Novel Insights Into the Genetic Causes of Short Stature in Children

Short stature is a common reason for consulting a growth specialist during childhood. Normal height is a polygenic trait involving a complex interaction between hormonal, nutritional and psychosocial components. Genetic factors are becoming very important in the understanding of short stature. After exclusion of the most frequent causes of growth failure, clinicians need to evaluate whether a genetic cause might be taken into consideration. In fact, genetic causes of short stature are probably misdiagnosed during clinical practice and the underlying cause of short stature frequently remains unknown, thus classifying children as having idiopathic short stature (ISS). However, over the past decade, novel genetic techniques have led to the discovery of novel genes associated with linear growth and thus to the ability to define new possible aetiologies of short stature. In fact, thanks to the newer genetic advances, it is possible to properly re-classify about 25–40% of children previously diagnosed with ISS. The purpose of this article is to describe the main monogenic causes of short stature, which, thanks to advances in molecular genetics, are assuming an increasingly important role in the clinical approach to short children.