Alternative titles; symbols
| Location | Phenotype | Inheritance | Phenotype mapping key | Phenotype MIM number | Gene/Locus | Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p33 | Anterior segment dysgenesis 2, multiple subtypes | AR | 3 | 610256 | FOXE3 | 601094 |
| 2p25.3 | Anterior segment dysgenesis 7, with sclerocornea | AR | 3 | 269400 | PXDN | 605158 |
| 2p22.2 | Anterior segment dysgenesis 6, multiple subtypes | AR | 3 | 617315 | CYP1B1 | 601771 |
| 4q25 | Anterior segment dysgenesis 4 | AD | 3 | 137600 | PITX2 | 601542 |
| 6p25.3 | Anterior segment dysgenesis 3, multiple subtypes | AD | 3 | 601631 | FOXC1 | 601090 |
| 10q24.32 | Anterior segment dysgenesis 1, multiple subtypes | AD | 3 | 107250 | PITX3 | 602669 |
| 11p13 | Anterior segment dysgenesis 5, multiple subtypes | AD | 3 | 604229 | PAX6 | 607108 |
| 19p13.11 | Anterior segment dysgenesis 8 | AR | 3 | 617319 | CPAMD8 | 608841 |
A number sign (#) is used with this entry because of evidence that anterior segment dysgenesis-4 (ASGD4) is caused by heterozygous mutation in the PITX2 gene (601542) on chromosome 4q25.
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 byCheong et al., 2016).
Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002).
Patients with ASGD4 have been reported with iridogoniodysgenesis or Peters anomaly subtypes.
Iridogoniodysgenesis, which is characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma, is the result of aberrant migration or terminal induction of the neural crest cells involved in the formation of the anterior segment of the eye (summary byMears et al., 1996).
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).
Berg (1932) described 22 affected individuals in 6 generations.McCulloch (1950) described 18 affected in 5 generations.Weatherill and Hart (1969) observed glaucoma in many members of 5 generations. Not only is the stroma of the iris hypoplastic but the iris is also light in color, a feature that antedates development of glaucoma and permits recognition of affected persons at birth. Jerndal (1970,1972) updated theBerg (1932) pedigree.Jerndal (1983) presented 3 pedigrees in which autosomal dominant glaucoma was shown to be the result of goniodysgenesis. The author suggested that it is improper to classify glaucoma on the basis of age of onset, which can be highly variable. In all 3 pedigrees, glaucoma was congenital in some and as late as age 34, 46, and 68 in others.
The disorder reported byWeatherill and Hart (1969),Jerndal (1970), andPearce et al. (1983) might be referred to as autosomal dominant iris hypoplasia associated with early-onset glaucoma. The term iridogoniodysgenesis has the virtue of correctly emphasizing the maldevelopment of the trabecular meshwork as well as the iris. The pathogenesis of the condition is thought to involve abnormal differentiation of neural crest cells.
Heon et al. (1995) described an extensively affected family of Scandinavian descent in which iris hypoplasia was found in 15 members, 9 of whom had associated glaucoma. Almost all affected individuals had a peculiar eye color (slate gray or chocolate brown) that resulted from the pigmented iris epithelium showing through the markedly hypoplastic anterior iris stroma. The normal pupillary sphincter stood out as an elevated tan-colored ring against a rather featureless background. Glaucoma usually was detected in the second decade of life but might begin at any age; when it did develop, it tended to be resistant to medical therapy, and if left untreated, total blindness could result.
In a Scandinavian family segregating iris hypoplasia,Heon et al. (1995) found linkage of the disorder to chromosome 4q25.
The transmission pattern of iris hypoplasia in the family reported byAlward et al. (1998) was consistent with autosomal dominant inheritance.
In the family with autosomal dominant iris hypoplasia with early-onset glaucoma reported byHeon et al. (1995),Alward et al. (1998) identified heterozygosity for a mutation in the PITX2 gene (601542.0007).
Kulak et al. (1998) demonstrated mutation in the PITX2 gene in a family with iridogoniodysgenesis (601542.0008).
In a child with Peters anomaly,Doward et al. (1999) identified a heterozygous splice site mutation in the PITX2 gene (601542.0009).
Alward, W. L. M., Semina, E. V., Kalenak, J. W., Heon, E., Sheth, B. P., Stone, E. M., Murray, J. C.Autosomal dominant iris hypoplasia is caused by a mutation in the Rieger syndrome (RIEG/PITX2) gene. Am. J. Ophthal. 125: 98-100, 1998. [PubMed:9437321,related citations] [Full Text]
Berg, F.Erbliches jugendliches Glaukom. Acta Ophthal. 10: 568-587, 1932.
