OI Type I

mildest, most comon form

autosomal dom inheritance

rarely fractures in utero, half have hearing loss, close to normal stature, mild to moderate bone fragility, no dentinogenesis imperfecta in IA (yes in IB), mitral valve prolapse, easy bruising, hyperextensiblity

OI type II

most severe form

death in utero or perinatal period due to respiratory failure

caused by new dominant mutations

multiple in utero fractures, deformed bones with very little cortex, triangular face, bluish-gray sclerae, deformed thorax

OI type III

dominant mutations, rare recessive

progressively deforming, most severe form compatible with life beyond infancy, long bone fractures, shortened life expectancy, spinal deformities, vertevral compression, macrocephaly, short stature, triangular midface, osteoporosis

OI type IV

dominantly inherited

moderately severe forms, mild to moderate bone fragility, some prenatal fractures or bowing, osteoporosis, progressive scoliosis, short stature, greyish sclerae, carcocephaly

IVA no dentinogenesis imperfecta, IVB yes

OI genetic mutation

90% caused by mutation of alpha1 or 2 chain of type I collagen

"null allele" OI mutation

frameshift mutation --> half the amt of collagen is produced, but it is fully functional collagen

null allele mutation of alpha 1 chain = primary cause of type I OI

on alpha 2=increased level of alpha 1 homotrimers--rare recessive forms of OI

OI structural mutation

COL1A1 and COL1A2 genes--abnormal collagen produced

aa subs, deletions or insertions cause OI II, III & IV

>80% have sub for glycine which throws of triple helical form

non-helical forms are not secreted-->degraded, will not form fibrils/fibers

OI therapy

no genetic cure

physical rehab, orthopedic intervention, bracing, surgical correction

biphosphonates (osteoporosis), cyclic pamindronate (decrease resorption of bone by osteoclasts)