Wilms' tumor aniridia-genitourinary anomalies (WAGR) syndrome and cancer
Wilms' tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome is a genetic disorder characterized by a specific genetic deletion on chromosome 11, which leads to a combination of symptoms including Wilms' tumor (a type of kidney cancer), aniridia (absence or underdevelopment of the iris), genitourinary anomalies, and varying degrees of intellectual disabilities. The incidence of WAGR syndrome is estimated to be between one in five hundred thousand to one in one million, with a notable risk of developing Wilms' tumor in 45 to 60 percent of affected individuals. Symptoms typically appear at birth, with aniridia being the most common manifestation, often resulting in significant vision problems.
Genitourinary abnormalities may include undescended testicles in males and developmental issues in the female reproductive system. Diagnosis often relies on the recognition of these symptoms, alongside screening for kidney tumors in individuals with known chromosomal deletions. Treatment primarily involves surgical removal of the tumor, with additional therapies like chemotherapy or radiation if metastasis occurs. While the prognosis for Wilms' tumor is generally favorable, lifelong challenges may arise from the other associated symptoms of WAGR syndrome. Ongoing research is focused on improving early diagnosis and treatment options for affected individuals.
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Subject Terms
Wilms' tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer
ALSO KNOWN AS: WAGRS, WAGR Complex, Chromosome 11p deletion syndrome, Wilms tumor aniridia-genitourinary anomalies-range of developmental delays
Related condition:Wilms’ tumor (in the absence of the associated abnormalities of WAGR syndrome)
DEFINITION: Wilms’ tumor aniridia-genitourinary anomalies-range of developmental delays (WAGR) syndrome is a genetic disorder that causes symptoms including Wilms’ tumor (also known as Wilms tumor or nephroblastoma), aniridia, genitourinary abnormalities, and intellectual disabilities.
Risk factors: The only known risk factor for WAGR syndrome is having a parent with an abnormal chromosome 11 arrangement.
Etiology and the disease process: The underlying cause of the syndrome is a genetic abnormality characterized by the loss of a portion of the short arm of chromosome 11 (11p13 deletion). Genetic information in this region includes the WT1 gene, a transcription factor that functions in an unknown manner as a Wilms’ tumor-suppressor gene. Loss of function contributes to genitourinary malformations. A second gene, PAX6, is considered a master control for regulating eye and neural development of the central nervous system. Mutation or deletion of the gene may result in aniridia and intellectual disabilities. Patients' symptoms depend on which specific genes are deleted.
Incidence: The combination of abnormalities inherent in WAGR syndrome is uncommon, and the incidence undetermined, with estimates ranging from one in five hundred thousand to one in one million people. However, those with WAGR syndrome have a 45 to 60 percent chance of developing Wilms’ tumor. The incidence of WAGR in the United States is estimated to be less than 5,000 total cases, with rates slightly higher among Black Americans, and it represents the most common form of kidney tumor in children. Cases are most common before the age of five.
Symptoms: The abnormalities of WAGR syndrome are generally observed immediately following birth, though diagnosis of an intellectual disability may not take place for months to years. Genitourinary abnormalities may include undescended testicles and hypospadias in male infants and abnormal development of the ovaries, uterus, fallopian tubes, or vagina in female infants.
Aniridia is the most common characteristic across all patients with WAGR syndrome; it is the underdevelopment or lack of the iris in the eye. The condition is apparent at birth and can result in significant loss of visual acuity and increased sensitivity to light. Other eye problems such as glaucoma and cataracts may also occur.
Symptoms of Wilms’ tumor include combinations of pain or swelling in the lower back, blood in the urine, and indistinct symptoms such as nausea or vomiting and loss of appetite. Since blood pressure is regulated in part by the kidneys, elevated blood pressure may also result from the presence of the tumor.
Intellectual disabilities may or may not be present and can range in severity.
Screening and diagnosis: Children known to have been born with the chromosomal deletion may be routinely screened for the development of a tumor. Diagnosis of the syndrome otherwise results from recognition of symptoms, particularly genitourinary malformations. Kidney function is assessed through several tests, including measurement of blood urea nitrogen (BUN), measurement of creatinine clearance, and X-ray or computed tomography (CT) examination of the kidneys or abdominal region. If a mass is detected in the kidney, a biopsy is performed. Staging is determined by the size and possible spread of the tumor:
- Stage I: The tumor is confined to the kidney.
- Stage II: The tumor extends into the capsule of the kidney.
- Stage III: The tumor is confined to the region but has spread beyond the surface of the kidney.
- Stage IV: Metastasis is taking place.
- Stage V: The tumor is present on both kidneys.
Treatment and therapy: Treatment is largely palliative. However, Wilms’ tumor can be removed surgically. Regional lymph nodes may be removed to determine possible metastasis and to observe other organs. If metastasis has occurred, radiation or chemotherapy may be included in the course of treatment.
Prognosis, prevention, and outcomes: Aniridia, genitourinary abnormalities, and intellectual disabilities present lifelong problems for patients but are not life-threatening. The prognosis of Wilms’ tumor depends on early diagnosis. In general, the prognosis is highly favorable, with an overall five-year survival rate of between 90 and 96 percent. Even patients diagnosed with Stage IV have an 87 percent survival rate after four years in cases with favorable histology.
Once metastasis has occurred, the tumor may be found in other organs, including the bones, lungs, and brain. Such spread is problematic, and chances for recovery are reduced. If both kidneys are involved, reduced kidney function may result following removal of the tumor. Advances continue to be made in the diagnosis and treatment of WAGR syndrome, including earlier tumor detection, earlier diagnosis of kidney issues, and gene editing techniques.
Bibliography
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