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Anterior segment dysgenesis 6(ASGD6)

MedGen UID:
934590
Concept ID:
C4310623
Disease or Syndrome
Synonyms: Anterior segment dysgenesis 6, multiple subtypes; ASGD6
 
Gene (location): CYP1B1 (2p22.2)
 
Monarch Initiative: MONDO:0015016
OMIM®: 617315

Definition

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). [from OMIM]

Additional description

From MedlinePlus Genetics
Nearly half of the individuals affected with Peters anomaly have low vision early in life and about a quarter are legally blind. Due to a lack of visual stimulation, some individuals develop "lazy eye" (amblyopia). Peters anomaly is often associated with other eye problems, such as increased pressure within the eye (glaucoma), clouding of the lens (cataract), and unusually small eyeballs (microphthalmia). In most cases, Peters anomaly is bilateral, which means that it affects both eyes, although the level of vision impairment may be different in each eye. These individuals may have eyes that do not point in the same direction (strabismus). In some people with Peters anomaly, corneal clouding improves over time leading to improved vision.

There are two types of Peters anomaly, which are distinguished by their signs and symptoms. Peters anomaly type I is characterized by an incomplete separation of the cornea and iris and mild to moderate corneal opacity. Type II is characterized by an incomplete separation of the cornea and lens and severe corneal opacity that may involve the entire cornea.

Peters anomaly is characterized by eye problems that occur in an area at the front part of the eye known as the anterior segment. The anterior segment consists of structures including the lens, the colored part (iris) of the eye, and the clear covering of the eye (cornea). During development of the eye, the elements of the anterior segment form separate structures. However, in Peters anomaly, development of the anterior segment is abnormal, leading to incomplete separation of the cornea from the iris or the lens. As a result, the cornea is cloudy (opaque), which causes blurred vision. The opaque area (opacity) of the cornea varies in size and intensity from a small, faint streak to a large, white cloudy area that covers the front surface of the eye. Additionally, the location of the opacity varies; the cloudiness may be at the center of the cornea or off-center. Large, centrally located opacities tend to cause poorer vision than smaller, off-center ones.  https://medlineplus.gov/genetics/condition/peters-anomaly

Clinical features

From HPO
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.
Corneal neovascularization
MedGen UID:
43103
Concept ID:
C0085109
Disease or Syndrome
Ingrowth of new blood vessels into the cornea.
Posterior synechiae of the anterior chamber
MedGen UID:
488784
Concept ID:
C0152253
Disease or Syndrome
Adhesions between the iris and the lens.
Glaucoma of childhood
MedGen UID:
453382
Concept ID:
C2981140
Disease or Syndrome
Structural abnormalities that impede fluid drainage in the eye increase ocular pressure. These abnormalities may be present at birth and usually become apparent during the first year of life. Such structural abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 3 without other associated abnormalities, it is called primary congenital glaucoma.\n\nUsually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.\n\nIn most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.\n\nOther individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.\n\nGlaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term "early-onset glaucoma" may be used when the disorder appears before the age of 40.
Abnormal Descemet membrane morphology
MedGen UID:
868919
Concept ID:
C4023330
Anatomical Abnormality
Abnormality of Descemet's membrane, which is the basement membrane of the corneal endothelium.

Professional guidelines

PubMed

Zhou L, Wang X, An J, Zhang Y, He M, Tang L
Exp Eye Res 2023 Jan;226:109307. Epub 2022 Nov 25 doi: 10.1016/j.exer.2022.109307. PMID: 36442680
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Recent clinical studies

Etiology

Vanathi M, Raj N, Kusumesh R, Aron N, Gupta N, Tandon R
Surv Ophthalmol 2022 Nov-Dec;67(6):1647-1684. Epub 2022 Jul 30 doi: 10.1016/j.survophthal.2022.07.010. PMID: 35918016
Seifi M, Walter MA
Clin Genet 2018 Jun;93(6):1123-1130. Epub 2018 Jan 25 doi: 10.1111/cge.13148. PMID: 28972279
de Paula Freitas B, Ventura CV, Maia M, Belfort R Jr
Curr Opin Ophthalmol 2017 Nov;28(6):595-599. doi: 10.1097/ICU.0000000000000420. PMID: 28795959
Ramappa M, Chaurasia S, Chakrabarti S, Kaur I
J AAPOS 2014 Oct;18(5):427-32. Epub 2014 Oct 21 doi: 10.1016/j.jaapos.2014.05.011. PMID: 25439301
Bollini G, Docquier PL, Viehweger E, Launay F, Jouve JL
J Bone Joint Surg Am 2006 May;88(5):1043-52. doi: 10.2106/JBJS.E.00530. PMID: 16651579

Diagnosis

Mansoori T
Indian J Ophthalmol 2023 Jun;71(6):2630-2631. doi: 10.4103/IJO.IJO_153_23. PMID: 37322722Free PMC Article
Seifi M, Walter MA
Clin Genet 2018 Jun;93(6):1123-1130. Epub 2018 Jan 25 doi: 10.1111/cge.13148. PMID: 28972279
de Paula Freitas B, Ventura CV, Maia M, Belfort R Jr
Curr Opin Ophthalmol 2017 Nov;28(6):595-599. doi: 10.1097/ICU.0000000000000420. PMID: 28795959
Ramappa M, Chaurasia S, Chakrabarti S, Kaur I
J AAPOS 2014 Oct;18(5):427-32. Epub 2014 Oct 21 doi: 10.1016/j.jaapos.2014.05.011. PMID: 25439301
Dureau P, Attie-Bitach T, Salomon R, Bettembourg O, Amiel J, Uteza Y, Dufier JL
Ophthalmology 2001 Oct;108(10):1912-6. doi: 10.1016/s0161-6420(01)00722-9. PMID: 11581073

