SNOMEDCT: 715339004; ORPHA: 2334; DO: 0111383;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11p13 | Keratitis | 148190 | Autosomal dominant | 3 | PAX6 | 607108 |
A number sign (#) is used with this entry because of evidence that autosomal dominant keratitis is caused by heterozygous mutation in the PAX6 gene (607108) on chromosome 11p13.
Keratitis is a rare ocular disorder presenting with congenital and progressive features predominantly involving the anterior segment of the eye. The major clinical symptoms are anterior stromal corneal opacification and vascularization of the peripheral cornea. Progression of the opacification and vascularization into the central cornea may occur with corresponding reduction in visual acuity. Other anterior segment features include variable radial defects of the iris stroma and foveal hypoplasia (summary by Mirzayans et al., 1995).
Kivlin et al. (1986) reported a unique form of hereditary childhood corneal clouding, characterized by recurrent stromal keratitis and vascularization. Male-to-male transmission as well as multiple affected generations without consanguinity indicated autosomal dominant inheritance. Male and female members of the family were equally affected. Nonpenetrance was encountered in several persons. Expressivity was also variable; some family members had only transient childhood episodes of ocular inflammation without sequelae. The extent and severity of the disease also varied between the 2 eyes of an affected individual. There was a marked propensity for early recurrence of the disorder after keratoplasty.
Pearce et al. (1995) reported a family in which 15 individuals were affected in 4 generations. All affected persons presented with, at a minimum, a circumferential 1- to 2-mm wide band of corneal opacification and vascularization at the level of Bowman membrane and in continuity with the limbus. There was considerable variation in the severity of the corneal changes, with generally more progressive keratitis among older affected persons. Foveal hypoplasia was found in all affected persons. There was no skin or mucous membrane involvement in patients with autosomal dominant keratitis, as has been shown to occur with keratitis in patients suffering from epidermolysis bullosa simplex (226670) by Granek and Baden (1980), in the EEC syndrome (129900) by Mawhorter et al. (1985), or the keratitis-ichthyosis-deafness syndrome (KID; 148210) by Wilson et al. (1991). Keratoendothelitis fugax hereditaria (148200) is distinct from autosomal dominant keratitis, as it is characterized by self-limiting intermittent attacks of keratoendothelitis affecting one or the other eye.
Keratitis is inherited as a fully penetrant autosomal dominant disease with variable clinical presentation (Mirzayans et al., 1995).
Mirzayans et al. (1995) used the candidate gene approach to investigate whether mutations in the PAX6 gene are responsible for keratitis. Significant linkage was found between 2 polymorphic loci in the PAX6 region and keratitis in the family originally described by Pearce et al. (1995) (peak lod score = 4.45 at theta = 0.00 with D11S914).
In affected members of a family with autosomal dominant keratitis, originally described by Pearce et al. (1995), Mirzayans et al. (1995) identified a splice site mutation in the PAX6 gene (607108.0011).
Granek, H., Baden, H. P. Corneal involvement in epidermolysis bullosa simplex. Arch. Ophthal. 98: 469-472, 1980. [PubMed: 7362501] [Full Text: https://doi.org/10.1001/archopht.1980.01020030465003]
Kivlin, J. D., Apple, D. J., Olson, R. J., Manthey, R. Dominantly inherited keratitis. Arch. Ophthal. 104: 1621-1623, 1986. [PubMed: 3778274] [Full Text: https://doi.org/10.1001/archopht.1986.01050230059031]
Mawhorter, L. G., Ruttum, M. S., Koenig, S. B. Keratopathy in a family with the ectrodactyly-ectodermal dysplasia-clefting syndrome. Ophthalmology 92: 1427-1431, 1985. [PubMed: 4069606] [Full Text: https://doi.org/10.1016/s0161-6420(85)33847-2]
Mirzayans, F., Pearce, W. G., MacDonald, I. M., Walter, M. A. Mutation of the PAX6 gene in patients with autosomal dominant keratitis. Am. J. Hum. Genet. 57: 539-548, 1995. [PubMed: 7668281]
Pearce, W. G., Mielke, B. W., Hassard, D. T. R., Climenhaga, H. W., Climenhaga, D. B., Hodges, E. J. Autosomal dominant keratitis: a possible aniridia variant. Canad. J. Ophthal. 30: 131-137, 1995. [PubMed: 7627897]
Wilson, G. N., Squires, R. H., Jr., Weinberg, A. G. Keratitis, hepatitis, ichthyosis, and deafness: report and review of KID syndrome. Am. J. Med. Genet. 40: 255-259, 1991. [PubMed: 1951425] [Full Text: https://doi.org/10.1002/ajmg.1320400302]