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Early-onset glaucoma

Reviewed February 2009

What is early-onset glaucoma?

Glaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term "early-onset glaucoma" may be used when the disorder appears before the age of 40.

In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.

Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.

Structural abnormalities that impede fluid drainage in the eye may be present at birth and usually become apparent during the first year of life. Such abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma.

Other individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.

How common is early-onset glaucoma?

Primary congenital glaucoma affects approximately 1 in 10,000 people. Its frequency is higher in the Middle East. Juvenile open-angle glaucoma affects about 1 in 50,000 people. Primary open-angle glaucoma is much more common after the age of 40, affecting about 1 percent of the population worldwide.

What genes are related to early-onset glaucoma?

Approximately 10 percent to 33 percent of people with juvenile open-angle glaucoma have mutations in the MYOC gene. MYOC gene mutations have also been detected in some people with primary congenital glaucoma. The MYOC gene provides instructions for producing a protein called myocilin. Myocilin is found in certain structures of the eye, called the trabecular meshwork and the ciliary body, that regulate the intraocular pressure.

Researchers believe that myocilin functions together with other proteins as part of a protein complex. Mutations may alter the protein in such a way that the complex cannot be formed. Defective myocilin that is not incorporated into functional complexes may accumulate in the trabecular meshwork and ciliary body. The excess protein may prevent sufficient flow of fluid from the eye, resulting in increased intraocular pressure and causing the signs and symptoms of early-onset glaucoma.

Between 20 percent and 40 percent of people with primary congenital glaucoma have mutations in the CYP1B1 gene. CYP1B1 gene mutations have also been detected in some people with juvenile open-angle glaucoma. The CYP1B1 gene provides instructions for producing a form of the cytochrome P450 protein. Like myocilin, this protein is found in the trabecular meshwork, ciliary body, and other structures of the eye.

It is not well understood how defects in the CYP1B1 protein cause signs and symptoms of glaucoma. Recent studies suggest that the defects may interfere with the early development of the trabecular meshwork. In the clear covering of the eye (the cornea), the CYP1B1 protein may also be involved in a process that regulates the secretion of fluid inside the eye. If this fluid is produced in excess, the high intraocular pressure characteristic of glaucoma may develop.

The CYP1B1 protein may interact with myocilin. Individuals with mutations in both the MYOC and CYP1B1 genes may develop glaucoma at an earlier age and have more severe symptoms than do those with mutations in only one of the genes. Mutations in other genes may also be involved in early-onset glaucoma.

Related Gene(s)

Changes in these genes are associated with early-onset glaucoma.

  • CYP1B1
  • MYOC

How do people inherit early-onset glaucoma?

Early-onset glaucoma can have different inheritance patterns. Primary congenital glaucoma is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Juvenile open-angle glaucoma is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some families, primary congenital glaucoma may also be inherited in an autosomal dominant pattern.

Where can I find information about diagnosis or management of early-onset glaucoma?

These resources address the diagnosis or management of early-onset glaucoma and may include treatment providers.

  • Gene Review: Primary Congenital Glaucoma (http://www.ncbi.nlm.nih.gov/books/NBK1135)
  • Genetic Testing Registry: Glaucoma (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0017601)
  • Genetic Testing Registry: Glaucoma, congenital (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0020302)
  • Genetic Testing Registry: Primary open angle glaucoma juvenile onset 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1842028)
  • MedlinePlus Encyclopedia: Glaucoma (http://www.nlm.nih.gov/medlineplus/ency/article/001620.htm)

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

You may find the following resources about early-onset glaucoma 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 early-onset glaucoma?

  • hereditary glaucoma

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 early-onset glaucoma?

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

What glossary definitions help with understanding early-onset glaucoma?

autosomal ; autosomal dominant ; autosomal recessive ; bulging eyes ; cell ; ciliary body ; congenital ; cornea ; cytochrome P450 ; diabetes ; diabetes mellitus ; family history ; gene ; glaucoma ; hereditary ; hypertension ; inheritance ; inherited ; intraocular ; juvenile ; peripheral ; photophobia ; population ; protein ; recessive ; secretion ; sensitivity ; syndrome ; trabecular meshwork

