Genetics of congenital adrenal hyperplasia

Best Pract Res Clin Endocrinol Metab. 2009 Apr;23(2):181-92. doi: 10.1016/j.beem.2008.10.014.


Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It comprises a group of autosomal recessive disorders caused by the deficiency of one of four steroidogenic enzymes involved in cortisol biosynthesis or in the electron donor enzyme P450 oxidoreductase (POR) that serves as electron donor to steroidogenic cytochrome P450 (CYP) type II enzymes. The biochemical and clinical phenotype depends on the specific enzymatic defect and the impairment of specific enzyme activity. Defects of steroid 21-hydroxylase (CYP21A2) and 11beta-hydroxylase (CYP11B1) only affect adrenal steroidogenesis, whereas 17alpha-hydroxylase (CYP17A1) and 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency also impact on gonadal steroid biosynthesis. Inactivating POR gene mutations are the cause of CAH manifesting with apparent combined CYP17A1-CYP21A2 deficiency. P450 oxidoreductase deficiency (ORD) has a complex phenotype including two unique features not observed in any other CAH variant: skeletal malformations and severe genital ambiguity in both sexes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Hyperplasia, Congenital / diagnosis
  • Adrenal Hyperplasia, Congenital / enzymology
  • Adrenal Hyperplasia, Congenital / genetics*
  • Animals
  • Genetic Testing
  • Humans
  • Mutation / physiology
  • NADPH-Ferrihemoprotein Reductase / deficiency
  • NADPH-Ferrihemoprotein Reductase / genetics
  • Progesterone Reductase / deficiency
  • Progesterone Reductase / genetics
  • Steroid 11-beta-Hydroxylase / genetics
  • Steroid 17-alpha-Hydroxylase / genetics
  • Steroid 21-Hydroxylase / genetics


  • 3 beta-hydroxysteroid dehydrogenase type II
  • Progesterone Reductase
  • CYP21A2 protein, human
  • Steroid 21-Hydroxylase
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • Steroid 11-beta-Hydroxylase
  • NADPH-Ferrihemoprotein Reductase