Osteogenesis imperfecta: an overview.
Osteogenesis imperfecta (brittle bone disease) is a rare hereditary disorder with an increased tendency to fracture. Chris Clark highlights the management needs of people with this condition.
Adult↗
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Psychosocial aspects of osteogenesis imperfecta: an update.
Osteogenesis imperfecta (OI) is an inherited disorder in which affected individuals are stigmatized by virtue of physical differences from their peers. The extent to which these differences alter life style depend on the severity of the disorder, its natural history, the extent to which it affects social integration, the effect on physical appearance, and the presence of other affected family members. Some of these factors may adversely influence the ability of affected individuals to effectively adjust to their social and work environment and recognition of these factors may aid individuals and helpers in easing the path to a constructive life.
Adolescent↗
Co-existence of osteogenesis imperfecta and hyperparathyroidism.
Osteogenesis imperfecta (OI) and hyperparathyroidism (HTP) are disorders affecting the skeletal system and calcium metabolism not evidently related to one another. We report a case in which both OI and HPT were present. Our female patient presented with hypercalcaemia (S-Ca2+ 1.59 mmol/l; normal range 1.15-1.30) and 4-gland parathyroid hyperplasia at 30 years of age. Since her first year she had fractures, blue sclera, hypermobile joints, short stature (height 1.51 m, weight 49.5 kg) but normal hearing, and dentiogenesis imperfecta (tooth disease caused by defective formation of dentin) was absent. This patient bears many similarities with the 5 patients reported previously but it is the only patient, to our knowledge, with OI and early onset of HPT (30 year old female). We have found the OI to be type 1. A minor improvement of the rate of bone turnover 10 months after parathyroidectomy indicates the HPT to be primary and suggests the OI type 1 and pHPT to be two different calcium metabolic diseases incidentally occurring in the same patient.
Adult↗
[Early use of BiPAP in the management of respiratory failure in an infant with osteogenesis imperfecta: case report].
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.
Bronchiolitis↗
Presentation on assistive technologies for the seating and mobility needs of persons with osteogenesis imperfecta.
Persons with Osteogenesis Imperfecta (OI) are often protected and sheltered because of the fragile nature of their bones. Regardless of the degree of OI. over protecting a person with OI can be just as devastating as fractured bones. It is important that persons with OI are given the opportunity to participate in a wide variety of activities to develop the experiential, physical, and sociological dimensions of their lives. Assistive technology can help to make this participation a reality. Assistive technology should help protect the person from fractures, provide support to assist with postural alignment, and stability so that function and comfort can be enhanced. Technologies such as contoured foam mattresses, seating supports, temperature regulation technologies, orthotic supports, walking and wheelchair mobility devices can enhance the quality of live of people with OI.
Beds↗
Elongating intramedullary rods in the treatment of osteogenesis imperfecta.
Patients with osteogenesis imperfecta who have undergone multiple osteotomies with realignment and intramedullary rod fixation of a deformed bone frequently require replacement of the rod because the bone grows and angulates when the rod no longer is long enough to support the bone from metaphysis to metaphysis. The Bailey-Dubow intramedullary rod, which elongates with growth, is an attempt to solve this problem. This is a review of 153 rod-fixations in seventy-two bones (twenty patients), forty-seven being Bailey-Dubow rods. Use of the elongating rod effectively increased the average length of time between replacement operations, yielded a lower removal rate, and showed no additional adverse effects. The Bailey-Dubow rod represents a measurable improvement over non-elongating rods.
Adolescent↗
The use of bisphosphonates in children with osteogenesis imperfecta.
Children with osteogenesis imperfecta (OI) suffer recurrent fractures resulting in pain, deformity and disability. There is no accepted medical therapy for the condition other than symptomatic pain relief, and surgical correction of the deformities. Recent experience with the bisphosphonate group of drugs suggests, however, that anti-resorptive therapy may reduce fracture frequency, increase bone density, promote remodeling of previously crush-fractured vertebrae, reduce chronic pain, and improve mobility in both children and infants. The prospects for preventing disability and deformity, and perhaps improving growth in affected children are good. Current studies are focusing on the evaluation of the efficacy of oral drug therapy, and protocols are under development to evaluate new, more efficient molecules. Until gene therapy becomes a reality, the use of bisphosphonates appears to be the most efficient way of altering the natural course of severe OI, and improving the quality of life of patients.
