U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from PMC

Coloboma, ocular, autosomal dominant(MCOPCB12)

MedGen UID:
1859952
Concept ID:
C5886785
Disease or Syndrome
Synonyms: MCOPCB12; Microphthalmia/coloboma 12
 
Gene (location): PAX6 (11p13)
 
Monarch Initiative: MONDO:0007350
OMIM®: 120200

Definition

Coloboma is an ocular birth defect resulting from abnormal development of the eye during embryogenesis. It is defined as a congenital defect in any ocular tissue, typically presenting as absent tissue or a gap, at a site consistent with aberrant closure of the optic fissure. Failure of fusion can lead to coloboma of one or multiple regions of the inferior portion of the eye affecting any part of the globe traversed by the fissure, from the iris to the optic nerve, including the ciliary body, retina, and choroid. Coloboma is also frequently associated with small (microphthalmic) or absent (anophthalmic) eyes as part of an interrelated spectrum of developmental eye anomalies, and can affect either one or both eyes (summary by Kelberman et al., 2014). Microphthalmia/coloboma-12 (MCOPCB12) is characterized by inter- and intrafamilial variability. In addition to microphthalmia and coloboma, other ocular anomalies include iris hypoplasia, aphakia or small lens, lens subluxation, congenital cataract, microcornea, and sclerocornea. Some patients also exhibit neurodevelopmental anomalies (Deml et al., 2016; Williamson et al., 2020). For a discussion of genetic heterogeneity of colobomatous microphthalmia, see MCOPCB1 (300345). [from OMIM]

Clinical features

From HPO
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Coloboma of optic nerve
MedGen UID:
57832
Concept ID:
C0155299
Congenital Abnormality
A cleft of the optic nerve that extends inferiorly.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Chorioretinal coloboma
MedGen UID:
66820
Concept ID:
C0240896
Congenital Abnormality
Absence of a region of the retina, retinal pigment epithelium, and choroid.
Persistent hyperplastic primary vitreous
MedGen UID:
120583
Concept ID:
C0266568
Congenital Abnormality
Persistence of the hyaloid artery, which is the embryonic artery that runs from the optic disc to the posterior lens capsule may persist; the site of attachment may form an opacity. The hyaloid artery is a branch of the ophthalmic artery, and usually regresses completely before birth. This features results from a failure of regression of the hyaloid vessel, which supplies the primary vitreous during embryogenesis and normally regresses in the third trimester of pregnancy, leading to a particular form of posterior cataract.
Irido-corneo-trabecular dysgenesis
MedGen UID:
91031
Concept ID:
C0344559
Congenital Abnormality
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).
Morning glory syndrome
MedGen UID:
767635
Concept ID:
C3554721
Congenital Abnormality
An abnormality of the optic nerve in which the optic nerve is large and funneled and displays a conical excavation of the optic disc. The optic disc appears dysplastic.
Optic nerve aplasia
MedGen UID:
866737
Concept ID:
C4021084
Finding
Congenital absence of the optic nerve.

Professional guidelines

PubMed

Mustillo PJ, Sullivan KE, Chinn IK, Notarangelo LD, Haddad E, Davies EG, de la Morena MT, Hartog N, Yu JE, Hernandez-Trujillo VP, Ip W, Franco J, Gambineri E, Hickey SE, Varga E, Markert ML
J Clin Immunol 2023 Feb;43(2):247-270. Epub 2023 Jan 17 doi: 10.1007/s10875-022-01418-y. PMID: 36648576Free PMC Article
Marszałek-Kruk BA, Wójcicki P, Dowgierd K, Śmigiel R
Genes (Basel) 2021 Sep 9;12(9) doi: 10.3390/genes12091392. PMID: 34573374Free PMC Article
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

