Anterior Segment Dysgenesis 6

A number sign (#) is used with this entry because of evidence that anterior segment dysgenesis-6 (ASGD6) is caused by compound heterozygous mutation in the CYP1B1 gene (601771) gene on chromosome 2p22.

Description

Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016).

Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002).

Patients with ASGD6 have been reported with the Peters anomaly subtype.

Peters anomaly consists of corneal opacity, defects in the posterior structures of the cornea, and iridocorneal and/or keratolenticular adhesions. Over 50% of patients develop glaucoma in childhood (summary by Vincent et al., 2001).

Clinical Features

Vincent et al. (2001) reported a 6-year-old boy of Native American (Mohawk)/French Canadian background with Peters anomaly and glaucoma. The patient presented with a history of bilateral cloudy corneas and tearing since birth. Examination at 3 weeks of age showed bilateral corneal edema with central corneal opacities, superficial pannus (corneal vascularization), and iridocorneal adhesions with a well-formed anterior chamber. The child was otherwise well, with no other malformations and no significant family history. The patient had a left corneal transplant for visual rehabilitation. Microscopic examination of the left corneal button showed that the corneal epithelium was of normal thickness, although there was some edema of the basal cells. Bowman membrane was not recognizable, and the anterior stroma was hypercellular with a disordered lamellar pattern. The posterior stroma was absent centrally, and there was a basophilic granular deposit containing a small amount of extracellular melanin. Descemet membrane was not identified; however, transmission electron microscopy showed a recognizable but abnormal Bowman membrane, which contained scattered keratocytes. A small segment of Descemet was observed, but it was thin with a poorly defined banding pattern. No endothelial cells were seen.

Molecular Genetics

In a Native American (Mohawk)/French Canadian male with Peters anomaly and secondary congenital glaucoma, Vincent et al. (2001) identified compound heterozygosity for mutations in the CYP1B1 gene (601771.0009-601771.0010).