Children with idiopathic short stature (ISS) are defined by height below 2 standard deviations (SD) of the mean for age and sex without any endocrine, metabolic or other disease explaining the short stature. The US Food and Drug Administration approves growth hormone (GH) treatment on children shorter than 2.25 SD of the mean for age and sex with a predicted adult height below the normal range. Given that stature in a population follows a Gaussian distribution, 2.3% of children will always be shorter than 2 SD below the mean for age and sex. However, a proportion of these children defined in childhood as having ISS will eventually achieve a normal adult height or a normal height in their families, even in the absence of expensive GH treatment.

Human height has a highly polygenic nature. It has been estimated that about 80% of variation in height can be attributed to genetics. Polygenic scores have been demonstrated to have an improving ability to identify individuals at significantly high/low predisposition towards complex diseases. Therefore, it has become possible to identify individuals who will lie at the extreme distribution of a trait, such as height.

Therefore, we posit that a polygenic risk score for adult height may be able to effectively predict which children diagnosed as having ISS are likely to achieve a normal adult height where indication of GH treatment would not be necessary.