Osteogenesis imperfecta

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

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. 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: 10/6/2015

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of dental color	Very frequent (present in 80%-99% of cases)
Abnormality of dental enamel	Very frequent (present in 80%-99% of cases)
Abnormality of the metaphysis	Very frequent (present in 80%-99% of cases)
Abnormality of tibia morphology	Very frequent (present in 80%-99% of cases)
Blue sclerae	Very frequent (present in 80%-99% of cases)
Brachycephaly	Very frequent (present in 80%-99% of cases)
Carious teeth	Very frequent (present in 80%-99% of cases)
Convex nasal ridge	Very frequent (present in 80%-99% of cases)
Decreased skull ossification	Very frequent (present in 80%-99% of cases)
Dentinogenesis imperfecta	Very frequent (present in 80%-99% of cases)
Diaphyseal thickening	Very frequent (present in 80%-99% of cases)
Gait disturbance	Very frequent (present in 80%-99% of cases)
Intrauterine growth retardation	Very frequent (present in 80%-99% of cases)
Macrocephaly	Very frequent (present in 80%-99% of cases)
Micrognathia	Very frequent (present in 80%-99% of cases)
Pectus carinatum	Very frequent (present in 80%-99% of cases)
Prominent occiput	Very frequent (present in 80%-99% of cases)
Thin ribs	Very frequent (present in 80%-99% of cases)
Abnormal cortical bone morphology	Frequent (present in 30%-79% of cases)
Biconcave vertebral bodies	Frequent (present in 30%-79% of cases)
Corneal opacity	Frequent (present in 30%-79% of cases)
Femoral bowing	Frequent (present in 30%-79% of cases)
Genu valgum	Frequent (present in 30%-79% of cases)
Glaucoma	Frequent (present in 30%-79% of cases)
Hyperhidrosis	Frequent (present in 30%-79% of cases)
Joint hyperflexibility	Frequent (present in 30%-79% of cases)
Large fontanelles	Frequent (present in 30%-79% of cases)
Narrow chest	Frequent (present in 30%-79% of cases)
Osteopenia	Frequent (present in 30%-79% of cases)
Osteoporosis	Frequent (present in 30%-79% of cases)
Protrusio acetabuli	Frequent (present in 30%-79% of cases)
Scoliosis	Frequent (present in 30%-79% of cases)
Slender long bone	Frequent (present in 30%-79% of cases)
Triangular face	Frequent (present in 30%-79% of cases)
Visual impairment	Frequent (present in 30%-79% of cases)
Abnormality of the endocardium	Occasional (present in 5%-29% of cases)
Hearing impairment	Occasional (present in 5%-29% of cases)
Inguinal hernia	Occasional (present in 5%-29% of cases)
Kyphosis	Occasional (present in 5%-29% of cases)
Micromelia	Occasional (present in 5%-29% of cases)
Pectus excavatum	Occasional (present in 5%-29% of cases)
Recurrent fractures	Occasional (present in 5%-29% of cases)
Thrombocytopenia	Occasional (present in 5%-29% of cases)
Umbilical hernia	Occasional (present in 5%-29% of cases)
Visceral angiomatosis	Occasional (present in 5%-29% of cases)
Wormian bones	Occasional (present in 5%-29% of cases)

Last updated: 9/1/2017

Cause Cause

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

OI is most commonly due to a mutation in either the COL1A1 or COL1A2 gene, causing OI types I through IV. These 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 mutation has on normal collagen production.^[3] OI caused by mutations in these genes is inherited in an autosomal dominant manner. In about 10% of people with OI, the COL1A1 and COL1A2 genes are normal and the condition is due to mutations in other genes; many of these people have an autosomal recessive form of OI.^[3]^[4]

Other genes in which mutations may be responsible for less common types of OI, some of which have been reported in only one individual or family, include:

IFITM5 (type V)
SERPINF1 (type VI)
CRTAP (type VII)
LEPRE1, also called P3H1 (type VIII)
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: 10/7/2015

Inheritance Inheritance

Osteogenesis imperfecta (OI) is most commonly inherited in an autosomal dominant manner. 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.^[5] If the child inherits the mutated gene, the child's symptoms may be milder, or more severe, than those of the parent.^[6]

Less commonly, OI is inherited in an autosomal recessive manner. 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.

