Coloboma Of Optic Nerve

A number sign (#) is used with this entry because of evidence that coloboma of the optic nerve and morning glory disc anomaly are each caused by mutation in the PAX6 gene (607108). One such patient has been reported for each of the phenotypes.

Clinical Features

Congenital coloboma of the optic nerve is often associated with serious detachment of the macula. Savell and Cook (1976) observed 15 affected persons in 1 kindred. In 21 of the 30 eyes, present or past detachment of the retina was found. The coloboma was bilateral in all. It appeared as enlargement of the physiologic cup with severely affected eyes showing huge cavities at the site of the disc. A variable amount of glial tissue was present in the coloboma. No male-to-male transmission was observed. It is not certain that this entity is separate from that discussed in 120200.

Jonas and Freisler (1997) used the designation 'bilateral congenital optic nerve pits' for this disorder, which they observed in 2 otherwise healthy female monozygotic sibs aged 15 years. In both twins, visual acuity was worse in the eye with the larger optic nerve head. The parents were ophthalmologically unremarkable; there were no other sibs. Retinal detachment extending from the optic disc to the ora serrata in the temporal upper quadrant developed in 1 eye.

Hornby et al. (2000) correlated visual function with clinical features and biometric findings in the eyes of children with coloboma. Of the 196 eyes with colobomatous malformations, 11 had microphthalmos with cyst (251505), and 185 eyes had coloboma (associated with microcornea in 155 eyes and with normal corneal diameter in 30 eyes). The visual prognosis depended on the phenotype of the more normal eye. Microphthalmos with cyst had the worst prognosis (all worse than 20/400). Microcornea with microphthalmos had a worse prognosis than microcornea without microphthalmos. For microcornea with microphthalmos, 67% saw worse than 20/400. Of the children with microcornea without microphthalmos, 76% saw better than 20/400. Simple coloboma (without microcornea or microphthalmos) had the best visual prognosis: only 7% saw 20/400 or worse. A corneal diameter of less than 6 mm had a poor visual prognosis, whereas a corneal diameter of more than 10 mm had a good prognosis.

Molecular Genetics

In a 5-year-old girl with bilateral morning glory disc anomaly and in a 1-year-old boy with iris anomaly, large coloboma of the optic nerve, retina, and choroid (120200), a remnant of hyaloid vessel proliferation (persistent hyperplastic primary vitreous; see 257910) bilaterally, and growth and mental retardation, Azuma et al. (2003) identified missense mutations in the PAX6 gene (607108.0017 and 607108.0019, respectively).