Gene affected: WT1 (Wilm tumor suppressor gene), which is important for normal development of the urogenital system. Klamt et al reported defective alternative splicing of WT1 leading to an altered ratio of WT1 +/1 FTS splice isoforms.
Chromosome: 11p13
Clinical features:
(1) female external genitalia with female or male karyotype (XY males show gonadal dysgenesis with streak gonads, male pseudohermaphroditism, hypergonadotropic hypogonadism)
(2) glomerulopathy with diffuse mesangial sclerosis and focal segmental glomerulosclerosis leading to renal failure
(3) high risk for Wilm’s tumor
(4) high rate of gonadoblastoma and/or dysgerminoma/seminoma
The patient may present as an apparent female with:
(1) nephrotic syndrome, hematuria and hypertension during childhood or adolescence (usually a later onset than for the Denys-Drash syndrome)
(2) primary amenorrhea.
(3) a urogenital malignancy
Prophylactic nephrectomy (with renal transplant) and gonadectomy may be performed due to the risk for malignancy.
