Neuropathology of brain and spinal malformations in a case of monosomy 1p36

Naoko Shiba, Ray A.M. Daza, Lisa G. Shaffer, A. James Barkovich, William B. Dobyns, Robert F. Hevner

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Monosomy 1p36 is the most common subtelomeric chromosomal deletion linked to mental retardation and seizures. Neuroimaging studies suggest that monosomy 1p36 is associated with brain malformations including polymicrogyria and nodular heterotopia, but the histopathology of these lesions is unknown. Here we present postmortem neuropathological findings from a 10 year-old girl with monosomy 1p36, who died of respiratory complications. The findings included micrencephaly, periventricular nodular heterotopia in occipitotemporal lobes, cortical dysgenesis resembling polymicrogyria in dorsolateral frontal lobes, hippocampal malrotation, callosal hypoplasia, superiorly rotated cerebellum with small vermis, and lumbosacral hydromyelia. The abnormal cortex exhibited "festooned" (undulating) supragranular layers, but no significant fusion of the molecular layer. Deletion mapping demonstrated single copy loss of a contiguous 1p36 terminal region encompassing many important neurodevelopmental genes, among them four HES genes implicated in regulating neural stem cell differentiation, and TP73, a monoallelically expressed gene. Our results suggest that brain and spinal malformations in monosomy 1p36 may be more extensive than previously recognized, and may depend on the parental origin of deleted genes. More broadly, our results suggest that specific genetic disorders may cause distinct forms of cortical dysgenesis.

Original languageEnglish (US)
Article number45
JournalActa Neuropathologica Communications
Issue number1
StatePublished - Jan 27 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2013 Shiba et al.; licensee BioMed Central Ltd.


  • Cortical dysgenesis
  • Epilepsy
  • Hippocampal malrotation
  • Hydromyelia
  • Malformations of cortical development
  • Mental retardation
  • Periventricular nodular heterotopia


Dive into the research topics of 'Neuropathology of brain and spinal malformations in a case of monosomy 1p36'. Together they form a unique fingerprint.

Cite this