Anophthalmia/Microphthalmia/Coloboma (MAC)

Abstract

Microphthalmia/anophthalmia/coloboma (MAC) are congenital anomalies of the eye that form a continuum from coloboma at the mild end to anophthalmia at the severe end. When we refer to anophthalmia, usually we mean clinical anophthalmia where there is so little eye tissue that it is not visible, but it is in fact severe microphthalmia. On magnetic resonance imaging (MRI) of the orbit, rudimentary tissue might be visible and in some cases, you can see a hypoplastic optic nerve. There may be eye adnexa present like tear ducts. Microphthalmia can be very variable from clinical anophthalmia to slightly small eye. Ultrasound of the orbit can help determine the actual size and structure of the eye.

MAC is genetically heterogeneous. This means that there are many different causes. MAC may be associated with other anomalies (syndromal) or alone (nonsyndromal). There are many developmental genes that can be implicated in these eye anomalies.

Key Concepts

  • Anophthalmia is a very small, abnormal eye and often has no useful vision.
  • Microphthalmia is more variable and can even be a small and normal looking eye.
  • Coloboma develops when the optic fissure does not close fully as the eye develops in the embryo, vision loss is variable.
  • Genetic causes of MAC can be due to mutations in many genes or chromosomal trisomies, deletions/duplications that include eye development genes.
  • Some teratogens such as alcohol can cause MAC.
  • MAC can occur in one eye or both the eyes and each eye can have a different problem.

Keywords: anophthalmia; microphthalmia; coloboma; genes; mutations; variability; penetrance

Figure 1. Embryology of the eye.
Figure 2. Coloboma of the iris.
Figure 3. The nucleus of the cell contains chromosomes made up of strands of DNA. Reproduced with permission (2013) © Encyclopaedia Britannica Inc.
Figure 4. (a) Autosomal dominant inheritance. (b) Autosomal recessive inheritance.
Figure 5. (a) Patient has unilateral microphthalmia. (b) Patient has bilateral anophthalmia. Reproduced from www.anophthalmia.org.
close

References

Srour M , Caron V , Pearson T , et al. (2016) Gain‐of‐Function Mutations in RARB Cause Intellectual Disability with Progressive Motor Impairment. Hum Mutat 37: 786–793. https://www.ncbi.nlm.nih.gov/pubmed/27120018

Verma A and FitzPatrick D (2007) Anophthalmia and microphthalmia. Orphanet Journal of Rare Diseases 2: 47.

Further Reading

Ashkenazi‐Hoffnung L , Lebenthal Y , Wyatt AW , et al. (2010) A novel loss‐of‐function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency. Human Genetics 127 (6): 721–729.

Bakrania P , Efthymiou M , Klein JC , et al. (2008) Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. American Journal of Human Genetics 82 (2): 304–319.

Chassaing N , Causse A , Vigouroux A , et al. (2014) Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia. Clinical Genetics 86 (4): 326–334.

Chou CM , Nelson C , Tarle SA , et al. (2015) Biochemical basis for dominant inheritance, variable penetrance, and maternal effects in RBP4 congenital eye disease. Cell 161 (3): 634–646.

GeneReviews® – NCBI Bookshelf.

Gerth‐Kahlert C , Williamson K , Ansari M , et al. (2013) Clinical and mutation analysis of 51 probands with anophthalmia and/or severe microphthalmia from a single center. Molecular Genetics & Genomic Medicine 1 (1): 15–31.

Glaser T , Jepeal L , Edwards JG , et al. (1994) PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nature Genetics 7 (4): 463–471.

Horn D , Chyrek M , Kleier S , et al. (2005) Novel mutations in BCOR in three patients with oculo‐facio‐cardio‐dental syndrome, but none in lenz microphthalmia syndrome. European Journal of Human Genetics 13 (5): 563–569.

Jimenez NL , Flannick J , Yahyavi M , et al. (2011) Targeted 'next‐generation' sequencing in anophthalmia and microphthalmia patients confirms SOX2, OTX2 and FOXE3 mutations. BMC Medical Genetics 12: 172. DOI: 10.1186/1471-2350-12-172.

National Center for Biotechnology Information by RA Pagon – 2015.

Ng D , Thakker N , Corcoran CM , et al. (2004) Oculofaciocardiodental and lenz microphthalmia syndromes result from distinct classes of mutations in BCOR. Nature Genetics 36 (4): 411–416.

Reis LM , Tyler RC , Schneider A , Bardakjian T and Semina EV (2010) Examination of SOX2 in variable ocular conditions identifies a recurrent deletion in microphthalmia and lack of mutations in other phenotypes. Molecular Vision 16: 768–773.

Reis LM , Tyler RC , Schneider A , et al. (2010) FOXE3 plays a significant role in autosomal recessive microphthalmia. American Journal of Medical Genetics Part A 152A (3): 582–590.

Schilter KF , Schneider A , Bardakjian T , et al. (2011) OTX2 microphthalmia syndrome: four novel mutations and delineation of a phenotype. Clinical Genetics 79 (2): 158–168.

Shah SP , Taylor AE , Sowden JC , et al. (2011) Anophthalmos, microphthalmos, and typical coloboma in the united kingdom: a prospective study of incidence and risk. Investigative Ophthalmology & Visual Science 52 (1): 558–564.

Shaw‐Smith C (2006) Oesophageal atresia, tracheo‐oesophageal fistula, and the VACTERL association: review of genetics and epidemiology. Journal of Medical Genetics 43 (7): 545–554.

Slavotinek AM (2011) Eye development genes and known syndromes. Molecular Genetics and Metabolism 104 (4): 448–456.

Slavotinek AM , Garcia ST , Chandratillake G , et al. (2015) Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. Clinical Genetics 88 (5): 468–473.

Other Resources

www.anophthalmia.org

www.macs.org.uk

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Schneider, Adele, and Kopinsky, Sarina(Mar 2017) Anophthalmia/Microphthalmia/Coloboma (MAC). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026852]