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Disease Profile

Osteogenesis imperfecta

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

All ages

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ICD-10

Q78.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

OI; Brittle bone disease; Vrolik disease;

Categories

Congenital and Genetic Diseases

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]

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.

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
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
Decreased bone formation of skull
0004331
Diaphyseal thickening
Thickening of shaft or central part of long bones
0005019
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Mixed hearing impairment
Hearing loss, mixed
Mixed hearing loss

[ more ]

0000410
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
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Bone pain
0002653
Corneal opacity
0007957
Cutis laxa
Loose and inelastic skin
0000973
Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches

[ more ]

0000689
Dentinogenesis imperfecta
0000703
Enlarged vertebral pedicles
0004621
Femoral bowing
Bowed thighbone
0002980
Fractures of the long bones
0003084
Genu valgum
Knock knees
0002857
Glaucoma
0000501
Hypercalciuria
Elevated urine calcium levels
0002150
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Large fontanelles
Wide fontanelles
0000239
Loss of ability to walk
0006957
Multiple rib fractures
0006640
Narrow chest
Low chest circumference
Narrow shoulders

[ more ]

0000774
Osteopenia
0000938
Osteoporosis
0000939
Progressive hearing impairment
0001730
Slender long bone
Long bones slender
Thin long bones

[ more ]

0003100
Vertebral compression fractures
Compression fracture
0002953
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
5%-29% of people have these symptoms
Abnormal endocardium morphology
0004306
Arthralgia
Joint pain
0002829
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising

[ more ]

0000978
Calcification of the interosseus membrane of the forearm
0030267
Constipation
0002019
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Dislocated radial head
0003083
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Flexion contracture
Flexed joint that cannot be straightened
0001371
Hyperplastic callus formation
0030268
Inguinal hernia
0000023
Intestinal obstruction
Bowel obstruction
Intestinal blockage

[ more ]

0005214
Micromelia
Smaller or shorter than typical limbs
0002983
Nephrolithiasis
Kidney stones
0000787
Osteoarthritis
Degenerative joint disease
0002758
Paresthesia
Pins and needles feeling
Tingling

[ more ]

0003401
Pectus excavatum
Funnel chest
0000767
Protrusio acetabuli
0003179
Relative macrocephaly
Relatively large head

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)

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.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    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.

      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

        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

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Osteogenesis imperfecta. This website is maintained by the National Library of Medicine.
        • 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.

            References

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

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