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Spectrum of Clinical Manifestations in Children With WT1 Mutation: Case Series and Literature Review
Patricia Arroyo-Parejo Drayer1, Wacharee Seeherunvong1, Chryso P Katsoufis1
1Division of Pediatric Nephrology, Department of Pediatrics, Holtz Children's Hospital, University of Miami Miller School of Medicine, Miami, FL, United States.
Insights
WT1 gene mutations cause serious kidney disease and development issues. Early detection is key for managing complications like Wilms tumor and ensuring proper care.
Area of Science:
- Genetics and Molecular Biology
- Pediatric Nephrology
- Endocrinology
Background:
- Wilms tumor suppressor-1 gene (WT1) mutations are linked to severe glomerulopathy, disorders of sexual development, Wilms tumor, and gonadal cancers.
- Understanding the clinical progression and complications of WT1 mutations is crucial for patient management.
Purpose of the Study:
- To detail the clinical presentations, progression rates, and complication onset in individuals with WT1 mutations.
- To analyze a case series and conduct a literature review for comprehensive insights into WT1 mutation-related conditions.
Main Methods:
- Retrospective analysis of patients diagnosed with WT1 mutation at a single institution (2000-2020).
- Comprehensive literature review of WT1 mutation cases focusing on clinical features, karyotype, and long-term outcomes.
Main Results:
- Nine pediatric patients with WT1 mutations presented with a median age of 0.9 years; all had XY karyotypes, with varied phenotypes (4 female, 5 with male genital abnormalities).
- All patients developed end-stage kidney disease (ESKD), requiring kidney transplantation by a median age of 5 years. Literature review revealed a majority female phenotype (66%) but a predominant XY karyotype (55%), with 32% of females exhibiting XY sex reversal.
- Wilms tumor occurred in 24% of cases, primarily in males with gonadal anomalies. Post-transplant follow-up showed no malignancies, though 2 allograft losses occurred.
Conclusions:
- Early identification of WT1 mutations is vital for proactive malignancy surveillance.
- Avoiding immunosuppression for glomerulopathy and establishing multidisciplinary, long-term care are essential for patients with WT1 mutations.
Background:
Mutations of the Wilms tumor suppressor-1 gene (WT1) are associated with life-threatening glomerulopathy, disorders of sexual development, Wilm's tumor, and gonadal malignancies. Our objectives were to describe the clinical presentations, age of progression, and onset of complications of WT1 mutation through a case series and literature review.
Methods:
A retrospective study included all patients followed at the University of Miami/Holtz Children's Hospital from January 2000 to December 2020 with a diagnosis of WT1 mutation. A literature review of WT1 mutation cases was analyzed for clinical manifestations, karyotype, and long-term outcomes.
Results:
The WT1 mutation was identified in 9 children, median age at presentation of 0.9 years (range 1 week to 7 years). A total of four had female phenotypes, and 5 had abnormalities of male external genitalia, while all had XY karyotypes. All progressed to end-stage kidney disease (ESKD) and received a kidney transplant at a median age of 5 years (1.5-15 years). During a median time of follow-up of 9 years (range 2-28 years), there were 2 allograft losses after 7 and 10 years and no evidence of post-transplant malignancy. From 333 cases identified from the literature review, the majority had female phenotype 66% (219/333), but the predominant karyotype was XY (55%, 183/333). Of the female phenotypes, 32% (69/219) had XY sex reversal. Wilm's tumor occurred in 24%, predominantly in males with gonadal anomalies.
Conclusions:
Early recognition of WT1 mutation is essential for comprehensive surveillance of potential malignancy, avoidance of immunosuppressants for glomerulopathy, and establishing long-term multidisciplinary management.
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