Growth plate extracellular matrix defects and short stature in children

Abstract

Many etiological factors causing short stature have already been identified in humans. In the last few years, the advent of new techniques for the detection of chromosomal and molecular abnormalities has made it possible to better identify patients with genetic causes of growth failure. Some of these factors directly affect the development and growth of the skeleton, since they damage the epiphyseal growth plate, where linear growth occurs, influencing chondrogenesis. In particular, defects in genes involved in the organization and function of the growth plate are responsible for several well-known conditions with short stature. These genes play a pivotal role in various mechanisms involving the extracellular matrix, intracellular signaling, paracrine signaling, endocrine signaling, and epigenetic regulation. In this review, we will discuss the genes involved in extracellular matrix disorders. The identification of genetic defects in linear growth failure is important for clinicians and researchers in order to improve the care of children affected by growth disorders.

Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age

“…The genetic causes of growth plate disorders have been recently investigated using next-generation sequencing (NGS) [3][4][5]. Growth plate disorders caused by defects in RAS-MAPK signaling and cartilage ECM disorders, which are difficult to diagnose due to genetic polymorphisms, are potential mechanisms of idiopathic or familial short stature (FSS) characterized by postnatal growth failure [6][7][8][9][10].…”

Molecular mechanisms of long bone growth and chondrocyte regulation: A narrative review

“…Long bone growth plays a pivotal role in determining overall height. The growth plate, a complex of cartilaginous structures situated between the epiphysis and the metaphysis of the long bones, orchestrates the process of endochondral ossification, which determines the linear growth of long bones [1][2][3]. Chondrocyte growth, metabolism, and differentiation are complex processes.…”

Commentary on "Genetic evaluation using next-generation sequencing of children with short stature: a single tertiary-center experience"

“…Numerous genetic variations affecting growth plate function, such as multiple hormones, paracrine factors, extracellular matrix molecules, and intracellular proteins have been discovered because the linear growth of children results from chondrogenesis at the growth plate. 4,5) In general, genetic analysis is indicated in patients with a clinical suspicion of monogenic disorders, such as severe short stature (below -3 standard deviations of their height score), microcephaly, or relative macrocephaly, intellectual disability, dysmorphic features, disproportional short stature, positive family history, and low birth weight (small for gestational age without catch-up growth). 6,7) In the case of familial short stature, many individuals with familial short stature are likely to exhibit polygenic short stature, characterized by inherited common gene variants.…”