Phenotype heterogeneity in inherited growth hormone insensitivity.

Growth hormone (GN) insensitivity is associated with several different muta tions of the GN receptor gene and a recently described nov genetic disorder of the IFGI gene. rile phenotype and biochemical characteristics were stud ied in 82 patients with growth hormone insensitivity, fi-om 23 different co untries, with a mean age of 8.25 years. Mean height SDS was -6.09, SDS of t he ICF binding protein -3 (IGF BP3) was 7.99 Twenty three per cent of the p atients Here GH binding protein (GHBP) positive (>10 %). Mean height SDS sc ore was -6.5 in the GHBP negative patients and -4.9 in the GHBP positive pa tients (p < 0.001). Fifteen different,mutations of the GH receptor gene wer e identified in 27 patients There were no relationships between the type of mutation or the involved GH receptor gene exon and height or IGFBP-3 SDS. The new phenotype due to a partial deletion of the IGFI gene Ic ns describe d in a 15-year-old boy who presented with a severe intrauterine growth reta rdation, a very poor postnatal statural growth, a neurosensorial deafness a nd a mild mental retardation. He had elevated GH In els, normal levels of I GFBP3, undetectable levels of IGFI, and showed no response in GH treatment. A partial deletion concerning the exons 4 and 5 of the IGFI gene was found , Thus, GH insensitivity is associated with large variations in the clinica l and biochemical phenotypes. (C) 1998 Elsevier, Paris.