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Genetics Home Reference: your guide to understanding genetic conditions
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Microphthalmia

Reviewed November 2011

What is microphthalmia?

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.

People 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.

People 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.

Between 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.

How common is microphthalmia?

Microphthalmia occurs in approximately 1 in 10,000 individuals.

What genes are related to microphthalmia?

Microphthalmia may be caused by changes in many genes involved in the early development of the eye, most of which have not been identified. The condition may also result from a chromosomal abnormality affecting one or more genes. Most genetic changes associated with isolated microphthalmia have been identified only in very small numbers of affected individuals.

Microphthalmia may also be caused by environmental factors that affect early development, such as a shortage of certain vitamins during pregnancy, radiation, infections such as rubella, or exposure to substances that cause birth defects (teratogens).

Related Gene(s)

Changes in these genes are associated with microphthalmia.

  • BCOR
  • BMP4
  • GDF3
  • GDF6
  • MFRP
  • OTX2
  • PAX6
  • PRSS56
  • RAX
  • SHH
  • SIX6
  • SOX2
  • STRA6
  • VSX2

How do people inherit microphthalmia?

Isolated microphthalmia is sometimes inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In some cases, parents of affected individuals have less severe eye abnormalities.

When microphthalmia occurs as a feature of a genetic syndrome or chromosomal abnormality, it may cluster in families according to the inheritance pattern for that condition, which may be autosomal recessive or other patterns.

Often microphthalmia is not inherited, and there is only one affected individual in a family.

Where can I find information about diagnosis or management of microphthalmia?

These resources address the diagnosis or management of microphthalmia and may include treatment providers.

  • Gene Review: Anophthalmia / Microphthalmia Overview (http://www.ncbi.nlm.nih.gov/books/NBK1378)
  • Genetic Testing Registry: Cataract, congenital, with microphthalmia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834919)
  • Genetic Testing Registry: Cataract, microphthalmia and nystagmus (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1859311)
  • Genetic Testing Registry: Microphthalmia, isolated, with coloboma 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1845877)
  • Genetic Testing Registry: Microphthalmia, isolated, with coloboma 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1854018)
  • Genetic Testing Registry: Microphthalmia, isolated, with coloboma 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1864721)
  • Genetic Testing Registry: Microphthalmia, isolated, with coloboma 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1855053)
  • Genetic Testing Registry: Microphthalmia, isolated, with coloboma 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1968843)
  • Genetic Testing Registry: Microphthalmia, isolated, with coloboma 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150968)
  • Genetic Testing Registry: Microphthalmia, isolated, with corectopia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834918)
  • Genetic Testing Registry: Microphthalmia, isolated 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1855052)
  • Genetic Testing Registry: Microphthalmia, isolated 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1864720)
  • Genetic Testing Registry: Microphthalmia, isolated 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1970237)
  • Genetic Testing Registry: Microphthalmia, isolated 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2751307)
  • Genetic Testing Registry: Microphthalmia, isolated 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1970236)
  • Genetic Testing Registry: Microphthalmia, isolated 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150757)
  • Genetic Testing Registry: Microphthalmia, isolated 7 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150969)
  • Genetic Testing Registry: Microphthalmia, isolated 8 (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN168068)
  • Genetic Testing Registry: Microphthalmos (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0026010)

You might also find information on the diagnosis or management of microphthalmia in Educational resources (http://www.ghr.nlm.nih.gov/condition/microphthalmia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/microphthalmia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about microphthalmia?

You may find the following resources about microphthalmia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for microphthalmia?

  • microphthalmos

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about microphthalmia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding microphthalmia?

anophthalmia ; autosomal ; autosomal recessive ; cataract ; cell ; choroid ; cornea ; gene ; inheritance ; inheritance pattern ; inherited ; palpebral fissure ; posterior ; radiation ; recessive ; retina ; syndrome ; teratogens ; tissue ; vitamins

