WAGR syndrome is a rare genetic disorder that affects children from birth. It is named for the primary conditions that characterize the syndrome: Wilms tumor, Aniridia, Genitourinary anomalies, and a Range of developmental delays. The combination and severity of these features differ between individuals, and not all will have every associated condition.
Genetic Origins of WAGR Syndrome
The root cause of WAGR syndrome is a deletion of a small segment of genetic material on chromosome 11. This specific region, known as 11p13, contains several genes that guide different aspects of development. In most instances, this deletion happens randomly during the formation of reproductive cells or very early in fetal development and is not inherited.
Within this deleted segment, two genes are significant: WT1 and PAX6. The WT1 gene provides instructions for making a protein important for the development of the kidneys and gonads. The PAX6 gene is a master control gene for eye development. The loss of one copy of these and surrounding genes disrupts normal development, leading to the syndrome’s characteristic signs and symptoms.
Core Conditions of WAGR Syndrome
A defining feature of WAGR syndrome is a significantly increased risk—between 45 and 60 percent—of developing Wilms tumor, a type of kidney cancer. This cancer most often appears in young children between the ages of one and three. Some individuals may first develop non-cancerous cell growths in the kidneys called nephrogenic rests, which are considered precursors to the tumor.
Aniridia, the partial or complete absence of the colored part of the eye (the iris), is present in nearly all individuals with WAGR syndrome and is often the first sign noticed. The lack of a functional iris impairs the eye’s ability to regulate incoming light, causing severe light sensitivity (photophobia). This condition also leads to reduced sharpness of vision.
Genitourinary anomalies are also common, though they present differently in males and females. In males, these can include undescended testicles (cryptorchidism) or a misplaced urethral opening (hypospadias). Females may have underdeveloped ovaries or structural abnormalities of the uterus and fallopian tubes, which can affect urinary function and future fertility.
A range of developmental delays is the fourth characteristic feature. These can manifest as mild learning disabilities or more significant intellectual challenges. Many individuals experience difficulties with processing information and may have delays in acquiring speech, language, and motor skills.
Diagnosis and Initial Assessment
A diagnosis of WAGR syndrome is often suspected at birth when a physician identifies aniridia in a newborn. The presence of this distinct eye abnormality, sometimes combined with observable genital anomalies in male infants, prompts further investigation. While clinical signs are strong indicators, genetic testing is required for a definitive diagnosis.
To confirm the diagnosis, specialists use laboratory tests that can visualize a person’s chromosomes. A test called fluorescence in situ hybridization (FISH) can reveal whether the gene region on chromosome 11 is missing. A more detailed test called a chromosomal microarray can detect even smaller deletions and precisely map the size of the missing genetic segment.
Management and Treatment Approaches
Managing WAGR syndrome requires a proactive, multidisciplinary team of providers, including pediatricians, oncologists, nephrologists, and ophthalmologists. The goal is to monitor for health issues and intervene early to support development and treat conditions as they arise.
A primary component of management is regular screening for Wilms tumor. Children with WAGR syndrome undergo kidney ultrasounds every three to four months until at least age eight to ensure any tumor is detected early. After this period, monitoring may continue with periodic ultrasounds and awareness of symptoms like abdominal swelling.
The management of aniridia focuses on preserving existing vision and mitigating symptoms. This includes using heavily tinted sunglasses or specialized contact lenses to manage light sensitivity. Regular monitoring by an ophthalmologist is necessary to check for and treat secondary conditions like glaucoma and cataracts.
For genitourinary anomalies, interventions depend on the specific issue. Surgical procedures may correct structural problems, such as undescended testicles or hypospadias. Early intervention programs with physical, occupational, and speech therapy help support motor and communication skills from a young age.
Associated Health Considerations
Beyond the four main conditions, individuals with WAGR syndrome have a higher likelihood of experiencing other health issues. A significant long-term concern is chronic kidney disease, which can progress to kidney failure in some adults. This risk is present even in individuals who never develop a Wilms tumor and necessitates lifelong monitoring of kidney function.
There is also a noted predisposition to obesity that can begin in childhood and persist into adulthood. The exact reasons for this are not fully understood but may be linked to the genetic deletion. Managing weight is an important aspect of long-term health to prevent related complications.
Some individuals with WAGR syndrome may face behavioral or psychiatric challenges. Conditions such as attention-deficit/hyperactivity disorder (ADHD), anxiety, and autism spectrum disorders are reported more frequently in this population. Addressing these aspects through behavioral therapies and other support systems is an important part of comprehensive care.