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[page 10] [Eye Reports 2011; 1:e4]

A rare case of WAGR syndrome
with Peter anomaly
Rohit S. Adyanthaya, Michael X. Repka
Wilmer Ophthalmological Institute, the
Johns Hopkins University School of
Medicine, Baltimore, Maryland, USA

Abstract 

We report a case of the WAGR syndrome
associated with the Peter anomaly. A 6-day-old
baby boy was found to have bilateral corneal
opacities, 360 degrees of iris hypoplasia and
cataracts. Physical examination revealed bilat-
eral undescended testicles. Family history was
unremarkable and genetic testing revealed a
deletion 11p11.2-13 indicating WAGR syn-
drome. A Wilms tumor developed and was
removed at age 2 years. There was moderate
developmental delay. The occurrence of WAGR
syndrome with Peter anomaly has been report-
ed in three other patients to our knowledge.

Introduction

WAGR syndrome is a disorder characterized
by microdeletions of the short arm of chromo-
some 11 at band p13 and is clinically associat-
ed with Wilms tumor, aniridia, genitourinary
anomalies and mental retardation (W-A-G-R).
Deletions of neighboring genes, the PAX6 ocu-
lar development gene and the Wilms tumor
gene (WT1), result in aniridia and Wilms
tumor, respectively. Peter anomaly is an anteri-
or segment dysgenesis in which there is abnor-
mal development of the anterior chamber.

Case Report

A 6-day-old infant boy was evaluated for
bilateral corneal opacities. His prenatal history
was uneventful with spontaneous vaginal deliv-
ery at 36 weeks gestation. The right eye had a
central white corneal opacity, which extended
to the limbus from 4 o'clock to 7 o'clock.  There
were 360 degrees of iris hypoplasia with iris
vessels visible. There was an area of irido-
corneal adhesion inferiorly. The anterior cham-
ber was shallow. The horizontal and vertical
corneal diameters were 8.8 mm. There was a
nuclear cataract visible behind the corneal
opacification.  The left eye had denser central
corneal opacification. There were 360 degrees
of iris hypoplasia with a vascular ring at the
poorly formed pupillary margin. The anterior

chamber was noted to be shallow, especially
inferiorly with an area of irido-corneal adhe-
sions. A dense nuclear and cortical cataract was
noted. The corneal diameters were 9.0 mm ver-
tical and 10.5 mm horizontal. The intraocular
pressure measured with a handheld applana-
tion tonometer (Tono-pen: Bio-Rad, Santa Ana,
CA, USA) varied from 18 to 22 mm of Hg in both
eyes.  B-scan ocular echography found bilateral
lenticular opacities and attached retinas.
Systemic examination revealed bilateral unde-
scended testicles. Abdominal sonography
showed normal kidneys. Family history was
unremarkable. Genetic testing revealed a dele-
tion on chromosome 11p11.2-13. Bilateral
(non-simultaneous) penetrating keratoplasties
with lensectomy were performed.  A second
corneal graft was performed in each eye after
about one year. Glaucoma developed in the
right eye, with subsequent retinal detachment,
and corneal graft failure. The graft in the left
eye remained clear at 6 years of age. In addi-
tion, quarterly sonograms of the abdomen were
conducted. A computed tomography (CT) scan
of the abdomen and pelvis at age 2 years
demonstrated a 2.0¥1.8¥2.4 cm mass in the
mid pole of the left kidney leading to the diag-
nosis of Wilms tumor, which was successfully
excised.
The pathology was consistent with a stage I

Wilms tumor, and was negative for tumor-spe-
cific loss of heterozygosity.  Furthermore, over
time, he was noted to have moderate develop-
mental delay with learning disability and atten-
tion deficit hyperactivity disorder (ADHD).

Discussion

The occurrence of WAGR syndrome with
Peter anomaly has been reported in three
other patients to our knowledge. These were a
2-month-old boy with the Peter anomaly and
deletion of 11p13 who did not have Wilms
tumor,1 a 6-day-old boy with the Peter anomaly
and a Wilms tumor (chromosomal analysis was
not performed)2 and a 1-month-old boy with
deletion on chromosome 11p13-15.1 with an
anomalous anterior segment and microphthal-
mos with bilateral Wilms tumors developing at
the age of 3 years.3 Our case of Peters anom-
aly plus Wilms tumor presents further evi-
dence of  an association of WAGR syndrome
and Peter anomaly.
WAGR syndrome (OMIM 194072) was first

described by Miller, et al.4 and is an extensive-
ly studied contiguous gene syndrome. Children
with WAGR syndrome invariably have a
germline chromosomal deletion at 11p of vari-
able size, but always affecting WT1 and PAX6
genes, both on band 13 (11p13).5

