WAGR syndrome

WAGR syndrome
Video explanation
Classification and external resources
OMIM 194072
DiseasesDB 14025
eMedicine ped/2423
MeSH D017624

WAGR syndrome (also known as WAGR complex, Wilms tumour-aniridia syndrome, aniridia-Wilms tumour syndrome) is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumour (a tumour of the kidneys), Aniridia (absence of the coloured part of the eye, the iris), Genitourinary anomalies, and Retardation.[1] The G is sometimes instead given as "gonadoblastoma," since the genitourinary anomalies can include tumours of the gonads (testes or ovaries).[2]

A subset of WAGR syndrome patients shows severe childhood obesity; the acronym WAGRO (O for obesity) has been used to describe this category.[3]

The condition, first described by Miller et al. in 1964 in its association with other congenital malformations,[4] 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.[3]

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.[1][5] Other common eye defects include cataracts and ptosis. About 50% of people develop Wilms' tumour.

Disease mechanism

WAGR syndrome is caused by a mutation on chromosome 11 in the 11p13 region.[3] Specifically, several genes in this area are deleted, including the PAX6 ocular development gene and the Wilms' tumour gene (WT1).[6] 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.[6][7][8][9]

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.[10] This strengthens the case for a role for BDNF in energy balance.

Treatment

Children with WAGR syndrome receive regular (3-4 monthly) 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 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.

See also

References

  1. 1 2 Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M (2005). "WAGR syndrome: a clinical review of 54 cases". Pediatrics. 116 (4): 984–8. PMID 16199712. doi:10.1542/peds.2004-0467.
  2. ↑ Clericuzio CL (2004). "WAGR syndrome". In Cassidy SB, Allanson JE. Management of Genetic Syndromes (2nd ed.). New York, NY: John Wiley & Sons. ISBN 0-471-30870-6.
  3. 1 2 3 Online Mendelian Inheritance in Man (OMIM) WAGR syndrome -194072
  4. ↑ Miller RW, Fraumeni JF, Manning MD (1964). "Association of Wilms's tumour with aniridia, hemihypertrophy and other congenital malformations". N Engl J Med. 270 (18): 922–7. PMID 14114111. doi:10.1056/NEJM196404302701802.
  5. ↑ Turleau C, de Grouchy J, Nihoul-Fékété C, Dufier J, Chavin-Colin F, Junien C (1984). "Del11p13/nephroblastoma without aniridia". Hum Genet. 67 (4): 455–6. PMID 6092262. doi:10.1007/BF00291410.
  6. 1 2 Glaser T, Jepeal L, Edwards J, Young S, Favor J, Maas R (1994). "PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects". Nat Genet. 7 (4): 463–71. PMID 7951315. doi:10.1038/ng0894-463.
  7. ↑ 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 (2002). "PAX6 mutation as a genetic factor common to aniridia and glucose intolerance". Diabetes. 51 (1): 224–30. PMID 11756345. doi:10.2337/diabetes.51.1.224.
  8. ↑ Mitchell T, Free S, Williamson K, Stevens J, Churchill A, Hanson I, Shorvon S, Moore A, van Heyningen V, Sisodiya S (2003). "Polymicrogyria and absence of pineal gland due to PAX6 mutation". Ann Neurol. 53 (5): 658–63. PMID 12731001. doi:10.1002/ana.10576.
  9. ↑ Talamillo A, Quinn J, Collinson J, Caric D, Price D, West J, Hill R (2003). "Pax6 regulates regional development and neuronal migration in the cerebral cortex". Dev Biol. 255 (1): 151–63. PMID 12618140. doi:10.1016/S0012-1606(02)00046-5.
  10. ↑ Han JC, Liu QR, Jones M, et al. (August 2008). "Brain-derived neurotrophic factor and obesity in the WAGR syndrome". N. Engl. J. Med. 359 (9): 918–27. PMC 2553704 Freely accessible. PMID 18753648. doi:10.1056/NEJMoa0801119.
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