A case of X-linked adrenal hypoplasia congenita, central precocious puberty and absence of the DAX-1 gene: implications for pubertal regulation

Horm Res. 2009;71(5):298-304. doi: 10.1159/000208804. Epub 2009 Apr 1.

Abstract

Background/aims: X-linked adrenal hypoplasia congenita (AHC) is typically associated with DAX-1 mutations and hypogonadotropic hypogonadism. However, atypical cases of X-linked AHC in association with central precocious puberty and even normal puberty have rarely been reported, although the mechanism of action remains unknown.

Case report: This is a case report of a boy with X-linked AHC associated with Duchenne muscular dystrophy, whose clinical presentation led to analysis of the DAX-1, glycerol kinase (GK1) and dystrophin genes, which were amplified by polymerase chain reaction, with Southern blot analysis of the AHC locus.

Results: There was a non-contiguous deletion of the DAX-1 and GK1 genes, with deletion of the dystrophingene from exons 3 to 79.

Conclusion: This is the first report of X-linked AHC, central precocious puberty in the absence of the DAX-1 gene. The fact that a 'loss of function' DAX-1 mutation can be associated with hypogonadotropic hypogonadism, precocious and normal puberty, suggests that DAX-1 is but one of several transcription factors which regulate puberty, and provides further evidence that other transcription factors may interact with DAX-1 and influence gonadal regulation in a complex, but hierarchical fashion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Gland Diseases / congenital*
  • Adrenal Gland Diseases / genetics
  • Child, Preschool
  • Cyproterone Acetate / therapeutic use
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins / genetics*
  • Genes, X-Linked*
  • Glycerol Kinase / genetics
  • Humans
  • Hypogonadism / genetics
  • Infant, Newborn
  • Male
  • Muscular Dystrophy, Duchenne / complications
  • Puberty / physiology
  • Puberty, Precocious / drug therapy
  • Puberty, Precocious / genetics*
  • Receptors, Retinoic Acid / genetics*
  • Repressor Proteins / genetics*

Substances

  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • NR0B1 protein, human
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Cyproterone Acetate
  • Glycerol Kinase