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Asai-Coakwell M, French CR, Ye M, Garcha K, Bigot K, Perera AG, Staehling-Hampton K, Mema SC, Chanda B, Mushegian A, Bamforth S, Doschak MR, Li G, Dobbs MB, Giampietro PF, Brooks BP, Vijayalakshmi P, Sauvé Y, Abitbol M, Sundaresan P, van Heyningen V, Pourquié O, Underhill TM, Waskiewicz AJ, Lehmann OJ. Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Hum Mol Genet. 2009 Mar 15;18(6):1110-21. doi: 10.1093/hmg/ddp008. Epub 2009 Jan 6. (http://www.ncbi.nlm.nih.gov/pubmed/19129173?dopt=Abstract)
  • Gal A, Rau I, El Matri L, Kreienkamp HJ, Fehr S, Baklouti K, Chouchane I, Li Y, Rehbein M, Fuchs J, Fledelius HC, Vilhelmsen K, Schorderet DF, Munier FL, Ostergaard E, Thompson DA, Rosenberg T. Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease. Am J Hum Genet. 2011 Mar 11;88(3):382-90. doi: 10.1016/j.ajhg.2011.02.006. (http://www.ncbi.nlm.nih.gov/pubmed/21397065?dopt=Abstract)
  • Gallardo ME, Rodríguez De Córdoba S, Schneider AS, Dwyer MA, Ayuso C, Bovolenta P. Analysis of the developmental SIX6 homeobox gene in patients with anophthalmia/microphthalmia. Am J Med Genet A. 2004 Aug 15;129A(1):92-4. (http://www.ncbi.nlm.nih.gov/pubmed/15266624?dopt=Abstract)
  • Gonzalez-Rodriguez J, Pelcastre EL, Tovilla-Canales JL, Garcia-Ortiz JE, Amato-Almanza M, Villanueva-Mendoza C, Espinosa-Mattar Z, Zenteno JC. Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated microphthalmia-anophthalmia-coloboma (MAC) spectrum cases. Br J Ophthalmol. 2010 Aug;94(8):1100-4. doi: 10.1136/bjo.2009.173500. Epub 2010 May 21. (http://www.ncbi.nlm.nih.gov/pubmed/20494911?dopt=Abstract)
  • Iseri SU, Wyatt AW, Nürnberg G, Kluck C, Nürnberg P, Holder GE, Blair E, Salt A, Ragge NK. Use of genome-wide SNP homozygosity mapping in small pedigrees to identify new mutations in VSX2 causing recessive microphthalmia and a semidominant inner retinal dystrophy. Hum Genet. 2010 Jul;128(1):51-60. doi: 10.1007/s00439-010-0823-6. Epub 2010 Apr 23. (http://www.ncbi.nlm.nih.gov/pubmed/20414678?dopt=Abstract)
  • Lequeux L, Rio M, Vigouroux A, Titeux M, Etchevers H, Malecaze F, Chassaing N, Calvas P. Confirmation of RAX gene involvement in human anophthalmia. Clin Genet. 2008 Oct;74(4):392-5. doi: 10.1111/j.1399-0004.2008.01078.x. Epub 2008 Sep 9. (http://www.ncbi.nlm.nih.gov/pubmed/18783408?dopt=Abstract)
  • Morrison D, FitzPatrick D, Hanson I, Williamson K, van Heyningen V, Fleck B, Jones I, Chalmers J, Campbell H. National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: investigation of genetic aetiology. J Med Genet. 2002 Jan;39(1):16-22. (http://www.ncbi.nlm.nih.gov/pubmed/11826019?dopt=Abstract)
  • Ragge NK, Subak-Sharpe ID, Collin JR. A practical guide to the management of anophthalmia and microphthalmia. Eye (Lond). 2007 Oct;21(10):1290-300. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17914432?dopt=Abstract)
  • Schimmenti LA, de la Cruz J, Lewis RA, Karkera JD, Manligas GS, Roessler E, Muenke M. Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia. Am J Med Genet A. 2003 Jan 30;116A(3):215-21. (http://www.ncbi.nlm.nih.gov/pubmed/12503095?dopt=Abstract)
  • Shah SP, Taylor AE, Sowden JC, Ragge NK, Russell-Eggitt I, Rahi JS, Gilbert CE; Surveillance of Eye Anomalies (SEA-UK) Special Interest Group. Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. Invest Ophthalmol Vis Sci. 2011 Feb 1;52(1):558-64. doi: 10.1167/iovs.10-5263. (http://www.ncbi.nlm.nih.gov/pubmed/20574025?dopt=Abstract)
  • Verma AS, Fitzpatrick DR. Anophthalmia and microphthalmia. Orphanet J Rare Dis. 2007 Nov 26;2:47. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18039390?dopt=Abstract)
  • Ye M, Berry-Wynne KM, Asai-Coakwell M, Sundaresan P, Footz T, French CR, Abitbol M, Fleisch VC, Corbett N, Allison WT, Drummond G, Walter MA, Underhill TM, Waskiewicz AJ, Lehmann OJ. Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. Hum Mol Genet. 2010 Jan 15;19(2):287-98. doi: 10.1093/hmg/ddp496. Epub 2009 Oct 28. (http://www.ncbi.nlm.nih.gov/pubmed/19864492?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2011
Published: October 27, 2014