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SOX2 anophthalmia syndrome

Reviewed March 2009

What is SOX2 anophthalmia syndrome?

SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body.

People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). The term anophthalmia is often used interchangeably with severe microphthalmia because individuals with no visible eyeballs typically have some remaining eye tissue. These eye problems can cause significant vision loss. While both eyes are usually affected in SOX2 anophthalmia syndrome, one eye may be more affected than the other.

Individuals with SOX2 anophthalmia syndrome may also have seizures, brain abnormalities, slow growth, delayed development of motor skills (such as walking), and mild to severe learning disabilities. Some people with this condition are born with a blocked esophagus (esophageal atresia), which is often accompanied by an abnormal connection between the esophagus and the trachea (tracheoesophageal fistula). Genital abnormalities have been described in affected individuals, especially males. Male genital abnormalities include undescended testes (cryptorchidism) and an unusually small penis (micropenis).

How common is SOX2 anophthalmia syndrome?

SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. About 10 percent to 15 percent of people with anophthalmia in both eyes have SOX2 anophthalmia syndrome.

What genes are related to SOX2 anophthalmia syndrome?

Mutations in the SOX2 gene cause SOX2 anophthalmia syndrome. This gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. The SOX2 protein regulates the activity of other genes, especially those that are important for normal development of the eyes.

Mutations in the SOX2 gene prevent the production of functional SOX2 protein. The absence of this protein disrupts the activity of genes that are essential for the development of the eyes and other parts of the body. Abnormal development of these structures causes the signs and symptoms of SOX2 anophthalmia syndrome.

Related Gene(s)

Changes in this gene are associated with SOX2 anophthalmia syndrome.

  • SOX2

How do people inherit SOX2 anophthalmia syndrome?

SOX2 anophthalmia syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the SOX2 gene and occur in people with no history of the disorder in their family. In a small number of cases, people with SOX2 anophthalmia syndrome have inherited the altered gene from an unaffected parent who has a SOX2 mutation only in their sperm or egg cells. This phenomenon is called germline mosaicism.

Where can I find information about diagnosis or management of SOX2 anophthalmia syndrome?

These resources address the diagnosis or management of SOX2 anophthalmia syndrome and may include treatment providers.

  • Gene Review: SOX2-Related Eye Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1300)
  • Genetic Testing Registry: Microphthalmia syndromic 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1859773)
  • MedlinePlus Encyclopedia: Vision Problems (http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm)

You might also find information on the diagnosis or management of SOX2 anophthalmia syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/sox2-anophthalmia-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/sox2-anophthalmia-syndrome/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 SOX2 anophthalmia syndrome?

You may find the following resources about SOX2 anophthalmia syndrome 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 SOX2 anophthalmia syndrome?

  • AEG syndrome
  • Anophthalmia-esophageal-genital syndrome
  • SOX2-related eye disorders
  • syndromic microphthalmia 3

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 SOX2 anophthalmia syndrome?

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

What glossary definitions help with understanding SOX2 anophthalmia syndrome?

anophthalmia ; atresia ; autosomal ; autosomal dominant ; cell ; cryptorchidism ; disabilities ; egg ; embryonic ; esophagus ; fistula ; gene ; germline ; germline mosaicism ; inherited ; micropenis ; mosaicism ; motor ; mutation ; protein ; sperm ; syndrome ; testes ; tissue

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

References

  • Bakrania P, Robinson DO, Bunyan DJ, Salt A, Martin A, Crolla JA, Wyatt A, Fielder A, Ainsworth J, Moore A, Read S, Uddin J, Laws D, Pascuel-Salcedo D, Ayuso C, Allen L, Collin JR, Ragge NK. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. Br J Ophthalmol. 2007 Nov;91(11):1471-6. Epub 2007 May 23. (http://www.ncbi.nlm.nih.gov/pubmed/17522144?dopt=Abstract)
  • Gene Review: SOX2-Related Eye Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1300)
  • Kelberman D, de Castro SC, Huang S, Crolla JA, Palmer R, Gregory JW, Taylor D, Cavallo L, Faienza MF, Fischetto R, Achermann JC, Martinez-Barbera JP, Rizzoti K, Lovell-Badge R, Robinson IC, Gerrelli D, Dattani MT. SOX2 plays a critical role in the pituitary, forebrain, and eye during human embryonic development. J Clin Endocrinol Metab. 2008 May;93(5):1865-73. doi: 10.1210/jc.2007-2337. Epub 2008 Feb 19. (http://www.ncbi.nlm.nih.gov/pubmed/18285410?dopt=Abstract)
  • Schneider A, Bardakjian TM, Zhou J, Hughes N, Keep R, Dorsainville D, Kherani F, Katowitz J, Schimmenti LA, Hummel M, Fitzpatrick DR, Young TL. Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two affected daughters. Am J Med Genet A. 2008 Nov 1;146A(21):2794-8. doi: 10.1002/ajmg.a.32384. (http://www.ncbi.nlm.nih.gov/pubmed/18831064?dopt=Abstract)
  • Tziaferi V, Kelberman D, Dattani MT. The role of SOX2 in hypogonadotropic hypogonadism. Sex Dev. 2008;2(4-5):194-9. doi: 10.1159/000152035. Epub 2008 Nov 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18987493?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)
  • Williamson KA, Hever AM, Rainger J, Rogers RC, Magee A, Fiedler Z, Keng WT, Sharkey FH, McGill N, Hill CJ, Schneider A, Messina M, Turnpenny PD, Fantes JA, van Heyningen V, FitzPatrick DR. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Hum Mol Genet. 2006 May 1;15(9):1413-22. Epub 2006 Mar 16. Erratum in: Hum Mol Genet. 2006 Jun 15;15(12):2030. (http://www.ncbi.nlm.nih.gov/pubmed/16543359?dopt=Abstract)
  • Zhou J, Kherani F, Bardakjian TM, Katowitz J, Hughes N, Schimmenti LA, Schneider A, Young TL. Identification of novel mutations and sequence variants in the SOX2 and CHX10 genes in patients with anophthalmia/microphthalmia. Mol Vis. 2008 Mar 24;14:583-92. (http://www.ncbi.nlm.nih.gov/pubmed/18385794?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: March 2009
Published: October 27, 2014