Denys-Drash Syndrome Workup

Updated: Oct 30, 2019
  • Author: Agnieszka Swiatecka-Urban, MD, FASN, FAAP; Chief Editor: Maria Descartes, MD  more...
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Workup

Laboratory Studies

Consider the following laboratory studies:

  • Urinalysis: Proteinuria is the hallmark of the nephropathy in Denys-Drash syndrome (DDS) and is usually in the nephrotic range. Hematuria (gross or microscopic) may also be revealed.

  • Renal function tests: BUN and serum creatinine levels may be within reference ranges in the early stages of Denys-Drash syndrome but worsen with advancing nephropathy or development of bilateral Wilms tumor. End-stage renal disease (ESRD) development is accompanied by hyperkalemia and hyperphosphatemia.

  • Wilms tumor markers: Increased levels of hyaluronic acid, hyaluronic acid-stimulating activity, erythropoietin, and renin prohormone are associated with Wilms tumor.

  • Chromosome analysis: Obtain karyotype determination in all patients with suspected Denys-Drash syndrome, even in the absence of ambiguous genitalia. Analysis of band 11p13 and determination of the WT1 mutation is important in all patients with the nephropathy of DDS, even in the absence of Wilms tumor or obvious intersex disorder. These findings confirm the genetic diagnosis and alert the physician to the significantly increased risk of Wilms tumor development.

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Imaging Studies

Consider the following imaging studies:

  • Abdominal and pelvic ultrasonography: Perform ultrasonography in all patients who present with signs and symptoms that suggest Denys-Drash syndrome. At regular intervals after the initial diagnosis, continue evaluating the kidneys for the quality of renal parenchyma and for the presence of Wilms tumor. Screen all individuals for the presence of abnormal internal genitalia (eg, undescended testes, undifferentiated and/or streak gonads) because of their risk of developing a gonadoblastoma (both in 46,XY and 46,XX individuals).

  • Abdominal and pelvic CT scanning: This scan is a more sensitive test for revealing Wilms tumor, especially to reveal unsuspected contralateral tumor or metastases, to demonstrate invasion of contiguous structures, to predict surgical resectability, and to monitor response to chemotherapy and surgical resection.

  • Chest radiography: Radiography reveals pulmonary metastases.

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Procedures

Biopsy is essential for the diagnosis of Denys-Drash syndrome because it confirms the presence of diffuse mesangial sclerosis. Obtain the kidney biopsy specimen by percutaneous biopsy in children without Wilms tumor at the time of presentation. In patients with Wilms tumor, obtain kidney tissue at the time of nephrectomy. Note the image below.

Gross nephrectomy specimen shows a Wilms tumor pus Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.
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Histologic Findings

The pathognomonic kidney lesion is termed diffuse mesangial sclerosis. Features of the early phase include expansion of the glomerular mesangial matrix, obliteration of the capillary lumens, thickening of the glomerular basement membrane, and hypertrophy of the podocytes. Features of the late phase are mesangial matrix sclerosis, glomerular tuft contraction, prominent tubular atrophy, and interstitial fibrosis.

Wilms tumor originates from pluripotential cells of the metanephric blastema and consists of blastemal, stromal, and epithelial cells. The presence of anaplasia suggests a poor prognosis.

Multiple gonadal abnormalities have been described, including the following:

  • Streak ovary containing primordial follicles

  • Müllerian and wolffian ducts

  • Streak gonad with ovarian-type stroma lacking primordial follicles and with primitive canalicular seminiferous tubules

  • Dysgenetic or atrophic intraabdominal testes

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