Genetic disorders in prenatal onset syndromic short stature identified by exome sequencing

Abstract

Identifying the diagnosis in children with syndromic short stature and those with recognized genetic growth disorders is often challenging, as they may share many clinical features (1)(2). The candidate gene approach has many limitations in unveiling the genetic cause. Therefore, whole exome sequencing (WES) has been proposed to improve the diagnostic rate in children with short stature of unknown etiology, including both idiopathic short stature (ISS) and SGA (3). In this study, 44 children with the following inclusion criteria were selected for WES analysis: available DNA samples, consent by the patient and family, a syndromic condition without an initial clinical diagnosis and a negative result on candidate gene testing based on clinical suspicion. Among these 44 patients, 40 had already been investigated by a genetic test before enrollment, mainly chromosomal microarray analysis, multiplex ligation-dependent probe amplification for Silver-Russell syndrome, or targeted gene panel sequencing, including genes frequently associated with growth disorders.