How and when to do genetic testing in young children

The first guide with advice on when to do genetic testing in children with short stature and which tests are best for each situation.

How and when to perform genetic testing in children with short stature: new international guidelines

An international guideline set out for the first time clear standards for the use of genetic testing in children with short stature.

The paper presents a clinical algorithm that guides the selection of tests according to patient characteristics.

Short stature in children is a frequent reason for pediatric consultation.Traditionally, a significant number of cases have been classified as idiopathic short stature, that is, without an identifiable cause.However, advances in genetics in recent decades have changed the situation, allowing an increasing number of causes to be identified.

In this context, the European Journal of Endocrinology published the first international consensus guideline focusing on the use of genetic testing in children with short stature.The document was prepared by a large international group of experts in pediatric psychology and genetics, and supported by eight international scientific societies for psychology and genetics.

The development of the manual responds to the need to systematize the use of genomic tools in clinical practice.Although sequencing technologies have greatly improved diagnostic capacity, their application has remained heterogeneous.The new paper provides recommendations based on a systematic review of the literature and the GRADE methodology.According to its authors, the goal is to facilitate clinical decision-making and improve the diagnosis of growth disorders.

"It is a pioneering and specific guide that focuses on when and how to do genetic studies in short children and it introduces a practical algorithm that helps pediatricians decide which genetic test to use depending on the case," says Jesus Argente, professor of pediatrics at the Autonomous University of Madrid and head of the Pediatric and Endocrinology Service at the University of Madrid in Niño.guide development.

Guidelines for the use of genetic testing in children with short stature

When dealing with short-term cases, experts recommend that you always start with a complete clinical evaluation before considering genetic studies.This includes a medical and family history (including a family tree), a thorough physical examination, laboratory tests, and radiological studies.

Genetic tests should not be performed.They are considered if there are genetic symptoms, such as growth defects, neurodevelopmental diseases, physical abnormalities, very short height, emotional family history or a significant difference with the height of the parents.They are shown in cases of suspicion of specific diseases, skeletal dysplasias or changes in the GH / IGF-1 axis.

Experts do not recommend genetic testing in cases with a high likelihood of polygenic origin or in cases of constitutional growth retardation.The choice of genetic technique should be tailored to the clinical situation, with targeted panels or exome/genome sequencing preferred.In this sense, the data indicate that the diagnostic yield of exome sequencing may be around 15% for individual cases, but exceeds 50% for syndromic cases and reaches up to 70% for skeletal dysplasia.

Another of the most important recommendations is the need for a multidisciplinary approach, with the collaboration of pediatric endocrinologists, clinical geneticists and laboratory specialists.The importance of pre- and post-test genetic counseling is also emphasized, as it is possible to identify variants of uncertain significance or secondary findings.

Finally, experts recommend periodic reevaluation of genetic data in undiagnosed patients, as the constant identification of new genes and variants may change the interpretation of previous results.

Clinical implications and health applications

Guidelines have a direct impact on clinical practice.First, by facilitating the identification of genetic causes, it helps to reduce the number of patients with idiopathic short stature.It helps to cure the real disease.

Second, genetic studies can influence patient management and treatment decisions.For example, it makes it possible to determine the indications or limitations of growth hormone treatment or to predict possible problems with certain diseases.

The guide also highlights the potential of technologies such as whole exome or whole genome sequencing in the study of developmental disorders.At present the diagnostic performance is limited to a few cases, but it is hoped that the introduction of new methods will increase the possibility of detection in the future.

Another related issue is the integration of genetic information with clinical and radiological data to improve the interpretation of mutations. Such an approach will allow progress towards more precision medicine in pediatric endocrinology.

Overall, the guideline is an important step toward standardizing the use of genetic testing in children with short stature and provides a basis for its gradual introduction into routine clinical practice.

Dauber A, J et al.International guidelines for genetic testing of children with short stature.Eur J Endocrinol.2026 Feb 4;194(2): R17-R36.DOI: 10.1093/ejendo/lvag013