WAGR syndrome/11p deletion syndrome is defined as a genetic syndrome in which there is a predisposition to Wilms’ tumor; aniridia; abnormalities of the reproductive and urinary tracts (genitourinary); and intellectual disability. The specific symptoms that occur depend upon the combination of disorders present.
Wilms’ tumor (nephroblastoma) is the most common form of kidney cancer in early childhood. It occurs in approximately one half of all cases of WAGR syndrome/11p deletion syndrome. In the early stages of Wilms’ tumor, there are usually no symptoms. The first signs of the disease may include blood in the urine (hematuria), low-grade fever, loss of appetite, paleness, weight loss, Fatigue and lack of energy (lethargy), and swelling of the abdomen. In the later stages, slight pain may occur at intervals (intermittent), or pain may be sudden and sharp. (For more information on this disorder, choose “Wilms’ tumor” as your search term in the Rare Disease Database.) Abnormally persistent clusters of embryonal cells within the kidneys (nephrogenic rests) are not uncommon in children with WAGR syndrome/11p deletion syndrome. This tissue is noticeable on ultrasound examination, and is sometimes difficult to distinguish from Wilms’ tumor. It is thought that nephrogenic rests, or clusters of rests (nephroblastomatosis), may give rise to Wilms’ tumor in some cases.
In infants with aniridia that is associated with WAGR syndrome/11p deletion syndrome, the irises fail to develop normally before birth (prenatally). This results in the partial or complete absence of the round, colored (pigmented) portion of the eye (iris). Aniridia is almost always present in individuals with WAGR syndrome/11p deletion syndrome; however, at least four cases of WAGR syndrome/11p deletion syndrome have been confirmed without aniridia. In almost all cases, aniridia occurs in combination with other disorders of the eye. These accompanying disorders may include clouding of the lens of the eye (cataract); rapid, Involuntary movements of the eye (nystagmus); and/or partial or complete loss of vision due to abnormally high pressure of the fluid in the eye (glaucoma). Progressive scarring and opacity of the cornea (aniridic keratopathy, also called corneal pannus) is common in adolescents and adults with aniridia, but may also occur in children.
In the medical literature, the “G” in the acronym WAGR refers to “Genitourinary abnormalities,” “ambiguous Genitalia,” or “Gonadoblastoma.” Gonadoblastoma, a cancer of the cells that form the testes in males or the ovaries in females (gonads), occurs exclusively in people with defective development of the gonads (gonadal dysgenesis), as is the case in some infants with WAGR syndrome/11p deletion syndrome. Although gonadoblastoma is not always manifested in WAGR syndrome/11p deletion syndrome, it is important to be aware of the genetic predisposition for this potentially serious disorder so that appropriate steps can be taken.
Other abnormalities of the reproductive and urinary tracts (genitourinary) may be present in many children with WAGR syndrome/11p deletion syndrome. In males, these may include the failure of one or both testes to descend into the scrotum (cryptorchidism) and placement of the urinary opening (meatus) on the underside of the penis (hypospadias). In females, these abnormalities may include underdeveloped (streak) ovaries, and malformations of the uterus, fallopian tubes, or vagina. These abnormalities may also include duplicate ureters or horseshoe kidney.
In addition, individuals with WAGR syndrome/11p deletion syndrome may have the gonads of one sex and external genitalia resembling that of the opposite sex (ambiguous genitalia), making their sexual assignment (i.e., male or female) uncertain (pseudohermaphroditism).
Intellectual disability is common in children with WAGR syndrome/11p deletion syndrome. However, the severity of the impairment varies greatly from case to case, ranging from severe to mild Intellectual disability (IQ of 20 to 70) ). Some children with WAGR syndrome/11p deletion syndrome may have normal intelligence (IQ at or above 100).
A variety of behavioral and psychiatric disorders have been reported in WAGR syndrome/11p deletion syndrome. These include autism spectrum disorders, attention-deficit disorder (with or without hyperactivity), obsessive-compulsive disorder, other Anxiety disorders, and depression.
Although hearing is usually normal in people with WAGR syndrome/11p deletion syndrome, many individuals have difficulty with the way the brain processes auditory information, particularly with recognizing and interpreting the sounds involved with speech (auditory processing disorder).
Metabolic abnormalities present in some individuals with WAGR syndrome/11p deletion syndrome may include early-onset overweight (obesity), and high serum cholesterol (hyperlipidemia). Some individuals with WAGR syndrome/11p deletion syndrome have a combination of conditions including insulin resistance, high blood pressure, and high serum cholesterol which can increase the risk for coronary artery disease, stroke, and type 2 diabetes (metabolic syndrome).
Chronic kidney failure occurs in approximately 60% of individuals with WAGR syndrome/11p deletion syndrome, most often after age 12. This failure is usually the result of Focal Segmental Glomerulosclerosis (FSGS) a disorder which results in scarring of the filtering tubes of the kidneys. Chronic kidney failure may occur in an individual with WAGR syndrome/11p deletion syndrome regardless of their history of Wilms tumor.
Frequent, recurrent upper respiratory infections, ear and sinus infections, asthma, and pneumonia are common in WAGR syndrome/11p deletion syndrome, particularly in young children with the disorder. Delayed loss of primary teeth and severely crowded or uneven teeth (dental malocclusion) are also common. A temporary suspension of Breathing occurring repeatedly during sleep (sleep apnea) may occur in both children and adults with WAGR syndrome/11p deletion syndrome.
Abnormalities of muscle tone or strength (hypertonia/hypotonia) are common in WAGR syndrome/11p deletion syndrome, particularly during infancy and early childhood. Seizure disorder (epilepsy) has been reported frequently and chronic inflammation of the pancreas (pancreatitis) has also been reported.
In rare cases, other symptoms of WAGR syndrome/11p deletion syndrome which may be present at birth (congenital) may include: defects of the heart or kidneys, partial or complete absence of the structure which connects the two hemispheres of the brain (agenesis of the corpus callosum) a weak area of the abdomen which allows part of the intestines to push through (inguinal hernia) an abnormal opening in the diaphragm which allows part of the abdominal organs to migrate into the chest cavity (diaphragmatic hernia) extra fingers or toes (polydactyly) webbing or fusing of fingers or toes (syndactyly) absence or closure of ducts which drain bile from the liver (biliary atresia) Weakness or floppiness of the walls of the windpipe (tracheomalacia) and hearing impairment.
In rare cases, other symptoms of WAGR syndrome/11p deletion syndrome which may develop or be diagnosed after birth may include: an abnormal enlargement of a part of the body (hemihypertrophy), growth retardation, communication disorders, inability of the brain to integrate information received from the body’s five sensory systems (sensory integration disorder) feeding/swallowing disorders, gastroesophageal reflux, multiple bony lumps or spurs on the bones (multiple exostoses) and curvature of the spine (scoliosis).
The disorders most commonly associated with WAGR syndrome/11p deletion syndrome (Wilms’ tumor, aniridia, genitourinary abnormalities, and intellectual disability) as well as those listed above may appear together or in a variety of combinations. In the medical literature, these various groupings (disorder subdivisions) have been referred to as distinct disorders including “Aniridia-Wilms’ Tumor Association” (AWTA); “Aniridia-ambiguous Genitalia-mental Retardation” (AGR triad); or “Aniridia- Wilms’ Tumor-Gonadoblastoma.” While all individuals with WAGR syndrome/11p deletion syndrome will be found to have deletions in chromosome 11p13, great variation in the size and nature of these deletions is possible among individuals. These variations in missing genetic material are thought to account for the differences in symptoms and manifestations of the disorder.