WT1-related disorders: more than Denys-Drash syndrome.

Autor: Lopez-Gonzalez M; Department of Pediatric Nephrology, University Hospital Vall d'Hebron, Barcelona, Spain. mercedes.lopgonz@gmail.com., Ariceta G; Department of Pediatric Nephrology, University Hospital Vall d'Hebron, Barcelona, Spain.; University Autonomous of Barcelona, Barcelona, Spain.
Jazyk: angličtina
Zdroj: Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2024 Sep; Vol. 39 (9), pp. 2601-2609. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1007/s00467-024-06302-y
Abstrakt: Historically, specific mutations in WT1 gene have been associated with distinct syndromes based on phenotypic characteristics, including Denys-Drash syndrome (DDS), Frasier syndrome (FS), Meacham syndrome, and WAGR syndrome. DDS is classically defined by the triad of steroid-resistant nephrotic syndrome (SRNS) onset in the first year of life, disorders of sex development (DSD), and a predisposition to Wilms tumor (WT). Currently, a paradigm shift acknowledges a diverse spectrum of presentations beyond traditional syndromic definitions. Consequently, the concept of WT1-related disorders becomes more precise. A genotype-phenotype correlation has been established, emphasizing that the location and type of WT1 mutations significantly influence the clinical presentation, the condition severity, and the chronology of patient manifestations. Individuals presenting with persistent proteinuria, with or without nephrotic syndrome, and varying degrees of kidney dysfunction accompanied by genital malformations should prompt suspicion of WT1 mutations. Recent genetic advances enable a more accurate estimation of malignancy risk in these patients, facilitating a conservative nephron-sparing surgery (NSS) approach in select cases, with a focus on preserving residual kidney function and delaying nephrectomies. Other key management strategies include kidney transplantation and addressing DSD and gonadoblastoma. In summary, recent genetic insights underscore the imperative to implement individualized, integrated, and multidisciplinary management strategies for WT1-related disorders. This approach is pivotal in optimizing patient outcomes and addressing the complexities associated with these diverse clinical manifestations.
(© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)
Databáze: MEDLINE
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