone formation in OI patients as it has exhibited health benefits on both muscle and bone mass in human and animal models. The present study has investigated the effects of WBV (45Hz, 0.3g, 15minutes/days, 5days/week) in young OI (oim) and wild type female mice from 3 to 8weeks of age. Vibration therapy resulted in a significant increase in the cortical bone area and cortical thickness in the femur and tibia diaphysis of both vibrated oim and wild type mice compared to sham controls. Trabecular bone was not affected by vibration in the wild type mice; vibrated oim mice, however, exhibited significantly higher trabecular bone volume fraction in the proximal tibia. Femoral stiffness and yield load in three point bending were greater in the vibrated wild type mice than in sham controls, most likely attributed to the increase in femur cortical cross sectional area observed in the μCT morphology analyses. The vibrated oim mice showed a trend toward improved mechanical properties, but bending data had large standard deviations and there was no significant difference between vibrated and non-vibrated oim mice. No significant difference of the bone apposition was observed in the tibial metaphyseal trabecular bone for both the oim and wild type vibrated mice by histomorphometry analyses of calcein labels. At the mid diaphysis, the cortical bone apposition was not significantly influenced by the WBV treatment in both the endosteum and periosteum of the oim vibrated mice while a significant change is observed in the endosteum of the vibrated wild type mice. As only a weak impact in bone apposition between the vibrated and sham groups is observed in the

  13. Cytoskeleton and nuclear lamina affection in recessive osteogenesis imperfecta: A functional proteomics perspective.

    PubMed

    Gagliardi, Assunta; Besio, Roberta; Carnemolla, Chiara; Landi, Claudia; Armini, Alessandro; Aglan, Mona; Otaify, Ghada; Temtamy, Samia A; Forlino, Antonella; Bini, Luca; Bianchi, Laura

    2017-09-07

    Osteogenesis imperfecta (OI) is a collagen-related disorder associated to dominant, recessive or X-linked transmission, mainly caused by mutations in type I collagen genes or in genes involved in type I collagen metabolism. Among the recessive forms, OI types VII, VIII, and IX are due to mutations in CRTAP, P3H1, and PPIB genes, respectively. They code for the three components of the endoplasmic reticulum complex that catalyzes 3-hydroxylation of type I collagen α1Pro986. Under-hydroxylation of this residue leads to collagen structural abnormalities and results in moderate to lethal OI phenotype, despite the exact molecular mechanisms are still not completely clear. To shed light on these recessive forms, primary fibroblasts from OI patients with mutations in CRTAP (n=3), P3H1 (n=3), PPIB (n=1) genes and from controls (n=4) were investigated by a functional proteomic approach. Cytoskeleton and nucleoskeleton asset, protein fate, and metabolism were delineated as mainly affected. While western blot experiments confirmed altered expression of lamin A/C and cofilin-1, immunofluorescence analysis using antibody against lamin A/C and phalloidin showed an aberrant organization of nucleus and cytoskeleton. This is the first report describing an altered organization of intracellular structural proteins in recessive OI and pointing them as possible novel target for OI treatment. OI is a prototype for skeletal dysplasias. It is a highly heterogeneous collagen-related disorder with dominant, recessive and X-linked transmission. There is no definitive cure for this disease, thus a better understanding of the molecular basis of its pathophysiology is expected to contribute in identifying potential targets to develop new treatments. Based on this concept, we performed a functional proteomic study to delineate affected molecular pathways in primary fibroblasts from recessive OI patients, carrying mutations in CRTAP (OI type VII), P3H1 (OI type VIII), and PPIB (OI type IX) genes

  14. Ultrastructural and histological findings on examination of skin in osteogenesis imperfecta: a novel study.

    PubMed

    Balasubramanian, Meena; Wagner, Bart E; Peres, Luiz C; Sobey, Glenda J; Parker, Michael J; Dalton, Ann; Arundel, Paul; Bishop, Nicholas J

