Denis-Drash syndrome

Denys–Drash syndrome (DDS) is a rare genetically determined disorder that is relatively severe and can be life‑threatening for affected individuals.

Causes

The cause is a congenital genetic mutation in the WT1 gene, which is responsible for the proper development of the urinary and genital systems and functions as a tumor‑suppressor gene for Wilms tumor. The vast majority of mutations occur in one of two regions of the gene located on chromosome 11, known as exon 8 or exon 9.

While mutations in a single copy of the WT1 gene are sufficient to cause nephropathy and disorders of sexual development, Wilms tumor develops only as a result of mutations in both copies of the WT1 gene. Wilms tumor therefore results from two independent events (the two‑hit hypothesis) that gradually lead to loss of function of both copies of the WT1 gene. The first mutation in one copy of the WT1 gene (the first hit) leads to persistence of undifferentiated tissue in the developing kidney, known as mesenchyme. Subsequently, a second mutation (the second hit) in the other copy causes uncontrolled cell growth in the kidney and development of Wilms tumor.

Most cases of this syndrome are not inherited from a parent but arise as a result of a new (de novo) gene mutation.

Symptoms

Affected individuals present with various disorders of sexual organ development (including ambiguous external genitalia), kidney failure, development of nephrotic syndrome with edema, and a frequent occurrence (approximately 90%) of Wilms tumor.

Wilms tumor is a specific form of renal malignancy that differs completely from adult kidney cancer. It originates from embryonic kidney tissue and is typical of childhood. It manifests with abdominal enlargement, abdominal pain, loss of appetite, weight loss, hematuria, and high blood pressure. Although malignant, it responds relatively well to treatment.

Diagnosis

Genetic testing can detect the WT1 gene abnormality, while kidney failure is identified by blood and urine tests. Wilms tumor may be detected by palpation (after initial palpation, however, it must no longer be palpated) and later identified using abdominal ultrasound.

Treatment

The development of the syndrome cannot be prevented, nor can it be cured. Management of symptoms falls under the care of a nephrologist. Renal failure is treated with the aim of slowing disease progression; however, despite all efforts, complete kidney failure usually occurs within three years. In the event of Wilms tumor development, radical treatment is required, consisting of removal of the affected kidney. In cases of loss of function of both kidneys, dialysis is necessary.

• poruchy vývoja pohlavných orgánov
• zlyhávanie obličiek
• vznik nefrotického syndrómu s opuchmi
• výskyt Wilmsovho tumoru (nádorové ochorenie obličiek)