11p deletion syndrome
|11p deletion syndrome|
|Other names: WARG syndrome, WAGR complex, Wilms tumour-aniridia syndrome, aniridia-Wilms tumour syndrome, Miller syndrome|
|Symptoms||Wilms tumor, absence of the colored part of the eye, undescended testicles, intellectual disability|
|Complications||Cataracts, childhood obesity, pancreatitis, kidney failure|
|Usual onset||Present at birth|
|Causes||Genetic deletion from the short arm of chromosome 11|
|Diagnostic method||Suspected based on examination, confirmed by karyotyping|
|Differential diagnosis||Drash syndrome, Frasier syndrome, Potocki-Shaffer syndrome|
|Treatment||Determined by the symptoms|
|Prognosis||Decrease life expectancy|
|Frequency||1 in 750,000|
11p deletion syndrome, previously known as WAGR syndrome, is genetic disorder in which people are at risk of Wilms tumor (a type of kidney cancer), aniridia (absence of the colored part of the eye), genitourinary abnormalities such as undescended testicles, and mental retardation. Other symptoms may include light sensitivity, cataracts, childhood obesity, pancreatitis, and kidney failure. Intellectual disabilities are generally in the mild to moderate range.
The cause is the deletion of genetic material on the short arm of chromosome 11. Most cases occur spontaneously during early development, though rarely it may be inherited from a parent. What is missing is a group of genes, including PAX6 and WT1, that sit next to each other. If the BDNF gene is also involved obesity occurs. Diagnosis is generally suspected based on examination at birth and confirmed by karyotyping.
Treatment is based on symptoms. Wilms' tumor is generally treated with surgery and chemotherapy, intellectual disabilities may be supported by special education, and kidney problems may be managed with ACE inhibitors or a kidney transplant. It is believed that life expectancy is reduced, but it is not clear by how much.
WAGR syndrome affects between 1 in 500,000 to 1 in a million people. Males are affected more often than females. The condition was first described by Miller in 1964. The associated genetic abnormality was discovered in 1978 by Riccardi.
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.
WAGR syndrome is caused by a mutation on chromosome 11 in the 11p13 region. Specifically, several genes in this area are deleted, including the PAX6 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.
In older children, 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.
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 (40% of patients with WAGR Syndrome over the age of 12 years). Females with WAGR syndrome may have streak ovaries, which can increase the risk for gonadoblastoma. Malformations of the vagina and/or uterus may also be present.
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