Aniridia occurs sporadically or as an autoso-
mal dominant inherited condition. One-third

of patients with sporadic aniridia will be found
to have WAGR syndrome.6 The PAX6 gene,
involved in ocular embryogenesis, has been
identified as a candidate gene for aniridia.
Therefore, it is reasonable that ocular anom-
alies other than aniridia might result from a
deletion in the PAX6 gene.
The second gene in this region is the WT1

gene (Wilms tumor gene). Individuals who
have a deletion in this gene have an increased
risk for developing Wilms tumor as well as hav-
ing abnormal genitalia. Their risk of having
Wilms tumor is around 45-57%.7,8 90% of Wilms
tumors present by the age of 4 years and 98%
by the age of 7 years. Screening for Wilms
tumor includes ultrasound every three months
during this period. There is also approximate-
ly a 40% chance of renal problems, including
renal failure in late adolescence in children
with WAGR and Wilms tumor.9 The associated
genitourinary findings include cryptorchidism
present in nearly 60% of the cases,8 hypospa-
dias, micropenis and other urinary tract abnor-
malities (also caused by WT1 gene deletions).
Peter anomaly is an anterior segment dysge-

nesis in which abnormal cleavage of the ante-
rior chamber occurs. Mutations may involve
the PAX6 gene.9,10 with reported cases of Peter
anomaly and aniridia.11,12 though Churchill, et
al. found no such association.13 Peter plus syn-
drome is characterized by genitourinary
abnormalities, syndactyly, brachycephaly, and
cardiac, neural, and hearing abnormalities.
Since the PAX6 gene is also involved in the
development of the central nervous system, a
wide variety of neurological, behavioral, and
psychiatric abnormalities can also be present.8

References

1. Hanson IM, Fletcher JM, Jordan T, et al.
Mutations at the PAX6 locus are found in

Eye Reports 2011; volume 1:e4

Correspondence: Rohit Adyanthaya, Stony Brook
University, HSC L-2, Rm 152, Stony Brook,
New York 11768, USA.
E-mail: rohiteyedoctor@gmail.com 

Key words: WAGR syndrome, Peter anomaly.

Received for publication: 9 April 2011. 
Accepted for publication: 31 July 2011. 

This work is licensed under a Creative Commons
Attribution NonCommercial 3.0 License (CC BY-
NC 3.0).

©Copyright R.S. Adyanthaya and M.X. Repka., 2011
Licensee PAGEPress, Italy
Eye Reports 2011; 1:e4
doi:10.4081/eye.2011.e4

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[Eye Reports 2011; 1:e4] [page 11]

heterogeneous anterior segment malfor-
mations including Peters' anomaly. Nat
Genet 1994;6:168-73.

2. Eiferman RA. Association of Wilms' tumor
with Peters' anomaly. Ann Ophthalmol
1984;16:933-4.

3. Kawase E, Tanaka K, Honna T, Azuma N. A
case of atypical WAGR syndrome with
anterior segment anomaly and microph-
thalmos. Arch Ophthalmol 2001;119:1855-
6.

4. Miller RW, Fraumeni JF Jr, Manning MD.
Association of Wilms tumor with aniridia,
hemihypertophy and other congenital mal-
formations. N Engl J Med 1964;270:922-7.

5. Crolla JA, Cawdery JE, Oley CA, et al. A
FISH approach to defining the extent and
possible clinical significance of deletions
at the WAGR locus. J Med Genet 1997;34:

207-12.
6. Ivanov I, Shuper A, Shohad M, et al.
Aniridia: recent achievements in clinical
practice. Eur J Pediatr 1995;154:795-800.

7. Muto R, Yamamori S, Ohashi H, Osawa M.
Prediction by FISH analysis of the occur-
rence of Wilms tumor in aniridia patients.
Am J Med Genet 2002;108:285-9.

8. Fischbach BV, Trout KL, Lewis J, et al.
WAGR syndrome: a clinical review of 54
cases. Pediatrics 2005;116:984-8.

9. Breslow NE, Collins AJ, Ritchey ML, et al.
End stage renal disease in patients with
Wilms tumor: results from the National
Wilms Tumor Study Group and the United
States Renal Data System. J Urol 2005;
174:1972-5.

9. Azuma N, Yamaguchi Y, Handa H, et al.
Missense mutation in the alternative

splice region of the PAX6 gene in eye
anomalies. Am J Hum Genet 1999;65:656-
63.

10. Sawada M, Sato M, Hikoya A, et al. A case
of aniridia with unilateral Peters anomaly.
J AAPOS 2011;15:104-6.

11. Mayer UM. Peters' anomaly and combina-
tion with other malformations (series of
16 patients). Ophthalmic Paediatr Genet
1992;13:131-5.

12. Koster R, van Balen AT. Congenital corneal
opacity (Peters' anomaly) combined with
buphthalmos and aniridia. Ophthalmic
Paediatr Genet 1985;6:241-6.

13. Churchill AJ, Booth AP, Anwar R, Markham
AF. PAX 6 is normal in most cases of
Peters' anomaly. Eye (Lond) 1998;12:299-
303.

Case Reports

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