Khandelwal MH, Piparva KG, Parchwani D. Familial WT1-associated nephropathy - 46, XY Frasier syndrome and 46, XX steroid-resistant nephrotic syndrome in female siblings: A case report and review of literature. World J Nephrol 2026; 15(1): 110867 [DOI: 10.5527/wjn.v15.i1.110867]
Corresponding Author of This Article
Deepak Parchwani, PhD, Professor, Department of Biochemistry, All India Institute of Medical Sciences, AIIMS Rajkot, Village Khandheri, Tehsil Paddhari, Rajkot 360001, Gujarāt, India. hodbiochem@aiimsrajkot.edu.in
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Case Report
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Mar 25, 2026 (publication date) through Mar 14, 2026
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World Journal of Nephrology
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Khandelwal MH, Piparva KG, Parchwani D. Familial WT1-associated nephropathy - 46, XY Frasier syndrome and 46, XX steroid-resistant nephrotic syndrome in female siblings: A case report and review of literature. World J Nephrol 2026; 15(1): 110867 [DOI: 10.5527/wjn.v15.i1.110867]
World J Nephrol. Mar 25, 2026; 15(1): 110867 Published online Mar 25, 2026. doi: 10.5527/wjn.v15.i1.110867
Familial WT1-associated nephropathy - 46, XY Frasier syndrome and 46, XX steroid-resistant nephrotic syndrome in female siblings: A case report and review of literature
Mahipal H Khandelwal, Kiran G Piparva, Deepak Parchwani
Mahipal H Khandelwal, Pediatric Nephrology, B.T. Savani Kidney Hospital, Rajkot 360005, Gujarāt, India
Kiran G Piparva, Department of Pharmacology, All India Institute of Medical Sciences, Rajkot 360001, Gujarāt, India
Deepak Parchwani, Department of Biochemistry, All India Institute of Medical Sciences, Rajkot 360001, Gujarāt, India
Co-first authors: Mahipal H Khandelwal and Kiran G Piparva.
Author contributions: Khandelwal MH and Piparva KG contributed equally to this manuscript and are co-first authors. Khandelwal MH contributed to diagnosis, case identification acquisition of clinical data, interpretation of clinical findings, clinical management, resource coordination, supervision, and final approval of the manuscript; Piparva KG and Parchwani D contributed to the literature review; Piparva KG contributed to conceptualization, wrote the original draft and revision; Parchwani D contributed to oversight, activity planning and execution, critical evaluation and preparation of final version of manuscript for submission.
Informed consent statement: Written informed consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Deepak Parchwani, PhD, Professor, Department of Biochemistry, All India Institute of Medical Sciences, AIIMS Rajkot, Village Khandheri, Tehsil Paddhari, Rajkot 360001, Gujarāt, India. hodbiochem@aiimsrajkot.edu.in
Received: June 20, 2025 Revised: July 28, 2025 Accepted: January 6, 2026 Published online: March 25, 2026 Processing time: 269 Days and 14.3 Hours
Abstract
BACKGROUND
The Wilms tumor 1 (WT1) mutation is significantly associated with steroid-resistant nephrotic syndrome (SRNS) in children. It causes a spectrum of disorders, including Frasier and Denys-Drash syndromes. The WT1 gene encodes a transcription factor essential for renal, gonadal, and mesothelial development. The prevalence of Frasier syndrome is 1 in 1000000. Frasier syndrome presents with childhood onset of SRNS, progressing to end-stage kidney disease, has an XY female phenotype, delayed puberty, and gonadal tumor risk. Two siblings with identical WT1 mutations but differing phenotypes offer important clinical insights.
CASE SUMMARY
We report a rare familial occurrence of shared mutation of WT1 (at intron 9 splice site: C.1432+5G>A) and COL4A5 genes in two siblings. The elder sibling (46, XY) presented with infantile steroid-resistant nephrotic syndrome and rapidly deteriorating and progressing to end-stage kidney disease with XY karyotype. The genetic testing confirmed the diagnosis of Frasier syndrome associated with a WT1 mutation in the elder sibling. She is currently on maintenance dialysis, awaiting renal transplantation. The younger sibling presented at age four with facial edema and SRNS with slower disease progression and no apparent gonadal anomalies. Her renal biopsy revealed minimal change disease, and she maintains stable renal function under antiproteinuric therapy. Genetic testing confirmed the diagnosis of WT1 mutation with 46, XX karyotype in the younger sibling. Both siblings also carried a COL4A5 gene variant of uncertain significance. Family history reveals consanguineous marriage and a similar presentation in a sibling.
CONCLUSION
Despite identical mutations, phenotypic differences highlight complex genotype-phenotype relations, stressing the need for research, genetic counseling, and family member screening.
Core Tip: This report describes two siblings with identical pathogenic Wilms tumor 1 but distinct karyotypes (46, XY and 46, XX) leading to divergent clinical presentations. The elder sibling had classical features with early-onset steroid-resistant nephrotic syndrome with rapidly deteriorating renal function, while the younger sibling presented with steroid-resistant nephrotic syndrome only without gonadal abnormalities. This rare familial occurrence emphasizes sex-dependent phenotypic variability despite identical mutations, expanding understanding of Wilms tumor 1-related disorders. The findings underscore the importance of genetic testing, detailed family evaluation, and long-term monitoring to guide management in such rare syndromic presentations.
