Analysis of the mutation frequency in isolated and syndromal forms of PIK3CA-associated overgrowth

Abstract

PROS (PIK3CA-Related Overgrowth Spectrum) is a tissue overgrowth syndrome associated with mutations in the PIK3CA gene. As approaches to pathogenetic treatment with PIK3-associated signaling pathway inhibitors (sirolimus, alpelisib, miransertib) are being developed, the demand for molecular genetic testing of patients with suspected PROS has arisen. 53 patients with tissue overgrowth affecting upper or lower extremities were observed in St.-Petersburg State Pediatric University Clinic in 2018-2023 yrs. Patients had molecular genetic testing using digital droplet PCR and targeted high-throughput sequencing. Pathogenic PIK3CA variants were identified in 17 cases. In the isolated form of the disease mutations were detected much more rarely in comparison with the syndromal form of this pathology (8 / 39 (21%) vs. 9 / 14 (64%), p = 0.006).