ESPE Abstracts

Introduction: Short stature (SS) is one of the most common reasons for referral to a pediatric endocrinologist. SS is defined as a condition in which an individual's height is below the 3rd percentile for age and sex. SS may be caused by hormonal (eg. growth hormone deficiency), environmental (eg. intrauterine growth retardation) and genetic disorders (eg. Turner syndrome, Noonan syndrome). The evaluation of children presenting with SS comprises detailed clinical, phenotypical, auxological and biochemical assessments alongside genetic analyses in selected cases. In many cases, however, no definite diagnosis is reached (Idiopathic SS, ISS), and not infrequently, an underlying genetic cause is suspected. A genetic diagnosis may highlight additional important health issues which require monitoring and surveillance, even if specific treatment for growth is not possible, as in most skeletal dysplasias.

Aim: We aim ed to determine a genetic etiology for children with short stature or growth failure.

Methodology: This was a retrospective, observational study of all genetic evaluations which were done in children with SS between 2016 and 2024. We identified patients as per the Grote criteria. Genetic analyses comprised Karotype, chromosomal microarray, targeted whole exome short stature gene panel, whole exome sequencing (WES) and whole genome sequencing (WGS).

Results: 101 patients suspected of having genetic causes for SS were assessed. 62 out of 101 patients tested positive, out of which 28 patients had a pathogenic mutation. 34 out of 101 had inconclusive results, and of which 27 patients out of 101 were likely positive phenotypically. Additionally, the identification of 2 novel mutations related to UFSP2 and FBXO22, as well as the confirmation of a diagnosis of Sitosterolemia in a family, were also identified by our SS custom panel.

Discussion: We characterized the SS due to Rasopathies, Turner syndrome, skeletal dysplasia, growth receptor disorders, growth/IGF1 axis disorders, Syndromic, Idiopathic or non-syndromic disorders and others. Clinical manifestations of SS in children extend beyond short stature and may exhibit developmental delays, learning difficulties and other organ system involvement, which can significantly impact their overall health and well-being. Moreover, the psychosocial implications of SS at a young age can lead to stigmatization and compromised quality of life for affected children. Early recognition of SS is crucial to mitigate these detrimental effects and provide timely interventions as well as possible treatment with growth hormone.

Conclusion: Diagnosing SS in children necessitates a comprehensive clinical, biochemical, and genetic evaluation, incorporating appropriate auxological measurements. Genetic testing plays a pivotal role in identifying specific mutations associated with SS, enabling precise molecular diagnosis and genetic counseling for affected families as well. Furthermore, positive genetic results prompted further monitoring and surveillance in these patients, which would otherwise have gone unrecognized.