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Denys-Drash syndrome (DDS) manifests in small children and consists of the triad of congenital nephropathy, Wilms tumor, and ambiguous genitalia.

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Drash Syndrome.

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Unknown. Approximately 150 cases have been reported. No racial predilection.

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Probably arises as a spontaneous mutation. The mutation is usually not present in parents; however, affected sibling pairs have been reported. DDS is the result of a so-called heterozygous dominant-negative mutation in the Wilms tumor suppressor gene 1 (WT1), with the gene locus mapping to 11p13. The same mutation has been reported in patients with isolated Wilms tumor. Most patients are pseudohermaphrodites with a 46,XY karyotype.

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The dominant-negative mutation results in cellular WT1 levels less than 50% of normal in these patients. Diffuse mesangial fibrosis of the kidney results in progressive nephropathy and subsequent renal failure and associated hypertension. Wilms tumor is present in 74% and gonadal malignancies (gonadoblastoma) in 4% of patients.

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The majority of patients have an ambiguous genitalia or appear phenotypically female. The combination of ambiguous genitalia with typical renal involvement and arterial hypertension is suggestive of the disease. Kidney biopsy shows diffuse mesangial sclerosis with expansion of the mesangial matrix and subcapsular atrophy. Intracytoplasmic deposits of fibrillary material results in mesangial cell expansion.

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Although pure gonadal dysgenesis with male pseudohermaphroditism is typical, the clinical variability of the external genitalia ranges from bifid scrotum with micropenis and palpable gonads to penoscrotal hypospadias with cryptorchidism or clitoral hypertrophy with labial fusion. Gonadal dysgenesis presents as streak ovaries and dysgenetic testes, respectively. Usually, patients present in their first year of life with the typical symptoms of nephrotic syndrome (marked proteinuria with hypoproteinemia [hypalbuminemia] resulting in recurrent infections, marked edema, abdominal distension secondary to ascites, hyperlipidemia, and hypercholesterolemia). Patients may have varying degrees of renal dysfunction/failure, but glomerular filtration rate usually declines quickly and results in end-stage renal disease requiring either dialysis or renal transplantation at approximately age 3 years. Hypertension, failure to thrive, and delayed psychomotor milestones may develop as a result of renal failure. Wilms tumor is usually detected at approximately age 2 years and is most often unilateral (80%). However, bilateral nephrectomy may be prudent management for unilateral nephropathy to reduce the high likelihood of developing a Wilms tumor in the contralateral kidney. Elective gonadectomy can be performed because of the difficulty in screening for gonadal malignancies. Most associated findings probably are incidental.

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Expect chronic renal anemia and evaluate renal function with serum electrolytes, creatinine, and urea preoperatively. Ask about the date of last hemodialysis, daily urine output, and maximal allowable daily fluid intake. Depending on the laboratory results and the clinical status (hypervolemia), hemodialysis may be necessary. Consider end-organ involvement related to arterial hypertension, hyperlipidemia, and/or hypercholesterolemia and whether chemotherapeutic agents were used preoperatively for treatment of Wilms tumor. The patient may have undergone renal transplantation requiring immunosuppressant drugs (corticosteroids) and manifest related adverse effects.

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Avoid hypovolemia ...

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