Genetics of Short Stature

Abstract

Short stature is a common and heterogeneous condition that is often genetic in etiology. For most children with genetic short stature, the specific molecular causes remain unknown; but with advances in exome/genome sequencing and bioinformatics approaches, new genetic causes of growth disorders have been identified, contributing to the understanding of the underlying molecular mechanisms of longitudinal bone growth and growth failure. Identifying new genetic causes of growth disorders has the potential to improve diagnosis, prognostic accuracy, and individualized management, and help avoid unnecessary testing for endocrine and other disorders.

Keywords: Exome sequencing; Genetic causes; Genome-wide association study; Growth plate; Short stature.

Figure 1

Molecular mechanisms of short stature. Short stature is caused by multiple molecular defects including intracellular signaling, extracellular matrix, paracrine and endocrine regulation. Ovoid shapes represent growth plate chondrocytes. Arrows indicate mechanisms regulating chondrocytes. Examples of clinical syndrome and the genetic cause under different molecular mechanisms are shown in each box.