Idiopathic Short Stature: What to Expect from Genomic Investigations
Nathalia Liberatoscioli Menezes Andrade,
Laurana Polli Cellin,
Raissa Carneiro Rezende,
Gabriela Andrade Vasques,
Alexander Augusto Lima Jorge
Affiliations
Nathalia Liberatoscioli Menezes Andrade
Unidade de Endocrinologia Genetica (LIM25), Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo 05403-000, Brazil
Laurana Polli Cellin
Unidade de Endocrinologia Genetica (LIM25), Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo 05403-000, Brazil
Raissa Carneiro Rezende
Unidade de Endocrinologia Genetica (LIM25), Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo 05403-000, Brazil
Gabriela Andrade Vasques
Unidade de Endocrinologia Genetica (LIM25) e Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular (LIM42), Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo 05403-000, Brazil
Alexander Augusto Lima Jorge
Unidade de Endocrinologia Genetica (LIM25) e Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular (LIM42), Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo 05403-000, Brazil
Short stature is a common concern for physicians caring for children. In traditional investigations, about 70% of children are healthy, without producing clinical and laboratory findings that justify their growth disorder, being classified as having constitutional short stature or idiopathic short stature (ISS). In such scenarios, the genetic approach has emerged as a great potential method to understand ISS. Over the last 30 years, several genes have been identified as being responsible for isolated short stature, with almost all of them being inherited in an autosomal-dominant pattern. Most of these defects are in genes related to the growth plate, followed by genes related to the growth hormone (GH)–insulin-like growth factor 1 (IGF1) axis and RAS-MAPK pathway. These patients usually do not have a specific phenotype, which hinders the use of a candidate gene approach. Through multigene sequencing analyses, it has been possible to provide an answer for short stature in 10–30% of these cases, with great impacts on treatment and follow-up, allowing the application of the concept of precision medicine in patients with ISS. This review highlights the historic aspects and provides an update on the monogenic causes of idiopathic short stature and suggests what to expect from genomic investigations in this field.
