Definition and subcategorization of idiopathic short stature: between consensus and controversy

Although various expert and consensus meetings have been held, there remains uncertainty about the definition of idiopathic short stature (ISS) and its subgroups. In this short review, the hypothetical pathophysiology, diagnosis and subcategorization of ISS are discussed. ISS in childhood may be the result of a combination of variants of three groups of genes: (1) single genes (or combinations of a few single genes) of which mutations, deletions or duplications are associated with a relatively large negative effect on height; (2) genes of which relatively frequently occurring polymorphisms are associated with a small negative effect on height; and (3) genes associated with delayed maturation of the epiphyseal plate. Differentiation between ISS and short children born small for gestational age and those with dysmorphic syndromes, systemic diseases or growth hormone deficiency and resistance can be difficult. Subcategorization based on distance to target height and onset of puberty is arbitrary, but useful.