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It is estimated that approximately one third of
patients with sporadic aniridia will develop a Wilms tumor, and
approximately half of patients with aniridia, genitourinary anomalies (e.g.,
hypospadias), and mental retardation will develop a Wilms tumor. The
association with genitourinary anomalies and mental retardation is known as WAGR Syndrome. Most patients have prominent lips and
macrognathia. Other features may include congenital cataracts, nystagmus,
ptosis, and blindness. The presence of ptosis and generalized hypotonia in a
subgroup of patients suggests a susceptibility to malignant hyperthermia.
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Estimated between 1:60,000 and 1:100,000 live births.
All races are affected.
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Both hereditary and sporadic forms exist.
Approximately 30% of cases arise spontaneously. The usual form of
inheritance is an autosomal dominant trait, but autosomal recessive
transmission has been suggested for the rare Gillespie syndrome. There are
two genetic loci for aniridia: aniridia type 1 (AN1) results from a defect
on the short arm of chromosome 2; aniridia type 2 (AN2) has been related to
a defect on 11p13. Aniridia as an isolated ocular malformation is an
autosomal dominant disorder caused by a mutation in the PAX6 (paired box gene
family) gene located on 11p13. Although patients with a positive family
history for aniridia do not have an increased risk for Wilms tumor, patients
without a positive family history for aniridia (sporadic cases) have a
30% risk of developing Wilms tumor.
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Aniridia is related to a primary arrest in the
neuroectodermal development and a secondary disturbance of the three neural
crest waves from the mesenchyme. Functional development of the anterior
segment is a complex interrelationship between neural ectoderm and the
neural crest waves mesenchyme. Cellular and/or biochemical aberrations may
result in malformation or regression of different layers of the anterior
segment of the eye. The iris stroma is hypoplastic, and the extent of the
defect ranges from slit-like lesions of the iris stroma only visible under
slitlamp examination to coloboma-like defects and almost complete absence of
the iris stroma. The root of the iris, however, is most often visible on
gonioscopy. Aniridia has been produced experimentally in mice with maternal
vitamin A deficiency.
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At birth, the iris is reduced to a small tube. In
general, vision is decreased, with numerous other contributing anomalies
including light scatter, corneal and lenticular opacities, severe glaucoma,
nystagmus, optic nerve agenesis, and foveal hypoplasia.
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Aniridia and Absent Patella
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This combination has been reported in
three generations of one family. Bilateral cataracts and glaucoma
complicated by aniridia and hypoplastic or aplastic patellae.
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Typical presentation is discovery of fixed
dilated pupils in a hypotonic infant. Neurologic signs include marked motor
delay, hypotonia, disabling ataxia, and usually mental retardation. The
combination with tetralogy of Fallot and/or cardiomyopathy has been
reported.
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Aniridia, Microcornea, and Spontaneously Reabsorbed Cataract
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This combination has been described in three generations ...