WAGR syndrome

Synonyms

6

Overview

WAGR syndrome is a disorder that affects many body systems and is named for its main features: Wilms tumor, anirida, genitourinary anomalies (such as undescended testicles or hypospadias in males, or internal genital or urinary anomalies in females), and intellectual disability (formerly referred to as mental retardation). A combination of two or more of these conditions is usually present in most individuals with WAGR syndrome.

Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). These patients often also have genitourinary abnormalities and intellectual disability (WAGR syndrome).

People with WAGR syndrome have a 45 to 60 percent chance of developing Wilms tumor, a rare form of kidney cancer. This type of cancer is most often diagnosed in children but is sometimes seen in adults.

Symptoms

Most people with WAGR syndrome have aniridia, an absence of the colored part of the eye (the iris). This can cause reduction in the sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). Aniridia is typically the first noticeable sign of WAGR syndrome. Other eye problems may also develop, such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), and involuntary eye movements (nystagmus).

Abnormalities of the genitalia and urinary tract (genitourinary anomalies) are seen more frequently in males with WAGR syndrome than in affected females. The most common genitourinary anomaly in affected males is undescended testes (cryptorchidism). Females may not have functional ovaries and instead have undeveloped clumps of tissue called streak gonads. Females may also have a heart-shaped (bicornate) uterus, which makes it difficult to carry a pregnancy to term.

Another common feature of WAGR syndrome is intellectual disability. Affected individuals often have difficulty processing, learning, and properly responding to information. Some individuals with WAGR syndrome also have psychiatric or behavioral problems including depression, anxiety, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or a developmental disorder called autism that affects communication and social interaction.

Other signs and symptoms of WAGR syndrome can include childhood-onset obesity, inflammation of the pancreas (pancreatitis), and kidney failure. When WAGR syndrome includes childhood-onset obesity, it is often referred to as WAGRO syndrome.

The congenital absence of the iris is usually the first and most striking feature. Although generally absent in the newborn period, scanning nystagmus may be present in infancy. The degree of vision loss varies among patients.

Causes

The syndrome is due to a microdeletion in the 11p13 region of chromosome 11. In most cases, this genetic change occurs spontaneously during early embryonic development (de novo) for unknown reasons (sporadic). Only rarely is the mutation inherited.

Diagnosis

Newborn children with WAGR syndrome are soon noted to have aniridia. The clinical suspicion for WAGR may be increased with the presence of other genital anomalies, though genitourinary anomalies are not always present, particularly in girls. In older children, clinical diagnosis of the syndrome can be made when aniridia and one of the other features are present. It must be noted that while aniridia is rarely absent in WAGR syndrome, cases have been reported without it. Chromosomal analysis is necessary for definitive diagnosis.Other common eye defects include cataracts and ptosis. About 5% of patients develop Wilms's tumor.

Treatment

WAGR syndrome/11p deletion syndrome can be diagnosed at birth, based upon a clinical evaluation, characteristic physical findings, and chromosomal studies (high-resolution karyotyping and molecular cytogenetic tests). In many cases, the partial or complete absence of the iris of the eye (aniridia) may be the only physical feature associated with WAGR Syndrome/11p deletion syndrome that is obvious at birth. In other cases, genitourinary abnormalities associated with the syndrome may also be apparent.

If a child has aniridia, chromosomal studies are necessary to determine whether the child has a genetic predisposition for the disorders associated with WAGR syndrome/11p deletion syndrome.

Treatment of WAGR syndrome/11p deletion syndrome is directed toward the specific symptoms that are apparent in each individual.