A Patients Guide to Glaucoma: Section 11-D: Genetic testing for glaucoma

Incredible progress in being made in the field of genetic research and important discoveries and innovations are being made at an increasingly rapid pace. In the last few years, several landmark discoveries have been made in ophthalmic genetics. The Online Mendelian Inheritance in Man (OMIM, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM) is a catalog of heritable diseases and syndromes. At the beginning of 2007, this database had 813 entries of heritable conditions that affect the eye and 171 conditions in which glaucoma is a feature. As new genes that cause various types of glaucoma are discovered, there will be more opportunities for genetic testing to enhance all aspects of patient care including diagnosis, prognosis, treatment, and family planning. Currently, genetic testing is available for several glaucoma genes including myocilin (MYOC), optineurin (OPTN), and cytochrome P450 1B1 (CYP1B1).

Genetic testing may be useful for patients with specific types of glaucoma and particular clinical features of the disease. Patients that are interested in testing should discuss it with their physician and/or a genetic counselor. Along with discussing whether genetic testing is appropriate for a particular type of glaucoma, physicians and counselors may discuss the implications of these investigations. Genetic testing for inherited diseases may provide information that is useful for a patient’s medical care; however, this information may also affect other family members. Consequently, it is possible that genetic testing may be a source of stress or anxiety for the patient and for family members. Additionally, the results of genetic tests are complex, and should be interpreted by experienced physicians and genetic counselors. The meaning of positive or negative results is not always obvious, and must be carefully explained for genetic testing to be helpful to the patient. For example, there are likely many more glaucoma-causing genes than what have been discovered so far. If a patient is tested for defects in the known glaucoma genes (i.e. myocilin and optineurin) and no disease-causing mutations are detected, it is still possible that this patient has as yet unidentified alterations in genes that play a crucial role in glaucoma development. A patient’s physician or counselor is best equipped to explain the meaning and consequences of such genetic test results.

Some general guidelines for who may benefit most from some specific types of genetic testing are provided below.

Myocilin genetic testing for JOAG.

The patients with the highest likelihood of having glaucoma that is associated with a defect in the myocilin gene are patients with an early onset of disease (< 40 years of age); extremely high intraocular pressure (> 30 mm Hg); and a strong family history of disease. Most patients with these characteristics have familial juvenile-onset primary open angle glaucoma (JOAG) that is due to a mutation in the myocilin gene. Genetic testing may provide patients with familial JOAG and their physicians useful information to help solidify a diagnosis of this form of glaucoma.

Myocilin (MYOC) genetic testing for POAG.

Mutations in the myocilin gene account for a smaller proportion of POAG cases (3-4%) than JOAG. At present, due to the relatively low prevalence of myocilin-associated POAG and the labor-intensive nature of the mutation detection tests, large-scale testing of the general population for myocilin defects are not feasible. However, testing those individuals who are at extremely high risk for developing myocilin-associated POAG may be warranted. Such patients would include family members of patients with known myocilin-associated glaucoma and members of families with a strong history of inherited POAG.

Optineurin (OPTN) genetic testing for NTG.

Most cases of normal tension glaucoma (NTG) occur sporadically, without a family history of disease. However, there are rare familial cases of NTG and testing these patients for mutations in the optineurin gene may be warranted.

Cytochrome P450 1B1 (CYP1B1) testing for PCG.

Many cases of PCG are due to mutations in the CYP1B1 gene. In certain European populations of patients, as much as 87% of family cases of PCG and 27% of sporadic cases of PCG are caused by mutations of the CYP1B1 gene. However, the frequency of CYP1B1 mutations in cases of PCG in the United States is not precisely known. Based on this information, it is usually reasonable to test for CYP1B1 mutations in PCG patients with a positive family history of disease. While the likelihood of detecting a CYP1B1 mutation in a PCG patient is lower when there is no family history of disease, genetic testing may be warranted in some of these sporadic cases.