Mustillo PJ, Sullivan KE, Chinn IK, Notarangelo LD, Haddad E, Davies EG, de la Morena MT, Hartog N, Yu JE, Hernandez-Trujillo VP, Ip W, Franco J, Gambineri E, Hickey SE, Varga E, Markert ML
J Clin Immunol 2023 Feb;43(2):247-270. Epub 2023 Jan 17 doi: 10.1007/s10875-022-01418-y. PMID: 36648576Free PMC Article
Lingam G, Sen AC, Lingam V, Bhende M, Padhi TR, Xinyi S
Eye (Lond) 2021 Aug;35(8):2086-2109. Epub 2021 Mar 21 doi: 10.1038/s41433-021-01501-5. PMID: 33746210Free PMC Article
Blake KD, Prasad C
Orphanet J Rare Dis 2006 Sep 7;1:34. doi: 10.1186/1750-1172-1-34. PMID: 16959034Free PMC Article
Friede H
Acta Odontol Scand 1995 Jun;53(3):203-9. doi: 10.3109/00016359509005973. PMID: 7572098
Pagon RA
Surv Ophthalmol 1981 Jan-Feb;25(4):223-36. doi: 10.1016/0039-6257(81)90092-8. PMID: 6782689

Diagnosis

Demetrio R, Ruiz-Sancho D, Rolón N, del Campo A, Blanco C
Arch Soc Esp Oftalmol 2015 Mar;90(3):142-3. Epub 2014 Nov 15 doi: 10.1016/j.oftal.2014.02.012. PMID: 25443185
Schimmenti LA
Eur J Hum Genet 2011 Dec;19(12):1207-12. Epub 2011 Jun 8 doi: 10.1038/ejhg.2011.102. PMID: 21654726Free PMC Article
Bloch-Zupan A, Goodman JR
Orphanet J Rare Dis 2006 Mar 21;1:5. doi: 10.1186/1750-1172-1-5. PMID: 16722606Free PMC Article
Onwochei BC, Simon JW, Bateman JB, Couture KC, Mir E
Surv Ophthalmol 2000 Nov-Dec;45(3):175-94. doi: 10.1016/s0039-6257(00)00151-x. PMID: 11094243
Sowka J, Aoun P
Optom Vis Sci 1999 Sep;76(9):618-23. doi: 10.1097/00006324-199909000-00018. PMID: 10498002

Therapy

Choudhary S, Katoch D, Pandav SS, Kaushik S
J Postgrad Med 2023 Jan-Mar;69(1):41-42. doi: 10.4103/jpgm.jpgm_1145_21. PMID: 35708396Free PMC Article
Angmo D, Dewan L, Behera A, Gagrani M
Eur J Ophthalmol 2021 Mar;31(2):NP116-NP118. Epub 2019 Jul 25 doi: 10.1177/1120672119866106. PMID: 31342778
Blake KD, Prasad C
Orphanet J Rare Dis 2006 Sep 7;1:34. doi: 10.1186/1750-1172-1-34. PMID: 16959034Free PMC Article
Peyman GA, Schulman JA, Sullivan B
Surv Ophthalmol 1995 Mar-Apr;39(5):375-95. doi: 10.1016/s0039-6257(05)80093-1. PMID: 7604361
Poswillo DE
Proc R Soc Med 1974 May;67(5):343-9. PMID: 4835278Free PMC Article

Prognosis

Ernst J, Medsinge A, Scanga HL, Hiasat J, Moore W, Ali A, Levin AV, Stahl ED, Nischal KK
J AAPOS 2022 Feb;26(1):4.e1-4.e5. Epub 2022 Jan 17 doi: 10.1016/j.jaapos.2021.09.008. PMID: 35051625
Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):13. doi: 10.1167/iovs.62.2.13. PMID: 33576794Free PMC Article
Demetrio R, Ruiz-Sancho D, Rolón N, del Campo A, Blanco C
Arch Soc Esp Oftalmol 2015 Mar;90(3):142-3. Epub 2014 Nov 15 doi: 10.1016/j.oftal.2014.02.012. PMID: 25443185
Onwochei BC, Simon JW, Bateman JB, Couture KC, Mir E
Surv Ophthalmol 2000 Nov-Dec;45(3):175-94. doi: 10.1016/s0039-6257(00)00151-x. PMID: 11094243
Pagon RA
Surv Ophthalmol 1981 Jan-Feb;25(4):223-36. doi: 10.1016/0039-6257(81)90092-8. PMID: 6782689

