What are inherited retinal diseases?

Hi, I’m Elena. As a genetic counselor, I’m often asked about how changes within our genes, or “gene variants,” can be inherited. Understanding key information about inherited retinal diseases is how we can start to take control.^1,2,3

Today, I’m going to walk us through 3 different ways retinal diseases can be passed down from our parents. The first is autosomal dominant inheritance.⁴ Whoa, that’s a mouthful! Here’s what it means: You might remember from the Genes 101 video that our genes are housed inside our chromosomes.⁵ We have 23 pairs of chromosomes.⁶ For each pair, we receive one chromosome from each parent. To explain how this inheritance pattern works, it helps to imagine two butterflies—one representing a mother, and one representing a father. In this case, the butterfly with the gene variant has an added spot. This spot represents inherited retinal disease in humans. For autosomal dominant inheritance, the child would only need to inherit a single gene variant to be affected by the condition.^4,7 So, in the case where a single parent has the gene variant, there’s a 50% chance that the child will inherit that parent’s retinal disease.⁷ This is represented by the added spot.

Next, we have autosomal recessive inheritance.⁴ Here, even if our parents don’t have an inherited retinal disease, they can still be “carriers.”⁴ A carrier is someone who carries the gene variant, but most of the time does not have symptoms.⁴ In rare cases, a “carrier” may experience symptoms. In either case, carriers can pass down the gene variant to their children.⁴ Unlike autosomal dominant inheritance, the child would have to inherit 2 copies of a gene variant, 1 from their mother and 1 from their father, to be affected by the condition.^4,8 What that means is, in the cases where both parents are carriers but are not affected by the condition, there’s a 25% chance that the child will inherit both copies of the gene variant and inherit a retinal disease, and a 50% chance that the child will inherit a single copy and only be a carrier.⁴

Now let’s examine X-linked recessive inheritance. For X-linked conditions, we need to take a closer look into the chromosomes of each parent because in this pattern, gene variants are passed through the X chromosome.⁴ Females have 2 X chromosomes, and males have 1 X and 1 Y.⁹ So, if a female were to inherit an X chromosome with a gene variant, she still has another healthy X chromosome that could act as a backup and function properly. However, males only inherit 1 X chromosome, and if that happens to have a variant, he doesn’t have that backup healthy chromosome.^4,9 This leaves them more at risk of being affected by an X-linked recessive condition.^4,9 In the case where the mother is a carrier, and the father is unaffected by the condition, if they have a son, there’s a 50% chance that he will be affected.¹⁰ However, if they have a daughter, there’s a 50% chance that she will be a carrier of the gene variant.¹⁰ It's important to remember that these outcomes can change depending on which parent possesses the gene variant.¹⁰

Now, we know that’s a whole lot to take in. Understanding inheritance patterns plays a big role in understanding how these conditions are passed down. It’s important to know that family history is only one of the pieces we use to solve the diagnosis puzzle. You can still inherit genes that cause retinal diseases with no known family history of these diseases.¹¹ A genetic test, along with the correct eye exams, may give us more answers.^2,12 Move forward with more answers and stay tuned for more episodes at EyesOnGenes.com.

References

¹ Branham K et al. Am J Med Genet C Semin Med Genet. 2020; 184(3):571–577.

² Lee K et al. Genet Med. 2015; 17(4):245–252.

³ Lam B.L et al. Orphanet J Rare Dis. 2021; 16,514.

⁴ Prevent Blindness.org. Inherited Retinal Diseases Factsheet. Available at: Inherited-Retinal-Diseases-Factsheet.pdf (preventblindness.org) Last accessed: October 2023.

⁵ MedlinePlus Genetics. National Institutes of Health. What is a chromosome? 2021. Available at: https://medlineplus.gov/genetics/understanding/basics/chromosome/ Last accessed: October 2023.

⁶ MedlinePlus Genetics. National Institutes of Health. How many chromosomes do people have? 2021. Available at: https://medlineplus.gov/genetics/understanding/basics/howmanychromosomes/ Last accessed: October 2023.

⁷ National Human Genome Research Institute. Autosomal Dominant Disorder. Available at: Autosomal Dominant Disorder (genome.gov) Last accessed: October 2023.

⁸ National Human Genome Research Institute. Autosomal Recessive Disorder. Available at: Autosomal Recessive Disorder (genome.gov) Last accessed: October 2023.

⁹ National Human Genome Research Institute. X-linked. Available at: X-Linked (genome.gov) Last accessed: October 2023.

¹⁰ Gocuk SA, et al. Female carriers of X-linked inherited retinal diseases – Genetics, diagnosis, and potential therapies. 2023; 96:101190.

¹¹ Moore A.T. Genetic Testing for Inherited Retinal Disease. Ophthalmology. 2017;124(9):1254-1255.

¹² Zanolli M et al. Genetic testing for inherited ocular conditions in a developing country. Ophthalmic Genet. 2020; 41(1):36.