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

References

  • Acharya M, Mookherjee S, Bhattacharjee A, Bandyopadhyay AK, Daulat Thakur SK, Bhaduri G, Sen A, Ray K. Primary role of CYP1B1 in Indian juvenile-onset POAG patients. Mol Vis. 2006 Apr 20;12:399-404. (http://www.ncbi.nlm.nih.gov/pubmed/16688110?dopt=Abstract)
  • Achary MS, Reddy AB, Chakrabarti S, Panicker SG, Mandal AK, Ahmed N, Balasubramanian D, Hasnain SE, Nagarajaram HA. Disease-causing mutations in proteins: structural analysis of the CYP1B1 mutations causing primary congenital glaucoma in humans. Biophys J. 2006 Dec 15;91(12):4329-39. Epub 2006 Sep 8. (http://www.ncbi.nlm.nih.gov/pubmed/16963504?dopt=Abstract)
  • Bayat B, Yazdani S, Alavi A, Chiani M, Chitsazian F, Tusi BK, Suri F, Narooie-Nejhad M, Sanati MH, Elahi E. Contributions of MYOC and CYP1B1 mutations to JOAG. Mol Vis. 2008 Mar 13;14:508-17. (http://www.ncbi.nlm.nih.gov/pubmed/18385784?dopt=Abstract)
  • Chakrabarti S, Kaur K, Rao KN, Mandal AK, Kaur I, Parikh RS, Thomas R. The transcription factor gene FOXC1 exhibits a limited role in primary congenital glaucoma. Invest Ophthalmol Vis Sci. 2009 Jan;50(1):75-83. doi: 10.1167/iovs.08-2253. Epub 2008 Aug 15. (http://www.ncbi.nlm.nih.gov/pubmed/18708620?dopt=Abstract)
  • Chavarria-Soley G, Sticht H, Aklillu E, Ingelman-Sundberg M, Pasutto F, Reis A, Rautenstrauss B. Mutations in CYP1B1 cause primary congenital glaucoma by reduction of either activity or abundance of the enzyme. Hum Mutat. 2008 Sep;29(9):1147-53. doi: 10.1002/humu.20786. (http://www.ncbi.nlm.nih.gov/pubmed/18470941?dopt=Abstract)
  • Chen Y, Jiang D, Yu L, Katz B, Zhang K, Wan B, Sun X. CYP1B1 and MYOC mutations in 116 Chinese patients with primary congenital glaucoma. Arch Ophthalmol. 2008 Oct;126(10):1443-7. doi: 10.1001/archopht.126.10.1443. (http://www.ncbi.nlm.nih.gov/pubmed/18852424?dopt=Abstract)
  • Choudhary D, Jansson I, Sarfarazi M, Schenkman JB. Characterization of the biochemical and structural phenotypes of four CYP1B1 mutations observed in individuals with primary congenital glaucoma. Pharmacogenet Genomics. 2008 Aug;18(8):665-76. doi: 10.1097/FPC.0b013e3282ff5a36. (http://www.ncbi.nlm.nih.gov/pubmed/18622259?dopt=Abstract)
  • Firasat S, Riazuddin SA, Khan SN, Riazuddin S. Novel CYP1B1 mutations in consanguineous Pakistani families with primary congenital glaucoma. Mol Vis. 2008;14:2002-9. Epub 2008 Nov 3. (http://www.ncbi.nlm.nih.gov/pubmed/18989382?dopt=Abstract)
  • Gene Review: Primary Congenital Glaucoma (http://www.ncbi.nlm.nih.gov/books/NBK1135)
  • OMIM: GLAUCOMA 1, OPEN ANGLE, A (http://omim.org/entry/137750)
  • OMIM: GLAUCOMA 3, PRIMARY CONGENITAL, A (http://omim.org/entry/231300)
  • Joe MK, Sohn S, Hur W, Moon Y, Choi YR, Kee C. Accumulation of mutant myocilins in ER leads to ER stress and potential cytotoxicity in human trabecular meshwork cells. Biochem Biophys Res Commun. 2003 Dec 19;312(3):592-600. (http://www.ncbi.nlm.nih.gov/pubmed/14680806?dopt=Abstract)
  • Kaur K, Reddy AB, Mukhopadhyay A, Mandal AK, Hasnain SE, Ray K, Thomas R, Balasubramanian D, Chakrabarti S. Myocilin gene implicated in primary congenital glaucoma. Clin Genet. 2005 Apr;67(4):335-40. (http://www.ncbi.nlm.nih.gov/pubmed/15733270?dopt=Abstract)
  • Ray K, Mukhopadhyay A, Acharya M. Recent advances in molecular genetics of glaucoma. Mol Cell Biochem. 2003 Nov;253(1-2):223-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14619973?dopt=Abstract)
  • Turalba AV, Chen TC. Clinical and genetic characteristics of primary juvenile-onset open-angle glaucoma (JOAG). Semin Ophthalmol. 2008 Jan-Feb;23(1):19-25. doi: 10.1080/08820530701745199. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18214788?dopt=Abstract)
  • Vasiliou V, Gonzalez FJ. Role of CYP1B1 in glaucoma. Annu Rev Pharmacol Toxicol. 2008;48:333-58. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17914928?dopt=Abstract)
  • Vincent AL, Billingsley G, Buys Y, Levin AV, Priston M, Trope G, Williams-Lyn D, Héon E. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Am J Hum Genet. 2002 Feb;70(2):448-60. Epub 2002 Jan 3. (http://www.ncbi.nlm.nih.gov/pubmed/11774072?dopt=Abstract)
  • Weisschuh N, Schiefer U. Progress in the genetics of glaucoma. Dev Ophthalmol. 2003;37:83-93. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12876831?dopt=Abstract)
  • Wiggs JL, Lynch S, Ynagi G, Maselli M, Auguste J, Del Bono EA, Olson LM, Haines JL. A genomewide scan identifies novel early-onset primary open-angle glaucoma loci on 9q22 and 20p12. Am J Hum Genet. 2004 Jun;74(6):1314-20. Epub 2004 Apr 23. (http://www.ncbi.nlm.nih.gov/pubmed/15108121?dopt=Abstract)
  • Willoughby CE, Chan LL, Herd S, Billingsley G, Noordeh N, Levin AV, Buys Y, Trope G, Sarfarazi M, Héon E. Defining the pathogenicity of optineurin in juvenile open-angle glaucoma. Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3122-30. (http://www.ncbi.nlm.nih.gov/pubmed/15326130?dopt=Abstract)
  • WuDunn D. Genetic basis of glaucoma. Curr Opin Ophthalmol. 2002 Apr;13(2):55-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11880716?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: February 2009
Published: September 8, 2014