Why some kids are short & understanding linear growth

If you want to explore the biological basis for short stature, then an excellent review (YH Jee, J Bacon. J Pediatr 2016; 173: 32-7) is worthwhile.

The article begins by explaining the reasons why linear growth is rapid in infancy, slows in childhood and accelerates in adolescence through a process of growth plate chondrogenesis.  In addition, the idea that growth plate fusion causes growth cessation is not accurate.  Fusion of the growth plate occurs because of growth cessation. In addition, in many with “catch-up growth” the “delay in maturation appears to be driven by subtle undernutrition due to diminished appetite.”

Altered Growth Plate Chondrogenesis:

  • Nutritional intake -excess and inadequate nutrient intake affects growth, often through modulation of endocrine hormones.  Overnutrition accelerates linear growth “but the adult height is not substantially affected.”
  • Hormones –thyroid hormones, growth hormone, IGF-1, androgen, and estrogen all positively regulate linear growth.  Glucocorticoids negatively regulate linear growth.
  • Inflammatory cytokines –these cytokines (including TNF-α, IL-6, IL-1β) negatively regulate chondrogenesis
  • Paracrine growth factors, Extracellular Matrix, Intracellular Proteins –local growth factors can be deficient in those with specific genetic mutations:  FGFR3 -achondroplasia, GNAS -Albright hereditary osteodystrophy, PTH1R -Blomstrand chrondrodysplasia, PTPN11 (& others) -Noonan, SHOX -Langer mesmeric dysplasia.  SHOX mutations accounts for 2-5% of children with formerly idiopathic short stature.  SHOX gene is also involved in Turner syndrome short stature. More listed in their Table (pg 35).

My take: It is cool to see the evolved understanding of the various factors affecting stature.  While the authors conclude that exome sequencing will alter the diagnostic approach to children with severe short or tall stature, it seems that a genetic panel would be quite practical and less expensive than many endocrinological evaluations.

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