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Anterior segment dysgenesis(ASMD; ASOD)

MedGen UID:
350766
Concept ID:
C1862839
Congenital Abnormality
Synonym: Ocular anterior segment dysgenesis
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related genes: CPAMD8, PXDN, PITX3, PITX2, PAX6, FOXE3, FOXC1, CYP1B1
 
HPO: HP:0007700
Monarch Initiative: MONDO:0019503
OMIM®: 107250
OMIM® Phenotypic series: PS107250
Orphanet: ORPHA88632

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). Some patients with ASGD1 have been reported with the Peters anomaly subtype. In its simplest form, Peters anomaly involves a central corneal opacity, but it may also involve adherent iris strands. Some patients have keratolenticular content or cataract. The underlying defects in this form of congenital corneal opacity reside in the posterior stroma, Descemet membrane, and corneal endothelium. The disorder results from abnormal migration or function of neural crest cells and may include abnormalities of other anterior segment structures, such as the lens and iris (summary by Withers et al., 1999). [from OMIM]

Conditions with this feature

Anterior chamber cleavage disorder, cerebellar hypoplasia, hypothyroidism, and tracheal stenosis
MedGen UID:
316973
Concept ID:
C1832362
Disease or Syndrome
A rare, congenital malformation syndrome characterized by the association of anterior ocular chamber cleavage disorder with developmental delay, short stature and congenital hypothyroidism. Additional manifestations include cerebellar hypoplasia, tracheal stenosis, narrow external auditory meatus, and hip dislocation. There have been no further description in the literature since 1995.
Lambotte syndrome
MedGen UID:
343380
Concept ID:
C1855550
Disease or Syndrome
Brachydactyly, coloboma, and anterior segment dysgenesis
MedGen UID:
355321
Concept ID:
C1864901
Disease or Syndrome
Chromosome 6pter-p24 deletion syndrome
MedGen UID:
393396
Concept ID:
C2675486
Disease or Syndrome
Distal monosomy 6p is responsible for a distinct chromosome deletion syndrome with a recognizable clinical picture including intellectual deficit, ocular abnormalities, hearing loss, and facial dysmorphism.
Oculoauricular syndrome
MedGen UID:
393758
Concept ID:
C2677500
Disease or Syndrome
Oculoauricular syndrome (OCACS) is characterized by complex ocular anomalies, including congenital cataract, anterior segment dysgenesis, iris coloboma, and early-onset retinal dystrophy, and dysplastic ears with abnormal external ear cartilage (summary by Gillespie et al., 2015).
Anterior segment dysgenesis 7
MedGen UID:
462967
Concept ID:
C3151617
Disease or Syndrome
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). In sclerocornea there is congenital, nonprogressive corneal opacification that may be peripheral, sectoral, or central in location. Visual prognosis is related to the central corneal involvement. The cornea has a flat curvature. The majority of cases are bilateral (summary by Smith and Traboulsi, 2012). Isolated sclerocornea is caused by displacement of the limbal arcades and may be associated with cornea plana; in this condition, the anterior chamber is visible and the eye is not microphthalmic. In complex sclerocornea, however, corneal opacification is associated with microphthalmia, cataract, and/or infantile glaucoma. The central cornea is usually relatively clear, but the thickness is normal or increased, never reduced (summary by Nischal, 2007).
Craniofacial anomalies and anterior segment dysgenesis syndrome
MedGen UID:
481729
Concept ID:
C3280099
Disease or Syndrome
Microphthalmia, isolated, with coloboma 9
MedGen UID:
767506
Concept ID:
C3554592
Disease or Syndrome
MCOPCB9 is characterized by microphthalmia and coloboma (Aldahmesh et al., 2012). MCOPS15 is characterized by microphthalmia and/or coloboma, with developmental delay in which speech appears to be more severely affected than motor abilities. Additional ocular anomalies that have been observed include ptosis, keyhole-shaped pupils, microcornea, sclerocornea, and anterior segment dysgenesis (Chassaing et al., 2016; Stephen et al., 2018; Singh et al., 2019). For a discussion of genetic heterogeneity of colobomatous microphthalmia, see MCOPCB1 (300345). For a discussion of genetic heterogeneity of syndromic microphthalmia, see MCOPS1 (309800).
Anterior segment dysgenesis 1
MedGen UID:
1631197
Concept ID:
C4551992
Disease or Syndrome

Professional guidelines

PubMed

Ma AS, Grigg JR, Jamieson RV
Hum Genet 2019 Sep;138(8-9):899-915. Epub 2018 Sep 21 doi: 10.1007/s00439-018-1935-7. PMID: 30242500
Plaisancié J, Ragge NK, Dollfus H, Kaplan J, Lehalle D, Francannet C, Morin G, Colineaux H, Calvas P, Chassaing N
Clin Genet 2018 Apr;93(4):837-845. doi: 10.1111/cge.13177. PMID: 29136273
Verma IC, Paliwal P, Singh K
Indian J Pediatr 2018 Mar;85(3):228-236. Epub 2017 Oct 2 doi: 10.1007/s12098-017-2453-7. PMID: 28971364

