What Is WAGR Syndrome?
WAGR syndrome is a contiguous gene syndrome in which the affected children are predisposed to develop several conditions, including certain malignancies, distinctive eye abnormalities, and intellectual disability. It was first described by Miller et al. in 1964. The word WAGR is an acronym for:
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Wilms' Tumor: Wilms' tumor, also known as nephroblastoma, is a rare childhood cancer that develops in the kidneys.
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Aniridia: A rare eye condition known as aniridia causes the iris (a flat and ring-shaped membrane that controls and regulates the amount of light entering the eye) to be absent entirely or partially.
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Genitourinary Anomalies: Genitourinary anomalies refer to abnormalities in the genital and urinary tract. In WAGR syndrome, males are more commonly affected by genitourinary abnormalities than females. Cryptorchidism is the most common genitourinary anomaly seen in WAGR syndrome patients.
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Mental Retardation: Intellectual disability is seen in WAGR syndrome patients.
Most people with WAGR syndrome will have two or more of the abovementioned conditions. In some cases, patients with WAGR syndrome show severe childhood obesity and hyperphagia; therefore, the acronym WAGRO (O for obesity) describes such patients.
What Are the Other Names of WAGR Syndrome?
The other names used for WAGR syndrome include:
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Chromosome 11p deletion syndrome.
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WAGR complex.
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Wilms' tumor-aniridia-genitourinary anomalies-mental disability syndrome.
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Wilms' tumor-aniridia-gonadoblastoma-mental disability syndrome.
What Causes WAGR Syndrome?
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A loss in a collection of genes on the short arm of chromosome 11 is the root cause of WAGR syndrome. The size of the deletion varies with each individual. The majority of WAGR syndrome cases are not inherited but rather originate at random either during egg or sperm production or in the first few weeks of fetal development.
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It is often referred to as contiguous gene deletion syndrome because it causes the deletion or duplication of several genes lying close to one another on chromosome 11. Specifically, PAX6 and WT1 genes are deleted in patients with WAGR syndrome.
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PAX6 (paired box 6) gene can affect ocular development; therefore, deletion of the PAX6 gene is responsible for causing aniridia in WAGR syndrome patients. Deletion of the PAX6 gene can also cause problems in the brain leading to mental retardation in WAGR syndrome patients.
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Wilm’s tumor and genitourinary abnormalities in WAGR syndrome are caused by mutations in the WT1 (Wilm’s tumor suppressor 1) gene.
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The BDNF (brain-derived neurotrophic factor) gene produces a protein responsible for managing drinking, eating, and body weight. Therefore loss of the BDNF gene causes childhood-onset obesity in individuals with WAGRO syndrome.
Does WAGR Syndrome Run in Families?
WAGR syndrome is referred to as a "contiguous gene deletion syndrome." This indicates that it results from the deletion of a gene cluster on chromosome 11 (11p13). Changes in chromosome 11p13 often occur by chance during egg or sperm formation or in the earliest phases of the baby's growth while in the womb. Less frequently, the gene alterations are inherited when one of the parents has a translocation, which is a rearrangement of two chromosomes that can result in the loss of some genes during pregnancy. Additionally, a baby's body may have both normal cells and cells with the 11p13 alterations. It is known as mosaic WAGR syndrome.
Finding out whether there may be a higher risk of having another kid with WAGR syndrome is possible with the aid of genetic counseling.
What Are The Symptoms of WAGR Syndrome?
The symptoms depend on the combination of disorders present in WAGR syndrome.
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Wilms' Tumor: Wilm’s tumor is present in nearly half of the individuals affected by WAGR syndrome. It is a rare childhood cancer that develops in the kidneys. Some children affected by Wilm’s tumor do not experience any symptoms; however, others may have;
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Abdominal pain.
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Abdominal swelling.
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Low-grade fever.
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Loss of appetite.
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Weight loss.
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Nausea and vomiting.
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Blood discharge in the urine.
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Aniridia: Aniridia associated with WAGR syndrome results in the failure of iris development normally before birth. As a result, it causes partial or complete absence of iris in infants. Aniridia is almost always present in WAGR syndrome leading to severe symptoms such as:
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Cataract (clouding of the lens of the eye).