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,images,related citations] [Full Text]
Doward, W., Perveen, R., Lloyd, I. C., Ridgway, A. E. A., Wilson, L., Black, G. C. M.A mutation in the RIEG1 gene associated with Peters' anomaly. J. Med. Genet. 36: 152-155, 1999. [PubMed:10051017,related citations]
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,related citations] [Full Text]
Heon, E., Sheth, B. P., Kalenak, J. W., Sunden, S. L. F., Streb, L. M., Taylor, C. M., Alward, W. L. M., Sheffield, V. C., Stone, E. M.Linkage of autosomal dominant iris hypoplasia to the region of the Rieger syndrome locus (4q25). Hum. Molec. Genet. 4: 1435-1439, 1995. [PubMed:7581385,related citations] [Full Text]
Jerndal, T.Goniodysgenesis and hereditary juvenile glaucoma: a clinical study of a Swedish pedigree. Acta Ophthal. Suppl. 107: 3-100, 1970. [PubMed:4320190,related citations]
Jerndal, T.Dominant goniodysgenesis with late congenital glaucoma: a re-examination of Berg's pedigree. Am. J. Ophthal. 74: 28-34, 1972. [PubMed:4624765,related citations] [Full Text]
Jerndal, T.Congenital glaucoma due to dominant goniodysgenesis: a new concept of the heredity of glaucoma. Am. J. Hum. Genet. 35: 645-651, 1983. [PubMed:6881141,related citations]
Kulak, S. C., Kozlowski, K., Semina, E. V., Pearce, W. G., Walter, M. A.Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome. Hum. Molec. Genet. 7: 1113-1117, 1998. [PubMed:9618168,related citations] [Full Text]
McCulloch, J. C.Iridoschisis as a cause of glaucoma. Am. J. Ophthal. 33: 1398-1400, 1950. [PubMed:14771214,related citations] [Full Text]
Mears, A. J., Mirzayans, F., Gould, D. B., Pearce, W. G., Walter, M. A.Autosomal dominant iridogoniodysgenesis anomaly maps to 6p25. Am. J. Hum. Genet. 59: 1321-1327, 1996. [PubMed:8940278,related citations]
Pearce, W. G., Wyatt, H. T., Boyd, T. A., Ombres, R. S., Salter, A. B.Autosomal dominant iridogoniodysgenesis: genetic features. Canad. J. Ophthal. 18: 7-10, 1983. [PubMed:6839205,related citations]
Peters, A.Ueber angeborene Defektbildung der Descemetschen Membran. Klin. Monatsbl. Augenheilkd. 44: 27-40 and 105-119, 1906.
Weatherill, J. R., Hart, C. T.Familial hypoplasia of the iris stroma associated with glaucoma. Brit. J. Ophthal. 53: 433-438, 1969. [PubMed:5804028,related citations] [Full Text]
Alternative titles; symbols
ORPHA: 91483; DO: 0080609; MONDO: 0007662;
| Location | Phenotype | Phenotype MIM number | Inheritance | Phenotype mapping key | Gene/Locus | Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4q25 | Anterior segment dysgenesis 4 | 137600 | Autosomal dominant | 3 | PITX2 | 601542 |
A number sign (#) is used with this entry because of evidence that anterior segment dysgenesis-4 (ASGD4) is caused by heterozygous mutation in the PITX2 gene (601542) on chromosome 4q25.
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 ASGD4 have been reported with iridogoniodysgenesis or Peters anomaly subtypes.
Iridogoniodysgenesis, which is characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma, is the result of aberrant migration or terminal induction of the neural crest cells involved in the formation of the anterior segment of the eye (summary by Mears et al., 1996).
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).
Berg (1932) described 22 affected individuals in 6 generations. McCulloch (1950) described 18 affected in 5 generations. Weatherill and Hart (1969) observed glaucoma in many members of 5 generations. Not only is the stroma of the iris hypoplastic but the iris is also light in color, a feature that antedates development of glaucoma and permits recognition of affected persons at birth. Jerndal (1970, 1972) updated the Berg (1932) pedigree. Jerndal (1983) presented 3 pedigrees in which autosomal dominant glaucoma was shown to be the result of goniodysgenesis. The author suggested that it is improper to classify glaucoma on the basis of age of onset, which can be highly variable. In all 3 pedigrees, glaucoma was congenital in some and as late as age 34, 46, and 68 in others.
The disorder reported by Weatherill and Hart (1969), Jerndal (1970), and Pearce et al. (1983) might be referred to as autosomal dominant iris hypoplasia associated with early-onset glaucoma. The term iridogoniodysgenesis has the virtue of correctly emphasizing the maldevelopment of the trabecular meshwork as well as the iris. The pathogenesis of the condition is thought to involve abnormal differentiation of neural crest cells.
