Osteogenesis Imperfecta Flashcards
What is the prevalance of OI?
1 in 10000
Most types of OI are the result of?
collagen abnormalities
What is the inheritance mode of OI?
mostly autosomal dominant but some forms are autosomal recessive
What are some clinical features of OI?
short stature, post-puberty and pre-senile hearing loss, dentinogenesis imperfecta, large head, blue/purple sclerae, fractures
What are some of symptoms and clinical manifestations of Type I OI?
most common type, mild, fractures after birth which decrease after puberty onset and increase again after age 50, blue sclerae (these are the collagen lining and it is thinner allowing the underlying coroid to show through), may have short stature
What might you see in a patient with Type I OI in an x-ray?
wormian bone skull (look like extra sutures), mild bowed extremities, flat “codfish” vertebrae
What are some other symptoms of Type I OI?
variable- hearing loss due to otosclerosis of ear bones (50%), dentinogenesis imperfect, joint hyper mobility, limb length discrepancy
What are some characteristic of type II OI?
sever, lethal perinatal, fractures in utero, blue sclerae (if not blue but all other symptoms are similar, think type VIII), small for gestational age, macrocephaly (large head), wormian bones
What is the outlook for type II OI?
80% die within a week (survival to 1 yo is rare). Cause of death is respiratory insufficiency due to rib fractures that retard rib growth that slow lung growth and a smaller chest size
What is the mode of inheritance of Type II OI?
new mutation AD
What are some characteristics of type III OI?
sever progressively deforming (live but with severe deformities and fractures, 200+), short statures, blue sclerae, respiratory failure, utero fractures, hearing loss, deformities of articulation between skull and atlas, broadness of forehead
may be associated with amniotic banding
What is the MOI of type III OI?
new mutation AD
What are some characteristics of type IV OI?
severity between I and III, fractures rare at birth, wormian bones, vertebral involvement is greater than with type I with flat vertebrae, short stature, hearing loss variable, sclerae NORMAL TO GREY, dentinogenesis imperfecta variable
What is the MOI of type IV OI?
AD
Other characteristics of OI?
easily bruising of skin, mitral valve prolapse, gross motor delays, reduced life expectancy, cognitive skills intact and normal, pregnancy affected in sever types- hard to carry child to full term, long bones more often affected than skull bones
How is OI tested?
analysis of structure and quantity of Type I collagen produced in vitro by cultures dermal fibroblasts
detects:
98% of type I OI
and 85% of types II and III OI
What genes are affected by OI?
COL1A1 and COL1A2 genes
What do the COL1A1 and COL1A2 genes code for?
pro-alpha col (1)– chromosome 17– and (2) proteins– chromosome 7
What is the structure of type I collagen?
2 strands of a1 and i strand of a2
What are the molecular bases of Type I OI? What do mutations result in?
a range of mutations that result in:
- premature termination sequences
- decreased stability of mRNA of proa1
- decrease the amount of proa1 chains
- decrase the amount of Type I collagen structure by altering ratio of chains
What are the molecular bases of Type II-IV OI? What do mutations result in?
mutations alter structure of the collagen by causing a substitution of glycine in the triple helix of either proa1 or proa2.
Mutations in the carboxy terminal is typically lethal
What are the molecular mutation detection rates of types I-IV OI?
I-100%
II-98%
III-70%
IV-80%
What are some of the characteristic of Type VIII OI?
Autosomal RECESSIVE (so it carries a higher risk of recurrence than type II and can be pre-natalilly diagnosed), normal sclerae, several congenital lethal type
What causes OI type VIII?
abnormality in the 3’-hydoxylation of a single proline (residue 986) in the pro alpha 1 chains of Type I precollagen
What proteins are involved in hydroxylation of residue 986 and can cause type VIII if malfunctioning?
prolyl 3-hydroxylase
cartilage-associated protein
cyclophilin B
How can prenatal diagnosis of OI be performed?
biochemical- CVS at 10 weeks
If defect known- CVS at week 10 or amniocentesis at week 14
fetal ultrasound in 2nd trimester (can’t really see type I or IV with this)
What is the treatment for OI?
limiting physical activity, physical therapy, mobility devices, repairing middle ear bones to combat hearing loss, biphosphonates to combat bone loss