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Nystagmus (a condition in which eyes make rapid, involuntary, and repetitive movements).
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Glaucoma (a group of eye conditions that cause partial or complete vision loss due to high pressure in the eye).
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Genital and Urinary Problems:
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In boys, WAGR syndrome may lead to specific genital and urinary problems like;
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Hypospadias (an uncommon congenital disorder in which the penis opening is on the underside).
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Cryptorchidism (the failure of one or both testes to travel into the scrotum).
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The most common genitourinary abnormalities seen in girls affected by WAGR syndrome include;
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Underdeveloped ovaries.
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Malformations of the fallopian tube, uterus, and vagina.
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Individuals with WAGR syndrome have a high risk of developing gonadoblastoma (a tumor that is made up of cells of the testicles and ovary).
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Mental Retardation: Individuals affected with WAGR syndrome often experience psychiatric or behavioral problems such as;
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Depression.
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Anxiety.
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Difficulty in learning.
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Obsessive-compulsive disorder (a mental condition marked by excessive worries and concerns that prompt compulsive actions).
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ADHD (attention-deficit or hyperactivity disorder).
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Autism (a developmental disability that impacts the ability of an individual to communicate and interact).
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Other Symptoms: Some of the other common symptoms of WAGR syndrome include;
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Pancreatitis (inflammation of the pancreas).
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Chronic kidney failure.
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Breathing problems like asthma and pneumonia.
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Hyperphagia (excessive eating due to intense hunger).
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How Is WAGR Syndrome Diagnosed?
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WAGR syndrome is a genetic disorder; therefore, diagnosis is made using genetic testing that looks for the deletion of a specific gene in chromosome 11. A genetic test named karyotype or chromosome analysis is carried out to look for chromosome 11p13 deletion associated with WAGR syndrome.
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Another specific genetic test called FISH (fluorescent in situ hybridization) is used in WAGR syndrome diagnosis. FISH test also looks for a deletion of a specific gene in chromosome 11.
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Apart from genetic testing, WAGR syndrome is diagnosed based on the symptoms caused by various conditions associated with WAGR syndrome.
How Is WAGR Syndrome Treated?
Treatment options for WAGR syndrome depend on the specific symptoms present in the individual.
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Wilms' Tumor: The treatment options for Wilm’s tumor are decided based on the location and stage of the tumor. Treatment options for Wilm’s tumor include surgery, chemotherapy, and radiation therapy. Even after the course of therapy is complete, the doctor urges the patient to undergo regular blood tests to monitor kidney function over the course of their lives.
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Aniridia: Vision therapy is suggested for aniridia in WAGR syndrome. It basically uses eye exercises, testing, occlusal lenses, and prisms to treat visual problems and improve vision. Medications and surgery may help treat aniridia-related conditions such as glaucoma and cataract.
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Genitourinary Abnormalities: Genitourinary abnormalities like gonadoblastoma require surgery to remove abnormal gonads. Hormone replacement therapy is given in patients after the surgical removal of gonads. Surgeries may also be performed on boys having undescended testes.
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Mental Retardation: Individuals affected with WAGR syndrome experience psychological and behavioral problems such as autism, anxiety, and depression. Treatments, including speech, occupational and physical therapies, are carried out to improve the physical and mental ability of the patient. In addition, special education services should also be provided to help children affected with WAGR syndrome develop their fullest potential.
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Kidney Failure: Chronic kidney failure in WAGR syndrome often causes high blood pressure, high cholesterol, and proteinuria. ACE (angiotensin-converting enzyme) inhibitors are used to treat high blood pressure and proteinuria. Dialysis and kidney transplant are done in some WAGR syndrome patients with renal failure.
Conclusion:
WAGR syndrome is a genetic disorder that cannot be prevented. It leads to various symptoms, and the treatment options for WAGR syndrome depend on the specific symptoms present in the individual. A multidisciplinary healthcare team will plan the treatment for children affected with WAGR syndrome. The main goals of treatment are to reduce symptoms and contribute to an improvement in quality of life.
