Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age

Overview

Journal J Clin Med

Specialty General Medicine

Date 2023 Oct 28

PMID 37892645

Authors

Yoo-Mi Kim

Han-Hyuk Lim

Eunhee Kim

Geena Kim

Minji Kim

Hyejin So

Byoung Kook Lee

Yoowon Kwon

Jeesu Min

Young Seok Lee

Affiliations

Soon will be listed here.

Abstract

The most common causes of short stature (SS) in children are familial short stature (FSS) and idiopathic short stature (ISS). Recently, growth plate dysfunction has been recognized as the genetic cause of FSS or ISS. The aim of this study was to investigate monogenic growth failure in patients with ISS and FSS. Targeted exome sequencing was performed in patients categorized as ISS or FSS and the subsequent response to growth hormone (GH) therapy was analyzed. We found 17 genetic causes involving 12 genes (, , , , , , , , , , , and ) and 2 copy number variants. A genetic cause was found in 45.5% and 35.7% of patients with FSS and ISS, respectively. The genetic yield in patients with syndromic and non-syndromic SS was 90% and 23.1%, respectively. In the 11 genetically confirmed patients, a gain in height from -2.6 to -1.3 standard deviations after 2 years of GH treatment was found. The overall diagnostic yield in this study was 41.7%. We identified several genetic causes involving paracrine signaling, the extracellular matrix, and basic intracellular processes. Identification of the causative gene may provide prognostic evidence for the use of GH therapy in non-SGA children.

Citing Articles

Monogenic causes of familial short stature.

Plachy L, Dusatkova P, Amaratunga S, Neuman V, Sumnik Z, Lebl J Front Endocrinol (Lausanne). 2025; 15:1506323.

PMID: 39749023 PMC: 11693446. DOI: 10.3389/fendo.2024.1506323.

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