    2015-04-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity for fractures. It is a variable condition with a range of clinical severities. The histological and ultrastructural findings in the skin of patients with OI have not been described in detail in the previously published literature. Although protein analysis of cultured fibroblasts has historically been used in the diagnostic work-up of OI patients, other aspects of skin examination are not routinely performed as part of the diagnostic pathway in patients with OI. The aims of this study were to perform histological and ultrastructural examination of skin biopsies in patients with OI. This was to identify common and distinguishing features in the numerous genetically distinct subtypes of OI and compare the findings with those in patients who did not present with fractures, and to enable the use of the results thus obtained to aid in the diagnostic work-up of patients with OI. As part of a larger research study set-up to identify clinical features and natural history in patients with atypical features of OI, skin biopsy and examination (histology and electron microscopy) were undertaken. Genetic analysis and ancillary investigations were also performed to identify similarities within this group and to differentiate this group from the 'normal' population. At the end of this study, we were able to demonstrate that the histological and electron microscopic findings on a skin biopsy may be an indicator of the likelihood of identifying a pathogenic mutation in type 1 collagen genes. This is because patients with specific findings on examination, such as elastic fibre area fraction (on histological analysis), collagen fibril diameter variability, deviation from the expected mean and collagen flowers (on electron microscopy), are more likely to be positive on genetic analyses. This has, in turn, provided more insight into the

  15. Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2-year prospective observational study.

    PubMed

    Otaify, G A; Aglan, M S; Ibrahim, M M; Elnashar, M; El Banna, R A S; Temtamy, S A

    2016-01-01

    Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. This is the first study reporting the use of bisphosphonates in patients with Bruck syndrome (BS). OI and BS are genetic disorders that result in bone fragility and reduced BMD. There is little literature describing the efficacy and safety of ZA in this population. In this study, we assess the response to treatment with ZA at six monthly intervals in Egyptian children with OI and BS for a period of 2 years. Thirty-three patients with OI and five patients with BS were treated with 0.1 mg/kg ZA intravenously every 6 months for 2 years during which they were followed up using different parameters. A clinical severity score (CSS) was applied to the patients before and 2 years after the start of therapy. Comparison of disease severity and response to ZA treatment between autosomal-dominant (AD) and autosomal-recessive (AR) OI patients was also done. After 6 months of treatment, OI and BS patients showed a significant increase in BMD Z-scores (P < 0.003 in the spine and P < 0.004 in the hip), together with a significant drop in fracture rate (P < 0.001), relief of pain (P < 0.001), and improvement in ambulation (P < 0.001). CSS was significantly reduced after 2 years of treatment in both OI and BS patients. AR-OI patients were more severely affected than AD-OI patients and showed more significant improvement. Zoledronic acid proved to be safe and effective in the treatment of OI and BS. The biannual infusion protocol was convenient to patients. There was a positive correlation between disease severity and benefits of the treatment. The use of the CSS proved to be of value in the assessment of the degree of severity in OI, and with some modifications, it was a valuable tool for the assessment of

  16. Gene Targeting of Mutant COL1A2 Alleles in Mesenchymal Stem Cells From Individuals With Osteogenesis Imperfecta

    PubMed Central

    Chamberlain, Joel R; Deyle, David R; Schwarze, Ulrike; Wang, Peirong; Hirata, Yi Li; Byers, Peter H; Russell, David W

    2014-01-01

    Mesenchymal stem cells (MSCs) are adult cells with the capacity to differentiate into multiple cell types, including bone, fat, cartilage, and muscle cells. In order to effectively utilize autologous MSCs in cell-based therapies, precise genetic manipulations are required to eliminate the effects of disease-causing mutations. We previously used adeno-associated virus (AAV) vectors to target and inactivate mutant COL1A1 genes in MSCs from individuals with the brittle bone disorder, osteogenesis imperfecta (OI). Here we have used AAV vectors to inactivate mutant COL1A2 genes in OI MSCs, thereby demonstrating that both type I collagen genes responsible for OI can be successfully targeted. We incorporated improved vector designs so as to minimize the consequences of random integration, facilitate the removal of potential antigens, and avoid unwanted exon skipping. MSCs targeted at mutant COL1A2 alleles produced normal type I procollagen and formed bone, thereby demonstrating their therapeutic potential. PMID:17955022

  17. [The hospitalization and the process of becoming ill through the children's and adolescents' perspective with cystic fibrosis and osteogenesis imperfecta].

