Genetic causes of proportionate short stature

Best Pract Res Clin Endocrinol Metab. 2018 Aug;32(4):499-522. doi: 10.1016/j.beem.2018.05.012. Epub 2018 Jun 6.


Human growth is a very complex phenomenon influenced by genetic, hormonal, nutritional and environmental factors, from fetal life to puberty. Although the GH-IGF axis has a central role with specific actions on growth, numerous genes are involved in the control of stature. Genome-wide association studies have identified >600 variants associated with human height, still explaining only a small fraction of phenotypic variation. Since short stature in childhood is a common reason for referral, pediatric endocrinologists must be aware of the multifactorial and polygenic contributions to height. Multiple disorders characterized by growth failure of prenatal and/or postnatal onset due to single gene defects have been described. Their early diagnosis, facilitated by advances in genomic technologies, is of upmost importance for their clinical management and to provide genetic counseling. Here we review the current clinical and genetic information regarding different syndromes and hormone abnormalities with proportionate short stature as the main feature, and provide an update of the approach for diagnosis and management.

Keywords: IGF system; MOPDs; exome; genome; growth hormone; growth syndromes.

Publication types

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

MeSH terms

  • Body Height / genetics*
  • Child
  • Genome-Wide Association Study
  • Growth Disorders / genetics*
  • Human Growth Hormone / genetics*
  • Human Growth Hormone / metabolism
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism


  • Human Growth Hormone
  • Insulin-Like Growth Factor I