However, more recent studies have also found some cases of autosomal recessive in nature. However, it is a systemic disorder, as evidenced by the occurrence of ocular complications, dentinogenesis imperfecta, hearing loss, joint. Metabolism molecular endocrinology es journals portal. Although there is no cure for oi, symptoms can be managed. Oi is most commonly due to a variation mutation in either the collagen genes col1a1 or col1a2 gene, which cause oi types i through iv. Although oi is considered a single disease, oi includes over 16 genotypes and clinical phenotypes with differing symptom severity. Osteogenesis imperfecta is a complex multisystem disorder characterised by bone fragility, frequent fractures and bony deformity, sarcopenia, ligamentous laxity we use cookies to enhance your experience on our website. This genetic defect accounts for almost 80% of all osteogenesis imperfecta cases 3. Neonatologia neonatal handbook 2006 free ebook download as pdf file. Osteogenesis imperfecta is characterised by all of the following features except. Mutations in several genes can cause oi but the condition is most commonly caused by mutations of colia1 or col1a2 resulting in the production of collagen which is abnormal or present in reduced amounts.
Osteogenesis imperfecta, also known as brittle bone disease, is a group of genetic disorders that mainly affect the bones. There are at least four clinical subtypes, most of which have an autosomal dominant inheritance, but new mutations occur, especially in the lethal forms. N2 the normal structure of skin consists of the epidermis, dermis and subcutaneous fat. It is characterised by bone fragility due to low bone mass giving an increased fracture incidence kocher and shaprio, 1998. Complications may include cervical artery dissection and aortic dissection. There are at least four clinical subtypes, most of which have an autosomal dominant inheritance, but. Treatment depends mainly on the severity of the disease with the primary goal to minimize fractures and maximize function. Multiple fractures are common, and in severe cases, can even occur before birth. Osteogenesis imperfecta, perioperative bleeding, and. The major cause of osteogenesis imperfecta is a mutation in the genes that produce collagen. It has an etiology related directly or indirectly to type i collagen, the most abundant.
Osteogenesis imperfecta oi can be recognized prenatally with ultrasound. Pathophysiology and therapeutic options in osteogenesis imperfecta. Osteogenesis imperfecta oi is a heterogeneous group of genetic. Nearly ninety percent are due to type i collagen mutations. Chu ml, williams cj, pepe g, hirsch jl, prockop dj, ramirez f.
Fewer than 10 percent of oi cases are believed to be caused by recessive mutations in other genes in the collagen pathway. Osteogenesis imperfectapathophysiology and therapeutic. Oi is marked by considerable clinical and genetic heterogeneity. Type ii also known as perinatally lethal osteogenesis imperfecta. Type i also known as classic nondeforming osteogenesis imperfecta with blue sclerae is the mildest form of osteogenesis imperfecta. 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. Osteogenesis imperfecta is a common heritable connective tissue disorder. Most prominent signs are fractures due to low traumata. Cell and gene therapies as potential treatments for oi are therefore.
In 95% of cases, oi is caused by mutations in the col1a1 and co. Osteogenesis imperfecta, also known as brittle bone disease, is a genetic disorder that causes bones to break easily without cause. Oi is defined by a continuum of phenotypes ranging from individuals with perinatal lethal oi, severe skeletal deformities, dentinogenesis imperfecta di and severe short stature to individuals with normal stature, dentition and. Osteogenesis imperfecta oi is the term used to describe a group of rare inherited skeletal disorders characterized by a greatly increased risk of fragility fractures 1. Fractures and bone deformities occur with trivial trauma. Airway management with proseal lma in a patient with osteogenesis. Reduced bone mass 7 and abnormalities of cortical thickness and trabecular architecture play a role 8 but these abnormalities are compounded by defects in bone matrix, which profoundly affect bone quality.
