Megalocornea is an inherited eye disorder in which the corneal diameter is bilaterally enlarged (greater than 13 mm) without an increase in intraocular pressure. It may also be referred to as 'anterior megalophthalmos,' since the entire anterior segment ... Megalocornea is an inherited eye disorder in which the corneal diameter is bilaterally enlarged (greater than 13 mm) without an increase in intraocular pressure. It may also be referred to as 'anterior megalophthalmos,' since the entire anterior segment is larger than normal. Features of megalocornea in addition to a deep anterior chamber include astigmatic refractive errors, atrophy of the iris stroma, miosis secondary to decreased function of the dilator muscle, iridodonesis, and tremulousness, subluxation, or dislocation of the lens. Whereas most affected individuals exhibit normal ocular function, complications include cataract development and glaucoma following lenticular dislocation or subluxation. X-linked recessive inheritance is the most common pattern, accounting for the male preponderance of the disorder (summary by Skuta et al., 1983). Megalocornea sometimes occurs as part of the Marfan syndrome (154700). - Genetic Heterogeneity of Megalocornea Autosomal recessive megalocornea has been reported (249300).
In a family reported by Riddell (1941), affected males showed large cornea as an isolated defect. Heterozygous women may show slight increase in corneal diameter. Two presumed homozygous females occurred in this family.
Skuta et al. ... In a family reported by Riddell (1941), affected males showed large cornea as an isolated defect. Heterozygous women may show slight increase in corneal diameter. Two presumed homozygous females occurred in this family. Skuta et al. (1983) studied 2 brothers with megalocornea and their 2 affected maternal uncles. The deceased maternal great-grandfather was reported to have had large eyes and cataracts. Examination of the 4 affected individuals revealed corneal diameters ranging from 13 to 15.5 mm, deep anterior chambers, and normal intraocular pressure. Additional features included atrophy of the iris stroma, iridodonesis, astigmatic refractive errors in the vertical meridian, lens subluxation, and cataract formation. Two of the patients exhibited transillumination of the irides, a feature not previously reported in this disorder, and the oldest patient, aged 54 years, displayed posterior 'crocodile shagreen' bilaterally, believed to represent opacities of the central stroma. Endothelial specular microscopy of affected individuals disclosed normal endothelial cell densities and morphologic characteristics and increased total endothelial cell populations, suggesting that the process involved in the development of megalocornea is one of primary overgrowth rather than secondary distention. Eye examination of 3 daughters of 1 of the affected men showed normal results except for amblyopia in 1 of them, and there was no history of women in the family with unusually large eyes or other ocular problems. Mackey et al. (1991) studied 16 affected males from 5 unrelated families, including a large 5-generation family ('family 1') with linkage to Xq21.3-q22 (Chen et al., 1989), and found that affected males had corneal diameters between 13.0 and 16.5 mm. Arcus juvenilis, mosaic corneal dystrophy, and cataracts were found only in adult affected males. No abnormality was identified in carrier females. Webb et al. (2012) ascertained 6 families segregating X-linked megalocornea. Affected individuals had corneal diameters ranging from 14 mm to 16 mm, large anterior chamber depths, decreased central corneal thickness, mosaic corneal degeneration ('shagreen'), corneal arcus juvenilis, and, in older patients, cataract. Iris transillumination with pigment dispersion was seen in all patients examined. No patient had glaucoma or significant vision loss, and no neurologic or systemic abnormalities were detected. Carrier females had no clinical signs of megalocornea.
Using dense X chromosome-specific array CGH, Webb et al. (2012) identified an approximately 250-kb segmental deletion on Xq23 in an affected male from a 4-generation family ('family 1') with megalocornea. The deletion encompassed the 3-prime end of the ... Using dense X chromosome-specific array CGH, Webb et al. (2012) identified an approximately 250-kb segmental deletion on Xq23 in an affected male from a 4-generation family ('family 1') with megalocornea. The deletion encompassed the 3-prime end of the CHRDL1 gene, extending proximally 238 kb from intron 5 of CHRDL1, and segregated with disease in the family. Analysis of CHRDL1 in affected individuals from 5 additional families with megalocornea revealed 5 different mutations, including 1 missense, 1 splice site, 1 nonsense, and 2 frameshift mutations (300350.0001-300350.0005, respectively). In a large 5-generation Tasmanian family with megalocornea mapping to Xq21.3-q22, originally studied by Chen et al. (1989), Webb et al. (2012) identified a 270- to 600-kb deletion, encompassing the entire CHRDL1 gene; this deletion did not share breakpoints with the previously identified segmental deletion in family 1. None of the patients had developmental or cognitive problems. Electrophysiologic evaluation of 2 affected individuals from family 1 revealed mild generalized cone system dysfunction, and 1 of them also showed interhemispheric asymmetry in visual evoked potentials; Webb et al. (2012) stated that evaluation of additional patients would be necessary to determine the association of a visual pathway or cone system phenotype with CHRDL1 mutations.