Evaluate the response of the growth hormone treatment in children with idiopathic short stature (ISS) based on genetic findings

Abstract

Growth disorders are a frequent complaint in pediatric and endocrinology clinical practice. Most children with height SDS < -2 are labeled as having idiopathic short stature (ISS). ISS corresponds to a healthy child with clinical and laboratory evaluation with no relevant findings that justify the growth disorder. It is known that genetic variability is the primary determinant of height. In this way, several genes with rare and pathogenic variants have been associated with growth disorders over the last years. The impact of these genetic findings on the response of recombinant human growth hormone (rhGH) therapy in children with ISS is still not understood. For this reason, the present study aims to assess if monogenic causes of growth failure in ISS children are responsible for a different response to the treatment with rhGH. The study will be retrospective longitudinal, assessing medical record data of children classified as having ISS, treated with rhGH for at least one year. In our database, we have about a hundred children in that condition. Most of these children were already genetically evaluated in previous studies. A monogenic cause associated with ISS was identified in thirty-three of these children until that moment. Patients without previous genetic investigations will be analyzed along with the present study. The patients with and without any pathogenic variant in genes associated with ISS will be compared as the growth velocity and change in Z-score of height. In that way, we intend to bring evidence related to the impact of genetic findings in the rhGH treatment of children, initially classified as ISS. (AU)