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What are inherited retinal DISEASES?

Inherited retinal diseases defined

Inherited retinal diseases are a group of rare eye disorders that can lead to serious vision impairment or loss. Note that inherited retinal diseases are sometimes also referred to as inherited retinal dystrophies or degenerations. These conditions can occur when one or more of your genes are not working properly.

You are not alone
Approximately 1 in 2000 people have inherited retinal diseases based on global estimates* *Prevalence may vary by region, locality, or subpopulation.

What are genes and gene variants?

Genes

Genes are often called the great blueprint for life. Genes are stored in nearly every cell of your body and contain DNA, also known as deoxyribonucleic acid, which carries instructions for how you look and everything that makes you unique. As the body’s instruction manual, genes tell parts of your body, including your eyes, how to grow and function.

Gene variants

A “gene variant” is a change in one or more of the DNA sequences that make up your genes. A change means something was added, missing, or replaced in the DNA sequence.

How do inherited retinal diseases happen?

Genetic counselor Elena breaks down what genes are and how gene variants can impact our vision.

View transcript

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. Humans have approximately 25,000 genes. Genes are stored in nearly every cell of our body, housed in small threadlike structures called chromosomes. We have 23 pairs of chromosomes. 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. 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 makes us unique. Each DNA sequence is made up of thousands of building blocks that are abbreviated as As, Cs, Gs, and Ts. These letters are strung together in long strands. The order of these letters provides specific instructions to our body. 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. Most gene variants are considered benign, which means they aren’t believed to have a serious impact on our health. However, some gene variants can affect how our bodies function, including our eyes. This could result in vision loss or impairment from an inherited retinal disease. A genetic test is the only way to precisely identify the genetic cause of vision loss or impairment. With the evolution of genetic testing comes the ability to potentially find the genetic cause of inherited retinal diseases in even more people. 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. 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. Move forward with more answers, and stay tuned for my next video about the different ways retinal diseases can be inherited at EyesOnGenes.com.

© Janssen Pharmaceuticals, Inc. 2021 10/21 cp-259572v1

Let’s take a closer look inside the eye:

Side view of an eye with light coming in from the left with cones and rods at the back of the eye

Inside your eye, there is an important light-sensitive structure known as the retina that contains millions of specialized cells called rods and cones. Rod cells are responsible for peripheral and night vision, while cones are responsible for color, daytime, and central vision.

These rods and cones work together inside your eye’s retina to gather visual information. They send these messages to the brain through the optic nerve. This process allows us to see life fully—in color, in black and white, and in shades of gray.

When your eye’s rods and/or cones aren’t working properly, your vision may not work properly.

How are retinal diseases inherited?

Narrated by genetic counselor Elena, this animated video brings to life three ways inherited retinal diseases can occur.

View transcript

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. 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. 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. We have 23 pairs of chromosomes. 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. 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. This is represented by the added spot. Next, we have autosomal recessive inheritance. Here, even if our parents don’t have an inherited retinal disease, they can still be “carriers.” A carrier is someone who carries the gene variant, but most of the time does not have symptoms. In rare cases, a “carrier” may experience symptoms. In either case, carriers can pass down the gene variant to their children. 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. 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. 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. Females have 2 X chromosomes, and males have 1 X and 1 Y. 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. This leaves them more at risk of being affected by an X-linked recessive condition. 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. However, if they have a daughter, there’s a 50% chance that she will be a carrier of the gene variant. It's important to remember that these outcomes can change depending on which parent possesses the gene variant. 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. A genetic test, along with the correct eye exams, may give us more answers. Move forward with more answers and stay tuned for more episodes at EyesOnGenes.com.

© Janssen Pharmaceuticals, Inc. 2021 10/21 cp-259571v1

Family history alone doesn’t tell the full story

Family history can reveal a lot about inherited retinal diseases, but it’s just one of the pieces genetic counselors and eye specialists use to try to solve the diagnosis puzzle.

of people with an inherited retinal disease called retinitis pigmentosa have no knowledge of previous family history.

If you do not have any known family history but have been suspected of having an inherited retinal disease, it’s still important to ask your eye specialist about genetic testing or retesting.

It’s hard to tell one inherited retinal disease from another

Overlapping symptoms can make diagnosing inherited retinal diseases challenging. Therefore, genetic testing has become the benchmark to uncover the genetic cause of your vision loss or impairment.