Diphosphonates↗
Use of molecular haplotypes specific for the human pro alpha 2(I) collagen gene in linkage analysis of the mild autosomal dominant forms of osteogenesis imperfecta.
Autosomal dominant osteogenesis imperfecta (OI) is a heterogeneous group of disorders. Molecular haplotypes associated with the pro alpha 2(I) gene of human type I procollagen were used for genetic linkage studies in a group of 10 families with OI. The clinical phenotypes of the families studied were those of OI type I and OI type IV. Evidence for linkage was highly suggestive in the four families with OI type IV (Z = 3.91 for theta = 0). In contrast, little or no indication for linkage was found in the six families with OI type I (Z = .055 for theta = .415). Heterogeneity between the two groups of families was highly significant (chi 2 = 11.14, P = .0008), suggesting that at least two separate gene defects may be the cause of the autosomal dominant forms of OI.
Alleles↗
Increased postoperative febrile response in children with osteogenesis imperfecta.
Children with osteogenesis imperfecta (OI) often require operative management to correct limb and spinal deformities. The authors reviewed the postoperative courses of 22 children with OI and compared the febrile responses of these children with those of matched subgroups within a published historical control ( 8). The subgroups were matched for perioperative conditions including the magnitude of surgery, estimated intraoperative blood loss, transfusion status, age, and gender. In all subgroups examined, the patients with OI exhibited a significant increase in total febrile response (TFR) compared with those in the historical control group. Within the OI group, TFR correlated with estimated blood loss and magnitude of surgery. There were three fever workups in the OI group with no evidence of infection found. In children with OI, fever workups and delays in hospital discharge should be avoided if physical signs of infection are absent.
Adolescent↗
Comprehensive rehabilitation of the child with osteogenesis imperfecta.
Children with osteogenesis imperfecta (OI) that results in considerable deformity are often viewed as poor candidates for aggressive physical therapy and rehabilitation. To determine if this view is realistic, we have entered almost 50 children with OI type III and OI type IV into a comprehensive graduated rehabilitation program, based at the National Institutes of Health, but designed to be implemented by continuing involvement of community resources. Children are begun in the program early with emphasis on gain of head and trunk control and progression to sitting and walking, if possible, with the aid of a variety of physical supports, including internal and external bracing. Although not conducted in a randomized fashion, the program's success in bringing children into graded exercise regimes and fostering their increased involvement in school and social situations suggest that aggressive physical therapy and rehabilitation have a major place in the overall care of the infants and children with OI.
Child↗
The spine and surgical treatment in osteogenesis imperfecta.
In the osteogenesis imperfecta patient, spinal deformity should be expected, particularly in the severely affected nonambulator with chest deformity. Curves develop early (age five to six) and generally progress rapidly. Early bracing, although somewhat effective, may well compress the soft osteoporotic rib cage without controlling the spinal curvature. The pulmonary compromise created by the scoliosis is compounded by the chest cage deformity secondary to bracing. In the patient with severe disease (thin bones and numerous fractures), posterior correction and fusion, with or without Harrington instrumentation, is the preferred approach. This should be done early as the osteoporotic bone does not tolerate the hook forces well; the correction is correspondingly limited. The use of methylmethacrylate bone cement around the hook provides redistribution of forces and more stable fixation. In the patient with mild disease (thick bones and few fractures) treatment should be similar to that of patients with idiopathic scoliosis. The chest cage should be carefully observed to avoid deformity from placement of the lateral or posterior pad.
Bone Cements↗
[Osteogenesis imperfecta - diagnostic challenges].
