Lissencephaly with agenesis of corpus callosum and rudimentary dysplastic cerebellum: a subtype of lissencephaly with cerebellar hypoplasia

Acta Neuropathol. 2004 Jan;107(1):69-81. doi: 10.1007/s00401-003-0776-0. Epub 2003 Oct 18.

Abstract

Lissencephaly with agenesis of the corpus callosum and rudimentary dysplastic cerebellum may represent a subset of lissencephaly with cerebellar hypoplasia (LCH) of unknown etiology, one that is distinct from other types of LCH. We present a detailed neuropathological description of an autopsy brain from a 7-day-old neonate born at 38-gestational weeks, presenting with this malformation. The brain was severely hydrocephalic and totally agyric. The corpus callosum was absent and deep gray matter structures indistinct. A rudimentary dysplastic cerebellum, dysplastic olivary nuclei and nearly complete absence of corticospinal tracts were also noted. Microscopic examination revealed various types of dysplastic and malformative features throughout the brain in addition to the classic four-layered neocortical structure characteristic of type I lissencephaly. Unique features in the present case were (1) bilateral periventricular undulating cortical ribbon-like structures mimicking fused gyri and sulci, associated with aberrant reelin expression, (2) large dysplastic neocortical neurons positive for phosphorylated neurofilament, calbindin-D28K, tuberin, hamartin, doublecortin, LIS1, reelin and Dab1, (3) derangement of radial glial fibers, and (4) disorganized cerebellar cortex and heterotopic gray matter composed exclusively of granule cells in the cerebellar deep white matter. The clinicopathological features in the present case are suggestive of a distinct category of lissencephaly with cerebellar involvement. We suggest a possible classification of this unique case among the LCH syndromes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agenesis of Corpus Callosum
  • Brain / abnormalities*
  • Brain / pathology
  • Brain Stem / abnormalities
  • Cerebellum / abnormalities
  • Cerebral Cortex / abnormalities
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Male
  • Microcephaly / pathology
  • Nervous System Malformations / pathology*
  • Reelin Protein