ORPHA: 708; DO: 0060673, 0080610;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11p13 | Anterior segment dysgenesis 5, multiple subtypes | 604229 | Autosomal dominant | 3 | PAX6 | 607108 |
A number sign (#) is used with this entry because of evidence that anterior segmental dysgenesis-5 (ASGD5) is caused by heterozygous mutation in the PAX6 gene (607108) on chromosome 11p13.
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 ASGD5 have been reported with the Peters anomaly, Axenfeld anomaly, and Rieger anomaly subtypes.
Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (Peters, 1906). It occurs as an isolated ocular abnormality or in association with other ocular defects.
In Axenfeld anomaly, strands of iris tissue attach to the Schwalbe line; in Rieger anomaly, in addition to the attachment of iris tissue to the Schwalbe line, there is clinically evident iris stromal atrophy with hole or pseudo-hole formation and corectopia (summary by Smith and Traboulsi, 2012).
Yang et al. (2004) reviewed the long-term outcome in 19 patients with Peters anomaly. Severe glaucoma was a prominent feature among their patients. Despite combined medical and surgical interventions, glaucoma could be controlled in only 32% of eyes with glaucoma associated with Peters anomaly. Visual results were poor due to uncontrolled glaucoma, amblyopia, neurologic impairment, and other anterior and posterior segment anomalies that might accompany Peters anomaly. Postoperative complications, including corneal graft failure, cataract, inoperable retinal detachment, and phthisis, also contributed to decreased visual acuity in these patients.
The transmission pattern of anterior segment dysgenesis in the family reported by Hanson et al. (1994) was consistent with autosomal dominant inheritance.
In a family with dominantly inherited anterior segment malformations with variable expression, including typical Peters anomaly and Rieger anomaly (family 3 of Holmstrom et al., 1991), Hanson et al. (1994) identified a heterozygous mutation in the PAX6 gene (R26G; 607108.0004).
In 3 Japanese families and in a sporadic Japanese case, Azuma et al. (1999) described a variety of eye anomalies caused by a heterozygous val54-to-asp (V54D) mutation (V54E; 607108.0015) in the PAX gene: Peters anomaly, congenital cataract, Axenfeld anomaly, and/or foveal hypoplasia (see 136520). Two patients had Peters anomaly and one had Axenfeld anomaly.
Azuma, N., Yamaguchi, Y., Handa, H., Hayakawa, M., Kanai, A., Yamada, M. Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies. Am. J. Hum. Genet. 65: 656-663, 1999. [PubMed: 10441571] [Full Text: https://doi.org/10.1086/302529]
Cheong, S.-S., Hentschel, L., Davidson, A. E., Gerrelli, D., Davie, R., Rizzo, R., Pontikos, N., Plagnol, V., Moore, A. T., Sowden, J. C., Michaelides, M., Snead, M., Tuft, S. J., Hardcastle, A. J. Mutations in CPAMD8 cause a unique form of autosomal-recessive anterior segment dysgenesis. Am. J. Hum. Genet. 99: 1338-1352, 2016. [PubMed: 27839872] [Full Text: https://doi.org/10.1016/j.ajhg.2016.09.022]
Gould, D. B., John, S. W. M. Anterior segment dysgenesis and the development glaucomas are complex traits. Hum. Molec. Genet. 11: 1185-1193, 2002. [PubMed: 12015278] [Full Text: https://doi.org/10.1093/hmg/11.10.1185]
Hanson, I. M., Fletcher, J. M., Jordon, T., Brown, A., Taylor, D., Adams, R. J., Punnett, H. H., van Heyningen, V. Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. Nature Genet. 6: 168-173, 1994. [PubMed: 8162071] [Full Text: https://doi.org/10.1038/ng0294-168]
Holmstrom, G. E., Reardon, W. P., Baraitser, M., Elston, J. S., Taylor, D. S. Heterogeneity in dominant anterior segment malformations. Brit. J. Ophthal. 75: 591-597, 1991. [PubMed: 1954207] [Full Text: https://doi.org/10.1136/bjo.75.10.591]
Peters, A. Ueber angeborene Defektbildung der Descemetschen Membran. Klin. Monatsbl. Augenheilkd. 44: 27-40 and 105-119, 1906.
Smith, J. E. H., Traboulsi, E. I. Malformations of the anterior segment of the eye. In: Traboulsi, E. (ed.): Genetic Disease of the Eye. 2nd ed. New York: Oxford University Press 2012. P. 94.
Yang, L. L. H., Lambert, S. R., Lynn, M. J., Stulting, R. D. Surgical management of glaucoma in infants and children with Peters' anomaly: long-term structural and functional outcome. Ophthalmology 111: 112-117, 2004. [PubMed: 14711722] [Full Text: https://doi.org/10.1016/j.ophtha.2003.02.002]