WAGR Syndrome Clinical Presentation

Updated: Oct 21, 2022
  • Author: Jacquelyn N Crane, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Presentation

History

Symptoms suggestive of aniridia, GU malformations, and mental retardation (AGR) syndrome are usually noted in the perinatal period. Note the following:

  • The mother's pregnancy and the patient's birth history are generally unremarkable.

  • Nephromegaly may be revealed using prenatal ultrasonography. [17]

  • The family history is rarely helpful.

Next:

Physical Examination

Wilms tumor

The development of Wilms tumor in patients with Wilms tumor, aniridia, GU abnormalities, and mental retardation (WAGR) syndrome is more rapid than in patients with a sporadic Wilms tumor. In one cohort, the average age of tumor diagnosis was 17-27 months compared with 38 months in patients who did not have WAGR syndrome. [18]

If AGR syndrome has been diagnosed, the tumor may be detected with routine ultrasonographic screening. Otherwise, the presence of a new or enlarging abdominal mass, hematuria, abdominal pain, or hypertension may indicate the development of malignancy.

Occasionally, patients may have a varicocele, which is due to obstruction of the spermatic vein by a thrombus in the inferior vena cava.

Aniridia

The congenital absence of the iris is usually the first and most striking feature. Although generally absent in the newborn period, scanning nystagmus may be present in infancy. The degree of vision loss varies among patients.

In a recent study of 125 patients who presented with aniridia, 74 were classified as sporadic, 24 were classified as familial, and 14 were classified as having WAGR syndrome. [19]  The 11p13 chromosomal analysis of these patients revealed that 10 of the 14 (71%) patients with WAGR syndrome had deletions (2 cryptic and 8 visible).

GU abnormalities

A range of GU abnormalities may be present at birth. Cryptorchidism and hypospadias are commonly observed in association with AGR and WAGR syndromes. The presence of pseudohermaphroditism should alert the clinician to the possibility of WT1 syndrome (includes the sydnromes previously known as Denys-Drash or Frasier syndromes), which result from mutations in the WT1 gene. Nephroblastomatosis, or the enlargement of one or both kidneys related to the presence of nephrogenic rests, may be detected by means of prenatal ultrasonography or careful palpation of the abdomen during the neonatal period.

Intellectual disability

The presence and degree of intellectual disability widely vary among patients with WAGR syndrome. [20]  Generally, determining the degree of intellectual disability is impossible in the newborn period, although parents should be alerted to the possibility.

As the patient ages, the reliability of neuropsychometric testing improves, and baseline testing should be performed. The presence of vision loss may complicate the testing process because children with vision difficulties may acquire developmental milestones differently from children with normal vision. Thorough developmental screening appropriate in individuals with visual impairment is required for the diagnosis of intellectual disability.

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