Denys-Drash Syndrome with Neonatal Renal Failure in Monozygotic Twins Due to C.1097G>A Mutation in the WT1 Gene

Abstract

Denys-Drash syndrome, characterized by nephrosis, dysgenetic gonads and a predisposition to Wilms tumor, is due to germline mutations in the WT1 gene. We report the pathologic findings on monozygotic twins, both of whom presented with male pseudohermaphroditism, nephrotic syndrome, and progressed to renal failure and death within the first month of life. Sequence analysis of WT1 demonstrated a G-to-A substitution in exon 8 of the gene (c.1097G > A), resulting in an arginine-to-histidine (R366H) substitution in the second zinc finger domain. To the best of our knowledge, this is only the second set of monozygotic twins with Denys-Drash syndrome reported to date.

Keywords :

• Denys-Drash syndrome
• WT1
• twins
• congenital nephrotic syndrome
• diffuse mesangial sclerosis
• gonadal dysgenesis