Septo-optic dysplasia and other midline defects: the role of transcription factors: HESX1 and beyond

Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):115-24. doi: 10.1016/j.beem.2010.06.008.


Septo-optic dysplasia (SOD) is a highly heterogeneous condition comprising variable phenotypes including midline and forebrain abnormalities, optic nerve and pituitary hypoplasia. Most instances of SOD are sporadic and several aetiologies including drug and alcohol abuse have been suggested to account for the pathogenesis of the condition. However, a number of familial cases have been described with an increasing number of mutations in developmental transcription factors including HESX1, SOX2, SOX3 and OTX2 being implicated in its aetiology. These factors are essential for normal forebrain/pituitary development, and disruptions to these genes could account for the features observed in SOD and other midline disorders. The variable phenotypes observed within the condition are most likely due to the varying contributions of genetic and environmental factors. This review will discuss the current knowledge about SOD. Further study of these and other novel factors may shed light on the complex aetiology of this condition.

Publication types

  • Review

MeSH terms

  • Animals
  • Environmental Exposure
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Mice
  • Otx Transcription Factors / genetics*
  • Phenotype
  • Pituitary Gland / abnormalities
  • Pituitary Gland / embryology
  • Prosencephalon / embryology
  • SOXB1 Transcription Factors / genetics
  • Septo-Optic Dysplasia / genetics*
  • Septo-Optic Dysplasia / pathology


  • HESX1 protein, human
  • Homeodomain Proteins
  • OTX2 protein, human
  • Otx Transcription Factors
  • SOX2 protein, human
  • SOX3 protein, human
  • SOXB1 Transcription Factors