Abnormalities in central nervous system development in osteogenesis imperfecta type II

Pediatr Dev Pathol. 1999 Mar-Apr;2(2):124-30. doi: 10.1007/s100249900100.


Osteogenesis imperfecta (OI) type II is a perinatally lethal condition resulting from mutations in type I collagen genes. In addition to characteristic skeletal anomalies, OI type II has recently been shown to be associated with neuropathological alterations, specifically perivenous microcalcifications, and impaired neuroblast migration. In light of these findings, and because type I collagen promotes neuritic maturation both in vitro and in vivo, we sought to determine if additional central nervous system (CNS) developmental anomalies could be found in previously autopsied OI type II cases, and 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. One 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, agyria, abnormal neuronal lamination, diffuse hemorrhage, and periventricular leukomalacia (PVL). The IIB brain had white matter gliosis, PVL, and perivascular calcifications, but was normally developed. Of the five type IIA brains, two showed migrational defects with coexisting PVL and gliosis, two were normally developed with similar white matter injuries, and one was grossly normal. These findings support the contention that collagen mutations might negatively impact CNS development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Central Nervous System / abnormalities*
  • Collagen / genetics*
  • Demography
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Male
  • Mutation
  • Osteogenesis Imperfecta / genetics*
  • Retrospective Studies


  • Collagen