Typical isolated ocular coloboma is a congenital abnormality caused by defective closure of the embryonic fissure of the optic cup. The defect is typically located in the inferonasal part of the iris. Gregory-Evans et al. (2004) provided a ... Typical isolated ocular coloboma is a congenital abnormality caused by defective closure of the embryonic fissure of the optic cup. The defect is typically located in the inferonasal part of the iris. Gregory-Evans et al. (2004) provided a detailed review of the molecular genetics of ocular coloboma, including a list of inherited disorders and syndromes in which coloboma is a feature. Barros-Nunez et al. (1995) described a 6-year-old boy in whom bilateral iris coloboma had been observed at birth. Psychomotor development was normal. He showed a typical inferonasal bilateral coloboma of the iris and ciliary body without coloboma of the choroid and retina or optic nerve. Retina, lens, corneal diameters, and visual acuity were normal in both eyes and there were no malformations elsewhere. A male and female first cousin of the proband related through their fathers had iris coloboma and the son of a sister of the father of the proband had unilateral coloboma. The parents in the case of all 3 sibships were normal as were the grandparents. Some unusual molecular mechanism, such as trinucleotide expansion, was suggested, giving the picture of 'delayed mutation' or 'premutation.' 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. Morrison et al. (2000) examined 75 children with iris colobomas. In 13 (17.3%) patients, noticeable iris heterochromia (142500) was present. In patients with unilateral coloboma, the heterochromia was characterized by the darker iris being the one affected with coloboma. In cases of bilateral iris colobomas with clinical microphthalmos and reduced corneal diameter, the variation in iris color was inconsistent. A fundus coloboma was not always present. The authors postulated that the iris coloboma-iris heterochromia association may result from the abnormal closure of the embryonic fissure, resulting in irregular or excessive migration of neural crest cells into the iris stroma. In addition, the high frequency of iris heterochromia-iris coloboma with microphthalmia suggests that an increased density of pigmented cells within the iris stroma may be a contributing factor. Pigment-dispersion syndrome (600510) and pigmentary glaucoma result from iridozonular friction causing disruption of the iris epithelium and deposition of iris pigment on the anterior segment structures. Tesser (2003) reported a 48-year-old patient with congenital bilateral iris colobomas. Elevated intraocular pressure was present in the eye with a partial iris coloboma and iris transillumination defects but pigment deposition on the ipsilateral corneal endothelium (Krukenberg spindle). The other eye was diagnosed as having mild ocular hypertension, without pigment dispersion or glaucoma, in association with a complete iris coloboma. Tesser (2003) concluded that pigment dispersion was prevented in the eye with the complete iris coloboma. Iris colobomas occur as part of complex malformation syndromes, e.g., iris coloboma with ptosis, hypertelorism, and mental retardation (243310), craniofacial dysmorphism with ocular coloboma, absent corpus callosum, and aortic dilatation (218340), and Hirschsprung disease, microcephaly, and iris coloboma (235730). Yuksel et al. (1999) described 2 female sibs with an MCA/MR syndrome consisting of pre- and postnatal growth retardation, iris colobomata, spasticity, facial dysmorphism, and dilated cerebral ventricles. Coloboma is a prime feature of the CHARGE association (see 214800).
Azuma et al. (2003) identified a mutation in the PAX6 gene (607108.0019) in a 1-year-old boy who had iris anomaly, large coloboma of the optic nerve (120430), retina, and choroid, a remnant of hyaloid vessel proliferation (persistent hyperplastic ... Azuma et al. (2003) identified a mutation in the PAX6 gene (607108.0019) in a 1-year-old boy who had iris anomaly, large coloboma of the optic nerve (120430), retina, and choroid, a remnant of hyaloid vessel proliferation (persistent hyperplastic primary vitreous) bilaterally, and growth and mental retardation. Asai-Coakwell et al. (2007) characterized a chromosome 8q21.2-q22.1 segmental deletion in a patient with chorioretinal coloboma and found elements of nonallelic homologous recombination and nonhomologous end joining. They demonstrated that the segmental deletion encompasses GDF6 (601147), and that inhibition of gdf6a in zebrafish accurately recapitulated the proband's phenotype. The spectrum of disorders generated by morpholino inhibition of gdf6a and the more severe defects (microphthalmia and anophthalmia) observed at higher doses illustrated the key role of GDF6 in ocular development. In Xenopus, Hanel and Hensey (2006) demonstrated that inhibition of gdf6 resulted in ocular developmental anomalies. Ye et al. (2010) identified heterozygosity for a missense mutation (606522.0002) in the GDF3 gene in an Asian female with bilateral iris coloboma.