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At least 19 recordsLinked to original sources

PubMed1990

[Case report of osteogenesis imperfecta].

Osteogenesis imperfecta (OGI) is a rare genetic disease which, as a result of a disorder in the formation of the organic stroma of the bone due to a defect in osteogenic function, induces brittle bones, whereby only weak forces bring about multiple, repeated pathological fractures. This disease is thought to entail various problems with regards to carrying out pediatric dentistry due to the ease with which bones may be fractured. We report here the findings obtained as a result of the careful examination of a 1-year-3-month-old girl encountered in our practice and who was diagnosed as having osteogenesis imperfecta. 1) Out of the three major symptoms for osteogenesis imperfecta, this case showed signs of fragile bones and blue scleras, but did not reveal signs of deafness. 2) There was retardation in system growth and development. 3) Aside from a high level of alkaline phosphatase, there were no notable abnormalities revealed in the biochemical blood tests. 4) Dentinogenesis imperfecta was observed throughout the erupted teeth. 5) There was a definite improvement in cooperation with each visit to the clinic.

Dental Care for Persons with Disabilities↗

PubMed1990

Osteogenesis imperfecta.

Osteogenesis imperfecta describes a group of heritable disorders characterized by excessive bony fragility and reduced skeletal mass. It is classified in terms of its clinical manifestations, but our understanding of the underlying genetic defects in collagen synthesis is increasing rapidly. The nonoperative and surgical orthopedic approaches to osteogenesis imperfecta aim at the maximum preservation of limb strength and the correction of deformities. Various pharmacologic agents have been administered to patients with osteogenesis imperfecta, but to date, none have proved effective in controlled trials. Prenatal diagnosis has been attempted and seems certain to assume greater importance as knowledge of the molecular genetic basis of the disease increases.

Child↗

PubMed1986

Psychosocial aspects of osteogenesis imperfecta.

Osteogenesis imperfecta is a heterogeneous group of inherited disorders characterized by bone fragility and recurrent fractures. It is currently classified into four types on clinical grounds and appears to arise from different disorders of bone collagen synthesis. The biochemical identification of disturbances in collagen metabolism and the genetic delineation of new mutations of collagen genes have made prenatal diagnosis by molecular methods feasible in some cases. Most people with osteogenesis imperfecta suffer frequent fractures (and sometimes consequent serious disability), for which there are few effective preventive measures. This disorder may have a profound psychosocial influence on patients and their families. In this report the extent of this influence is reviewed and aspects important to the medical community are highlighted; these include the emotional burdens imposed by unfounded suspicions of child abuse, the social and financial costs of repeated hospitalization and immobility, and the frustrations generated by the lack of helpful, practical information for families and health care workers. An important social outcome has been the rise of self-help organizations, exemplified by the Canadian Osteogenesis Imperfecta Society. For Canadian families the society has been an important vehicle for exchange of information and an active, positive response to a lifelong, often severely disabling disorder.

Canada↗

PubMed1988

Infantile chronic subdural hematoma with local protrusion of the skull in a case of osteogenesis imperfecta.

Osteogenesis imperfecta with infantile chronic subdural hematoma is extremely rare and has not been previously described in the literature. Our patient was a baby girl suffering from osteogenesis imperfecta tarda (Type I) who had an acute subdural hematoma at birth and who developed a progressive chronic subdural hematoma with local protrusion of the overlying skull. She was treated surgically with a good result. This rare complication is due to weakness of an insufficiently calcified skull, which is peculiar to this disorder of bone and connective tissue development.

Chronic Disease↗

PubMed1978

Metacarpal morphometry in adults with osteogenesis imperfecta.

Osteogenesis imperfecta is often regarded as a form of osteoporosis. In many cases, particularly those in whom the first fracture occurs outside the neonatal period, bones that have not been fractured may appear radiologically normal. In a group of 24 adults with osteogenesis imperfecta the thickness of the metacarpal cortex was normal but their bones were often slender. Osteoporosis is probably not an inevitable feature of such cases, and some of the radiological abnormalities reported may be the results of previous fractures and their treatment.

Adult↗

PubMed1988

Obstetric management of a fetus with nonlethal osteogenesis imperfecta.

