WT1 deletion leading to severe 46,XY gonadal dysgenesis, Wilms tumor and gonadoblastoma: case report.

Abstract

BACKGROUND:

Heterozygous missense mutations in the WT1 gene that affect the function of the wild-type allele have been identified in Denys-Drash syndrome, which is characterized by severe gonadal dysgenesis, early-onset nephropathy and a predisposition to renal and gonadal cancer. Intron 9 splice-site mutations that influence the balance between WT1 isoforms cause a nearly similar phenotype, known as Frasier syndrome. Nonsense mutations and deletions only lead to WT1 haploinsufficiency and, hence, to less severe gonadal dysgenesis and late-onset nephropathy. WT1 analysis is mandatory in 46,XY gonadal dysgenesis with renal abnormality.

PATIENT:

We describe a newborn with 46,XY severe partial gonadal dysgenesis, in whom structural renal anomalies and proteinuria were excluded. Gonadectomy was performed at the age of 1 month and the microscopy was thought to be suggestive for a gonadoblastoma. At the age of 9 months, the patient presented with a bilateral Wilms tumor.

RESULTS:

We found a heterozygous WT1 whole-gene deletion but no other gene defects.

CONCLUSIONS:

This case description illustrates that a WT1 deletion might be associated with a more severe phenotype than previously thought. It also illustrates that, even in the absence of renal abnormality, it is recommended to test promptly for WT1 defects in 46,XY gonadal dysgenesis.

• Authors: Martijn J J Finken, Yvonne M C Hendriks, J Patrick van der Voorn, Margreet A Veening, M Paola Lombardi, Joost Rotteveel
• Journal: Hormone research in paediatrics (Horm Res Paediatr) Vol. 83 Issue 3 Pg. 211-6 ( 2015) ISSN: 1663-2826 [Electronic] Switzerland
• PMID: 25613702 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• WT1 Proteins
• WT1 protein, human

Topics

• Female
• Gene Deletion
• Gonadal Dysgenesis, 46,XY (genetics)
• Gonadoblastoma (genetics)
• Humans
• Infant, Newborn
• Neoplasms, Second Primary (genetics)
• WT1 Proteins (genetics)
• Wilms Tumor (genetics)