WAGR syndrome

The WAGR syndrome (syn.: WAGR complex, Wilms' Tumour - Aniridia syndrome, aniridia - Wilms Tumour syndrome ) is a rare genetic symptom complex. From it affected children have a predisposition to Wilms' tumors ( a kidney tumor), aniridia (absence of the iris in the eye), ( uro ) genital malformations and mental retardation. The "G " can also stand for gonadoblastoma, here can be found next to urogenital malformations tumors of the gonads.

In some of the affected shows up in childhood severe obesity, here the acronym WAGRO (O for obesity, obesity English ) will be used.

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

Clinical manifestations

Newborns with WAGR syndrome fall by the absence of the iris of the eye. The suspicion of the syndrome is amplified by the presence of other abnormalities. Urogenital malformations are - especially for girls - not always available. In rare cases, aniridia is not available. Here in older children can be assumed the diagnosis, if one of the three other symptoms are present.

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

In female patients, the ovarian tissue may be replaced by connective tissue, resulting in an increased risk of gonadoblastoma result. Malformations of the vagina and / or uterus may be present.

For a reliable diagnosis, a chromosome analysis is required.

Investigation

Children should until they are at least 6-8 years old, 3-4 months are examined for development of a Wilms' tumor in the kidney. Similarly, renal function should be monitored regularly.

Treatment

The gene defects are not treatable. The lack of aperture function of the iris can be compensated by visual aids, tumors should be surgically removed.

Formation mechanism

The WAGR syndrome is caused by mutations on chromosome 11 in the region 11p13. Here missing several consecutive genes, including the important for eye development PAX6 and WT1, which caused defect for the formation of Wilms' tumor. Abnormalities in the gene WT1 can also cause urogenital malformations. Mutations in PAX6 are also blamed for problems in the brain and pancreas in addition to the ocular abnormalities. The gene for the growth factor BDNF in the region 11p14.1 is made as a possible cause for obesity and excessive food intake in a part of the person concerned responsible. This supports the hypothesis that BDNF plays a role in homeostasis in the energy budget.

History

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