Reclassifying Idiopathic Short Stature as 'Healthy Short Stature' to reduce stigma and align with genetic insights

Idiopathic Short Stature (ISS) has long been used for children with height below -2 SDS lacking an identified cause. Originally a pragmatic diagnosis of exclusion, ISS has become reified as a disease, influencing clinical guidelines and growth hormone therapy indications. However, modern genomic technologies reveal a spectrum of monogenic and chromosomal variants within this group, alongside the continuous, polygenic nature of height. This renders the "idiopathic" construct increasingly unstable and misleading, necessitating a re-evaluation of how short stature is classified.

This article reviews the historical evolution and current clinical application of Idiopathic Short Stature (ISS). Researchers synthesized literature on the impact of modern genetic testing on short stature classification, examining how genomic discoveries have revealed monogenic and chromosomal variants previously categorized as ISS. The authors then propose a new classification, "Healthy Short Stature," based on current understanding of human growth biology, discussing its implications for clinical practice, research, and health policy.

The review highlights that the "idiopathic" construct for short stature is increasingly misleading as genetic technologies uncover specific etiologies. It argues that every new etiological discovery conceptually undermines the Idiopathic Short Stature (ISS) category. The authors emphasize that the continuous, polygenic architecture of height further supports this reclassification.

Most children currently labeled with ISS are better described as having "Healthy Short Stature," defined as short stature in otherwise healthy children without systemic, syndromic, or endocrine disease, where short stature represents the lower extreme of normal growth variation. Adopting this new classification can reduce stigma associated with a "disease" label, remain compatible with ongoing genetic investigation, and provide a more robust framework for aligning clinical practice, research, and health policy with contemporary knowledge of human growth biology.