WAGR syndrome

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 cataracts and ptosis. About 50% of people with WAGR syndrome develop Wilms' tumour.

Pathophysiology

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.

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 (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.

References

See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a discussion of different citation methods and how to generate footnotes using the and tags

References

1. (2005). "WAGR syndrome: a clinical review of 54 cases". Pediatrics.
2. Clericuzio CL. (2004). "Management of Genetic Syndromes". John Wiley & Sons.
3. {{OMIM. 194072. WAGR syndrome
4. (August 2008). "Brain-derived neurotrophic factor and obesity in the WAGR syndrome". The New England Journal of Medicine.
5. (1964). "Association of Wilms's tumour with aniridia, hemihypertrophy and other congenital malformations". N Engl J Med.
6. Reference, Genetics Home. "WAGR syndrome".
7. (1984). "Del11p13/nephroblastoma without aniridia". Hum Genet.
8. (1994). "PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects". Nat Genet.
9. (2002). "PAX6 mutation as a genetic factor common to aniridia and glucose intolerance". Diabetes.
10. (2003). "Polymicrogyria and absence of pineal gland due to PAX6 mutation". Ann Neurol.
11. (2003). "Pax6 regulates regional development and neuronal migration in the cerebral cortex". Dev Biol.
12. (August 2008). "Brain-derived neurotrophic factor and obesity in the WAGR syndrome". N. Engl. J. Med..
13. Starcević M, Mataija M. WAGR syndrome--a case report. Acta Clin Croat. 2009;48(4):455-459.
14. ,