Osteogenesis imperfecta is the common term for a heterogeneous group of heritable disorders of connective tissue with lethal and nonlethal forms. Prenatal diagnosis presents difficult medical and ethical issues. Of concern are the following: 1) the certainty of diagnosis, 2) the severity of disease, 3) the prognosis for survival and ambulation, and 4) the appropriate mode of delivery. A case of nonlethal fetal osteogenesis imperfecta managed by vaginal delivery is discussed.

Adult↗

PubMed1990

Transgenic mouse model of the mild dominant form of osteogenesis imperfecta.

Osteogenesis imperfecta type I is a mild, dominantly inherited, connective tissue disorder characterized by bone fragility. Mutations in type I collagen account for all known cases. In Mov-13 mice, integration of a murine retrovirus within the first intron of the alpha 1(I) collagen gene results in a null allele blocked at the level of transcription. This study demonstrates that mutant mice heterozygous for the null allele are a model of osteogenesis imperfecta type I. A defect in type I collagen production is associated with dominant-acting morphological and functional defects in mineralized and nonmineralized connective tissue and with progressive hearing loss. The model provides an opportunity to investigate the effect of a reduced amount of type I collagen on the structure and integrity of extracellular matrix. It also may represent a system in which therapeutic strategies to strengthen connective tissue can be developed.

Animals↗

PubMedDate not supplied

Part 2. Osteogenesis imperfecta.

Osteogenesis imperfecta (OI), the most common genetic disorder of bone, is characterized by frequent, unpredictable fractures of the long bones with progressive skeletal deformity. Often diagnosed in the early years of life, OI requires a comprehensive, interdisciplinary plan of care involving patient, family, and community. The nurse's role as caregiver, educator, and patient advocate is to foster normal physical and psychosocial growth and development and minimize the opportunity for fracture.

Child↗

PubMed1989

Fatal intraoperative hemorrhage during spinal fusion surgery for osteogenesis imperfecta.

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.

Child↗

PubMed1976

Psychosocial factors in low-incidence genetic disease: the case of osteogenesis imperfecta.

Osteogenesis imperfecta (OI), a dominant genetic disorder, was examined in an exploratory case study of psychosocial implications. The cross-sectional survey sample consisted of 13 OI-affected adults and 21 families with an OI-affected child who were interviewed. Findings revealed numerous psychosocial concerns and problems in addition to their complex and lifelong medical problems. Specific problem areas differed according to the severity of the disease, type, and mode of genetic inheritance. The results indicate the need for local as well as national policy changes through legislation and extensions of existing services for low-incidence disease groups such as OI-affected persons. Implications for social work practice interventions call for greater involvement with genetic diseases, more aggressive approaches in case identification and service coordination, and performing longer-range monitoring functions than is usually the case.

Adult↗

PubMed1992

Hyperplastic callus formation in osteogenesis imperfecta.

Osteogenesis imperfecta, an inherited disorder of connective tissues, affects roughly (OI) 4000 people in Germany (11). The main clinical symptoms are fragile bones, progressing skeletal deformities, generalized osteoporosis and short stature. Incidentally, the clinical manifestations can range from perinatal lethal forms to phenotypical normal adults. In many instances the underlying causes of the disease are mutations in gene coding for collagen I, the predominant protein in most connective tissues. Fracture healing is usually not impaired, although in a unique group of OI-patients, a tumor-like hyperplastic callus occurs with excessive deposition of extracellular matrix constituents. Biochemical analysis of the callus is reminiscent of bone from early stages of human development and normal fracture healing (e.g. collagen type composition, degree of posttranslational modification). This underlines that, besides collagen mutations, the regulation of collagen synthesis and their posttranslational processing might be disturbed in patients with hyperplastic callus formation.

