The several forms of osteogenesis imperfecta (OI) have been classified, representing wide variation in appearance and severity, and clinical features vary widely not only between types but within types.
Osteogenesis imperfecta was initially classified by type according to a scheme developed by David Sillence, Australian clinical geneticist, based mainly on family history, clinical presentation and radiologic findings. It has since been modified due to the advance in genetics, with the following classification described by Glorieux and Rauch. Further detail can be found on the Osteogenesis Imperfecta Foundation website 1,2,4.
Type I - mild
Type I is the commonest form (accounting for up to 50% of all cases) and is fortunately also the mildest form. It demonstrates autosomal dominant inheritance. Clinical features include:
- general bone fragility and predisposition to fracture
- stature is normal or near-normal
- loose joints and muscle weakness
- bone deformity absent or minimal
- head and neck features
- sclera often have a blue, purple, or grey tint
- brittle teeth (dentinogenesis imperfecta) differentiates between the two subtypes IA (without) and IB (with)
- predisposed to hearing loss
Type II - perinatal lethal
Type II is the most severe form and is lethal at or shortly after birth mostly due to multiple rib fractures and pulmonary hypoplasia. It results from new dominant mutations to type 1 collagen genes. Clinical features include:
Type III - progressive deforming
OI Type III is the most severe type among children who survive the neonatal period. The degree of bone fragility and the fracture rate vary widely. The majority of OI Type III cases result from dominant mutations in type I collagen genes. Clinical features include:
- at birth, infants generally have mildly shortened and bowed limbs, small chests, and a soft calvarium
- bones fracture easily; fractures are often present at birth, and x-rays may reveal healed fractures that occurred before birth
- short stature
- rotoscoliosis and vertebral compression fractures.
- the altered structure of the growth plates gives a popcorn-like appearance to the metaphyses and epiphyses.
- head and neck features
- sclera have a blue, purple, or grey tint
- triangular face
- hearing loss
- dentinogenesis imperfecta
Type IV - moderate-severe
People with OI Type IV are moderately affected. Type IV can range in severity from relatively few fractures, as in OI Type I, to a more severe form resembling OI Type III. Clinical features include:
- bones fracture easily, most before puberty
- shorter than average stature for age
- mild to moderate bone deformity
- head and neck features:
- sclerae are often light blue in infancy, but the color intensity varies - the sclerae may lighten to white later in childhood or early adulthood
- triangular face
- dentinogenesis imperfecta possible
- hearing loss possible
Similar to Type IV in appearance and symptoms of OI. Dominant inheritance pattern.
Clinical features include:
- large hypertrophic calluses at the fracture or surgical procedure sites
- calcification of the interosseous membrane between the radius and ulna restricts forearm rotation and may cause dislocation of the radial head
OI Type VI is extremely rare. It is moderate in severity and similar in appearance and symptoms to OI Type IV and is distinguished by a characteristic mineralization defect seen in biopsied bone. Mode of inheritance is unknown.
Types VII and VIII
Two recessive types of OI, types VII and VIII, were recently identified.
Recessively inherited OI has been discovered in people with lethal, severe, and moderate OI. There is no evidence of a recessive form of mild OI. Recessive inheritance probably accounts for fewer than 10 percent of OI cases.
- some cases of OI type VII resemble OI type IV in many aspects of appearance and symptoms
- other cases resemble OI type II, except that infants have white sclerae, small heads and round faces
- cases of OI type VIII are similar to OI types II or III in appearance and symptoms except for white sclerae
Additional forms of OI
The following conditions are rare, but they feature fragile bones plus other significant symptoms.
More detailed information on them can be found in Pediatric Bone: Biology and Diseases, Glorieux et al, 2003 3.
- osteoporosis-pseudoglioma syndrome: severe form of OI that also causes blindness
- Cole-Carpenter syndrome: OI with craniosynostosis and ocular proptosis.
- Bruck syndrome: OI with congenital joint contractures
- OI / Ehlers-Danlos syndrome: recently identified syndrome features fragile bones and extreme ligament laxity
- 2. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363 (9418): 1377-85. doi:10.1016/S0140-6736(04)16051-0 - Pubmed citation
- 3. Lovell WW, Winter RB, Morrissy RT et-al. Lovell & Winter's Pediatric Orthopaedics. Lippincott Williams & Wilkins. (2006) ISBN:0781753589. Read it at Google Books - Find it at Amazon
- 4. http://www.oif.org/site/DocServer/pediatricians_guide.pdf?docID=7941