    PubMed

    de Mello, Daniele Borges; Moreira, Martha Cristina Nunes

    2010-03-01

    The present article intends to discuss the results of a study completed in a hospital located in the municipal district of Rio de Janeiro, considered most prominent for child, adolescent and woman's health. We analyzed the meanings of hospitalization and chronic illness in childhood and adolescence through the perspective of children and adolescents with cystic fibrosis and osteogenesis imperfecta during their hospitalizations in order to explore their experience and communicative possibilities as knowledgeable informants. Hence, we privileged the observation and the construction of their productions through games, using drawings and/or story-telling as a relevant approach to childhood and adolescence contents. The data collected signify the acquisition and knowledge production capacity of children and adolescents concerning their illness processes.

  18. Prenatal diagnosis of osteogenesis imperfecta type II by three-dimensional computed tomography: the current state of fetal computed tomography.

    PubMed

    Akizawa, Yoshika; Nishimura, Gen; Hasegawa, Tomonobu; Takagi, Masaki; Kawamichi, Yayoi; Matsuda, Yoshio; Matsui, Hideo; Saito, Kayoko

    2012-12-01

    We report a case of osteogenesis imperfecta (OI) (OMIM166210) type II, in which a prenatal diagnosis was made by three-dimensional computed tomography (3D-CT). Subsequent molecular analysis revealed a recurrent, heterozygous mutation in COL1A2. Fetal CT is a powerful tool for visualizing the fetal skeleton and can provide a definitive diagnosis of fetal skeletal dysplasias; however, whether or not its employment for prenatal diagnosis is warranted in terms of fetal radiation risks remains controversial, both medically and ethically. Based on our experience, we review the current state of fetal CT for the diagnosis of skeletal dysplasias, with a discussion of the relevant literature. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

  19. A novel splicing mutation in COL1A1 gene caused type I osteogenesis imperfecta in a Chinese family.

    PubMed

    Peng, Hao; Zhang, Yuhui; Long, Zhigao; Zhao, Ding; Guo, Zhenxin; Xue, Jinjie; Xie, Zhiguo; Xiong, Zhimin; Xu, Xiaojuan; Su, Wei; Wang, Bing; Xia, Kun; Hu, Zhengmao

    2012-07-10

    Osteogenesis imperfect (OI) is a heritable connective tissue disorder with bone fragility as a cardinal manifestation, accompanied by short stature, dentinogenesis imperfecta, hyperlaxity of ligaments and skin, blue sclerae and hearing loss. Dominant form of OI is caused by mutations in the type I procollagen genes, COL1A1/A2. Here we identified a novel splicing mutation c.3207+1G>A (GenBank ID: JQ236861) in the COL1A1 gene that caused type I OI in a Chinese family. RNA splicing analysis proved that this mutation created a new splicing site at c.3200, and then led to frameshift. This result further enriched the mutation spectrum of type I procollagen genes. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Use of intrapulmonary percussive ventilation (IPV) in the management of pulmonary complications of an infant with osteogenesis imperfecta.

    PubMed

    Nino, Gustavo; McNally, Paul; Miske, Laura J; Hickey, Eileen; Panitch, Howard B

    2009-11-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by abnormal collagen formation and short stature. These patients present with frequent vertebral, rib, and long bone fractures. There are many respiratory complications associated with OI including pneumonia, the most common cause of mortality in the severe forms of the disease. We present a case of an infant with OI (type III/IV) and significant tracheobronchomalacia who had required multiple hospitalizations for recurrent atelectasis and respiratory failure in the setting of acute respiratory infections. External chest percussion and vibration were avoided because of the risk of rib fractures. intrapulmonary percussive ventilation (IPV) was initiated during an acute illness with good effect, and continued successfully after discharge from hospital. We conclude that IPV represents a safe and effective alternative to airway clearance in infants with OI.