A defect in the PAX6 gene on band 11p13 is the cause of aniridia, which can be sporadic or familial. The familial form is autosomal dominant with complete penetrance but variable expressivity. There are reports of autosomal dominant pedigrees in which patients have severe glaucoma but normal maculae and good central vision. Two-thirds of all aniridic children have affected parents. The PAX6 gene is the master control gene for eye morphogenesis. This gene is involved in the complex interactions between the optic cup, surface ectoderm, and neural crest during formation of the iris and other ocular structures. Many mutations of the PAX6 gene have been reported. It is likely that they cause aniridia by reducing the amount of functional PAX6 protein.

Sporadic aniridia is associated with Wilms tumor (nephroblastoma) in as many as one-third of cases. When associated with aniridia, Wilms tumor is diagnosed before patients reach age 5 in 80% of cases. The combination of aniridia and Wilms tumor represents a contiguous gene syndrome in which the adjacent PAX6 and Wilms tumor (WT1) genes are both deleted. Some deletions create the WAGR complex of Wilms tumor, aniridia, genitourinary malformations, and mental retardation. All children with sporadic aniridia should undergo chromosomal deletion analysis to exclude the possibility of Wilms tumor formation. Positive results require consultation with an oncologist along with repeated abdominal ultrasonographic examinations. Because Wilms tumor has been reported in patients with familial aniridia, these patients should also undergo chromosomal analysis.

Congenital iris ectropion

Ectropion of the posterior pigment epithelium onto the anterior surface of the iris is called ectropion uveae in much of the literature. This term is a misnomer, however, because the iris posterior epithelium is derived from neural ectoderm and is not considered part of the uvea. Iris ectropion can occur as an acquired tractional abnormality, often associated with rubeosis iridis, or as a congenital nonprogressive abnormality. The combination of unilateral congenital iris ectropion, a glassysmooth cryptless iris surface, a high iris insertion, dysgenesis of the drainage angle, and glaucoma has been called congenital iris ectropion syndrome. Congenital iris ectropion may occur in patients with neurofibromatosis, facial hemihypertrophy, and Prader-Willi syndrome.

Abnormalities in the Size, Shape, or Location of the Pupil

Dyscoria

Dyscoria is an abnormality of the shape of the pupil. The term is usually reserved for congenital malformations, which include iris colobomas and sectoral hypoplasia. Slitlike pupils have been described in Axenfeld-Rieger syndrome (see Fig 20-9), in ectopia lentis et pupillae, and, in rare cases, as an isolated condition with normal vision. Acquired inflammatory conditions can lead to posterior synechiae, which can also produce a misshapen pupil.

Congenital miosis

Congenital miosis, or microcoria, may represent an absence or malformation of the dilator pupillae muscle. Congenital miosis can also occur secondary to contracture of fibrous material on the pupil margin due to remnants of the tunica vasculosa lentis or neural crest cell anomalies. The condition may be unilateral or bilateral and sporadic or hereditary. Severe cases require surgical pupilloplasty.

The pupil rarely exceeds 2 mm in diameter, is often eccentric, and reacts poorly to mydriatic drops. Some patients with eccentric microcoria also have lens subluxation; this combination is thus part of the spectrum of ectopia lentis et pupillae. Congenital miosis may be associated with microcornea, cataract, megalocornea, iris atrophy, iris transillumination, myopia, glaucoma, congenital rubella syndrome, hereditary ataxia, and Lowe syndrome.

Congenital mydriasis