14. Genetics/Osteogenica Imperfecta Flashcards
Osteogenesis Imperfecta: definition?
“Brittle Bone disease”
•Heterogeneous heritable disorder of bone matrix formation and homeostasis
Type I Collagen disorder
Osteogenesis Imperfecta: cardinal features?
–Low bone mass
–Reduced bone mineral strength
–Increased bone fragility
–Increase bone deformity
–Fractures
What is the #1 cause of fracture in children?
Non accidental trauma: ie child abuse
Define genetic pleotropy. Example?
A single gene product/mutation yields many different effects (different signs and symptoms).
Example: Osteogenesis Imperfecta, since it can cause a number of findings including blue sclera, joint hypermobility, scoliosis, dentinogenesis imperfecta, learing loss, extremity deformities, short stature
Define Genetic Heterogeneity. Example?
Different gene mutations that cause identical disease states.
Example: Osteogenesis Imperfecta. –> Type II OI can be caused by mutation of Pro-alpha 1 OR Pro-alpha 2 genes.
Type I, Type III, Type IV: each can also be caused by mutations of various genes that lead to the same phenotype.
Define variable expression. Example?
Same disease, different symptoms are present.
Example = OI: within each type, patients have slightly different presentations (some will have blue sclera, some will not. some have dentinogenesis, some do not)
OI: Tarda vs Congenita?
Congenita = forms diagnosed either in utero or shortly post birth. More severe forms.
Tarda = diagnosed later on, generally less severe.
Type I OI: severity?
stature?
systemic symptoms?
etiology?
Tarda form, Mildest.
Normal stature, little or no deformity.
Possibly: blue sclerae, hearing loss, dentinogenesis imperfecta, joint hypermobility, incr bruising, aortic root dilatation, mitral valve prolapse.
etiology: low quantity, normal quality, normal assembly of collagen
Type I OI: age onset of bone fractures?
Fracture prognosis over the lifespan?
Rarely: prenatally or during infancy.
Occasionally during diaper changes but usually with onset of walking.
Frequency is constant through childhood, decr after puberty, increases in 60s/70s
Type II OI:
severity?
symptoms?
etiology?
Universally Lethal. Most severe type.
May be detected by fetal US.
Extremities are obviously deformed, small thorax -> lung hypoplasia, platyspondyly (shortened vertebrae), hypomineralization of calvaria
etiology: low quantity, low quality, normal assembly of collagen
Type III OI:
Severity?
Symptoms?
etiology?
Severe but not lethal.
Progressively deforming bones.
Some deformity at birth. Dentinogenesis is common, hearling loss common, very short stature. Otherwise healthy.
etiology: normal quantity, normal quality, mal-assembly of collagen
OI Type III: how do the bones look on imaging?
Short and curved bones, “washed out” appearance on imaging
Osteoporosis
Accordion effect of long bones (thorax ok so no lung issues)
Type IV OI: severity?
symptoms?
etiology?
Mild to Moderate
Normal sclerae,
moderate bone deformity.
possible: short stature, dentinogenesis, hearing loss
etiology: normal quantity, low quality, normal assembly of collagen
Type I vs Type IV OI: difference in disease presentation?
- Type IV has more fractures, more deformity, shorter stature than Type I
- Both have been mistaken for child abuse
- Type IV sometimes presents in adult women as “osteoporosis”
Type IV OI: bone features?
Osteoporosis
Bone curvature
short bones
If fixes are attempted via rod placement, rods may extrude