Hi, I’m Elena the genetic counselor, here to help you find more answers. You might be wondering, “How do inherited retinal diseases happen?” To find the answer, let’s take a closer look at our genes.

Genes are often called the great blueprint for life. As the body's instruction manual, our genes tell all parts of our body, including our eyes, how to grow and function.^1,2

Humans have approximately 25,000 genes.¹ Genes are stored in nearly every cell of our body, housed in small threadlike structures called chromosomes.³ We have 23 pairs of chromosomes.⁴ For each pair, we inherit one chromosome from our mother and one from our father.

Within each of our chromosomes are strands of deoxyribonucleic acid, commonly known as DNA.² If genes are the blueprint for life, think of DNA as the instructions within those blueprints. They carry very specific instructions for how tall we can grow, the color of our hair, and the many characteristics that make us unique.²

Each DNA sequence is made up of thousands of building blocks that are abbreviated as As, Cs, Gs, and Ts.² These letters are strung together in long strands. The order of these letters provides specific instructions to our body.² When the inherited DNA sequence contains a slight change—like a missing letter, or a letter is replaced by another, or there are a few added letters—that's when we inherit a gene variant from our parents and can potentially pass it to future generations.⁵

Most gene variants are considered benign, which means they aren’t believed to have a serious impact on our health.^5,6 However, some gene variants can affect how our bodies function, including our eyes.⁶ This could result in vision loss or impairment from an inherited retinal disease.^7,8

A genetic test is the only way to precisely identify the genetic cause of vision loss or impairment.^8,9 With the evolution of genetic testing comes the ability to potentially find the genetic cause of inherited retinal diseases in even more people.^10,11 Just in the past 10 years alone, nearly 100 new genes related to inherited retinal diseases have been discovered, bringing the total identified to over 270 genes.¹² And science continues to advance.

So, if you’ve never had a genetic test, or a prior test showed negative or inconclusive results, talk to your eye specialist or genetic counselor about genetic testing or retesting.^10,11,13 Move forward with more answers, and stay tuned for my next video about the different ways retinal diseases can be inherited at EyesOnGenes.com.

References

¹ MedlinePlus Genetics. National Institutes of Health. What is a gene? 2021. Available at: https://medlineplus.gov/genetics/understanding/basics/gene. Last accessed: January 2024.

² MedlinePlus Genetics. National Institutes of Health. What is DNA? 2021. Available at: https://medlineplus.gov/genetics/understanding/basics/dna/. Last accessed: January 2024.

³ MedlinePlus Genetics. National Institutes of Health. What is a chromosome? 2021. Available at: https://medlineplus.gov/genetics/understanding/basics/chromosome/ Last accessed: January 2024.

⁴ MedlinePlus Genetics. National Institutes of Health. How many chromosomes do people have? 2021. Available at: https://medlineplus.gov/genetics/understanding/basics/howmanychromosomes/ Last accessed: January 2024.

⁵ MedlinePlus Genetics. National Institutes of Health. What is a gene variant and how do variants occur? 2021. Available at: https://medlineplus.gov/genetics/understanding/mutationsanddisorders/genemutation/#:~:text=A%20gene%20variant%20is%20a,is%20a%20more%20accurate%20term. Last accessed: January 2024.

⁶ MedlinePlus Genetics. National Institutes of Health. How can gene variants affect health and development? 2021. Available at: https://medlineplus.gov/genetics/understanding/mutationsanddisorders/mutationscausedisease/ Last accessed: January 2024.

⁷ Cremers FP, et al. Special Issue Introduction: Inherited Retinal Disease: Novel Candidate Genes, Genotype–Phenotype Correlations, and Inheritance Models. Genes. 2018; 9(4):215

⁸ Ziccardi L, et al. Gene Therapy in Retinal Dystrophies. Int J Mol Sci. 2019; 20(22):5722.

⁹ Tatour Y, et al. Syndromic Inherited Retinal Diseases: Genetic, Clinical and Diagnostic Aspects. Diagnostics (Basel). 2020;10(10):779

¹⁰ Lee K, et al. Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies. Genet Med. 2015; 17(4):245-252

¹¹ Méjécase C, et al. Practical guide to genetic screening for inherited eye diseases. Ther Adv Ophthalmol. 2020; 12:1S28.

¹² Ben-Yosef, T. Inherited Retinal Diseases. Int J Mol Sci. 2022 Nov; 23(21): 13467.

¹³ Birtel J et al. Diagnosis of Inherited Retinal Diseases. Klin Monbl Augenheilkd. 2021; 238(3):249–259.

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.