Growth Hormone Insensitivity Associated with aSTAT5bMutation

Abstract

The syndrome of growth hormone insensitivity is characterized by phenotypic features consistent with the presence of a growth hormone deficiency, but with normal-to-elevated circulating concentrations of growth hormone and resistance to exogenous growth hormone therapy.¹ Originally described by Laron and colleagues,² the syndrome, it has become increasingly apparent, involves considerable phenotypic heterogeneity, reflecting, at least in part, the complexity of the growth hormone signaling cascade. The majority of patients described to date have low serum concentrations of growth hormone–binding protein, the extracellular domain of the growth hormone receptor, as a result of mutations or deletions that affect the growth hormone–binding region of the receptor.^3-5 A number of patients, however, have been described who have normal or even elevated serum concentrations of growth hormone–binding protein.^6,7 These include patients with mutations in the growth hormone receptor that affect dimerization⁸ or the transmembrane and intracellular regions.^9-12