Osteogenesis imperfecta (OI) is one of the commonest skeletal disorders with an incidence about one in 10,000. It is characterized by clinical and genetic heterogeneity. Congenital lethal OI (OI type II) is the most severe from with a possibility of the early prenatal sonographic diagnosis. The authors present two clinical cases of antenatal diagnosis of OI in 26 and 24 weeks of gestation. The pregnancies were terminated. The accurate specific diagnosis was based on the clinical examination and radiographic features. In case N 2 additional findings were ascites and hydrothorax, that may occasionally be found in literature. The accurate prenatal sonographic diagnosis of lethal skeletal dysplasias and particularly of OI is possible and based on the specific sonographic findings during the second trimester of pregnancy. Ultrasound screening of all pregnant women in early second trimester is an efficient method for detection of many fetal malformations. It requires a participation of the both clinician sonographer and geneticist in a team in order to achieve a specific genetic diagnosis.
Abortion, Induced↗
Epidural hematoma formation following trivial head trauma in a child with osteogenesis imperfecta. Case report.
Osteogenesis imperfecta (OI) represents a rare heterogeneous group of inherited disorders characterized by low bone mass, increased bone fragility, and other connective tissue manifestations. This condition can contribute to dramatic complications after a seemingly insignificant injury. A large epidural hematoma that developed in a child with OI after a trivial fall highlights the importance of close monitoring in these patients. After an injury that occurred several months prior to the head trauma the authors describe, this child had been placed in foster care because it was believed that his skeletal injuries were caused by nonaccidental injury. Subsequent genetic analysis confirmed that the child was heterozygous for the missense mutation c767G>T,pG256V at exon 16 of COLIA2, consistent with OI, and the foster care order was overturned. The authors review the literature concerning OI, its relationship to head injury, and the importance of genetic analysis in its diagnosis.
Child Abuse↗
Perinatal lethal osteogenesis imperfecta.
Perinatal lethal osteogenesis imperfecta is the result of heterozygous mutations of the COL1A1 and COL1A2 genes that encode the alpha 1(I) and alpha 2(I) chains of type I collagen, respectively. Point mutations resulting in the substitution of Gly residues in Gly-X-Y amino acid triplets of the triple helical domain of the alpha 1(I) or alpha 2(I) chains are the most frequent mutations. They interrupt the repetitive Gly-X-Y structure that is mandatory for the formation of a stable triple helix. Most babies have their own private de novo mutation. However, the recurrence rate is about 7% owing to germline mosaicism in one parent. The mutations act in a dominant negative manner as the mutant pro alpha chains are incorporated into type I procollagen molecules that also contain normal pro alpha chains. The abnormal molecules are poorly secreted, more susceptible to degradation, and impair the formation of the extracellular matrix. The collagen fibres are abnormally organised and mineralisation is impaired. The severity of the clinical phenotype appears to be related to the type of mutation, its location in the alpha chain, the surrounding amino acid sequences, and the level of expression of the mutant allele.
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Abnormalities in central nervous system development in osteogenesis imperfecta type II.
Osteogenesis imperfecta (OI) type II is a perinatally lethal condition resulting from mutations in type I collagen genes. In addition to characteristic skeletal anomalies, OI type II has recently been shown to be associated with neuropathological alterations, specifically perivenous microcalcifications, and impaired neuroblast migration. In light of these findings, and because type I collagen promotes neuritic maturation both in vitro and in vivo, we sought to determine if additional central nervous system (CNS) developmental anomalies could be found in previously autopsied OI type II cases, and if specific abnormalities correlate with OI subtypes. We retrospectively studied brains of nine patients diagnosed with OI. Of these, seven were OI type II: five were OI type IIA, one was type IIB, and one was type IIC. One OI type I specimen and one OI type III brain were included for comparison, as well as five controls. The IIC brain showed hippocampal malrotation, agyria, abnormal neuronal lamination, diffuse hemorrhage, and periventricular leukomalacia (PVL). The IIB brain had white matter gliosis, PVL, and perivascular calcifications, but was normally developed. Of the five type IIA brains, two showed migrational defects with coexisting PVL and gliosis, two were normally developed with similar white matter injuries, and one was grossly normal. These findings support the contention that collagen mutations might negatively impact CNS development.
Adult↗
Mutations in type I collagen genes resulting in osteogenesis imperfecta in humans.
