WAGR syndrome
Encyclopedia
WAGR syndrome is a rare genetic syndrome
in which affected children are predisposed to develop Wilms tumour (a tumour of the kidney
s), Aniridia
(absence of the coloured part of the eye, the iris
), Genitourinary
anomalies, and mental Retardation
. The G is sometimes instead given as "gonadoblastoma," since the genitourinary anomalies are tumours of the gonads (testes or ovaries
).
A subset of WAGR syndrome patients shows severe childhood obesity
; the acronym WAGRO (O for obesity) has been used to describe this category.
The condition results from a deletion
on chromosome 11 resulting in the loss of several genes
. As such, it is one of the best studied examples of a condition caused by loss of neighbouring (contiguous) genes.
In older children, clinical diagnosis of the syndrome can be made when aniridia and one of the other features are present. It must be noted that 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
s and ptosis
. About 50% of patients develop Wilms' tumour.
(40% of patients over the age of 12 years). Females with WAGR syndrome may have streak ovaries, which can increase their risk for gonadoblastoma. Malformations of the vagina and/or uterus may also be present.
ocular development gene and the Wilms' tumour gene (WT1
). Abnormalities in WT1
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
(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
.
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
in which affected children are predisposed to develop Wilms tumour (a tumour of the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s), Aniridia
Aniridia
Aniridia is the absence of the iris. Aniridia usually involves both eyes. It can be congenital or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular and optic nerve hypoplasia,...
(absence of the coloured part of the eye, the iris
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
), Genitourinary
Genitourinary system
In anatomy, the genitourinary system or urogenital system is the organ system of the reproductive organs and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathways, like the male urethra...
anomalies, and mental Retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
. The G is sometimes instead given as "gonadoblastoma," since the genitourinary anomalies are tumours of the gonads (testes or ovaries
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
).
A subset of WAGR syndrome patients shows severe childhood obesity
Childhood obesity
Childhood obesity is a condition where excess body fat negatively affects a child's health or wellbeing. As methods to determine body fat directly are difficult, the diagnosis of obesity is often based on BMI. Due to the rising prevalence of obesity in children and its many adverse health effects...
; the acronym WAGRO (O for obesity) has been used to describe this category.
The condition results from a deletion
Genetic deletion
In genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome...
on chromosome 11 resulting in the loss of several genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
. As such, it is one of the best studied examples of a condition caused by loss of neighbouring (contiguous) genes.
Clinical features and diagnosis
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. It must be noted that 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
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
s and ptosis
Ptosis (eyelid)
Ptosis is a drooping of the upper or lower eyelid. The drooping may be worse after being awake longer, when the individual's muscles are tired. This condition is sometimes called "lazy eye", but that term normally refers to amblyopia...
. About 50% of patients develop Wilms' tumour.
Treatment
Children with WAGR syndrome receive regular (3-4 monthly) kidney surveillance for Wilm's tumour until at least the age of 6–8 years and thereafter remain under some follow-up because of the risk of late onset nephropathyNephropathy
Nephropathy refers to damage to or disease of the kidney. An older term for this is nephrosis.-Causes:Causes of nephropathy include administration of analgesics, xanthine oxidase deficiency, and long-term exposure to lead or its salts...
(40% of patients over the age of 12 years). Females with WAGR syndrome may have streak ovaries, which can increase their risk for gonadoblastoma. Malformations of the vagina and/or uterus may also be present.
Disease mechanism
WAGR syndrome is caused by a mutation on chromosome 11 in the 11p13 region. Specifically, several genes in this area are deleted, including the PAX6PAX6
Paired box protein Pax-6 also known as aniridia type II protein or oculorhombin is a protein that in humans is encoded by the PAX6 gene.- Function :PAX6 is a member of the Pax gene family...
ocular development gene and the Wilms' tumour gene (WT1
WT1
Wilms tumor protein is a protein that in humans is encoded by the WT1 gene.- Function :This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich DNA-binding domain at the N-terminus...
). Abnormalities in WT1
WT1
Wilms tumor protein is a protein that in humans is encoded by the WT1 gene.- Function :This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich DNA-binding domain at the N-terminus...
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
Brain-derived neurotrophic factor, also known as BDNF, is a protein 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 canonical "Nerve Growth Factor", NGF...
(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
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
.