Each inherited retinal disease is different and can have one or more of these common symptoms:

  • Difficulty seeing at night
  • Loss of central and peripheral vision
  • Sensitivity to light
  • Farsightedness
  • Blind spots
  • Color blindness
  • Uncontrolled eye movements
  • Difficulty seeing at night
  • Sensitivity to light
  • Blind spots
  • Uncontrolled eye movements
  • Loss of central and peripheral vision
  • Farsightedness
  • Color blindness

There are many different types of inherited retinal diseases. Some include:

Disclaimer: All prevalence rates are global estimates and may vary across regions.

  • RP is one of the most common inherited retinal diseases
  • Symptoms may begin in childhood or adulthood
  • Up to 1 in 3,000 people have RP
  • Approximately 15% of RP can be inherited in an X-linked pattern and can result in X-linked retinitis pigmentosa (XLRP). This type of RP typically affects more males than females and can result in severe vision impairment or loss
  • Variants in more than 60 genes are known to cause a form of retinitis pigmentosa that only affects the eyes
  • Some symptoms may include:
  • Progressive vision loss
  • Difficulty seeing at night
  • Blind spots that progress into loss of peripheral vision
  • Loss of central vision over time which makes it difficult to read, drive, or recognize faces
  • Symptoms usually begin at birth (Usher syndrome type I and type II) or by mid-childhood or adulthood (Usher syndrome III)
  • Up to 1 in 6,000 people have USH
  • There are 3 types of Usher syndrome (USH1, USH2, USH3)
  • Variants in 16 genes are known to cause Usher syndrome
  • Some symptoms may include:
  • Hearing loss (usually at birth)
  • Loss of night vision, the first visual symptom
  • Blind spots that progress into loss of peripheral vision
  • Symptoms usually appear in late childhood to early adulthood
  • Up to 1 in 8,000 people have Stargardt disease
  • Variants in 2 genes are known to cause Stargardt disease
  • Some symptoms may include:
  • Loss of central vision over time
  • Night blindness
  • Color blindness
  • Symptoms usually begin during childhood and worsen over time
  • Up to 1 in 30,000 people have CRD
  • Variants in more than 30 genes are known to cause cone-rod dystrophy
  • Some symptoms may include:
  • Decreased sharpness of vision
  • Sensitivity to light
  • Problems recognizing colors
  • Blind spots
  • Loss of peripheral vision over time
  • Blindness by mid-adulthood
  • Symptoms develop in the first few months of life
  • Up to 1 in 30,000 people have achromatopsia
  • Variants in 5 genes are known to cause achromatopsia
  • Some symptoms may include:
  • Partial or total loss of color vision
  • Can only see black, white, and shades of gray
  • Sensitivity to light
  • Involuntary eye movements
  • Reduced sharpness of vision
  • Farsightedness, or less commonly, nearsightedness
  • Symptoms usually appear during infancy
  • Up to 1 in 33,000 people have LCA
  • Variants in at least 14 genes are known to cause Leber congenital amaurosis
  • Some symptoms may include:
  • Vision loss at infancy
  • Sensitivity to light
  • Involuntary eye movements
  • Extreme farsightedness
  • Pupils not reacting normally to light
  • Eye poking, pressing, or rubbing
  • Symptoms usually begin in early childhood
  • Up to 1 in 50,000 people have CHM
  • More males are affected by CHM than females
  • Variants in the CHM gene cause choroideremia
  • Some symptoms may include:
  • Night blindness in early childhood
  • Loss of peripheral vision
  • Less ability to see details over time
  • Loss of vision over time, most commonly in late adulthood
  • Affects multiple parts of the body; symptoms begin early- to mid-childhood
  • Up to 1 in 160,000 people have BBS
    • While BBS is one of the rarest inherited diseases, its prevalence may be higher in some geographic regions
  • Variants in at least 14 genes are known to cause Bardet-Biedl syndrome
  • Some symptoms may include:
  • Night vision loss
  • Blind spots that progress into loss of peripheral vision
  • Blurred central vision
  • Problems with kidneys and eyes
  • Weight gain
  • Born with extra fingers or toes
  • Learning problems
  • Developmental delays