Osteogenesis Imperfecta

Question 1

What is decreased in OI?

Answer 1

Type 1 collagen

Question 2

Pathophysiology of OI:

Answer 2

Insufficient osteoid production
- decreased collagen secretion
- inc production of abnormal collagen
Physeal osteoblasts cannot produce sufficient osteoid and and periosteal osteoblasts cannot remodel normally

Question 3

Genetic mutation OI:

• causes?
• what is switched?
• inheritance?
• Other genes?

Answer 3

COL 1A1 and COL 1A2
- abnormal collagen cross-linking 
- COL 1A1 - alpha 1 chain
- COL 1A2 - alpha 2 chain
- Glycine substitution in procollagen molecule --> disrupts the triple helix
Auto Dom: milder forms - 1 and IV
Auto Rec: severe forms: II and III
CRTAP and LEPREI genes with severe, lethal forms of OI not associated with structural deficit in type I collagen

Question 4

OI Presentation:

Answer 4

• Increased # of fracture
• bones heal normally but won’t remodel –> bowing
• ligament laxity
• short stature
• scoliosis and comp fx
• basilar invagination
• olecranon apophyseal fracture
• blue sclera
• dentinogenesis imperfecta (brown see-through teeth)
• hearing loss
• wormian skull bones (puzzle piece)
• hyper metabolism -> inc risk of malignant hyperthermia

Question 5

Type I OI:

• Inheritance?
• Sclerae?
• Features?

Answer 5

Inheritance: Auto dom - quantitative disorder in collagen
Blue sclera 
Features:
- mildest form
- presents late (preschool)
- Type A vs B based on tooth involvment

Question 6

Type II OI:

• Inheritance?
• Sclerae?
• Features?

Answer 6

Inheritance: auto rec - qualitative disorder
Blue scleare
Features: leathal in perinatal period

Question 7

Type III OI:

• Inheritance?
• Sclerae?
• Features?

Answer 7

Inheritance: auto rec- qualitative
Normal sclerae
Features:
- fx at birth
- short stature
- most severe but survivable form

Question 8

Type IV OI:

• Inheritance?
• Sclerae?
• Features?

Answer 8

Inheritance: auto dom - qualitative
Normal sclerae 
Features:
- mod sever
- bowing and vertebral fx common
- hearing normal
- Type A vs B based on tooth involvement

Question 9

Type V OI:

• Inheritance?
• Sclerae?
• Features?

Answer 9

Inheritance: Auto dom
Features:
- hypertrophic callus after fx
- congenital anterolateral radial head d/l
- ossification of IOM between rad/ulna and tib/fib

Question 10

Type VI OI:

• Inheritance?
• Sclerae?
• Features?

Answer 10

Inheritance - ?
Features:
- similar to type IV

Question 11

Type VII OI:

• Inheritance?
• Sclerae?
• Features?

Answer 11

Inheritance - Auto rec
Features:
- assoc with rhizomelia (disproportion of length of proximal limbs) and coxa vara

Question 12

Feature of OI that presents with apnea, AMS, ataxia nad myelopathy?
- When does it present?

Answer 12

Basilar Invagination

- 3rd/4th decade of life, can present in teenage years