WT1-Related Nephropathy in a Phenotypically Female Child: A Case of Clinical and Genetic Discordance

WT1-Related Nephropathy in a Phenotypically Female Child: A Case of Clinical and Genetic Discordance

WT1-related disorders comprise a spectrum of conditions resulting from mutations or deletions of the WT1 gene. Alteration in this gene have been associated with many syndromes, including WAGR syndrome, Denys–Drash syndrome (DDS), Frasier syndrome (FS) and Meacham syndrome. We present the case of an...

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Main Authors: Mariana Costin, Eliza Elena Cinteză, Anca Croitoru, Ionela-Loredana Popa, Alexandra Stanciu, Irina Popescu, Nicoleta Petre, Bettyna Olivotto, Andrei Căpitănescu, Sofia Resceanu, Elena Cotfasa, Cristina Bologa
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Children
Subjects:
Frasier syndrome (FS)
Denys–Drash syndrome (DDS)
end-stage kidney disease (ESKD)
thrombotic microangiopathy (TMA)
focal segmental glomerulosclerosis (FSGS)
Wilms Tumor 1 (WT1)
Online Access:https://www.mdpi.com/2227-9067/12/5/595
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Summary:WT1-related disorders comprise a spectrum of conditions resulting from mutations or deletions of the WT1 gene. Alteration in this gene have been associated with many syndromes, including WAGR syndrome, Denys–Drash syndrome (DDS), Frasier syndrome (FS) and Meacham syndrome. We present the case of an 8-year-old phenotypically female child with symptoms of end-stage kidney disease (ESKD), hypertension and anasarca, requiring renal replacement therapy. This case is distinctive due to its unusual onset, the presence of thrombotic microangiopathy (TMA), and the detection of a heterozygous missense mutation in the <i>WT1</i> gene (c.1298G>A, p.Cys433Tyr) located in exon 8, in association with a 46 XY karyotype. The kidney biopsy indicated advanced focal segmental glomerulosclerosis (FSGS) with characteristics of TMA, implying a possible alternative diagnosis. In light of the heightened malignancy risk, the patient had preventative laparoscopic gonadectomy, which revealed rudimentary testicular tissues. The identified genotype points toward a diagnosis of DDS. However, the clinical presentation is more consistent with features typically seen in FS. This discrepancy highlights the significant phenotypic and genotypic overlap between the two syndromes. As a result, there is ongoing discussion in the literature about whether DDS and FS should be considered distinct clinical entities or rather variable expressions along a shared disease spectrum.
ISSN:2227-9067

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