ESPE Abstracts

Introduction: Genetic investigation in patients with short stature allows diagnostic definition and impacts therapeutic decisions, clinical follow-up, and genetic counseling. That said, next-generation sequencing has created a new clinical challenge by allowing the identification of findings unrelated to the complaint that prompted testing. The ACMG published a list of actionable incidental findings that includes genes whose variants should be reported to patients, regardless of whether they justify the phenotype studied, because of their impact on the patient's health.

Objectives: The present study aimed to describe the frequency of actionable incidental findings in a cohort of patients with short stature undergoing exome sequencing.

Methods: We selected children monitored at a tertiary hospital for short stature (height SD < -2) from 2015 to 2024 who underwent whole-exome sequencing following usual procedures. The pipeline for WES analysis was conducted using the Franklin-Genoox platform. We searched for pathogenic or likely pathogenic variants in the genes from the ACMG list of actionable secondary findings (v4).

Results: During the proposed period, 442 children with short stature were subjected to exome sequencing. After filtering, we identified 21 deleterious variants in 19 genes associated with diseases that did not explain the phenotype motivating the test (20:442 4.5%). Six of these genes belongs to the ACMG list of actionable findings (6 variants from 5 patients:442 = 1.1%). Table 1 describes each variant. None of the children presented a genetic finding that could justify their short stature.

Conclusion: Actionable incidental findings should be expected with increased genetic evaluation in clinical practice. The dissemination of this concept and its appropriate management is essential for good patient care in the era of genomic medicine.