Therapy

Mori R, Macaya F, Giacobbe F, Salinas P, Rolfo C, Porto I, Gonzalo N, Varbella F, Cerrato E, Escaned J
Int J Cardiol 2023 Apr 15;377:22-25. Epub 2023 Jan 27 doi: 10.1016/j.ijcard.2023.01.067. PMID: 36716971
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Eur J Ophthalmol 2022 Sep;32(5):2920-2927. Epub 2022 Jan 10 doi: 10.1177/11206721211073208. PMID: 35001688Free PMC Article
Güemes Villahoz N, Morales Fernández L, Narváez Palazón C, Moreno MN, Gómez de Liaño Sánchez MR
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JDR Clin Trans Res 2020 Oct;5(4):319-331. Epub 2019 Dec 20 doi: 10.1177/2380084419887336. PMID: 31860800
Alshamrani AA, Al-Shahwan S
J Glaucoma 2018 Jun;27(6):e110-e112. doi: 10.1097/IJG.0000000000000946. PMID: 29557836

Prognosis

Vanathi M, Raj N, Kusumesh R, Aron N, Gupta N, Tandon R
Surv Ophthalmol 2022 Nov-Dec;67(6):1647-1684. Epub 2022 Jul 30 doi: 10.1016/j.survophthal.2022.07.010. PMID: 35918016
Magan T, Tanner A, Fajardo-Sanchez J, Lim KS, Goyal S, Rodrigues I, Amaya L, Trikha S, Kulkarni A, Hammond C, Lascaratos G, Yu-Wai-Man C
Eur J Ophthalmol 2022 Sep;32(5):2920-2927. Epub 2022 Jan 10 doi: 10.1177/11206721211073208. PMID: 35001688Free PMC Article
Burdon KP
Clin Exp Ophthalmol 2021 Aug;49(6):615-625. Epub 2021 Jul 23 doi: 10.1111/ceo.13970. PMID: 34231298
Kokotas H, Petersen MB
Clin Genet 2010 May;77(5):409-20. Epub 2010 Jan 6 doi: 10.1111/j.1399-0004.2010.01372.x. PMID: 20132240
Bollini G, Docquier PL, Viehweger E, Launay F, Jouve JL
J Bone Joint Surg Am 2006 May;88(5):1043-52. doi: 10.2106/JBJS.E.00530. PMID: 16651579

Clinical prediction guides

Lee CY, Wu CL, Chang HK, Wu JC, Huang WC, Cheng H, Tu TH
Clin Neurol Neurosurg 2021 Oct;209:106934. Epub 2021 Sep 3 doi: 10.1016/j.clineuro.2021.106934. PMID: 34543827
Alshamrani AA, Al-Shahwan S
J Glaucoma 2018 Jun;27(6):e110-e112. doi: 10.1097/IJG.0000000000000946. PMID: 29557836
de Paula Freitas B, Ventura CV, Maia M, Belfort R Jr
Curr Opin Ophthalmol 2017 Nov;28(6):595-599. doi: 10.1097/ICU.0000000000000420. PMID: 28795959
D'Antoni AV, Donaldson OI, Schmidt C, Macchi V, De Caro R, Oskouian RJ, Loukas M, Shane Tubbs R
Childs Nerv Syst 2017 Jun;33(6):909-914. Epub 2017 Apr 10 doi: 10.1007/s00381-017-3406-1. PMID: 28396968
Kokotas H, Petersen MB
Clin Genet 2010 May;77(5):409-20. Epub 2010 Jan 6 doi: 10.1111/j.1399-0004.2010.01372.x. PMID: 20132240

Recent systematic reviews

Mahmoud A, Pomar L, Lambert V, Picone O, Hcini N
Ocul Immunol Inflamm 2024 Nov;32(9):2217-2227. Epub 2024 Feb 13 doi: 10.1080/09273948.2024.2314086. PMID: 38350011
Le H, Jin E, Jewell A, Jackson-Cook C, Haskell GT, Couser N
Am J Med Genet A 2023 Jun;191(6):1639-1645. Epub 2023 Mar 20 doi: 10.1002/ajmg.a.63186. PMID: 36941760
Merdler-Rabinowicz R, Prat D, Pode-Shakked B, Abel G, Chorin O, Somech R, Raas-Rothschild A
Eur J Med Genet 2021 Jun;64(6):104210. Epub 2021 Mar 30 doi: 10.1016/j.ejmg.2021.104210. PMID: 33794347
Rakhshan V, Rakhshan A
Int Orthod 2016 Sep;14(3):273-94. Epub 2016 Aug 10 doi: 10.1016/j.ortho.2016.07.016. PMID: 27522615
Evangelou P, Meixensberger J, Bernhard M, Hirsch W, Kiess W, Merkenschlager A, Nestler U, Preuss M
Childs Nerv Syst 2013 Apr;29(4):657-64. Epub 2012 Dec 9 doi: 10.1007/s00381-012-1990-7. PMID: 23224408

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