Osteogenesis imperfecta

Información en español Title

Other Names:

OI; Brittle bone disease; Vrolik disease; OI; Brittle bone disease; Vrolik disease; Fragilitas ossium; Lobstein disease; Osteopsathyrosis; Porak and Durante disease See More

Categories:

Congenital and Genetic Diseases

Subtypes:

Osteogenesis imperfecta Levin type; Osteogenesis imperfecta type I; Osteogenesis imperfecta type II; Osteogenesis imperfecta Levin type; Osteogenesis imperfecta type I; Osteogenesis imperfecta type II; Osteogenesis imperfecta type III; Osteogenesis imperfecta type IV; Osteogenesis imperfecta type IX; Osteogenesis imperfecta type V; Osteogenesis imperfecta type VI; Osteogenesis imperfecta type VII; Osteogenesis imperfecta type VIII; Osteogenesis imperfecta type X See More

This disease is grouped under:

Osteogenesis imperfecta type XI

Summary Summary

Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. People with this condition have bones that break easily, often from little or no trauma, however, severity varies among affected people. Multiple fractures are common, and in severe cases, can even occur before birth. Milder cases may involve only a few fractures over a person's lifetime. People with OI also have dental problems (dentinogenesis imperfecta) and hearing loss in adulthood. Other features may include muscle weakness, loose joints, and skeletal malformations.^[1]^[2] There are various recognized forms of OI which are distinguished by their features and genetic causes.^[3] Depending on the genetic cause, OI may be inherited in an autosomal dominant (more commonly) or autosomal recessive manner. Treatment is supportive and aims to decrease the number of fractures and disabilities.^[1]^[2]

Last updated: 2/16/2018

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 47 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of dental color	Abnormality of tooth color Abnormality of tooth shade [ more ]	0011073
Abnormality of dental enamel	Abnormal tooth enamel Enamel abnormalities Enamel abnormality [ more ]	0000682
Abnormality of the metaphysis	Abnormality of the wide portion of a long bone	0000944
Abnormality of tibia morphology	Abnormality of the shankbone Abnormality of the shinbone [ more ]	0002992
Blue sclerae	Whites of eyes are a bluish-gray color	0000592
Brachycephaly	Short and broad skull	0000248
Carious teeth	Dental cavities Tooth cavities Tooth decay [ more ]	0000670
Convex nasal ridge	Beaked nose Beaklike protrusion Hooked nose Polly beak nasal deformity [ more ]	0000444
Decreased skull ossification		0004331
Dentinogenesis imperfecta		0000703
Diaphyseal thickening		0005019
Gait disturbance	Abnormal gait Abnormal walk Impaired gait [ more ]	0001288
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Pectus carinatum	Pigeon chest	0000768
Prominent occiput	Prominent back of the skull Prominent posterior skull [ more ]	0000269
Thin ribs	Slender ribs	0000883
30%-79% of people have these symptoms
Abnormal cortical bone morphology		0003103
Biconcave vertebral bodies		0004586
Corneal opacity		0007957
Femoral bowing	Bowed thighbone	0002980
Genu valgum	Knock knees	0002857
Glaucoma		0000501
Hyperhidrosis	Excessive sweating Increased sweating Profuse sweating Sweating Sweating profusely Sweating, increased [ more ]	0000975
Joint hyperflexibility		0005692
Large fontanelles	Wide fontanelles	0000239
Narrow chest	Low chest circumference Narrow shoulders [ more ]	0000774
Osteopenia		0000938
Osteoporosis		0000939
Protrusio acetabuli		0003179
Scoliosis	Abnormal curving of the spine	0002650
Slender long bone	Long bones slender Thin long bones [ more ]	0003100
Triangular face	Face with broad temples and narrow chin Triangular facial shape [ more ]	0000325
Visual impairment	Impaired vision Loss of eyesight Poor vision [ more ]	0000505
5%-29% of people have these symptoms
Abnormal endocardium morphology		0004306
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Inguinal hernia		0000023
Kyphosis	Hunched back Round back [ more ]	0002808
Micromelia		0002983
Pectus excavatum	Funnel chest	0000767
Recurrent fractures	Increased fracture rate Increased fractures Multiple fractures Multiple spontaneous fractures Varying degree of multiple fractures [ more ]	0002757
Short stature	Decreased body height Small stature [ more ]	0004322
Thrombocytopenia	Low platelet count	0001873
Umbilical hernia		0001537
Visceral angiomatosis		0100761
Wormian bones	Extra bones within cranial sutures	0002645

Showing of 47 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2018

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Osteogenesis imperfecta (OI) may be caused by changes (mutations) in any of several genes.