Osteogenesis imperfecta also known as brittle bone disease or oi is a genetic condition that causes a defect in a protein found in bonescalled collagen. Symptoms and classification of oi osteogenesis imperfecta. Osteogenesis imperfecta oi, also known as brittle bone disease, is an inherited disorder of the connective tissue. The collagen genes play a role in how the body makes collagen, a material that helps to strengthen the bones. Osteogeneis imperfecta glass bone disease 1 brittle bone disease lobsteins disease 2 porak and durantes disease 3 definitiondiagnosis criteria osteogenesis imperfecta oi is a group of orphan diseases characterized by varying degrees of skeletal fragility. Other names for oi are lobstein disease, brittlebone disease, bluesclera syndrome, and fragilebone disease. Depending on its severity, affected individuals can live a mostly unrestricted, independent life, or they are severely impaired in their mobility, require a wheelchair, and may depend on the support of caregivers. Management of patients with oi involves medical treatment by bisphosphonates as the most promising therapy to inhibit bone resorption and. Osteogenesis imperfecta pathophysiology, genetics, causes. Mar 26, 2021 osteogenesis imperfecta oi is a group of genetic disorders that mainly affect the bones. The overall treatment goal for children with oi is to maximize mobility. It is now known that osteogenesis imperfecta is one of the most common skeletal dysplasias, affecting approximately 6 to.
Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta. Osteogenesis imperfecta oi is an inherited connective tissue disorder with many phenotypic presentations. The disease may cause cardiac valvular lesions, kidney stones, neurologic abnormalities, and. Osteogenesis imperfect results from autosomal dominant inheritance of gene defects of connective tissue formation. Anesthetic considerations for pediatric patients with. Individuals with this disorder will produce less collagen than needed, which causes the bone development to be endangered. Osteogenesis imperfecta oi, also known as brittle bone disease, is a group of genetic disorders that mainly affect the bones. Its major feature is a fragile skeleton, but many other body systems are also affected.
There are four types of osteogenesis imperfecta, which vary greatly in how severe they are. Skin in osteogenesis imperfecta johns hopkins university. It is a generalized disease of connective tissue in 1835, lobstein coined the term osteogenesis imperfecta and was one of the first to correctly understand the etiology of the condition. Osteogenesis imperfecta an overview sciencedirect topics.
Oi is caused by defects in or related to a protein called type 1 collagen pronounced koluhjuhn. Osteogenesis imperfecta nursing care management and study guide. Osteogenesis imperfecta was classified several years ago into four types based on clinical, radiological and genetic features sillence, 1988. Osteogenesis imperfecta oi, or brittle bone disease, is a rare genetic connective tissue disorder characterized by severe bone fragility. Transplantation of mesenchymal stem cells mscs has the. Osteogenesis imperfectapathophysiology and therapeutic options. A person who has this defect has either less collagen or a poorer quality of collagen than normal, leading to weak bones that fracture easily. Jay r shapiro, caressa lietman, monica grover, james t lu, sandesh cs nagamani, brian c dawson, dustin m baldridge, matthew n bainbridge, dan h cohn, maria blazo, timothy t roberts, fengshu.
People with this condition have bones that break fracture easily, often from mild trauma or with no apparent cause. Aug 14, 2020 osteogenesis imperfecta oi is a rare congenital disease with a wide spectrum of severity characterized by skeletal deformity and increased bone fragility as well as additional, variable extraskeletal symptoms. Osteogenesis imperfecta oi is a rare clinically and genetically heterogeneous systemic disorder of bone and connective tissue characterized by bone fragility and physical findings related to the underlying connective tissue disorder. Collagen is the main protein that works toward the production of connective tissue. Gene therapy approaches for osteogenesis imperfecta gene therapy. Osteogenesis imperfecta is a complex multisystem disorder characterised by bone fragility, frequent fractures and bony deformity, sarcopenia, ligamentous laxity. Most commonly, however, oi presents in childhood with multiple fractures and related complications. Feb 24, 2020 osteogenesis imperfecta oi is a disorder of bone fragility chiefly caused by mutations in the col1a1 and col1a2 genes that encode type i procollagen. Osteogenesis imperfecta oi is a generalized disorder of connective tissue manifested by bone fragility, blue sclerae, and other variable soft tissue manifestations. What causes osteogenesis imperfecta and its clinical characteristics. However, it is a systemic disorder, as evidenced by the occurrence of ocular complications, dentinogenesis imperfecta, hearing loss, joint laxity, restrictive pulmonary disease, and short stature. In 95% of cases, oi is caused by mutations in the col1a1 and col1a2 genes 17q21. Frontiers management of osteogenesis imperfecta endocrinology. Osteogenesis imperfecta gillette childrens specialty healthcare.