Osteogenesis imperfecta (OI), commonly known as "brittle bone disease", is a dominant autosomal disorder characterized by bone fragility and abnormalities of connective tissue. Biochemical and molecular genetic studies have shown that the vast majority of affected individuals have mutations in either the COL1A1 or COL1A2 genes that encode the chains of type I procollagen. OI is associated with a wide spectrum of phenotypes varying from mild to severe and lethal conditions. The mild forms are usually caused by mutations which inactivate one allele of COL1A1 gene and result in a reduced amount of normal type I collagen, while the severe and lethal forms result from dominant negative mutations in COL1A1 or COL1A2 which produce structural defects in the collagen molecule. The most common mutations are substitutions of glycine residues, which are crucial to formation and function of the collagen triple helix, by larger amino acids. Although type I collagen is the major structural protein of both bone and skin, the mutations in type I collagen genes cause a bone disease. Some reports showed that the mutant collagen can be expressed differently in bone and in skin. Since most mutations identified in OI are dominant negative, the gene therapy requires a fundamentally different approach from that used for genetic-recessive disorders. The antisense therapy, by reducing the expression of mutant genes, is able to change a structural mutation into a null mutation, and thus convert severe forms of the disease into mild OI type I.
Collagen Type I↗
Diminished type I collagen synthesis and reduced alpha 1(I) collagen messenger RNA in cultured fibroblasts from patients with dominantly inherited (type I) osteogenesis imperfecta.
Type I osteogenesis imperfecta (OI) is characterized clinically by a moderate fracture frequency with minimal bone deformity and dominant inheritance. Previous studies of the collagenous proteins synthesized by dermal fibroblasts obtained from unrelated patients with this form of OI suggested that the biochemical basis of the disease was reduced production of type I collagen. This study was designed to determine if this biochemical finding segregated with the disease within an individual family. Dermal fibroblast strains were established from three generations of a family having the typical features of type I OI. Analysis of the collagenous proteins made in culture revealed an elevated alpha 1(III) to alpha 1(I) collagen type ratio and an elevated alpha 1(I) to alpha 2(I) collagen chain ratio. The procollagen that accumulated in the medium reflected these ratios to the same degree. Total collagen synthesis was significantly reduced in affected family members. Therefore, the most striking abnormality in affected members was a 50-75% reduction of type I collagen production. Furthermore, the ratio of the alpha 1(I)/alpha 2(I) collagen messenger RNA (mRNA), measured by dot hybridization, was one-half of the value of uninvolved family members and unrelated controls. Since the reduction in the production of type I collagen and the altered alpha 1(I)/alpha 2(I) mRNA ratio clearly segregated with affected individuals within this family, these biochemical measurements may be a useful genetic marker for type I OI.
Adult↗
[The radiotherapy of hyperplastic heterotopic ossification in osteogenesis imperfecta. 2 case reports].
PURPOSE: Osteogenesis imperfecta is a rare hereditary disease of connective tissue with a genetic defect in collagen synthesis. In osteogenesis imperfecta hyperplastic heterotopic ossification can be induced by hyperplastic callus formation caused by trauma or operation. Heterotopic ossifications can be found in numerous benign diseases. The successful use of low dose radiotherapy in the treatment of heterotopic ossifications is well-known from the literature. PATIENTS AND METHODS: We treated two children (a 13-year-old girl and a ten-year-old boy) with heterotopic ossifications of the lower extremities in osteogenesis imperfecta type IV (Lobstein) with a low dose irradiation (10 x 1 Gy, respectively 6 x 1 Gy) under megavoltage conditions. RESULTS: After radiotherapy the children were painfree and the hyperplastic callus was considerably reduced. The previously immobilized patients could partly be mobilized. Thereby it could be contributed to the rehabilitation of the patients. New hyperplastic callus formation was not observed in the irradiated areas so far. CONCLUSION: Analogous to the successful radiation of heterotopic ossifications in other benign diseases radiation therapy seems to be a successful treatment of hyperplastic callus formation in osteogenesis imperfecta. Despite the late risks of radiotherapy radiation treatment of benign diseases in children might be indicated.
Adolescent↗