P201: The clinical utility of next-generation sequencing (NGS)-based genetic testing in pediatric polycystic kidney disease

Trenaunay syndrome, clinical diagnosis of congenital lipomatous overgrowth with vascular anomalies, epidermal nevi and scoliosis (CLOVES) syndrome, and venous malformation.The presence of this variant in these 5 patients demonstrates the phenotypic spectrum of vascular anomalies and the importance of a molecular diagnosis, which has further treatment implications.Patients with activating variants in PIK3CA may benefit from utilization of the PI3K inhibitor, alpelisib.A single patient was identified to harbor a RASA1 germline variant as well as a somatic RASA1 variant at 3.0% VAF, which is consistent with the second-hit hypothesis.In our patient population, the diagnostic yield for testing was lower for patients with primarily lymphatic malformations (11% or 1/9) vs those who had venolymphatic malformations or other vascular malformations (89.3% or 42/47).Conclusion: Ultra-deep sequencing of VA affected tissue and other appropriate sample types increases precision molecular diagnosis of VAs and provides opportunities for targeted therapeutics.Importantly, in this cohort we found 8 positive results in patients who were previously negative by standard NGS sequencing.Additional investigation is needed to understand molecular mechanisms involved in patients with primarily lymphatic malformations given the low yield in our patient population.These results emphasize that the combination of ultra-deep sequencing with multiple sample procurement methods and sample types is effective in establishing a molecular diagnosis for patients with VAs.Further, utilization of a multidisciplinary approach assists in achieving an individualized care plan for each patient.