Bony Callus↗

PubMed1988

A cysteine for glycine substitution at position 1017 in an alpha 1(I) chain of type I collagen in a patient with mild dominantly inherited osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited diseases of connective tissue manifested primarily by excessive fracturing of bone but associated with other abnormalities such as blue sclera, thin skin, herniae, ligamentous laxity, reduced stature and hearing loss. We report here molecular studies on a patient with the mild, dominantly inherited, variety of OI (OI type I) previously shown (Nicholls et al., 1984) to be heterozygous for an abnormal alpha 1(I) chain of type I collagen which contained cysteine near the carboxyl terminus (Steinmann et al., 1986). The cognate alpha 1(I) mRNA region was selected for generation of cDNAs which were subsequently amplified by the polymerase chain reaction (PCR), cloned and sequenced. Two sequences were obtained, one of which corresponded to the normal allele, and the other of which harbored a G to T transversion and resulted in a cysteine for glycine substitution. This is the first single amino acid substitution found in type I OI. Surprisingly, the mutation occurs just outside the triple-helical region of the alpha 1(I) chain, a result that accounts for the strikingly different phenotypic and molecular consequences of this mutation as compared with similar cysteine for glycine substitutions within the same region. The PCR appears to be a useful approach for elucidation of structural mutations in collagen chains.

Adolescent↗

PubMed2025

Real-world data of fracture rates and musculoskeletal disorders for patients living with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and recurrent fractures. Fracture rate has been advocated as an important endpoint for evaluating investigative therapies in OI, but real-world data on fracture burden in the OI population are lacking. This retrospective US claims database study aimed to quantify fracture rate and the occurrence of musculoskeletal disorders among patients with OI of all ages and in a subgroup of patients who were treated with ≥1 off-label therapies. 5722 patients with OI were identified in the IQVIA PharMetrics Plus database and 2095 (55.7% female; 35.1% peds; 20% with OI-related treatments; 87.1% commercial-insured) met eligibility criteria and were included in analyses. About 40% of patients with OI and 37% of those with off-label treatments had a fracture within 1 yr of diagnosis (index date for all OI) or treatment (index date for OI-treated). The annual average fracture rates of these groups were 0.84 and 0.98, respectively. Matched non-OI comparators had 3% fracture occurrence and a 0.03 annual fracture rate. Among patients with ≥1 fracture episode, the annualized median fracture rate was 2 per year for both OI and OI-treated cohorts and 1 for the non-OI cohort. Pediatric patients had the highest fracture occurrence and fracture rate, both among patients with OI and the subgroup of treated OI patients. Musculoskeletal disorders and diagnosed pain were more frequent in OI patients compared with the non-OI cohort, especially among pediatric age groups and adults 18-<45 yr. Pain and musculoskeletal disorders occurred frequently among OI patients, regardless of fracture occurrence, demonstrating impacts of OI beyond those that can be attributed to fractures. Together, these results highlight a high burden of fracture and other musculoskeletal disorders in a commercially insured population of OI patients, which are not effectively managed by current management strategies or off-label treatments.

bone and mineral diseases-other↗

PubMed2026

Inhibition of EED enhances osteogenic differentiation and bone formation: a potential therapeutic strategy for osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited connective tissue disorders primarily caused by dominant mutations in COL1A1 or COL1A2 that impair type I procollagen folding and secretion. Misfolded collagen accumulates in the endoplasmic reticulum (ER), triggering ER stress and osteoblast dysfunction, and bone fragility. Current pharmacologic therapy focuses on inhibiting bone resorption but has limited efficacy and does not address the underlying biology of the disease. The epigenetic regulator polycomb-repressive complex 2 (PRC2) has emerged as an important regulator of bone formation. Genetic and pharmacologic disruption of PRC2 enhanced osteogenic differentiation in WT cells. Here, we demonstrate that inhibition of the PRC2 through targeting its essential component embryonic ectoderm development (EED) enhances osteogenic differentiation, improves bone architecture in male Col1a2 +/G610C OI mouse models, modulates the integrated stress response (ISR), and improves ER morphology in OI cells. These findings identify EED inhibition as a novel epigenetic strategy to restore collagen homeostasis and improve skeletal integrity in OI.

ER stress↗

PubMed1979

[Osteogenesis imperfecta cystica (Fairbank)--a special form of osteogenesis imperfecta congenita (Vrolik) (author's transl)].

