WAGR syndrome (also known as WAGR complex, Wilms tumour-aniridia syndrome, aniridia-Wilms tumour syndrome) is a rare genetic
syndrome
A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...
in which affected children are predisposed to develop
Wilms tumour (a tumour of the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s),
Aniridia (absence of the coloured part of the eye, the
iris
Iris most often refers to:
*Iris (anatomy), part of the eye
*Iris (mythology), a Greek goddess
* ''Iris'' (plant), a genus of flowering plants
* Iris (color), an ambiguous color term
Iris or IRIS may also refer to:
Arts and media
Fictional ent ...
),
Genitourinary anomalies, and
mental Retardation.
The G is sometimes instead given as "gonadoblastoma," since the genitourinary anomalies can include tumours of the gonads (
testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
or
ovaries
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
).
Some WAGR syndrome patients show severe
childhood obesity
Childhood obesity is a condition where excess body fat negatively affects a child's health or well-being. As methods to determine body fat directly are difficult, the diagnosis of obesity is often based on BMI. Due to the rising prevalence of ...
and hyperphagia; the acronym WAGRO (O for obesity) has been used to describe this category and may be associated with the coinciding loss of
BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
a gene that is also on chromosome 11.
The condition, first described by Miller et al. in 1964 in its association with other congenital malformations,
results from a
deletion on
chromosome 11
Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...
resulting in the loss of several
genes
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. As such, it is one of the best studied examples of a condition caused by loss of neighbouring (contiguous) genes.
It is possible for those with WAGR syndrome to develop
Wilms tumor
Wilms' tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children, rarely in adults.; and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German ...
, a rare form of kidney cancer.
Signs and symptoms
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. 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
cataract
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
s and
ptosis. About 50% of people develop Wilms' tumour.
Pathophysiology
WAGR syndrome is caused by a mutation on
chromosome 11
Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...
in the 11p13 region.
Specifically, several genes in this area are deleted, including the
PAX6
Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the ''PAX6'' gene.
Function
PAX6 is a member of the Pax gene family which is responsible for carrying the geneti ...
ocular development gene and the Wilms' tumour gene (
WT1
Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p.
Function
This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-ric ...
).
Abnormalities in
WT1
Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p.
Function
This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-ric ...
may also cause genitourinary anomalies. Mutations in the PAX6 gene have recently been shown to not only cause ocular abnormalities, but also problems in the brain and pancreas.
The gene for
brain-derived neurotrophic factor
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
(BDNF), located on 11p14.1, has been proposed as a candidate gene for the obesity and
excessive eating in a subset of WAGR patients.
This strengthens the case for a role for BDNF in energy
balance
Balance or balancing may refer to:
Common meanings
* Balance (ability) in biomechanics
* Balance (accounting)
* Balance or weighing scale
* Balance as in equality or equilibrium
Arts and entertainment Film
* ''Balance'' (1983 film), a Bulgaria ...
.
Diagnosis
Diagnosis for WAGR syndrome can be made by confirming microdeletion of 11p13 utilizing FISH (fluorescent in situ hybridization), the primary method of choice for diagnosis. FISH which will demonstrate a lack of a fluorescent signal coordinating to the specific location of the gene.
Treatment
Children with WAGR syndrome receive regular (3-4 yearly) kidney surveillance for Wilms' tumour until at least the age of 6–8 years and thereafter remain under some follow-up because of the risk of late onset
nephropathy
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
(40% of patients with WAGR Syndrome over the age of 12 years). Females with WAGR syndrome may have
streak ovaries
Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system
in the male or female. It is the atypical development of the gonads in an embryo,
with reproductive tissue replaced with functionless, fibrous ti ...
, which can increase the risk for gonadoblastoma. Malformations of the vagina and/or uterus may also be present.
See also
*
Denys–Drash syndrome
Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or syndrome characterized by gonadal dysgenesis, nephropathy, and Wilms' tumor.
Signs and symptoms
Clinically, Denys–Drash is characterized by the triad of pseudohermaphroditism ...
References
External links
* {{DECIPHER, 35
Autosomal monosomies and deletions
Syndromes
Rare diseases