Aniridia

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.

Estimated between 1:60,000 and 1:100,000 live births. All races are affected.

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.

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.

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.

Aniridia and Absent Patella

This combination has been reported in three generations of one family. Bilateral cataracts and glaucoma complicated by aniridia and hypoplastic or aplastic patellae.

Gillespie Syndrome

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.

Aniridia, Microcornea, and Spontaneously Reabsorbed Cataract

This combination has been described in three generations of one family. Patients have a poor prognosis of ocular function because of a high incidence of cataracts, glaucoma, corneal pannus, nystagmus, and foveal hypoplasia.

Aniridia, Partial, with Unilateral Renal Agenesis and Psychomotor Retardation

Congenital glaucoma, telecanthus, and frontal bossing; unilateral renal agenesis and mental retardation.

If the clinical findings are limited to the eye, no specific considerations arise from this syndrome, except use of an anesthetic technique that does not cause further increase in intraocular pressure in patients with glaucoma. In contrast, some patients have cardiomyopathy, tetralogy of Fallot, generalized hypotonia, and scoliosis. Preoperative echocardiography is recommended to determine the lesions and their hemodynamic significance. The presence of Wilms tumor requires further diagnostic measures, such as abdominal ultrasound, CT scanning, and/or MRI. Preoperative blood workup should include a complete blood count (anemia), electrolytes, and assessment of renal function (creatinine, BUN). Mental and neurologic status (decreased vision/blindness) must be assessed for a thoughtful approach to premedication and induction.

Considerations are in reference to pediatric eye surgery and are the same for normal children as those with syndromes associated with congenital aniridia. Avoid measures that increase intraocular pressure and be aware of oculocardiac reflex. In patients with congenital cardiac lesions, the anesthetic approach must consider their hemodynamic consequences and the drug effects. Large-bore intravenous access and invasive blood pressure monitoring are recommended in patients undergoing surgery for Wilms tumor removal.

Presence of ptosis and generalized hypotonia in Gillespie syndrome may suggest a susceptibility to malignant hyperthermia. Consequently, it would be prudent to avoid triggering drugs. Due to glaucoma, patients may be taking beta blockers (e.g., timolol, to reduce production of aqueous humor), parasympathomimetics (e.g., pilocarpine, to lower outflow resistance of aqueous humor), and carbonic anhydrase inhibitors (e.g., acetazolamide, to reduce secretion of aqueous humor), or a combination of these drugs. Even though these drugs are applied locally (except acetazolamide), they may have systemic side effects, which should be kept in mind while providing anesthesia.

The following syndromes are associated with Wilms tumor:

WAGR Syndrome: Unusual association of Wilms tumor, ocular signs, and mental retardation.

Denys-Drash Syndrome: Manifests in small children and consists of the triad of congenital nephropathy, Wilms tumor, and ambiguous genitalia.

Beckwith-Wiedemann Syndrome: Most often sporadically occurring syndrome with exomphalos, macroglossia, gigantism, and hypoglycemia resulting from hyperinsulinism.

Perlman Syndrome: Neonatal gigantism accompanied by visceromegaly (especially renal dysplasia or tumour) and at risk for hypoglycemia. This condition consists of nephromegaly, renal dysplasia, Wilms tumor, macrosomia, hypotonia, cryptorchidism, and multiple facial dysmorphism (round full face, micrognathia, macrosomia).