WAGR syndrome

Infobox_Disease
Name = PAGENAME


Caption =
DiseasesDB = 14025
ICD10 =
ICD9 =
ICDO =
OMIM = 194072
MedlinePlus =
eMedicineSubj = ped
eMedicineTopic = 2423
MeshID = D017624

WAGR syndrome is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumor (a tumor of the kidneys), Aniridia (absence of the colored part of the eye, the iris), Genitourinary anomalies, and mental Retardation.cite journal | author=Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M | title=WAGR syndrome: a clinical review of 54 cases | journal=Pediatrics | year=2005 | pages=984–8 | volume=116 | issue=4 | pmid=16199712 | doi=10.1542/peds.2004-0467] The G is sometimes instead given as "gonadoblastoma," since the genitourinary anomalies are tumors of the gonads (testes or ovaries).cite book | author = Clericuzio CL | year = 2004 | title = Management of Genetic Syndromes | chapter = WAGR syndrome | editor = Cassidy SB, Allanson JE | edition = 2nd edition | publisher = John Wiley & Sons | location = New York, NY | id = ISBN 0-471-30870-6 ]

A subset of WAGR syndrome patients shows severe childhood obesity; the acronym WAGRO (O for obesity) has been used to describe this category.OMIM|194072|WAGR syndrome]

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.OMIM|194072|WAGR syndrome]

ynonyms

WAGR complex, Wilms tumor-aniridia syndrome, aniridia-Wilms tumor syndrome.

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.cite journal |author=Turleau C, de Grouchy J, Nihoul-Fékété C, Dufier J, Chavin-Colin F, Junien C |title=Del11p13/nephroblastoma without aniridia |journal=Hum Genet |volume=67 |issue=4 |pages=455–6 |year=1984 |pmid=6092262 |doi=10.1007/BF00291410] Other common eye defects include cataracts and ptosis. About 50% of patients develop Wilms' tumor.

Disease mechanism

WAGR syndrome is caused by a mutation on chromosome 11 in the 11p13 region.OMIM|194072|WAGR syndrome] Specifically, several genes in this area are deleted, including the PAX6 ocular development gene and the Wilms' tumor gene (WT1).cite journal |author=Glaser T, Jepeal L, Edwards J, Young S, Favor J, Maas R |title=PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects |journal=Nat Genet |volume=7 |issue=4 |pages=463–71 |year=1994 |pmid=7951315 |doi=10.1038/ng0894-463] 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.cite journal |author=Yasuda T, Kajimoto Y, Fujitani Y, Watada H, Yamamoto S, Watarai T, Umayahara Y, Matsuhisa M, Gorogawa S, Kuwayama Y, Tano Y, Yamasaki Y, Hori M |title=PAX6 mutation as a genetic factor common to aniridia and glucose intolerance |journal=Diabetes |volume=51 |issue=1 |pages=224–30 |year=2002 |pmid=11756345 |doi=10.2337/diabetes.51.1.224] cite journal |author=Mitchell T, Free S, Williamson K, Stevens J, Churchill A, Hanson I, Shorvon S, Moore A, van Heyningen V, Sisodiya S |title=Polymicrogyria and absence of pineal gland due to PAX6 mutation |journal=Ann Neurol |volume=53 |issue=5 |pages=658–63 |year=2003 |pmid=12731001 |doi=10.1002/ana.10576] cite journal |author=Talamillo A, Quinn J, Collinson J, Caric D, Price D, West J, Hill R |title=Pax6 regulates regional development and neuronal migration in the cerebral cortex |journal=Dev Biol |volume=255 |issue=1 |pages=151–63 |year=2003 |pmid=12618140 |doi=10.1016/S0012-1606(02)00046-5]

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.cite journal |author=Han JC, Liu QR, Jones M, "et al" |title=Brain-derived neurotrophic factor and obesity in the WAGR syndrome |journal=N. Engl. J. Med. |volume=359 |issue=9 |pages=918–27 |year=2008 |month=August |pmid=18753648 |doi=10.1056/NEJMoa0801119 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18753648&promo=ONFLNS19] This strengthens the case for a role for BDNF in energy balance.

History

WAGR syndrome was first described by Miller "et al".cite journal |author=Miller RW, Fraumeni JF, Manning MD |title=Association of Wilms's tumor with aniridia, hemihypertrophy and other congenital malformations |journal=N Engl J Med |volume=270 |issue= |pages=922–7 |year=1964 |pmid=14114111]

ee also

* Denys-Drash syndrome

References

External links

* [http://www.wagr.org International WAGR Syndrome Association]