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Known as {  { a
, or "Lobstein syndrome" which is a genetic bone disorder.
People with OI are born with defective connective tissue, or without the ability to make it,
usually because of a deficiency of Type-I collagen. This deficiency arises from an amino acid
substitution of glycine to bulkier amino acids in the collagen triple helix structure. The
larger amino acid side-chains create steric hindrance that creates a "bulge" in the collagen
complex. As a result, the body may respond by hydrolyzing the improper collagen
structure. If the body does not destroy the improper collagen, the relationship between the
collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness.

Osteogenesis imperfecta (OI) is "a rare genetic disorder of collagen synthesis associated
with broad spectrum ofmusculoskeletal problems, most notably bowing and fractures
of the extremities, muscle weakness, ligamentous laxity,and spinal deformities." Other
collagen-containing extraskeletal tissues, such as the sclerae, the teeth, and the heart valves
are also affectedto a variable degree. OI has a "common feature of bony fragility associated
with defective formation of collagenby osteoblasts and fibroblasts." (Smith, 1983, 13)

This disease, involving defective development of the connective tissues, is usually the result
of the autosomal dominant gene, but can also be the result of the autosomal recessive gene.
Spontaneous mutations are common and the clinical presentation of the disease remains to
be quite broad.

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p „ragilitas ossium,
p [ypolasia of the
mesenchyme
p Osteopsathyrosis.

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It is a congenital disease, meaning it is present at birth. It is frequently caused by defect in


the gene that produces type 1 collagen, an important building block of bone. There are
many different defects that can affect this gene. The severity of OI depends on the specific
gene defect.

OI is an autosomal dominant disease. That means if you have one copy of the gene, you will
have the disease. Most cases of OI are inherited from a parent, although some cases are the
result of new genetic mutations.
à à   

seen through an x-ray, this infant's


developing skeleton appears to be healthy.
[owever, infants with osteogenesis imperfect
frequently experience bone fractures as they
develop inside their mother's wombs.

The task largely falls to cells called   


 , which create new bone tissue, while cells
called   
 break down old bone. This ongoing process is called    

Osteoblasts form new bones and increase the size of growing bones. This process is called
ossificiation.

Think of workers constructing a building -- the process has a lot in common with the way
osteoblasts build new bone. „irst, both need strong building blocks with which to form the
finished product. Construction workers use bricks or concrete blocks to form walls.
Osteoblasts form bone from inorganic mineral salts, mainly calcium carbonateand calcium
phosphate. This is the reason a calcium-rich diet is important to maintain strong bones.

But you can't erect a building using only blocks and bricks. You need a metal framework to
give it flexibility and tensile strength, the amount of stress a construction can endure
without falling apart. An earthquake or strong wind could destroy a skyscraper, no matter
the strength of the pieces, without a flexible steel framework. In bones, fibers of collagen a
protein produced by all vertebrates, supply this framework. Osteoblasts secrete these
collagen fibers to form the framework and then initiate calcification -- calcium fills the
flexible framework, providing strength.

In cases of OI, the body either creates poor-quality collagen or doesn't create enough of it.
The resulting bones lack flexibility and tensile strength, making them far more susceptible
to fracture than normal, healthy bones.

    

 

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

p Bones fracture easily


p Slight spinal curvature
p Loose joints
p Poor muscle tone
p aiscolouration 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 underlying choroidal veins
which show through. This is due to the sclera being thinner than normal because of
the defective Type I Collagen not forming correctly.
p Êarly loss of hearing in some children
p Slight protrusion of the eyes

 

Collagen is not of a sufficient quality or quantity

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

 

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

p Bones fracture easily, sometimes even before birth


p Bone deformity, often severe
p mespiratory problems possible
p Short stature, spinal curvature and sometimes barrel-shaped rib cage
p Loose joints
p Poor muscle tone in arms and legs
p aiscolouration of the sclera (the 'whites' of the eyes)
p Êarly loss of hearing possible

 


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

p Bones fracture easily, especially before puberty


p Short stature, spinal curvature and barrel-shaped rib cage
p Bone deformity is mild to moderate
p Êarly loss of hearing


 


p
p Same clinical features as Type IV. aistinguished histologically by "mesh-like" bone
appearance. „urther characterized by the "V Triad" consisting of
2p a) radio-opaque band adjacent to growth plates,
2p b) hypertrophic calluses at fracture sites, and
2p c) calcification of the radio-ulnar interosseous membrane [4].
p 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.