The body uses type 1 collagen to make bones strong and to build tendons, ligaments, teeth, and the whites of the eyes. Oi is caused by a mutation change in a gene that affects bone formation, bone strength and the structure of other tissues. Apr 26, 2009 abstract osteogenesis imperfecta oi is the most common of the inherited connective tissue disorders that primarily affect bone. This collagen is needed to produce sturdy and strong bone, dentin, sclera, and ligaments in the body. A mutation in the 5utr of ifitm5 creates an inframe start codon and causes autosomaldominant osteogenesis imperfecta type v with hyperplastic callus. Osteogenesis imperfecta oi is a heritable bone dysplasia. F care for broken bones f care for brittle teeth f pain medication f physical therapy f use of wheelchairs, braces, and other aids f surgery such as rodding.
A single recurrent mutation in the 5utr of ifitm5 causes osteogenesis imperfecta type v. Osteogenesis imperfecta oi, also known as brittlebone disease, is a genetic inherited disorder characterized by bones that break easily without a specific cause. A child born with oi may have soft bones that fracture easily, bones that are not formed normally, and other problems. Osteogenesis imperfecta, pathophysiology, genetic heterogeneity, therapy, bisphosphonates introduction osteogenesis imperfecta oi is a congenital disease which presents with a wide range of phenotypes. Osteogenesis imperfecta, bone, type i collagen, gene mutation, bisphosphonate therapy, classification. Osteogenesis imperfecta oi is a rare congenital disease with a wide spectrum of severity characterized by skeletal deformity and increased.
Osteogenesis imperfecta oi is a group of genetic disorders that mainly affect the bones. Collagen is an essential building block of the body. Osteogenesis imperfecta is a rare hereditary disease mostly caused by mutations impairing collagen synthesis and modification. A classification system of different types of oi is commonly used to help describe how severely a person with oi is affected. Osteogenesis imperfecta oi is a rare, complicated and variable disorder. The term osteogenesis imperfecta means imperfect bone formation. Pathophysiology and therapeutic options in osteogenesis. Osteogenesis imperfecta oi is a disorder of bone fragility chiefly caused by mutations in the col1a1 and col1a2 genes that encode type i. By continuing to use our website, you are agreeing to our use of cookies.
Jan, 2001 in osteogenesis imperfecta causal mutations in the genes for type i collagen explain the skeletal fragility, but the clinical range is wide and the relation between genotype and phenotype complex. Osteogenesis imperfecta oi is a rare, heritable systemic disorder of bone and connective tissue, which in almost 90% of cases is due to mutations affecting the normal synthesis of type i collagen. Osteogenesis imperfecta is a heterogenous group of inherited disorders of collagen type i caused by mutations of the col1a1 or col1a2 genes. Osteogenesis imperfecta is a genetic disorder that causes increased bone fractures and collagen defects.