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
Kaushik S, Dubey S, Choudhary S, Ratna R, Pandav SS, Khan AO
Indian J Ophthalmol 2022 Jul;70(7):2293-2303. doi: 10.4103/ijo.IJO_3223_21. PMID: 35791109Free PMC Article
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
Stahl ED
Int Ophthalmol Clin 2014 Summer;54(3):95-104. doi: 10.1097/IIO.0000000000000031. PMID: 24879108
Chang TC, Summers CG, Schimmenti LA, Grajewski AL
Br J Ophthalmol 2012 Mar;96(3):318-22. Epub 2011 Dec 23 doi: 10.1136/bjophthalmol-2011-300801. PMID: 22199394

Diagnosis

Kaushik S, Dubey S, Choudhary S, Ratna R, Pandav SS, Khan AO
Indian J Ophthalmol 2022 Jul;70(7):2293-2303. doi: 10.4103/ijo.IJO_3223_21. PMID: 35791109Free PMC Article
Kylat RI
Acta Paediatr 2022 May;111(5):948-951. Epub 2022 Jan 31 doi: 10.1111/apa.16260. PMID: 35044009
Thomas MG, Papageorgiou E, Kuht HJ, Gottlob I
Br J Ophthalmol 2022 May;106(5):593-599. Epub 2020 Nov 4 doi: 10.1136/bjophthalmol-2020-316348. PMID: 33148537
Verma IC, Paliwal P, Singh K
Indian J Pediatr 2018 Mar;85(3):228-236. Epub 2017 Oct 2 doi: 10.1007/s12098-017-2453-7. PMID: 28971364
Chang TC, Summers CG, Schimmenti LA, Grajewski AL
Br J Ophthalmol 2012 Mar;96(3):318-22. Epub 2011 Dec 23 doi: 10.1136/bjophthalmol-2011-300801. PMID: 22199394

Therapy

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
Güemes Villahoz N, Morales Fernández L, Narváez Palazón C, Moreno MN, Gómez de Liaño Sánchez MR
Arch Soc Esp Oftalmol (Engl Ed) 2021 Jun;96(6):293-298. Epub 2021 Jan 6 doi: 10.1016/j.oftale.2020.09.004. PMID: 34092283
Alshamrani AA, Al-Shahwan S
J Glaucoma 2018 Jun;27(6):e110-e112. doi: 10.1097/IJG.0000000000000946. PMID: 29557836
Young TL
Curr Opin Ophthalmol 2003 Oct;14(5):296-303. doi: 10.1097/00055735-200310000-00011. PMID: 14502058
Cook CS
Ophthalmic Paediatr Genet 1989 Mar;10(1):33-46. doi: 10.3109/13816818909083771. PMID: 2662095

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
Kylat RI
Acta Paediatr 2022 May;111(5):948-951. Epub 2022 Jan 31 doi: 10.1111/apa.16260. PMID: 35044009
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
Thomas MG, Papageorgiou E, Kuht HJ, Gottlob I
Br J Ophthalmol 2022 May;106(5):593-599. Epub 2020 Nov 4 doi: 10.1136/bjophthalmol-2020-316348. PMID: 33148537
Verma IC, Paliwal P, Singh K
Indian J Pediatr 2018 Mar;85(3):228-236. Epub 2017 Oct 2 doi: 10.1007/s12098-017-2453-7. PMID: 28971364

Clinical prediction guides

Sihota R, Mahalingam K, Maurya AK, Sharma A, Bukke AN, Dada T
Indian J Ophthalmol 2024 Mar 1;72(3):328-334. Epub 2023 Dec 15 doi: 10.4103/IJO.IJO_370_23. PMID: 38099353Free PMC Article
Guardia A, Fernández A, Seruggia D, Chotard V, Sánchez-Castillo C, Kutsyr O, Sánchez-Sáez X, Zurita E, Cantero M, Rebsam A, Cuenca N, Montoliu L
Invest Ophthalmol Vis Sci 2023 Oct 3;64(13):32. doi: 10.1167/iovs.64.13.32. PMID: 37862028Free PMC Article
Wang P, Wu P, Wang J, Zeng Y, Jiang Y, Wang Y, Li S, Xiao X, Zhang Q
Invest Ophthalmol Vis Sci 2023 Mar 1;64(3):19. doi: 10.1167/iovs.64.3.19. PMID: 36892533Free PMC Article
Thomas MG, Papageorgiou E, Kuht HJ, Gottlob I
Br J Ophthalmol 2022 May;106(5):593-599. Epub 2020 Nov 4 doi: 10.1136/bjophthalmol-2020-316348. PMID: 33148537
Alshamrani AA, Al-Shahwan S
J Glaucoma 2018 Jun;27(6):e110-e112. doi: 10.1097/IJG.0000000000000946. PMID: 29557836

Recent systematic reviews

Procopio R, Pulido JS, Gunton KB, Syed ZA, Lee D, Moster ML, Sergott R, Neidich JA, Reynolds MM
Genes (Basel) 2023 Mar 17;14(3) doi: 10.3390/genes14030738. PMID: 36981008Free PMC Article
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
Li X, Sun W, Xiao X, Fang L, Li S, Liu X, Zhang Q
Br J Ophthalmol 2022 Dec;106(12):1710-1715. Epub 2021 Jun 21 doi: 10.1136/bjophthalmol-2020-318668. PMID: 34154991

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