What is Osteogenesis Imperfecta?

Osteogenesis Imperfecta (OI) – also known as OI or ‘brittle bone disease’ is a rare genetic disease of bone and connective tissue. The diagnose is known all around the world and occurs regardless of gender or ethnic origin.

Characteristics

Major characteristics of OI are:

  • bone fragility
  • short stature (but people can also have normal height)
  • scoliosis and other skeletal deformities
  • loose joints
  • blue sclerae
  • hearing impairment
  • dentinogenesis imperfecta
  • fragile teeth

Causes of OI

OI is caused by a genetic defect resulting in insufficient production or imperfectly formed collagen, which is the main component of connective tissue such as bone. OI can affect all parts of the body involving collagen including eyes and internal organs. In around 90 per cent of the cases OI is due to mutations in type I collagen. But in later years many rare forms of OI caused by other genes than type I collagen (see table) have been discovered. However – all the genes coding for OI are related to the formation and resorption of bone.

Inheritance

Inheritance of OI is usually dominant (approximately 90 percent of the cases), which means that an OI-gene from one parent can cause disease, even though the matching gene from the other parent is normal. New mutations also occur which can be passed on to future generations in a dominant way (50 per cent chance of having a child with OI). Rare recessive forms of OI also exist (approximately 10 percent), where OI is inherited from two healthy parents who carry the OI-gene.

Classification

OI has been classified into several clinical types based on severity. Within one clinical type (and severity), OI can however be caused by different genetic mutations. Until recently each newly discovered gene was given a new number in the classification system (OI type VI - …) but since 2015/2016 it has been more common to divide OI into five types based on clinical type/severity and in addition include the specific mutations + mode of inheritance.

Even if a genetic cause is not found – OI can still be diagnosed clinically. There are still mutations causing OI waiting to be found and/or described. There is a large variation in how severely a person is affected.

OI nameClinical typeGene mutationInheritance

Non-deforming OI with blue sclerae

I

COL1A1, COL1A2

Dominant

Common variable OI with normal sclerae

IV

COL1A1, COL1A2

WNT1

CRTAP, PPIB

PLS3

Dominant

Dominant

Recessive

X-linked

OI with calcification in interosseous membranes

V

IFITM5

Dominant

Progressively deforming OI

III

COL1A1, COL1A2

BMP1, CRTAP, FKBP10

LEPRE1, PLOD2, PPIB

SERPINF1, SERPINH1

TMEM38, WNT1

CREB3L1

Dominant

Recessive

Recessive

Recessive

Recessive

Recessive

Perinatally lethal OI

II

COL1A1, COL1A2

CRTAP, LEPRE1, PPIB

Dominant

Recessive

At present OI cannot be cured. Treatment is aimed at preventing or correcting its symptoms. This usually involves orthopaedic surgery and physiotherapy, possibly the prescription of certain drugs and sometimes audiological or dental treatment.

Mutual support through the exchange of experience and information is of prime importance, both for those affected and for their families.

OI can lead to physical disability, requiring the use of crutches, wheelchair or other mobility aids. The use of hearing aids are also common and some get cochlea implants. People with OI usually rely more on their intellect than on physical strength and therefore benefit from the best possible education

People with OI mostly have a positive attitude to life, develop skills and pursue careers. Under favorable circumstances they can lead quite independent and happy lives in spite of disabilities. Many live with partners and have families of their own.

For more detailed information about OI in English we advice you to check out the information from our member organizations BBS and OIF:  

See also scientific overview articles and books about OI (free available):