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. The collagen genes play a role in how the body makes collagen, a material that helps to strengthen the bones. The type and severity of OI depends on the effect that the specific variation has on normal collagen production.^[3] OI caused by mutations in these genes is inherited in an autosomal dominant manner. Most of the variations that cause OI type I occur in the COL1A1 gene.

In about 10% of people with OI, the COL1A1 and COL1A2 genes are normal and the condition is due to variations in other genes; many of these people have an autosomal recessive form of OI.^[3]^[4] Variation in the CRTAP gene usually cause OI type VII; and variations in the LEPRE1 gene (also called P3H1 gene) are classified as type VIII.

Types V and VI do not have a type 1 collagen variation, but the genes causing them have not yet been identified. However, there are other genes in which variations may be responsible for these types or other less common types of OI, which have been reported in only one individual or family:

IFITM5 (type V)
SERPINF1 (type VI)
PPIB (type IX)
SERPINH1 (type X)
FKBP10 (type XI)
SP7 (type XII)
BMP1 (type XIII)
TMEM38B (type XIV)
WNT1 (type XV)
SPARC (type XVII)

Last updated: 2/16/2018

Inheritance Inheritance

Osteogenesis imperfecta (OI) types I, II, III, IV, V and VI, are inherited in an autosomal dominant manner.^[5]^[1] This means that having only one changed (mutated) copy of the responsible gene in each cell is enough to cause features of OI. The mutated copy of the gene may be inherited from an affected parent, or it may occur for the first time in an affected person (a de novo mutation). When a person with an autosomal dominant form of OI has children, each child has a 50% (1 in 2) chance of inheriting the mutated gene.^[6] If the child inherits the mutated gene, the child's symptoms may be milder, or more severe, than those of the parent.^[7]

OI subtypes VII and VIII (and some cases of type III) are inherited in an autosomal recessive manner.^[5] This means that both copies of the responsible gene in each cell must have a mutation for a person to be affected. The parents of a person with an autosomal recessive condition typically are unaffected, but each carry one mutated copy of the gene. When two carriers of an autosomal recessive form of OI have children, each child has a 25% (1 in 4) chance to be affected, a 50% (1 in 2) chance to be a carrier like each parent, and a 25% chance to be unaffected and not be a carrier.^[7]

People concerned about inheritance risks for OI should talk with a genetic professional.

Last updated: 2/16/2018

Diagnosis Diagnosis

Genetic testing is available for individuals with osteogenesis imperfecta. The rate for detecting mutations in the genes that are responsible for OI varies depending on the type.^[8] Carrier testing may be available to relatives of affected individuals if the type of OI, disease-causing gene, and specific mutation in the affected individual are known.

Prenatal testing for at-risk pregnancies can be performed by analysis of collagen made by fetal cells obtained by chorionic villus sampling (CVS) at about ten to 12 weeks' gestation if an abnormality of collagen has been identified in cells from the affected individual. Analysis of collagen after an amniocentesis (usually performed at 15-20 weeks gestation) is not useful, because the cells obtained do not produce type I collagen. However, prenatal testing can be performed by analyzing the genes (molecular genetic testing) if the specific mutation has been identified in the affected relative.^[8]

GeneTests lists the names of laboratories that are performing genetic testing for different types of osteogenesis imperfecta. To view the contact information for the clinical laboratories conducting testing, click here and click on "Testing" next to the type of OI in which you are interested. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or genetics professional. Genetics professionals, such as genetic counselors, can also explain the inheritance of OI in detail including information about genetic risks to specific family members.

Last updated: 4/5/2012

Testing Resources

Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.
Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include in utero diagnosis of chondrodysplasia, idiopathic juvenile osteoporosis, osteoporosis-pseudoglioma syndrome, Cole-Carpenter and Bruck syndromes, hyper or hypophosphatasia, panostotic form of polyostotic fibrous dysplasia (see these terms), non-accidental injury (multiple fractures without osteoporosis), and osteoporosis due to medication, nutritional deficiency, metabolic disease, or leukemia. The presence of several fractures should not lead to the assumption of child abuse. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnoses include in utero diagnosis of chondrodysplasia, idiopathic juvenile osteoporosis, osteoporosis-pseudoglioma syndrome, Cole-Carpenter and Bruck syndromes, hyper or hypophosphatasia, panostotic form of polyostotic fibrous dysplasia (see these terms), non-accidental injury (multiple fractures without osteoporosis), and osteoporosis due to medication, nutritional deficiency, metabolic disease, or leukemia. The presence of several fractures should not lead to the assumption of child abuse.

Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Osteogenesis imperfecta. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

The Brittle Bone Disorders Consortium (BBD) is an integrated group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research on Osteogenesis Imperfecta (OI). The goal of the consortium is to learn more about the disease, develop therapies, and to inform the public about the latest research and information about OI. The BBD has a contact registry for patients who wish to be contacted about clinical research opportunities and updates on the progress of the research projects.

For more information on the registry see: https://www.rarediseasesnetwork.org/registry/index.htm

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Canadian Osteogenesis Imperfecta Society
128 Thornhill Crescent
Chatham, Ontario, Canada, N7L 4M3
Canada
Telephone: 519-436-0025
E-mail: rkhayes@ccat.on.ca
Children's Brittle Bone Foundation
7701 95th Street
Pleasant Prairie, WI 53158
Telephone: 773-236-2223
Fax: 262-947-0724
E-mail: info@cbbf.org
Website: http://www.cbbf.org/
Hypermobility Syndromes Association (HMSA)
49 Greek Street
London, WD1 4EG United Kingdom
Telephone: 033 3011 6388
E-mail: http://hypermobility.org/contact-us/
Website: http://hypermobility.org/
Osteogenesis Imperfecta Foundation
804 West Diamond Avenue, Suite 210
Gaithersburg, MD 20878
Toll-free: 844-889-7579
Telephone: 301-947-0083
Fax: 301-947-0456
E-mail: bonelink@oif.org
Website: http://www.oif.org
The Brittle Bone Society
30 Guthrie Street
Dundee
DD1 5BS
United Kingdom
Telephone: (+44) 01382- 204446
Fax: (+44) 01382- 206771
E-mail: bbs@brittlebone.org
Website: http://www.brittlebone.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Osteogenesis imperfecta. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. Click on the link to view information on this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Osteogenesis imperfecta. Click on the link to view a sample search on this topic.

News & Events News & Events

News

NCATS Rare Diseases Are Not Rare! Challenge
October 9, 2018
The NIH Undiagnosed Diseases Network Expands
September 26, 2018
2016 Osteogenesis Imperfecta Foundation National Conference
July 19, 2016

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

Can a person have osteogensis imperfecta (OI) without having any fractures? Can people with osteogenesis imperfecta (OI) have bone pain in areas where a fracture wasn't present? See answer
I am a restorative dentist. I have an eight year old patient diagnosed with osteogenesis imperfecta. Her brother does not have the disease. Her parents also do not have the disease. But, her mother's father has the disease. What could be the inheritance pattern? See answer
I have a cousin with osteogenesis imperfecta. Neither of his parents has the dominant gene. Is there a genetic test that can be done to determine whether I am a carrier? See answer
What are the chances of passing osteogenesis imperfecta on to a child while pregnant? Can a vaginal delivery be perfomed or will a C-section be necessary? See answer

Have a question? Contact a GARD Information Specialist.

References References

Osteogenesis imperfecta. Genetics Home Reference. April, 2013; http://ghr.nlm.nih.gov/condition/osteogenesis-imperfecta.
Learning About Osteogenesis Imperfecta. NHGRI. August 15, 2012; http://www.genome.gov/25521839.
John F Beary, III and Arkadi A Chines. Osteogenesis imperfecta: Clinical features and diagnosis. UpToDate. Waltham, MA: UpToDate; September, 2015;
Rush ET. Genetics of Osteogenesis Imperfecta. Medscape Reference. 2016; http://emedicine.medscape.com/article/947588-overview.
Types of OI. Osteogenesis imperfecta Foundation. 2015; http://www.oif.org/site/PageServer?pagename=AOI_Types.
Steiner RD, Pepin MG & Byers PH. COL1A1/2-Related Osteogenesis Imperfecta. GeneReviews. 2013; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=oi.
Krakow D. OI Issues: Pregnancy Considerations for women with OI. Osteogenesis Imperfecta Foundation. http://www.oif.org/site/PageServer?pagename=PregOI.
Steiner RD, Pepin MG & Byers PH. COL1A1/2-Related Osteogenesis Imperfecta. GeneReviews. 2013; http://www.ncbi.nlm.nih.gov/books/NBK1295/.
Osteogenesis imperfecta. Genetics Home Reference (GHR). 2013; http://ghr.nlm.nih.gov/condition=osteogenesisimperfecta.