Osteogenesis Imperfecta TBL Flashcards
Osteogenesis Imperfecta Type I
- Severity
- Symptoms: Skeletal, Eyes, Hearing, Teeth
Severity:
Mild (most common)
Symptoms: Skeletal 1. Recurrent Fracts. (dec. at puberty) 2. ∆ Face 3. Normal Height
Eyes
- Blue Sclerae
Hearing
- Presenile Deafness
Teeth: N/A
Osteogenesis Imperfecta Type II
- Severity
- Symptoms
Severity:
- Most Severe (prenatal/lethal)
Symptoms: Skeletal 1. IN utero fractures 2. Bowed bones/deformities 3. Small Chest (due to rib fracts)
Eyes:
- DARK Blue Sclerae
Teeth and Hearing: N/A
Osteogenesis Imperfecta Type III
- Severity
- Symptoms
Severity: Moderately Severe (progressively deforming)
Symptoms Skeletal 1. Recurrent Fractures 2. Bony Deformities 3. Short stature
Eyes
- Blue Sclera
Hearing
- Presenile Deafness
Teeth
- Dentinogenesis imperfecta
Osteogenesis Imperfecta Type IV
- Severity
- Symptoms
Severity:
Mild/moderate
Symptoms: Skeletal - multiple recurrent fracts. - Bone Deformities (MORE than Type I) - Short Stature
Eyes
- normal or nearly normal sclerae
Hearing
- Presenile Deafness
Teeth
- Dentinogenesis Imperfecta
Osteogenesis Imperfecta Type VIII
- Severity
- Symptoms
Severity:
- Lethal congenital
Symptoms: same as type II Skeletal 1. IN utero fractures 2. Bowed bones/deformities 3. Small Chest (due to rib fracts)
Eyes:
- NORMAL scelera
Teeth and Hearing: N/A
What is the only type of OI that is autosomal recessive?
Type VIII
What types of OI are familial?
- why is this important?
Type I and IV
*If genetic its AUTOSOMAL dominant, and there is a 1/2 chance of having an affected child
Explain Autosomal Dominant new mutations.
- No family history of the disease
- ONLY one bad allele leads to disease (AD)
What are the recurrence risks for a family with a child who has and AUTOSOMAL DOMINANT version of OI that has come about from a new mutation?
- Low, because its a spontaneous mutation
What risk does a child with AutoDom OI that arose from a new mutation have of passing the same disease to their kids?
50% - typically the risk is less than this because of reduced fertility in affected people
What may be the case for a family that has no history of OI, but has multiple Children with OI?
Germline Mosaicism
How does germline mosaicism manifest?
Early in embryonic Development a mutation happens in the cells that will become germ cells
- this means only germ and no somatic cell are affected
T or F: Cardiovascular issues as well as motor delays are sometimes associated with OI
True
T or F: miscarriages are frequent with severe types of OI
True
What causes shortened stature of patients with OI?
- Compression Fractures in Vertebrae
Codfish Vertebrae
Where do most OI fractures occur?
Long Bones > Ribs/Skull
What two genes are responsible for making strands used in type I Collagen?
- Strand Type?
COLA1 - pro-alpha1
COLA2 - pro-alpha2
How many of each chain type are used to make type Collagen type I?
2 Pro-alpha1 chains
1 Pro-alpha2 chain
What happens with a change in expression of pro-alpha1 or pro-alpha2?
Type 1 collagen will get messed up because RATIO will be off
What is the chromosome location for the pro-alpha1 and pro-alpha2 gene?
Pro-alpha1 - Chrom. 17
Pro-alpha2 - Chrom. 7
What is the incidence of OI?
1/10,000 births in every race
What other diseases/issues could result in fractures early in childhood?
- Ehlers-Danlos - hypermobility causing inc. fracts.
- Child abuse
- osteoporosis
- other genetic diseases
What chromosome is most commonly mutated resulting in defective type I collagen?
Chromosome 17
T or F: the are only a small number of mutations that lead to OI?
False, there is TONS of allelic heterogeneity in OI mutations, more than 200 described
