Aprosencephaly and cerebellar dysgenesis in sibs

Am J Med Genet. 1996 Jun 28;63(4):542-8. doi: 10.1002/(SICI)1096-8628(19960628)63:4<542::AID-AJMG6>3.0.CO;2-Q.


Aprosencephaly is a rare, lethal malformation sequence of the central nervous system that has been attributed to a postneuralation encephaloclastic process. We describe autopsy findings consistent with aprosencephaly in 2 fetuses conceived from a consanguineous mating (first cousins). Both showed anencephalic manifestations; however, the crania were intact, with fused sutures. The neuropathologic findings were essentially identical. Each fetus had complete absence of the telecephalon and pyramidal tracts, rudimentary diencephalic and mesencephalic structures, primitive cerebellar hemispheres, posterolateral clusters of primitive neural cells in the medullas suggesting an abnormality of neural migration, a normally-formed spinal cord, and retinal dysplasia within normally-formed globes. In addition, both fetuses manifested a peculiar perivascular mesenchymal proliferation seen only within the central nervous system. The similarity of these cases, coupled with parental consanguinity, suggests a primary malformation in brain development due to the homozygous representation of a mutant allele. We hypothesize that these patients may represent a defect in a gene important in brain development, the nature of which has yet to be elucidated.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Abnormalities, Multiple
  • Abortion, Induced
  • Adult
  • Cerebellar Diseases / congenital*
  • Cerebellar Diseases / genetics
  • Cerebellum / abnormalities*
  • Consanguinity
  • Female
  • Fetus / abnormalities
  • Fetus / pathology
  • Head / abnormalities
  • Homeodomain Proteins*
  • Humans
  • Male
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Otx Transcription Factors
  • Pedigree
  • Pregnancy
  • Prosencephalon / abnormalities*
  • Trans-Activators / genetics


  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Otx Transcription Factors
  • Trans-Activators