Ajl Clark

Relationship between phenotype and genotype in growth hormone insensitivity syndrome

Woods KA, Clark AJL, Amselem S, Savage MO. Relationship between phenotype and genotype in growth hormone insensitivity syndrome. Acta Pædiatr 1999; Suppl 428: 158–62. Stockholm. ISSN 0803–5326

Relations phenotype-genotype dans l'insensibilite a l'hormone de croissance

Growth hormone (GH) insensitivity is associated with several different mutations of the GH receptor gene and a recently described new genetic disorder of the IFGI gene. The phenotype and biochemical characteristics were studied in 82 patients with growth hormone insensitivity, from 23 different countries, with a mean age of 8.25 years. Mean height SDS was -6.09. SDS of the IGF binding protein -3 (IGF BP3) was 7.99. Twenty three per cent of the patients were GH binding protein (GHBP) positive (> 10%). Mean height SDS score was -6.5 in the GHBP negative patients and -4.9 in the GHBP positive patients (p < 0.001). Fifteen different mutations of the GH receptor gene were 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 was described in a 15-year-old boy who presented with a severe intrauterine growth retardation, a very poor postnatal statural growth, a neurosensorial deafness and a mild mental retardation. He had elevated GH levels, normal levels of IGFBP3, undetectable levels of IGFI, and showed no response to 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 clinical and biochemical phenotypes.

Growth hormone insensitivity.

Growth hormone insensitivity (GHI) describes a group of disorders characterized by deficient biological action of GH. GH insensitivity may be of primary origin, that is, related to defects in genes coding for functional proteins essential for GH action or secondary to acquired pathology such as inflammatory or nutritional disorders. This article will describe GH insensitivity of primary origin, which in children presents as growth failure leading to adult short stature. Metabolic symptoms, such as hypoglycaemia, may also occur. Cardinal biochemical features are normal or elevated GH secretion and IGF-1 deficiency. Therapy for GH insensitivity consists of recombinant human IGF-1, which can lead to height gain resulting in catch-up growth and adult height within the normal range.