WAGR syndrome

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The WAGR syndrome (Syn .: WAGR complex, Wilms tumor aniridia syndrome, aniridia Wilms tumor syndrome) is a rare, genetically determined complex of symptoms . He affected children have a predisposition for W ILMS tumors (a kidney tumor), A niridie (absence of the iris in the eye), (uro) g enitale malformations and mental R etardierung . The "G" can also stand for g onadoblastoma ; besides urogenital malformations, tumors of the gonads are found here .

In some of the affected already evident in childhood severe obesity , here is the acronym WAGRO (O for obesity, english obesity ) is used.

The syndrome is the result of a deletion on chromosome 11 that results in the loss of several genes . It is one of the best-studied examples of a syndrome resulting from the loss of multiple consecutive genes.

Clinical manifestations

Newborns with WAGR syndrome are noticeable for the lack of the iris in the eye. The presence of other abnormalities increases the suspicion of the syndrome. Urogenital malformations are not always present, especially in girls. In rare cases, aniridia is absent. The diagnosis can be suspected here in older children if any of the other three symptoms are present.

Other visible symptoms are cataract and ptosis . About 50% of patients develop Wilms' tumor. A nephropathy is found in 40% of 12-year-old patient.

In female patients, the tissue of the ovaries can be replaced by connective tissue, which increases the risk of gonadoblastoma. There may be deformities of the vagina and / or uterus .

A chromosomal examination is required for a reliable diagnosis.

examination

Children should be checked for development of Wilms' tumor in the kidneys every 3–4 months until they are at least 6-8 years old. Kidney function should also be checked regularly.

treatment

The genetic defects cannot be treated. The missing diaphragm function of the iris can be compensated for with visual aids ; tumors should be surgically removed.

Mechanism of origin

WAGR syndrome is caused by mutations on chromosomes 11 in the 11p13 region. Several consecutive genes are missing here, including PAX6 , which is important for eye development, and WT1 , the defect of which is responsible for the formation of Wilms' tumor. Anomalies in the WT1 gene can also cause urogenital malformations. Mutations in the PAX6 gene are thought to be responsible for both eye anomalies and problems in the brain and pancreas. The gene for the growth factor BDNF in the 11p14.1 region is held responsible as a possible cause of obesity and excessive food intake in some of those affected. This supports the assumption that BDNF plays a role in homeostasis in the energy balance.

history

WAGR syndrome was first described in 1964 by Robert W. Miller, Joseph F. Fraumeni, and Miriam D. Manning.

See also

Web links

Individual evidence

  1. ^ A b B.V. Fischbach, KL Trout, J. Lewis, CA Luis, M. Sika: WAGR syndrome: a clinical review of 54 cases . In: Pediatrics . tape 116 , no. 4 , 2005, p. 984-988 , doi : 10.1542 / peds.2004-0467 , PMID 16199712 .
  2. ↑ CL Clericuzio: Management of Genetic Syndromes . Ed .: SB Cassidy, JE Allanson. 2nd Edition. John Wiley & Sons, New York, NY 2004, ISBN 0-471-30870-6 , WAGR syndrome.
  3. ↑ a b c WAGR syndrome.  In: Online Mendelian Inheritance in Man . (English)
  4. ↑ C. Turleau, J. de Grouchy, C. Nihoul-Fékété, J. Dufier, F. Chavin-Colin, C. Junien: Del11p13 / nephroblastoma without aniridia . In: Hum Genet . tape 67 , no. 4 , 1984, pp. 455-456 , doi : 10.1007 / BF00291410 , PMID 6092262 .
  5. ^ A b T. Glaser, L. Jepeal, J. Edwards, S. Young, J. Favor, R. Maas: PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects . In: Nat Genet . tape 7 , no. 4 , 1994, pp. 463-471 , doi : 10.1038 / ng0894-463 , PMID 7951315 .
  6. ↑ T. Yasuda, Y. Kajimoto, Y. Fujitani, H. Watada, S. Yamamoto, T. Watarai, Y. Umayahara, M. Matsuhisa, S. Gorogawa, Y. Kuwayama, Y. Tano, Y. Yamasaki, M Hori: PAX6 mutation as a genetic factor common to aniridia and glucose intolerance . In: Diabetes . tape 51 , no. 1 , 2002, p. 224-230 , doi : 10.2337 / diabetes.51.1.224 , PMID 11756345 .
  7. ↑ T. Mitchell, S. Free, K. Williamson, J. Stevens, A. Churchill, I. Hanson, S. Shorvon, A. Moore, V. van Heyningen, S. Sisodiya: Polymicrogyria and absence of pineal gland due to PAX6 mutation . In: Ann Neurol . tape 53 , no. 5 , 2003, p. 658-663 , doi : 10.1002 / ana.10576 , PMID 12731001 .
  8. ↑ A. Talamillo, J. Quinn, J. Collinson, D. Caric, D. Price, J. West, R. Hill: Pax6 Regulates regional development and neuronal migration in the cerebral cortex . In: Dev Biol . tape 255 , no. 1 , 2003, p. 151-163 , doi : 10.1016 / S0012-1606 (02) 00046-5 , PMID 12618140 .
  9. ↑ JC Han, QR Liu, M. Jones et al .: Brain-derived neurotrophic factor and obesity in the WAGR syndrome . In: N. Engl. J. Med. Band 359 , no. 9 , August 2008, p. 918-927 , doi : 10.1056 / NEJMoa0801119 , PMID 18753648 , PMC 2553704 (free full text).
  10. ^ Robert W. Miller, Joseph F. Fraumeni, Miriam D. Manning: Association of Wilms's tumor with aniridia, hemihypertrophy and other congenital malformations . In: N Engl J Med . tape 270 , no. 18 , 1964, pp. 922-927 , doi : 10.1056 / NEJM196404302701802 , PMID 14114111 .