Osteogenesis imperfecta

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Osteogenesis imperfecta is a genetic bone disorder. People with OI are born without the proper protein (collagen), or the ability to make it, usually because of a deficiency of Type-I collagen.^[1] People with OI either have less collagen than normal or the quality is poorer than normal. As collagen is an important protein in bone structure, this impairment causes those with the condition to have weak or fragile bones.^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The condition, or types of it, have had various other names over the years and in different nations. Among some of the most common alternatives are Ekman-Lobstein syndrome, Vrolik syndrome, and the colloquial glass-bone disease. The name “Osteogenesis Imperfecta” dates to at least 1895^[1] and has been the usual medical term in the twentieth century to present. The current four type system began with Sillence in 1979.^[2] An older system deemed less severe types “Osteogenesis Imperfecta Tarda” while more severe forms were deemed “Osteogenesis Imperfecta Congenita.”^[3] As this did not differentiate well, and all forms are congenital, this has since fallen out of favour.

The condition has been found in an Ancient Egyptian mummy from 1000 BC. The Norse king Ivar the Boneless may have had this condition as well. The earliest studies of it began in 1788 with the Swede Olof Jakob Ekman. He described the condition in his doctoral thesis and mentioned cases of it going back to 1678. In 1831, Edmund Axmann described it in himself and two brothers. Johann Friedrich Georg Christian Martin Lobstein dealt with it in adults in 1833. Willem Vrolik did work on the condition in the 1850s. The idea that the adult and newborn forms were the same came in 1897 with Martin Benno Schmidt.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

There are eight types of OI, Type I being the most common, though the symptoms range from person to person.

Collagen is of normal quality but is produced in insufficient quantities:

• Bones fracture easily
• Slight spinal curvature
• Loose joints
• Poor muscle tone
• Discolouration of the sclera (whites of the eyes), usually giving them a blue-gray color. The blue-gray color of the sclera is due to the reflection of underlying choroidal veins. The underlying choroidal veins reflect through the sclera because there is defective synthesis of type 1 collagen.
• Early loss of hearing in some children
• Slight protrusion of the eyes

IA and IB are defined to be distinguished by the absence/presence of dentinogenesis imperfecta (characterized by opalescent teeth.) (Absent in IA, present in IB.)

Collagen is not of a sufficient quality or quantity

• Most cases die within the first year of life due to respiratory failure or intracerebral hemorrhage
• Severe respiratory problems due to underdeveloped lungs
• Severe bone deformity and small stature

Type II can be further subclassified into groups A, B, C, which are distinguished by radiographic evaluation of the long bones and ribs. Type IIA demonstrates broad and short long bones with broad and beaded ribs. Type IIB demonstrates broad and short long bones with thin ribs that have little or no beading. Type IIC demonstrates thin and longer long bones with thin and beaded ribs.

Collagen quantity is sufficient but is not of a high enough quality

• Bones fracture easily, sometimes even before birth
• Bone deformity, often severe
• Respiratory problems possible
• Short stature, spinal curvature and sometimes barrel-shaped rib cage
• Loose joints
• Poor muscle tone in arms and legs
• Discolouration of the sclera (whites of the eyes)
• Early loss of hearing, sometimes

Type III is distinguished among the other classifications as being the “Progressive Deforming” type, wherein a neonate presents with mild symptoms at birth and develops the aforementioned symptoms throughout life. Lifespan may be normal, albeit with severe physical handicapping.

Collagen quantity is sufficient but is not of a high enough quality

• Bones fracture easily, especially before puberty
• Short stature, spinal curvature and barrel-shaped rib cage
• Bone deformity is mild to moderate
• Early loss of hearing

Similar to Type I, Type IV can be further subclassified into types IVA and IVB characterized by absence (IVA) or presence (IVB) of dentinogenesis imperfecta.

Same clinical features as Type IV. Distinguished histologically by “mesh-like” bone appearance. Further characterized by the “V Triad” consisting of a) radio-opaque band adjacent to growth plates, b) hypertrophic calluses at fracture sites, and c) calcification of the radio–ulnarinterosseous membrane.

• As per Doctors Francis Glorieux, Frank Rauch, and Leanne Ward in the Shriners Hospital for Children in Quebec^[1]

OI Type V leads to calcification of the membrane between the two forearm bones, making it difficult to turn the wrist. Another symptom is abnormally large amounts of repair tissue (hyperplasic callus) at the site of fractures. At the present time, the cause for Type V is unknown, though doctors have determined that it is inherited.

X-Ray OI Type V in Adult X-Ray OI Type V Kid

More on Type V Research More on OI Study

Same clinical features as Type IV. Distinguished histologically by “fish-scale” bone appearance.

• In 2005 a recessive form called “Type VII” was discovered. Thus far it seems to be limited to a First Nations people in Quebec.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

As a genetic disorder, OI is an autosomal dominant defect. Most people with OI receive it from a parent but it can also be an individual (de novo or “sporadic”) mutation.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Osteogenesis imperfecta must be differentiated from other diseases that cause lowering bone mineral density (BMD), such as osteoporosis, scurvy, osteomalacia, multiple myeloma, and homocysteinuria.

• Osteogenesis imperfecta must be differentiated from other diseases that cause lowering bone mineral density (BMD), such as osteoporosis, scurvy, osteomalacia, multiple myeloma, and homocysteinuria.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Frequency is approximately the same across groups, but for unknown reasons the Shona and Ndebele of Zimbabwe seem to have a higher proportion of Type III to Type I than other groups.^[1]. However, a similar pattern was found in segments of the Nigerian and South African population. In these varied cases the total number of OIs of all four types was roughly the same as any other ethnicity.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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