Periventricular heterotopia: an X-linked dominant epilepsy locus causing aberrant cerebral cortical development

Neuron. 1996 Jan;16(1):77-87. doi: 10.1016/s0896-6273(00)80025-2.


Periventricular heterotopia (PH) involves dramatic malformations of the human cerebral cortex. Here we show that PH is closely linked to markers in distal Xq28 (maximal two-point lod score = 4.77 for F8C at theta = 0; maximal multipoint lod score = 5.37), so that affected females are obligatory mosaics for the mutation; that PH is lethal to at least some affected males; that PH malformations consist of well-differentiated cortical neurons filling the adult subependymal zone; and that individuals with PH are at high risk for epilepsy, though they have no other neurological or external stigmata. The PH gene may represent an important epilepsy susceptibility locus in addition to playing a key role in normal cortical development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / genetics
  • Adult
  • Brain Diseases / genetics*
  • Brain Diseases / pathology
  • Cerebral Cortex*
  • Choristoma / genetics*
  • Choristoma / pathology
  • Epilepsy / genetics*
  • Epilepsy / pathology
  • Epilepsy, Generalized / genetics
  • Epilepsy, Generalized / pathology
  • Epilepsy, Temporal Lobe / genetics
  • Epilepsy, Temporal Lobe / pathology
  • Female
  • Fetal Death / genetics
  • Genes, Dominant
  • Genes, Lethal
  • Humans
  • Infant, Newborn
  • Lod Score
  • Magnetic Resonance Imaging
  • Male
  • Pedigree
  • Pregnancy
  • X Chromosome*