Sterol metabolism disorders and neurodevelopment-an update

Dev Disabil Res Rev. 2013;17(3):197-210. doi: 10.1002/ddrr.1114.


Cholesterol has numerous quintessential functions in normal cell physiology, as well as in embryonic and postnatal development. It is a major component of cell membranes and myelin, and is a precursor of steroid hormones and bile acids. The development of the blood brain barrier likely around 12-18 weeks of human gestation makes the developing embryonic/fetal brain dependent on endogenous cholesterol synthesis. Known enzyme defects along the cholesterol biosynthetic pathway result in a host of neurodevelopmental and behavioral findings along with CNS structural anomalies. In this article, we review sterol synthesis disorders in the pre- and post-squalene pathway highlighting neurodevelopmental aspects that underlie the clinical presentations and course of Smith-Lemli-Opitz Syndrome (SLOS), mevalonic aciduria (MVA) or the milder version hyper-immunoglobulinemia D and periodic fever syndrome (HIDS), Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1), congenital hemidysplasia with icthyosiform nevus and limb defects (CHILD) syndrome, CK syndrome, sterol C4 methyl oxidase (SC4MOL) deficiency, X-linked dominant chondrodysplasia punctata 2(CDPX2)/ Conradi Hunermann syndrome, lathosterolosis and desmosterolosis, We also discuss current controversies and share thoughts on future directions in the field.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / metabolism
  • Animals
  • Cholesterol / deficiency
  • Chondrodysplasia Punctata / metabolism*
  • Genetic Diseases, X-Linked / metabolism
  • Humans
  • Ichthyosiform Erythroderma, Congenital / metabolism
  • Limb Deformities, Congenital / metabolism
  • Lipid Metabolism, Inborn Errors / metabolism
  • Mevalonate Kinase Deficiency / enzymology
  • Mevalonate Kinase Deficiency / metabolism*
  • Oxidoreductases Acting on CH-CH Group Donors / deficiency
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Smith-Lemli-Opitz Syndrome / enzymology
  • Smith-Lemli-Opitz Syndrome / metabolism*
  • Steroid Metabolism, Inborn Errors / metabolism*
  • Sterols / metabolism*


  • Sterols
  • Cholesterol
  • Oxidoreductases Acting on CH-CH Group Donors

Supplementary concepts

  • Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects
  • Desmosterolosis
  • Lathosterolosis