AUTHOR=Arroyo-Parejo Drayer Patricia , Seeherunvong Wacharee , Katsoufis Chryso P. , DeFreitas Marissa J. , Seeherunvong Tossaporn , Chandar Jayanthi , Abitbol Carolyn L. 

TITLE=Spectrum of Clinical Manifestations in Children With WT1 Mutation: Case Series and Literature Review

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.847295

DOI=10.3389/fped.2022.847295

ISSN=2296-2360

ABSTRACT=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
WT1 mutation was identified in 9 children, median age at presentation of 0.9 year (range 1 week to 7 years). Four had female phenotype, 5 had abnormalities of male external genitalia, while all had XY karyotypes. All progressed to end stage kidney disease 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 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.