Clinical prediction guides

Kalinousky AJ, Luperchio TR, Schrode KM, Harris JR, Zhang L, DeLeon VB, Fahrner JA, Lauer AM, Bjornsson HT
Genes (Basel) 2023 Dec 28;15(1) doi: 10.3390/genes15010048. PMID: 38254937Free PMC Article
Smallwood K, Watt KEN, Ide S, Baltrunaite K, Brunswick C, Inskeep K, Capannari C, Adam MP, Begtrup A, Bertola DR, Demmer L, Demo E, Devinsky O, Gallagher ER, Guillen Sacoto MJ, Jech R, Keren B, Kussmann J, Ladda R, Lansdon LA, Lunke S, Mardy A, McWalters K, Person R, Raiti L, Saitoh N, Saunders CJ, Schnur R, Skorvanek M, Sell SL, Slavotinek A, Sullivan BR, Stark Z, Symonds JD, Wenger T, Weber S, Whalen S, White SM, Winkelmann J, Zech M, Zeidler S, Maeshima K, Stottmann RW, Trainor PA, Weaver KN
Am J Hum Genet 2023 May 4;110(5):809-825. Epub 2023 Apr 18 doi: 10.1016/j.ajhg.2023.03.014. PMID: 37075751Free PMC Article
Demetrio R, Ruiz-Sancho D, Rolón N, del Campo A, Blanco C
Arch Soc Esp Oftalmol 2015 Mar;90(3):142-3. Epub 2014 Nov 15 doi: 10.1016/j.oftal.2014.02.012. PMID: 25443185
Pian D, Ferrucci S, Anderson SF, Wu C
Optom Vis Sci 2003 Aug;80(8):556-63. doi: 10.1097/00006324-200308000-00008. PMID: 12917574
Warburg M
J Med Genet 1993 Aug;30(8):664-9. doi: 10.1136/jmg.30.8.664. PMID: 8411053Free PMC Article

Recent systematic reviews

Polito MV, Ferraioli M, Nocilla A, Coppola G, D'Auria F, Marzano A, Barnabei L, Malinconico M, Bossone E, Ferrara F
Monaldi Arch Chest Dis 2023 Sep 6;94(3) doi: 10.4081/monaldi.2023.2661. PMID: 37675914
Thomas AT, Waite J, Williams CA, Kirk J, Oliver C, Richards C
J Neurodev Disord 2022 Aug 31;14(1):49. doi: 10.1186/s11689-022-09459-5. PMID: 36045324Free PMC Article
Hou X, Guo Y, Liu J, Li S, Fan W, Lin M, Rokohl AC, Heindl LM
Curr Eye Res 2021 Jul;46(7):913-918. Epub 2021 Jan 22 doi: 10.1080/02713683.2020.1853779. PMID: 33478254
Rooijers W, Caron CJJM, Loudon SE, Padwa BL, Dunaway DJ, Forrest CR, Koudstaal MJ
Int J Oral Maxillofac Surg 2020 Sep;49(9):1107-1114. Epub 2020 Mar 23 doi: 10.1016/j.ijom.2020.03.003. PMID: 32217034
Plomp RG, van Lieshout MJS, Joosten KFM, Wolvius EB, van der Schroeff MP, Versnel SL, Poublon RML, Mathijssen IMJ
Plast Reconstr Surg 2016 Jan;137(1):191-204. doi: 10.1097/PRS.0000000000001896. PMID: 26710023

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...