WAGR Syndrome


What Is WAGR Syndrome?

Wagr Syndrome is a genetic condition that affects one to two of every one million people. The condition can be passed from a parent to a child, but is most often a random genetic event.

Humans generally have 23 pairs of chromosomes, for a total of 46 chromosomes. One of these twenty two pairs of chromosomes determine a person’s sex; the other twenty two pairs of chromosomes are considered autosomal (they determine the characteristics of a person except for the person’s sex). The autosomal chromosomes are numbered one through twenty-two. Wagr Syndrome is caused by a problem on chromosome number eleven.

WAGR Syndrome


Wagr Syndrome is a chromosomal microdeletion disorder. Chromosomes – our bodies instructions for development and function, are inherited from our parents. One chromosome of each pair comes from our biological mother; the other chromosome of each pair comes from our biological father.

When a sperm and an egg come together to start the process of fetal growth and development, the genetic information from our mothers and the genetic information from our fathers must be shared correctly and completely in order to create a human being. There can be various types of errors in the way this genetic information is shared. In Wagr Syndrome, there is missing, or deleted, genetic information along chromosome eleven.

Chromosomes each have two arms. The “p” arm is the shorter arm of a chromosome and the “q” arm is the longer arm of the chromosome. Wagr Syndrome occurs because of lost genes on the short arm (p arm) of chromosome 11 in the location that is defined as 11p13. For this reason, Wagr Syndrome is also known as 11p deletion syndrome.

The DNA material lost in this position includes the genes named PAX6 and WT1. The PAX6 gene affects the developing structure and the function of eyes and parts of the brain. The WT1 gene is a gene that affects genitourinary tract development and function.

The loss of PAX6 and WT1 genes cause some of the key features of Wagr Syndrome – aniridia (the absence of the irises of the eyes) and genitourinary malformations (which predispose people with Wagr Syndrome to a cancerous tumor of the kidneys called Wilms Tumor). Likely there are other, yet undiscovered genes, the absence of which play a role in Wagr Syndrome.


WAGR Syndrome Picture 1

Symptoms

Syndromes are a collection of some or several signs and/or symptoms of a disorder. Wagr Syndrome may include the presence of a Wilms tumor, aniridia, genitourinary abnormalities and/or a range of developmental delays. The syndrome sometimes includes a predisposition to childhood obesity.

Wilms Tumor

About 50% of people with Wagr syndrome develop a Wilms tumor (the “W” in Wagr Syndrome). Wilms tumor is an otherwise rare cancer that starts in the kidney. This occurs most often in childhood, but may also occur in adults affected by Wagr Syndrome.

Aniridia

Aniridia (the “A” in Wagr Syndrome) means absence of the iris of the eye. The iris is the part of the eye that determines a person’s eye color. In the absence of the iris of the eye, the pupil (the black spot in the middle of the eye) may appear unusually large. This affects how well a person sees (visual acuity) and sensitivity to light. Those with Wagr Syndrome have increased risks of cataracts and glaucoma. Aniridia is perhaps the most obvious sign of Wagr Syndrome and can even be noticed in newborns.

Genitourinary Abnormalities

Genitourinary (the “G” in Wagr Syndrome) refers to the structure and function of the organs that make up the reproductive system, or genitals, and the urinary system (which includes the kidneys, ureters, bladder and urethra). Structural abnormalities may cause women with Wagr Syndrome to have a malformed uterus or ovaries.

Men with Wagr Syndrome may have cryptorchidism, or, the failure of one or more of the testicles to descend down along the inguinal canal into the scrotal sac. People with Wagr Syndrome may have other genitourinary conditions such as duplicate ureters (four instead of two of the tubes that carry urine from the kidneys to the bladder), a horseshoe kidney (in which a person’s two kidneys are fused together) and/or ambiguous genitals (making it difficult to know if a person is male or female).

Range of developmental delays

People with Wagr Syndrome can experience a range (the “R” of Wagr Syndrome) of developmental delays. Learning difficulties, psychiatric problems like anxiety, depression, and others, and behavioral problems like OCD (obsessive compulsive disorder) and ADHD (attention deficit hyperactivity disorder) are not uncommon in Wagr Syndrome.

Obesity

Some people with Wagr Syndrome also have a predisposition to childhood obesity due to a loss of yet another gene (named BDNF) along the short arm of chromosome 11, near the PAX6 and WT1 genes. BDNF indirectly regulates eating. When the BDNF gene is missing along with the PAX6 and WT1 genes, the condition is named Wagro Syndrome.

Diagnosis

Wagr Syndrome is a difficult diagnosis to make. None of the characteristics of Wagr Syndrome are particular to the syndrome. In fact, most people with Wilms tumor, aniridia, genitourinary malformations, developmental delays or childhood obesity will not have Wagr Syndrome.

A finding of aniridia in a newborn or young child or a Wilms tumor of a person of any age should prompt genetic testing specifically for the absence of the PAX6 and WT1 genes. This can be accomplished by testing a small amount of blood or saliva.

WAGR Syndrome definition

Treatment

While it is not possible to treat the syndrome itself (there is no cure), medical management of Wagr Syndrome is founded on the treatment of the conditions of the syndrome. The syndrome involves multiple body systems, and thus requires the attention of multiple medical specialists including, but not limited to, geneticists, ophthalmologists, urologists, physical and occupational therapists and oncologists.

Early intervention with physical and occupational therapy has a significantly beneficial effect on the attenuation of developmental delays. Monitoring for the complications of Wagr syndrome can aid in early detection, which may facilitate treatment and improve outcome. For example, people with Wagr syndrome should have regular kidney ultrasounds to monitor for the development of Wilms tumor and have periodic eye exams to detect the development of cataracts and glaucoma.

Prevention

It is not possible to prevent Wagr Syndrome. There are documented cases of prenatal diagnosis of Wagr Syndrome, found incidentally when abnormal ultrasound findings have prompted genetic testing.


It is possible to find genetic deletions during prenatal diagnostic testing such as amniocentesis, or even during preimplantation genetic testing (genetic testing on an embryo that developed via in virto fertilization). Though this early diagnosis offers no cure, it does offer parents the option of not proceeding with a pregnancy affected by Wagr Syndrome or other genetic conditions.

Pictures

WAGR Syndrome Picture 2

WAGR Syndrome Picture 3

References

  1. (2017). Retrieved March 18, 2017, from http://wagr.org/
  2. Chromosome 11 – Genetics Home Reference. (2017, March 14). Retrieved March 18, 2017, from https://ghr.nlm.nih.gov/chromosome/11
  3. Han, J., & Kryger, J. (2007). WAGR Syndrome: A Guide for Physicians [Pdf].
  4. INSERM US14 — ALL RIGHTS RESERVED. (2017, March 118). Orphanet: WAGR syndrome. Retrieved March 18, 2017, from http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=893
  5. Tezcan, B., Rich, P., & Bhide, A. (2015). Prenatal Diagnosis of WAGR Syndrome. Case Reports in Obstetrics and Gynecology,2015, 1-4. doi:10.1155/2015/928585
  6. WAGR syndrome – Genetics Home Reference. (2017, March 14). Retrieved March 18, 2017, from https://ghr.nlm.nih.gov/condition/wagr-syndrome

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