Genetic testing in pediatric renovascular hypertension identified diverse etiologies, most commonly moyamoya disease (25%) and vasculopathy of unknown origin (25%), with RNF213 variants as a major cause.
Observational (n=58)
No
What is the genetic landscape and underlying etiology of pediatric renovascular hypertension?
Systematic genetic evaluation, particularly for RNF213 variants, is crucial in pediatric renovascular hypertension to identify specific etiologies and guide management.
Objective: Pediatric renovascular hypertension (RVH) differs significantly from adult forms, often arising from underlying vascular anomalies or monogenic syndromes rather than atherosclerosis. Identifying the specific etiology of renal artery stenosis is essential for guiding optimal management plans—such as selecting between revascularization and medical therapy—and for improving long-term clinical outcomes. Therefore, we aimed to investigate the genetic landscape of pediatric RVH in a single-center cohort Design and method: We conducted a retrospective review of pediatric patients (aged 0–18 years) diagnosed with RVH and managed at Samsung Medical Center over a 10-year period between 2016 and 2025. We analyzed demographic data, clinical features, and genetic test results. Genetic testing strategies included targeted Sanger sequencing, whole exome sequencing (WES), or whole genome sequencing (WGS). The specific testing modality was selected based on clinical judgment, phenotypic presentation, and the availability of tests at the time of diagnosis. Results: A total of 58 pediatric patients with RVH were managed during the study period. Genetic testing was performed in 40 patients, of whom 60% were female. The spectrum of underlying etiologies was diverse: moyamoya disease (MMD, 25%) and vasculopathy of unknown origin (25%) were the most common, followed by RNF213-related vasculopathy without MMD (15%). Less frequent causes included Takayasu arteritis (7.5%), fibromuscular dysplasia (5%), Klippel-Trenaunay-Weber syndrome (2.5%), ROHHAD syndrome (2.5%), and others (17.5%). Targeted evaluation of the RNF213 c.14429G>A variant in 37 patients identified 5 heterozygous and 9 homozygous cases. Additionally, broad screening via WES (n=10) and WGS (n=1) was performed, identifying diagnostic variants in 2 patients by WES, including pathogenic mutations in ANO1 and a distinct RNF213 variant (c.14749G>A). Conclusions: RNF213 variants are a major cause of pediatric RVH in this population, presenting both as MMD with renal artery stenosis and isolated vasculopathy. The detection of additional variants via WES highlights the genetic heterogeneity of the disease. Given the advancements in and improved accessibility of genetic testing, systematic genetic evaluation has become crucial. Integrating this into the diagnostic workup is essential for identifying specific etiologies and for optimizing long-term management strategies.
Kim et al. (Fri,) conducted a observational in Pediatric renovascular hypertension (n=58). Genetic testing (Sanger sequencing, WES, WGS) was evaluated on Spectrum of underlying genetic etiologies. Genetic testing in pediatric renovascular hypertension identified diverse etiologies, most commonly moyamoya disease (25%) and vasculopathy of unknown origin (25%), with RNF213 variants as a major cause.