SKELETAL DYSPLASIA IN PERINATAL LETHAL OSTEOGENESIS IMPERFECTA - A COMPLEX DISORDER OF ENDOCHONDRAL AND INTRAMEMBRANOUS OSSIFICATION

Osteogenesis imperfecta (OI) Type II is a rare heritable disorder of b one matrix that results in catastrophic congenital skeletal dysplasia. Two cases of OI Type II had symmetric rhizomelic skeletal dysplasia a pparent on ultrasound at 16 and 20 weeks' gestation. Histologic and hi stochemical studies performed on skeletal tissue from fetal autopsies showed the following: (1) abnormal growth plate tissue characterized b y failure of formation of primary bony spongiosa; (2) persistence of c alcified cartilage bars in the diaphysis; (3) metaphyseal microfractur es; (4) abundant cartilaginous fracture callus; (5) absence of bony ca llus; (6) failure of formation of intramembranous cortical diaphyseal bone; (7) angulation of long bones in portions of the metadiaphyses bo rdered by fracture callus; and (8) mechanical failure of the perichond ral ring of LaCroix with a normal fibrous ossification groove of Ranvi er. These findings suggest that skeletal dysplasia in OI Type II resul ts from the action of muscular forces on a skeleton weakened by a comp lex disorder of endochondral and intramembranous ossification. The pau city of primary metaphyseal trabeculae and subperiosteal cortical bone leads to pathologic fractures of the immature fiber bone and an imper fect attempt at fracture repair. Angulation and shortening of long bon es occurs between numerous sites of focal endochondral fracture callus . Mechanical failure of the fibrous perichondral ring leads to further collapse and shortening without obvious functional impairment of the fibrous ossification groove. Perinatal lethal OI provides insight into how a molecular disorder predominantly of Type I collagen metabolism results in pathology of numerous tissues, leading to severe skeletal d ysplasia without primarily affecting chondrogenesis.