Last updated: 10/9/2015

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.^[7] 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.^[7]

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

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.
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.

Do you have updated information on this condition? Let us know.

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 studying or have studied 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: 03330 116 388
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? Send us your suggestions.

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

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

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017
2016 Osteogenesis Imperfecta Foundation National Conference
July 19, 2016

NCATS Co-Sponsored Conferences

2015 Collagen Gordon Research Conference and Gordon Research Seminar Sunday, July 12, 2015 - Friday, July 17, 2015
Location: New London, NH
Description: The 2015 Collagen GRC program will include invited and platform presentations as well as posters on (a) new data and concepts about the genetics, chemistry, biology and pathology of collagens; (b) advances in closely related areas of research, such as cell-matrix interactions, developmental biology and diseases of connective tissues, and bioengineering, that are relevant to the collagen field; (c) new and emerging technologies and approaches that may be applied to the collagen field.

Contact: Hung Tseng, Ph.D., (301) 496-0810, tsengh@mail.nih.gov

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Rare Diseases Research
Assessing the Impact of Osteogenesis Imperfecta on Non-Skeletal Systems Wednesday, April 18, 2012 - Friday, April 20, 2012
Location: Sheraton Gateway Suites, Rosemont, IL
Description: This meeting will focus on the impact of abnormal collagen on health in an effort to broaden professional awareness of the full spectrum of issues faced by persons with OI as they age. The goals are: 1)-to review current knowledge regarding the impact of OI on a wide range of bodily systems during the aging process, 2)-identify major information gaps, 3)-make recommendations to expand the OI research agenda. A Workshop Report will be compiled following the meeting in order to share these findings with health professionals and the OI community.

Contact: Theresa Smith, NIAMS(301) 435-5595smiththe@mail.nih.gov

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Rare Diseases Research
Improving Musculoskeletal Outcomes for Individuals with Osteogenesis Imperfecta Wednesday, April 7, 2010 - Friday, April 9, 2010
Location: Sheraton Gateway Suites, Rosemont, Illinois
Description: The goals of this workshop were to (1) assess the state of knowledge regarding the musculoskeletal aspects of aging with osteogenesis imperfecta (OI); (2) explore the potential for new diagnostic and therapeutic techniques for OI; and (3) build a consensus on essential measures for documenting OI treatment outcomes.

Contact: Dr. Theresa Smith, NIAMS(301) 435-5595smiththe@mail.nih.gov

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Rare Diseases Research
- Agenda ( - 36KB)
- Report ( - 17KB)

Related Diseases Related Diseases

The following diseases are related to Osteogenesis imperfecta. If you have a question about any of these diseases, you can contact GARD.

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;
Eric T Rush. Genetics of Osteogenesis Imperfecta. Medscape Reference. October 3, 2014; http://emedicine.medscape.com/article/947588-overview.
Steiner RD, Pepin MG, Byers PH. Osteogenesis Imperfecta. GeneReviews. 2005; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=oi. Accessed 4/29/2009.
Krakow D. OI Issues: Pregnancy Considerations for women with OI. Osteogenesis Imperfecta Foundation. 2007; http://www.oif.org/site/PageServer?pagename=PregOI. Accessed 4/29/2009.
Robert D Steiner, Melanie G Pepin, Peter H Byers. Osteogenesis Imperfecta. GeneReviews. January 28, 2005; http://www.ncbi.nlm.nih.gov/books/NBK1295/. Accessed 10/5/2011.
Osteogenesis imperfecta. Genetics Home Reference (GHR). 2007; http://ghr.nlm.nih.gov/condition=osteogenesisimperfecta. Accessed 11/11/2011.