Denys-Drash syndrome and cancer
Denys-Drash syndrome (DDS) is a rare genetic disorder primarily characterized by kidney failure, often by age three, and the development of Wilms' tumor, a type of kidney cancer, in about 90% of affected individuals. The syndrome is linked to mutations in the WT1 gene and is associated with male pseudohermaphroditism, leading to ambiguous genitalia in males and normal development in females. Patients typically exhibit symptoms related to kidney dysfunction, such as abdominal swelling, high blood pressure, and hematuria (bloody urine).
Diagnosis involves genetic testing for WT1 mutations and imaging studies to identify tumors. Treatment strategies may include surgery, chemotherapy, and radiation to manage tumor growth, with preventive measures like nephrectomy often recommended to avert cancer development. The prognosis for individuals with DDS can be challenging, as they are at risk for end-stage renal disease and various complications, including infections and secondary cancers. Early detection and intervention are crucial for improving outcomes, making regular screening and potential kidney transplantation important aspects of care.
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Denys-Drash syndrome and cancer
ALSO KNOWN AS: DDS, Nephropathy associated with male pseudohermaphroditism and Wilms' tumor
RELATED CONDITIONS: Wilms’ tumor (WT), Frasier syndrome, WAGR syndrome
DEFINITION: Denys-Drash syndrome is a rare disorder that usually causes kidney failure by the age of three, ambiguous genitalia in males, and 90 percent of patients develop the rare kidney cancer called Wilms’ tumor. It is caused by mutations in the WT1 gene (Wilms tumor suppressor gene). The syndrome was named for two pediatricians, Pierre Denys and Allan Drash, who initially described the condition.
Risk factors: The primary risk factor is having a relative with a WT1-related disorder. Genetic mutations can result from environmental factors or viruses.
Etiology and the disease process: Denys-Drash syndrome originates with the mutation of the WT1 gene on chromosome 11, band p13. Children with Denys-Drash syndrome are usually born with kidney disease, which becomes apparent between two weeks and eighteen months after birth. Malignant Wilms’ tumor growth in one or two kidneys occurs in approximately 90 percent of Denys-Drash patients. Cancer occasionally extends from the kidneys into the livers, lungs, and lymph nodes.
Incidence: The precise number of Denys-Drash syndrome cases is uncertain. More than two hundred cases have been reported between 1967 and the early twenty-first century. In the United States, physicians diagnose approximately five hundred children annually with Wilms’ tumor, which accounts for more than 95 percent of pediatric kidney cancers and about 6 percent of all pediatric cancers. Though these tumors can occur up to age fifteen, they are most common in those under five.
Symptoms: Denys-Drash syndrome patients often exhibit symptoms commonly associated with kidney disorders and Wilms’ tumors, including swollen abdomens, elevated blood pressure, and bloody urine. Male Denys-Drash syndrome patients have abnormal external or internal genitalia. Most have gonadal dysgenesis, which causes ambiguous genitalia and undescended testes. Most female patients have normal genitalia, which may lead to a misdiagnosis of isolated nephrotic syndrome.
Screening and diagnosis: Physicians test young children born with genitalia irregularities for Denys-Drash syndrome. Chromosome analysis verifies WT1 gene mutations. During infancy, biopsies and blood tests detect kidney problems. Computed tomography (CT) scanning, magnetic resonance imaging (MRI), or an abdomen ultrasound can locate tumors. Pediatricians apply the National Wilms’ Tumor Study Group (NWTS) staging system’s five stages to determine effective treatments.
Treatment and therapy: Medical strategies to combat Denys-Drash syndrome primarily consist of surgery, radiation, or chemotherapy, either separately or in combination, to impede tumor growth and eliminate malignancies. Preventive kidney removal (nephrectomy) is typically recommended when diagnosis precedes the development of Wilms' tumor. Some Denys-Drash syndrome patients undergo kidney transplantation or dialysis. Removal of the internal reproductive organs (gonadectomy) is generally recommended as well, as gonadal malignancy is common. Additional pharmaceutical and dietary therapies reduce blood pressure and aid kidney functioning.
Prognosis, prevention, and outcomes: Denys-Drash syndrome patients often develop infections, circulatory problems, and additional cancers that exacerbate their condition. Preventive options include replacing kidneys with healthy transplants and routine screening for malignancies. Children with Denys-Drash syndrome typically develop end-stage renal disease (ESRD) before age three.
Bibliography
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