 


p Same clinical features as Type IV.


p aistinguished histologically by "fish-scale" bone appearance

 


p A new recessive form was discovered in Quebec @ 2005


p Mutations in the gene CmTAP causes this type

 


p OI caused by mutation in the gene LÊPmÊ1 is classified as type VIII


à  
Type I collagen fibers are found in the bones, organ capsules, fascia, cornea, sclera, tendons,
meninges, and dermis. Type I collagen, which constitutes approximately 30% of the human
body by weight, is the defective protein in OI.

In structural terms, type I collagen fibers are composed of a left-handed helix formed by
intertwining of pro-alpha 1 and pro-alpha 2 chains. Mutations in the loci that encode these
chains cause OI (ie, ›  on band 17q21 and ›  on band 7q22.1, respectively).
Other mutations may cause congenital bone fragility associated with distinctive clinical or
histologic features (eg, redundant callus formation, pseudoglioma, defective mineralization
of bone). These conditions have been grouped as syndromes resembling osteogenesis
imperfecta.

Qualitative defects (eg, an abnormal collagen I molecule) and quantitative defects (eg,
decreased production of normal collagen I molecules) are described. Of note, recent studies
have reported that quantitative defects can cause very severe (even lethal) syndromes
resembling osteogenesis imperfecta through posttranslational modifications of collagen.2

Cartilage-associated protein (CmTAP) is a protein required for prolyl 3-hydroxylation. Loss


of CmTAP in mice causes an osteochondrodysplasia characterized by severe osteoporosis
and decreased osteoid production. In humans, › mutations cause excess
posttranslational modification of collagen, and may be associated with syndromes
resembling osteogenesis imperfecta, including recessive forms of lethal syndromes
resembling OI and syndromes resembling osteogenesis imperfecta with redundant callus
formation.
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1.p „amily history and characteristic features  blue sclerae or deafness
2.p Performing collagen biochemical studies of cultured skin fibroblasts
3.p Prenatal ax for the families with identified mutation
4.p Prenatal ultrasound @ 16 wks  evidence of severe OI
5.p o-rays
6.p aiagnostic Serial UTZ for future pregnancies for those families with OI history
To verify:
2p to detect limb shortening
2p utero fractures
2p polyhydramnios.
7.p Children may undergo physical examination  show that the whites of their eyes
have a blue tint.
8.p ùSkin punch biopsydz removal of a piece of skin to diagnose or rule out an illness.
9.p Chronic villi sampling for those pregnant mothers with history of OI  to determine
if the baby has the condition.

Êà Ê 
1.p  


*Muscle strength and bone mass can be increased through therapy (though
patients can't overcome bone weakness).
'exercise can improve mobility and help prevent future fractures.
'Swimming is an ideal form of exercise for those with OI since it offers exertion
without putting much stress on the limbs.
*Maintaining a healthy weight can also cut down on bone stress.
2.p a 
'Vitamin a and calcium are very important for ensuring bone strength
'avoidance of steroids
*avoid large amts of caffeine and alcohol
3.  


  
 aa  to help strengthen long bones against fracture and prevent or correct
deformities.
p This involves implanting metal rods to run along the lengths of the
bones. To help growing children, these rods can be expanded to keep
pace with developing bones. 
›    
  to immobilize the bone so that healing
can occur. 

M  a  
A. à Êaà
Up Strengthens the bones and reduces the fracture rate of individual
Up Usually taken 3Ȅ6 months 
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Up |itrogen-containing biphosphonates
Up Being increasingly administered to increase bone mass and reduces
incidence of fracture
Up Proven efficacy in reducing fracture rates in children
C.  Ê Êà  à 
Cold compress VS. [ÊAT COMPmÊSS
p |umbs the area * relief to stiffed muscles
p reduces inflammation
p provides relief

a. à   à ÊÊÊ  à Ê
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Use of small machine which emits an electrical pulse to block pain signals
from being sent to the brain.

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The prognosis for a person with OI varies greatly depending on the number and severity of
symptoms. mespiratory failure is the most frequent cause of death for people with OI,
followed by accidental trauma. aespite numerous fractures, restricted activity, and small
stature, most adults and children with OI lead productive and successful lives. They attend
school, develop friendships and other relationships, have careers, raise families, participate
in sports and other recreational activities, and are active members of their communities.