The underlying mechanism is usually a problem with connective tissue d. In individuals with osteogenesis imperfecta there is evidence of an imbalance in this process. Osteogenesis imperfecta overview nih osteoporosis and. Osteogenesis imperfecta oi is a condition that is caused by a genetic defect. A mutation in the 5utr of ifitm5 creates an inframe start codon and causes autosomaldominant osteogenesis imperfecta type. Osteogenesis imperfecta in children what is osteogenesis imperfecta. It has an etiology related directly or indirectly to type i coll. Osteogenesis imperfecta oi is a heterogeneous disease of connective tissue, the. The main causes for developing the disorder are a result of mutations in the col1a1 and col1a2 genes which are responsible for the production of collagen type 1. Treatment of osteogenesis imperfecta by bisphosphonate therapy can improve bone mass in all types of the disorder, and while not being a cure for the disorder does improve the quality of life of the patient. In 1979, four oi phenotypes were categorized which were inherited as autosomal dominant characteristics.
Fast facts on osteogenesis imperfecta definition osteogenesis imperfecta oi is a genetic disorder characterized by bones that break easily, often from little or no apparent cause. Type iiv are autosomal dominant, and type vixiii are. Pathophysiology of bone fragility in osteogenesis imperfecta bone fragility is greatly increased in osteogenesis imperfecta. Jan 01, 2018 osteogenesis imperfecta oi is a disorder of bone characterized by hypomineralization of the skeleton and by lifelong bone fragility and fracture predisposition. Phenotypic variability of osteogenesis imperfecta type v caused by an ifitm5 mutation. Osteogenesis imperfecta type 1 is the mildest form of oi and is characterized by bone fractures during childhood and adolescence that often result from minor trauma. Nih osteoporosis and related bone diseases national resource center. Osteogenesis imperfecta type i genetic and rare diseases. Nov 09, 2016 osteogenesis imperfecta 5 pathophysiology in most cases, oi is caused by a dominant mutation in the col1a1 or the col1a2 genes that encode type i collagen. Osteogenesis imperfecta oi comprises a heterogeneous group of genetic disorders characterized by increased. Clocksstriggered archive article metadata 04 mar 2020.
Other symptoms may include a blue tinge to the whites of the eye, short height, loose joints, hearing loss, breathing problems and problems with the teeth. The basic pathophysiology seen osteogenesis imperfecta is the absence of one of the two genes responsible for the production of collagen type 1. Osteogenesis imperfecta type iv, 2, i, ii, pictures, symptom. Consensus statement on physical rehabilitation in children and. A moderate form of osteogenesis imperfecta characterized by increased bone fragility and low bone mass that clinically. Four types of osteogenesis imperfecta were originally described by sillence in 1979 and are now used broadly as the sillence criteria. Oi can be inherited from parents, but some cases may also be a result of sporadic. Here, we present an overview of the genetic heterogeneity and pathophysiological background of oi as well as oirelated bone fragility disorders and highlight current therapeutic. Osteogenesis imperfecta oi may be caused by changes mutations in any of several genes.
Osteogenesis imperfecta oi is a genetic disorder causing increased. Osteogenesis imperfecta oi is the most common of the inherited connective tissue disorders that primarily affect bone. Osteogenesis imperfecta columbia orthopedic surgery. Osteogenesis imperfecta oi is a heritable disorder of bone formation that may affect more than 1. Thus in type i osteogenesis imperfecta a nonfunctional allele for type i collagen halves collagen synthesis and causes mild bone disease. Neonatologia neonatal handbook 2006 blood pressure. The mutated genes the specific osteogenesis imperfecta causes are known as the col1a1 and col1a2 genes. Anesthetic implications for the patient with osteogenesis. The condition affects the bodys ability to produce collagen, a protein in the bodys connective tissue. The two genes primarily affected have been identified and are named col1a1 found on chromosome 17 and col1a2 found on chromosome 7.
Notwithstanding the advances in genetic and biochemical pathophysiology of oi, there is probably still utility in typing oi to provide patients and. Dec 02, 2015 osteogenesis imperfecta oi is a group of genetic disorders that mainly affect the bones. Historically, oi has been grouped into four major types iiv, with oi type ii defined as perinatal lethal. Depending on its severity, affected individuals can live a. Increasingly, genetic causes are used to define rarer forms of osteogenesis imperfecta. Osteogenesis imperfecta oi is a congenital disease which presents with a wide range of phenotypes.
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