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Kidney Week

Abstract: PO2342

Spectrum of Clinical Manifestations in Children with WT1 Mutation

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Arroyo Parejo Drayer, Patricia Alejandra, University of Miami School of Medicine, Miami, Florida, United States
  • Katsoufis, Chryso P., University of Miami School of Medicine, Miami, Florida, United States
  • Defreitas, Marissa J., University of Miami School of Medicine, Miami, Florida, United States
  • Seeherunvong, Tossaporn, University of Miami School of Medicine, Miami, Florida, United States
  • Abitbol, Carolyn L., University of Miami School of Medicine, Miami, Florida, United States
  • Chandar, Jayanthi, University of Miami School of Medicine, Miami, Florida, United States
  • Seeherunvong, Wacharee, University of Miami School of Medicine, Miami, Florida, United States
Background

Advances in genetic testing increases our ability to diagnose genetic causes of nephrotic syndrome (NS). The WT1 gene is a tumor suppressor gene necessary for kidney and gonadal development. Mutations in the WT1 gene are associated with NS and pose an increased risk of Wilms tumor and gonadoblastoma.

Methods

A retrospective chart review was performed in patients followed at the University of Miami from January 1990 to December 2019 with NS and WT1 gene mutation.

Results

WT1 mutations were identified in 9 children, included 5 Hispanic, 2 Caucasian, 1 Asian and 1 Middle Eastern. The mean age at renal presentation was 2.4 years (1 week to 7 years). Five presented with congenital NS (CNS). Three presented with steroid resistant NS (SRNS), at age 3 to 6 years, and received immunosuppressive treatments. One presented in advanced kidney failure at 7 years. Four had normal female external genitalia, and 5 had various abnormalities of male genitalia. Karyotype study showed XY in all. Two males developed Wilms tumor, found incidentally. All progressed to end stage kidney disease at a median age of 5 years (1 month to 14 years). Genetic diagnosis was delayed in 2 females and ultimately WT1 mutation was confirmed when they presented with primary amenorrhea. All phenotypic females underwent gonadectomy and required long term estrogen. Of two pubertal males, one had hypogonadism, and both were monitored for gonadal tumor. The median age from renal presentation to diagnosis of WT1 mutation was 7.6 years for females and 2.2 years for males (p < 0.05), (Figure).

Conclusion

Early recognition of NS associated with WT1 gene mutation is important for management which includes avoidance of immunosuppressive therapy, prevention of complications such as malignancy, and establishing long-term management of reproductive health. All females with infantile CNS or SRNS should get karyotype testing to identify WT1 gene mutation.

Funding

  • Clinical Revenue Support