Genetic regulation of linear growth

Abstract

Linear growth occurs at the growth plate. Therefore, genetic defects that interfere with the normal function of the growth plate can cause linear growth disorders. Many genetic causes of growth disorders have already been identified in humans. However, recent genome-wide approaches have broadened our knowledge of the mechanisms of linear growth, not only providing novel monogenic causes of growth disorders but also revealing single nucleotide polymorphisms in genes that affect height in the general population. The genes identified as causative of linear growth disorders are heterogeneous, playing a role in various growth-regulating mechanisms including those involving the extracellular matrix, intracellular signaling, paracrine signaling, endocrine signaling, and epigenetic regulation. Understanding the underlying genetic defects in linear growth is important for clinicians and researchers in order to provide proper diagnoses, management, and genetic counseling, as well as to develop better treatment approaches for children with growth disorders.

Keywords: Genome-wide association study; Next generation sequencing; Short stature; Linear growth.

Fig. 1.

Mechanisms regulating chondrocytes in the growth plate. (A) Growth plate on X-ray. Black box indicates where growth plate is located. (B) Diagram of the 3 layers in the growth plate. (C) Diagram of chondrocyte-regulating mechanisms. RZ, resting zone; PZ, proliferative zone; HZ, hypertrophic zone. Modified from Jee YH, et al. Endocrinol Metab Clin North Am 2017;46:259-81 [15].