LARON SYNDROME. (Growth Hormone Insensitivity) Geographical distribution and relationship to the genetic defects in the growth hormone receptor gene.

Abstract

Laron Syndrome (LS), caused by defects in the GH receptor (GH-R) gene, is a rare recessively inherited disease of severe short stature. The number of patients with LS worldwide is so far unknown. To determine the reported number of patients with LS, and analyse their geographical distribution, in relation to the repertoire of pathogenic GH-R variants. Using the keywords: Laron Syndrome, GH insensitivity and GH receptor defects or deficiencies, we searched the following indices: PubMed, SCOPUS, EMBASE, ScienceDirect, Web of Science, Google and Cochrane Reviews. Eight hundred and one publications, including references published between the years 1966-2025, were reviewed. We generated a list of patients with LS, their geographical distributions and their pathogenic variants in the GH-R gene. Patients cited repeatedly were included only once. Eight hundred forty patients with Laron Syndrome (412 males, 361 females, 67 sex not stated) were identified in 801 publications. The majority of patients are concentrated in East and South Asia, the Mediterranean Basin, and South America. Four hundred and two patients out of 411 had a genetic analysis, revealing 109 different genetic defects. The majority of pathogenic variants were in the extracellular domain of the GH-R gene with fewer defects identified in the transmembrane or intracellular domains and in introns. Large geographic clusters of patients with LS were associated with one predominant or several different GH-R gene defects. Review of the scientific literature between 1966-2025 revealed 840 patients with Laron Syndrome. Shared ancestors, human migration and the practice of consanguinity explain the geographic distribution of these patients.