Kidney Week

Abstract: FR-PO0150

WT1-Associated Nephropathy Beyond Childhood: Phenotypic Spectrum and Kidney Outcomes in an International Cohort

Session Information

• Hereditary Glomerular and Tubulointerstitial Kidney Diseases
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Pichette, Maude, Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada

Maude Pichette, MD

• Caux, Aurélien, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

Aurélien Caux, PharmD

• Beck, Bodo B., University of Cologne Medical Center, Cologne, Germany

Bodo B. Beck, MD

• Dirim, Ahmet Burak, Istanbul Universitesi Istanbul Tip Fakultesi, Istanbul, Turkey

Ahmet Burak Dirim, MD

• Sayer, John Andrew, Newcastle University, Newcastle upon Tyne, England, United Kingdom

John Andrew Sayer, MBChB, PhD

• Boyer, Olivia, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

Olivia Boyer, MD, PhD

• Heidet, Laurence, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

Laurence Heidet, MD, PhD

• Knebelmann, Bertrand, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

Bertrand Knebelmann, MD, PhD

• Dorval, Guillaume, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

Guillaume Dorval, MD, PhD

• Cornec-Le Gall, Emilie, Centre Hospitalier Regional et Universitaire de Brest, Brest, Brittany, France

Emilie Cornec-Le Gall, MD, PhD

Background

WT1-associated nephropathies are well described in pediatric populations, including in Denys-Drash and Frasier syndromes, but data regarding adult-onset or adult-diagnosed forms remain limited. We aimed to characterize the phenotypic variability, penetrance, renal outcomes, and extrarenal manifestations, including tumor-associated complications, in patients with WT1-associated nephropathy.

Methods

This international multicenter study included pediatric and adult patients diagnosed with WT1-associated nephropathy carrying a heterozygous likely pathogenic or pathogenic WT1 variant. Clinical, biological, genetic, and histological data were retrospectively collected.

Results

Sixty-six patients from 44 families across centers in France, Germany, UK and Turkey were included: 38 men and 28 self-reported women (including 4 with a 46,XY karyotype). Mean age at inclusion was 46±22y, including 59 adults. Initial symptoms occurred at a mean age of 22±15y, with 41% presenting before 18 years of age. Indications for genetic testing were proteinuria (32%), nephrotic syndrome (30%), kidney failure (26%), and familial screening (12%). Proteinuria was present in 61/62 patients and was in the nephrotic range in 78% of cases. One 56-year-old WT1 variant carrier had preserved kidney function without proteinuria despite a strong family history of early kidney failure (KF), illustrating incomplete penetrance. Among the 48 available kidney biopsies, 85% showed focal segmental glomerulosclerosis lesions. KF occurred in 66% of patients at a mean age of 32±18y, with no significant difference in time to KF from diagnosis between pediatric and adult cases. Genital anomalies were reported in 12 patients, including 7 adults. Two pediatric nephroblastomas and one gonadoblastoma in a 7-year-old child were identified.

Conclusion

This study highlights the variable expressivity and incomplete penetrance of WT1-associated nephropathy, as well as the high risk of progression to KF, including in patients diagnosed during adulthood. WT1-associated nephropathy should be considered even in adults with late presentations and no extrarenal manifestations.