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Abstract: FR-PO674

Genetic Insights into Pediatric Polycystic Kidney Disease

Session Information

  • Pediatric Nephrology - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology


  • Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Yang, Hana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Schauer, Rachel S., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sas, David J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Tran, Cheryl L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Cramer, Carl H., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Pediatric polycystic kidney disease (PKD) exhibits genetic heterogeneity, including autosomal dominant and recessive PKD, as well as ciliopathies with syndromic involvement. Relying solely on gene-specific analyses may lead to missed diagnoses. Our objective was to summarize genetic findings in pediatric patients (pts) with bilateral kidney cysts seen at our clinic, emphasizing unique cases.


We reviewed resolved cases from Jan 2020 to Apr 2023 involving clinical or research genetic testing. Targeted next-generation sequencing, encompassing known and candidate PKD/ciliopathy genes, was performed at our research lab. Variants were assessed using disease-specific and population databases, along with in silico variant assessment tools. Categorization followed ACMG guidelines.


Genetic screening identified pathogenic changes in 9 genes, accounting for 49 pts (45 families): 40 with monoallelic and 9 with biallelic variants. Monoallelic genes included PKD1 (n=18), HNF1B (n=9), PKD2 (n=5), PKHD1 (n=2), IFT140 (n=2), NEK8 (n=1), GANAB (n=1), TSC2 (n=1), and TSC2/PKD1 deletion (n=1). Biallelic genes were PKHD1 (n=6) and NPHP1 (n=3). Among PKD1 pts, 83% (15/18) had a positive family history, while 60% (3/5) of PKD2 pts did. Incident discovery or family screening diagnosed 67% (12/18) of PKD1 pts, 28% (5/18) had prenatal presentation, and one case involved an early onset intracranial aneurysm rupture. PKD2 pts were all incidentally diagnosed. Children with monoallelic variants in IFT140, GANAB, or PKHD1 exhibited mild PKD phenotypes and were incidentally diagnosed through abdominal imaging. The NEK8 variant pt presented with severe neonatal PKD and kidney failure requiring dialysis at 6 years old, representing a novel manifestation for this gene. Nearly all HNF1B variant/deletion pts (8/9) presented in utero with kidney cysts and/or hyperechoic kidneys.


Comprehensive analysis of clinical and research-related genetic screening reveals the complexity of monogenic causes of PKD. This study reports the first pathogenic variant in IFT140 found in pediatric pts, an additional case involving GANAB, and a new monoallelic NEK8 disorder. Genetic screening in pediatric PKD pts, irrespective of family history, offers a definitive diagnosis, informs prognosis and therapy discussions, and facilitates enrollment in clinical trials.


  • NIDDK Support