Neuropathological findings of very low-density lipoprotein receptor-related cerebellar hypoplasia in a full-term fetus.

Mutations in the reelin (RELN) extracellular matrix protein gene are known to cause cortical and cerebellar malformations due to disruption of normal neuroblast migration and localization during fetal neurodevelopment. More recently, mutations in genes encoding transmembrane receptors involved in the recognition of reelin, including very low-density lipoprotein receptor (VLDLR), have been linked to various dysequilibrium and ataxia syndromes. Radiologic findings in cases of VLDLR mutations include cerebellar hypoplasia with marked vermis hypoplasia and cortical simplification without lissencephaly. However, the gross and histologic findings in VLDLR-related cerebellar hypoplasia in humans have yet to be described in the literature. Neuropathologic analysis of a confirmed human case could serve to illuminate unique findings and further elucidate the underlying pathophysiologic mechanism of VLDLR gene mutations. We report the autopsy neuropathological findings in a genetically confirmed third-trimester gestation fetal example.