Genetics of short stature.

Purpose of review: This review highlights recent genetic discoveries and therapeutic advancements in evaluating and managing children with short stature. With an increasing diagnostic yield from genetic testing and the emergence of genotype-specific treatments, a comprehensive update is necessary for timely application in clinical practice.

Recent findings: New pathogenic variants have been identified in genes, including FBN1, IHH, NPR2, ACAN, FGFR3, COMP, MATN3, EXT2, and LZTR1, associated with syndromic and nonsyndromic short stature. Their clinical significance is underscored by sequencing studies showing a diagnostic yield of up to 33% in idiopathic short stature. Concurrently, targeted pharmacologic agents, such as vosoritide or infigratinib, are advanced treatment options for genetically defined achondroplasia. In addition, more data is available on growth hormone responses in children with various genetic short statures.

Summary: Incorporating genetic testing into the routine investigation of short stature improves diagnostic accuracy, enables early discussion of prognostic outcomes, and facilitates precision therapy. Timely identification of specific gene variants helps avoid ineffective treatments - such as growth hormone in resistant genotypes - and supports the adoption of personalized medicine interventions.