Two patients, aged 13 and 19 years, with osteogenesis imperfecta congenita (Vrolik) have been seen at the rehabilitation centre at Neckargemund. The younger patient showed the typical appearances of osteogenesis imperfecta cystica (Fairbank), while the older patient failed to show these changes in the skeleton. Contrary to the frequently expressed view that patients with osteogenesis imperfecta congenita always die in the perinatal period, they may survive for a considerable length of time. The change of osteogenesis imperfecta congenita (Vrolik) into osteogensis imperfecta cystica (Fairbank) has been described as a sequence in the occasional survivors by Spranger, but is not a necessary condition for survival. Osteogenesis imperfecta cystica should be regarded as an extremely rare special type of Vrolik's disease.

Adolescent↗

PubMed1992

Unusual dentinal changes in dentinogenesis imperfecta associated with osteogenesis imperfecta. A case report.

A case is described of a boy with dentinogenesis imperfecta associated with osteogenesis imperfecta. The dentin of extracted deciduous teeth was found to show an abrupt transition to a normal tubular structure before a reversion to the more typical structure seen in dentinogenesis imperfecta. This change in the dentin appeared to have occurred in a chronologic manner. The possibilities that either a metabolic disturbance or a temporary reduced expression of the mutant gene had caused the abnormality and could account for the unusual histologic findings are discussed.

Child↗

PubMed1986

Dentine is biochemically abnormal in osteogenesis imperfecta.

In osteogenesis imperfecta the bones are brittle but the teeth, whose dentine contains the same genetic collagen as bone (type I), may be clinically normal. To investigate this paradox we have measured the amino acid composition of insoluble dentine collagen from 16 deciduous and 18 permanent teeth in control subjects and in 59 patients with different forms of osteogenesis imperfecta. In 55 of the patient samples significant differences from normal were found, especially in the number of lysine residues, and in the relative amounts of hydroxylysine to lysine. These results demonstrate the high frequency of biochemical abnormalities in osteogenesis imperfecta. They also suggest that classifications of this disorder based on the presence or absence of clinical dentiogenesis imperfecta are likely to be unsound.

Amino Acids↗

PubMed2026

A Novel Splice Variant in the COL1A1 Gene Leads to Exon 46 Skipping and Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a clinical and genetic disorder characterised by bone fragility, growth deficiency and skeletal deformity. Ninety per cent of OI cases are attributable to autosomal dominant variants in the COL1A1 and COL1A2 genes. METHODS: Candidate variants were identified and verified through trio whole-exome sequencing (trio-WES), copy number variation sequencing (CNV-seq) and Sanger sequencing. Minigene splicing assays were performed in HeLa and HEK293T cells with pcDNA3.1 and pcMINI-C vectors to investigate the function of the candidate variants. A systematic review of COL1A1 splicing variants and the corresponding genotype-phenotype spectrum was performed. RESULTS: Trio-WES revealed a novel heterozygous variant in the C-terminal region of the COL1A1 gene: NM_000088.4:c.3423+5G>A. Sanger sequencing confirmed the variant in both the proband (II-2) and her foetus (III-1) who were clinically suspected of having OI. The c.3423+5G>A variant causes complete skipping of Exon 46, as demonstrated by a minigene splicing assay. We retrieved 419 COL1A1 splicing variants from PubMed, excluded 15 without phenotypic data and 2 linked to Ehlers-Danlos syndrome and stratified the remaining 402 variants into three types on the basis of splice site location: (1) Variants at canonical splicing sites (77.8%, 313/402) mostly cause mild phenotypes, whereas a minority may be severe. (2) Intron variants in other locations, such as splice region variants (17.9%, 72/402), usually cause mild clinical phenotypes, and deep intronic splice variants (0.4%, 2/402) that may result in severe phenotypes. (3) Other variants (3.7%, 15/402), such as exon variants or fragment loss, are extremely rare. We also preliminarily discuss the mechanisms underlying phenotypic variability and the characteristics of C-terminal variants. CONCLUSIONS: This intron variant in COL1A1 was classified as likely pathogenic and was confirmed to disrupt COL1A1 expression. The summary analysis results also revealed a correlation among splicing variants, C-terminal region variants and disease, suggesting that variant location provides a useful framework for prognosis prediction.

Female↗