Management of Inherited Retinal Diseases through Genetic testing

Inherited retinal diseases (IRDs) are genetic disorders that affect the retinal layers, layers that are responsible for converting the photos of light into three-dimensional images that we finally see. They are a significant global cause of visual impairment. They can affect individuals of all ages, can progress at different rates, and may get worse over time leading to vision loss and blindness.

Knowing the genetic cause of an inherited disease or the risk of developing the disease can help manage the other factors; environmental, lifestyle etc., decide on the rehabilitation options, help in the overall disease management, and make us better prepared to take the right decisions and care for one’s health. Disease-causing mutations can be identified with genetic testing which allows us to accurately study the inheritance pattern, thereby improving genetic counselling for affected individuals and their families.

Inherited Retinal Diseases

Inherited Retinal Diseases (IRDs) comprise of, over 20 different phenotypes like congenital stationary night blindness (CSNB), Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), cone-dystrophy (CD), cone-rod dystrophy (CRD) optic atrophy (OA) and others. These conditions result from mutations in various genes that play a role in retinal structure and function. To date more than 250 genes have been identified to cause IRD. Some mutations follow dominant inheritance, requiring a single copy of the mutated gene for the condition to develop. Others will have recessive inheritance, necessitating two copies of the mutated gene for the condition to manifest. In the X-linked recessive (XLR) inheritance, the mutation is in a gene on the X chromosome, and since there is only one X chromosome in males, they manifest the disease, the females might either be asymptomatic or present with mild disease as they harbour two X chromosomes. With advancements in the field of genomics and genetic testing, if the firstborn suffers from an inherited eye disorder, today we have tests (like clinical exome, and whole exome sequencing) that can identify the genetic cause of his/her disease, test the parents and other unaffected siblings to know their carrier status and offer prenatal genetic testing for the unborn child.

Genetics in developing IRDs

When one parent carries a dominant mutation for an IRD, there is a 50% chance that each of their children will inherit the mutation and develop the condition. When both parents carry a copy of the recessive mutation for an IRD, there is a 25% chance that each of their children will inherit two copies of the mutation and develop the condition. For the X-linked recessive inheritance, when the mother is a carrier of the mutation, there is a 50% chance that each of her daughters will be a carrier and 50% chance that each of her sons will be affected. Whereas, when a man is affected with X-linked recessive IRD, all his daughters will be carriers, whereas none of his sons will be affected.

Symptoms and impact on vision

Symptoms of IRDs typically include night blindness, loss of peripheral vision, and decreased central visual acuity, which can progress to complete blindness over time. The impact of IRDs on vision can be profound, affecting an individual's ability to perform daily activities and significantly impacting their quality of life. There is currently no cure for IRDs, but treatments such as gene therapy and retinal implants are being developed and tested to slow or halt disease progression and improve vision.

Eligibility for genetic testing

• Individuals presenting with the symptoms of an inherited retinal disorder.
• Individuals with a positive family history of IRD.
• Carrier testing of an individual whose spouse is affected with IRD.
• Prenatal testing is recommended only in families with affected individuals and genetic testing in the affected have identified the disease-causing mutation.

Genetic Testing for Inherited Retinal Diseases

Genetic testing plays a vital role in identifying mutations, providing clinicians with better understanding of the disease, prognosis, leading to better disease management and possible therapy options. Depending on the genetic testing methodology used, results can be provided within 3-6 weeks.

Another vital part of genetic testing is the genetic counselling services which help individuals, and their families understand the inheritance pattern and thus the risk of developing the disease in other family members and for the next generation.   Eye disorders if diagnosed correctly and early, can be managed better, resulting in better healthcare outcomes.

This article was authored by Dr N Soumittra, Disease Head, Ophthalmology, MedGenome