Abnormalities in central nervous system development in osteogenesis imperfecta type II

Osteogenesis imperfecta (OI) type II is a perinatally lethal condition resu lting from mutations in type I collagen genes. In addition to characteristi c skeletal anomalies, OI type II has recently been shown to be associated w ith neuropathological alterations, specifically perivenous microcalcificati ons, and impaired neuroblast migration. In light of these findings, and bec ause type I collagen promotes neuritic maturation both in vitro and in vivo , we sought to determine if additional central nervous system (CNS) develop mental anomalies could be found in previously autopsied OI type II cases, a nd if specific abnormalities correlate with OI subtypes. We retrospectively studied brains of nine patients diagnosed with OI. Of these, seven were OI type II: five were OI type IIA, one was type IIB, and one was type IIC. On e OI type I specimen and one OI type III brain were included for comparison , as well as five controls. The IIC brain showed hippocampal malrotation, a gyria, abnormal neuronal lamination, diffuse hemorrhage, and periventricula r leukomalacia (PVL). The IIB brain had white matter gliosis, PVL, and peri vascular calcifications, but was normally developed. Of the five type IIA b rains, two showed migrational defects with coexisting PVL and gliosis, two were normally developed with similar white matter injuries, and one was gro ssly normal. These findings support the contention that collagen mutations might negatively impact CNS development.