Many inherited diseases are caused by mutations in a single gene (Mendelian disorder), and detection of the responsible mutation can predict development of the disease with relatively high accuracy. If your clinical findings suggest the presence of an inherited eye disease, such as those described below, genetic testing is worth considering and discussing with your patient.
Some heritable disorders are complex, meaning that they are the result of multiple genetic and environmental factors. The presence of any one of the disease-associated gene variants in complex disorders, such as age-related macular degeneration, may not be highly predictive of the development of the disease. In these cases, standard diagnostic methods such as biomicroscopy, ophthalmoscopy, tonography, and perimetry – rather than genetic testing – will more accurately assess a patient’s risk of vision loss.
Inherited Retinal Degenerations
Patients with clinical features of inherited retinal degenerations can benefit from genetic testing. Identifying disease-causing mutations aids genetic counseling by establishing the inheritance pattern (autosomal dominant, recessive, X-linked, or mitochondrial [maternal] inheritance), and identifying patients who are eligible to take part in clinical trials evaluating gene-based and cellular therapies. Many patients with inherited retinal degenerations have similar clinical features. For this reason, the GEDi-R panel is the most efficient method of screening, simultaneously testing 250 genes known to cause retinal degenerations.
Early-onset Glaucoma
When glaucoma develops in a patient before age forty (early-onset glaucoma), the disease is more likely to be caused by one of eight known high-risk genes. Early-onset glaucoma genes contribute to a broad range of phenotypes that can be difficult to distinguish by clinical features alone. The most efficient method to screen for early-onset glaucoma gene mutations is to use a panel test, such as GEDi-O, that simultaneously screens all eight genes. This information can aid genetic counseling by defining the inheritance pattern and identifying mutation carriers presymtomatically.
Primary Optic Atrophy
Approximately 50 percent of patients with primary optic atrophy have disease-causing mutations in either the OPA1 gene (inherited as a dominant trait and causing Kjer optic neuropathy), or mitochondrial DNA (inherited through maternal lineage and causing Leber Hereditary Optic Neuropathy). Nine other gene variants with dominant or recessive inheritance traits are also known to cause optic atrophy. Therefore, identifying the patient’s disease-causing genes will help define the inheritance pattern and phenotype. Since primary optic atrophy can overlap phenotypically with the normal tension type of glaucoma, it is useful to screen patients for both optic atrophy and glaucoma genes using the GEDi-O panel test. Additionally, clinical trials of gene therapy for specific genetic forms of optic neuropathy are in progress; genetic testing can help determine if patients are eligible for these studies.
For further reading, please see: Wiggs JL, Pierce EA. Genetic testing for inherited eye disease: who benefits? JAMA Ophthalmol. 2013 Oct;131(10):1265-6.