Payne family

Choroideremia (CHM) is a rare inherited disorder that causes progressive vision loss and ultimately leads to complete blindness. The disease affects the retina, which is the area at the back of the eye.

CHM often presents with similar symptoms and exam images to another more common retinal degenerative condition called retinitis pigmentosa (RP). Both conditions cause similar damage, yet the root cause is different. A genetic test is the only way to know what is causing the vision loss.

Team CHM ran in the 2021 NYC Marathon!

Testing may be available for free or covered by insurance. It is important to know the correct cause of vision loss as new treatment options in development target specific genetic mutations. What works to treat an RP patient, may not work for the CHM mutation and vice versa.

Pronounced  kuh-roid-er-eemia

Many CHM patients are often initially misdiagnosed with retinitis pigmentosa (RP), as these two conditions have similar symptoms and Electroretinogram (ERG) and Optical Coherence Tomography (OCT) findings. To learn more about the differences, please see this Clinical Differential Diagnosis PDF.

CHM is considered a rare disease because it only affects an estimated 1 in 50,000 individuals.

This is what happens to the eye once Choroideremia has advanced.
The fundus is the inside, back surface of the eye.

Retina with normal fundus

Retina with Advanced CHM

Living with Choroideremia

The below picture series shows the progression of a person’s diminished vision as he ages with Choroideremia (CHM).

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Symptoms

The first symptom is generally night-blindness, followed by vision loss in the mid-periphery. These “blind spots” appear in an irregular ring, only leaving patches of peripheral vision, while central vision is still maintained. Over time the peripheral vision loss extends in both directions leading to “tunnel vision” and most likely complete loss of sight.

Loss of acuity, depth perception, color perception and an increase in the severity of night blindness may also occur during this progression. Both the rate of change and the degree of visual loss are variable among those affected, even within the same family.

Inheritance

Choroideremia (CHM) is genetically passed through families by an X-linked pattern of inheritance. In this type of inheritance, the gene for choroideremia is located on the X chromosome. Females have two X chromosomes, but generally, only one of the X chromosomes will carry the defective gene. Because females have a healthy version of the gene on their other X chromosome that produces REP-1 (Rab escort protein-1), they normally do not suffer the full effects of CHM.

In many cases, female carriers suffer mild symptoms of CHM later in life, such as night blindness and glare sensitivity. In rare cases, female carriers even suffer the full effects of CHM. Males have only one X chromosome (paired with one Y chromosome) and are therefore genetically susceptible to inherit X-linked diseases.

Males cannot be carriers of X-linked diseases, but they will pass the gene on their X chromosome to their daughters, who then become carriers. Affected males never pass an X-linked disease gene to their sons because fathers pass only the Y chromosome to their sons. Female carriers have a 50 percent chance (or 1 chance in 2) of passing the X-linked disease gene to their daughters, who as a result will become carriers

Cause

The choroideremia (CHM) gene protein is called REP-1 (for Rab escort protein-1). This protein functions to bring other small proteins (think of them as signals) into association with an enzyme that adds 20-carbon long chains to the small signals. These signal proteins can then fit into the lipid membrane that surrounds the cell.

The small signals are thought to play a role in allowing nutrients to pass across cells. Imagine that this process occurs constantly at the back of the eye as special nutrients are required to keep the biochemical pathways of vision operating at capacity while our eyes are open.

There is another protein called REP-2 in all cells that allows normal cell function if REP-1 is not present. Scientists suggest that the amount of REP-2 may not be sufficient to allow the normal cell processes to occur in some cells such those of the eye. Unfortunately, the male patient with choroideremia makes a defective REP-1 protein that is rapidly lost from the eye and REP-2 is not able to replace its function.

You recall that the gene is on the X chromosome. Males only have one X and so only one copy of the gene that makes the protein. If the gene copy is changed, there is no other normal copy around to mask the effect of not having the normal protein available.

One area of research that the Choroideremia Research Foundation (CRF) supports is finding ways for cells in the eye to make the normal protein.

Treatment

Currently, there is no treatment or cure for choroideremia (CHM). However, what we have is hope. In our short history, we have already seen incredible advances made in CHM research. Gene therapy treatment has been in clinical trials. Individuals wishing to participate in future clinical trials will need to have their diagnosis of CHM verified with a genetic test.  Some results from these clinical trials have been very positive and in the future may offer individuals the first-ever treatment for CHM.

The Choroideremia Research Foundation (CRF) is dedicated to helping researchers find a cure or treatment. Your help is urgently needed to accomplish our goal of restoring sight to CHMers worldwide. Please navigate through our site to learn more about clinical trials, becoming a member, attending an event, locating resources, volunteering, or making a donation.