Heon et al. (1995) described an extensively affected family of Scandinavian descent in which iris hypoplasia was found in 15 members, 9 of whom had associated glaucoma. Almost all affected individuals had a peculiar eye color (slate gray or chocolate brown) that resulted from the pigmented iris epithelium showing through the markedly hypoplastic anterior iris stroma. The normal pupillary sphincter stood out as an elevated tan-colored ring against a rather featureless background. Glaucoma usually was detected in the second decade of life but might begin at any age; when it did develop, it tended to be resistant to medical therapy, and if left untreated, total blindness could result.
In a Scandinavian family segregating iris hypoplasia, Heon et al. (1995) found linkage of the disorder to chromosome 4q25.
The transmission pattern of iris hypoplasia in the family reported by Alward et al. (1998) was consistent with autosomal dominant inheritance.
In the family with autosomal dominant iris hypoplasia with early-onset glaucoma reported by Heon et al. (1995), Alward et al. (1998) identified heterozygosity for a mutation in the PITX2 gene (601542.0007).
Kulak et al. (1998) demonstrated mutation in the PITX2 gene in a family with iridogoniodysgenesis (601542.0008).
In a child with Peters anomaly, Doward et al. (1999) identified a heterozygous splice site mutation in the PITX2 gene (601542.0009).
Alward, W. L. M., Semina, E. V., Kalenak, J. W., Heon, E., Sheth, B. P., Stone, E. M., Murray, J. C.Autosomal dominant iris hypoplasia is caused by a mutation in the Rieger syndrome (RIEG/PITX2) gene. Am. J. Ophthal. 125: 98-100, 1998. [PubMed: 9437321] [Full Text: https://doi.org/10.1016/s0002-9394(99)80242-6]
Berg, F.Erbliches jugendliches Glaukom. Acta Ophthal. 10: 568-587, 1932.
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]
Doward, W., Perveen, R., Lloyd, I. C., Ridgway, A. E. A., Wilson, L., Black, G. C. M.A mutation in the RIEG1 gene associated with Peters' anomaly. J. Med. Genet. 36: 152-155, 1999. [PubMed: 10051017]
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]
Heon, E., Sheth, B. P., Kalenak, J. W., Sunden, S. L. F., Streb, L. M., Taylor, C. M., Alward, W. L. M., Sheffield, V. C., Stone, E. M.Linkage of autosomal dominant iris hypoplasia to the region of the Rieger syndrome locus (4q25). Hum. Molec. Genet. 4: 1435-1439, 1995. [PubMed: 7581385] [Full Text: https://doi.org/10.1093/hmg/4.8.1435]
Jerndal, T.Goniodysgenesis and hereditary juvenile glaucoma: a clinical study of a Swedish pedigree. Acta Ophthal. Suppl. 107: 3-100, 1970. [PubMed: 4320190]
Jerndal, T.Dominant goniodysgenesis with late congenital glaucoma: a re-examination of Berg's pedigree. Am. J. Ophthal. 74: 28-34, 1972. [PubMed: 4624765] [Full Text: https://doi.org/10.1016/0002-9394(72)91121-x]
Jerndal, T.Congenital glaucoma due to dominant goniodysgenesis: a new concept of the heredity of glaucoma. Am. J. Hum. Genet. 35: 645-651, 1983. [PubMed: 6881141]
Kulak, S. C., Kozlowski, K., Semina, E. V., Pearce, W. G., Walter, M. A.Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome. Hum. Molec. Genet. 7: 1113-1117, 1998. [PubMed: 9618168] [Full Text: https://doi.org/10.1093/hmg/7.7.1113]
McCulloch, J. C.Iridoschisis as a cause of glaucoma. Am. J. Ophthal. 33: 1398-1400, 1950. [PubMed: 14771214] [Full Text: https://doi.org/10.1016/0002-9394(50)91835-6]
Mears, A. J., Mirzayans, F., Gould, D. B., Pearce, W. G., Walter, M. A.Autosomal dominant iridogoniodysgenesis anomaly maps to 6p25. Am. J. Hum. Genet. 59: 1321-1327, 1996. [PubMed: 8940278]
Pearce, W. G., Wyatt, H. T., Boyd, T. A., Ombres, R. S., Salter, A. B.Autosomal dominant iridogoniodysgenesis: genetic features. Canad. J. Ophthal. 18: 7-10, 1983. [PubMed: 6839205]
Peters, A.Ueber angeborene Defektbildung der Descemetschen Membran. Klin. Monatsbl. Augenheilkd. 44: 27-40 and 105-119, 1906.
Weatherill, J. R., Hart, C. T.Familial hypoplasia of the iris stroma associated with glaucoma. Brit. J. Ophthal. 53: 433-438, 1969. [PubMed: 5804028] [Full Text: https://doi.org/10.1136/bjo.53.7.433]
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