Optic atrophy 1, also known as optic atrophy type 1 is a disease that affects the optic nerve. The optic nerve carries signals from the eye to the brain about what is seen. People with optic atrophy type 1 have an optic nerve that has lost some tissue (atrophy). This atrophy causes the optic nerve not to work as well as it should, which affects the vision. Signs and symptoms of optic atrophy type 1 include vision loss, difficulty distinguishing colors, and an abnormally pale appearance (pallor) of the optic nerve. The vision loss typically begins at age 4-6 years-old. The disease can occur in people of any ethnicity but seems to be more common in people of Danish descent.

Other symptoms of optic atrophy type 1 may include sensorineural hearing loss, difficulty coordinating movements (ataxia) and muscle disease (myopathy). When people have optic atrophy type 1 and signs and symptoms other than vision loss, it is known as autosomal dominant optic atrophy plus syndrome.

Optic atrophy type 1 is caused by a genetic change (pathogenic variant or mutation) in the OPA1 gene. The disease is inherited in an autosomal dominant manner. Optic atrophy type 1 may be suspected when a person has signs and symptoms of the disease on an exam done by an ophthalmologist. Genetic testing may be used to confirm the diagnosis. Treatment for optic atrophy type 1 may include vision and hearing aids when necessary.

Other signs and symptoms of optic atrophy type 1 may affect other parts of the body. People who have signs and symptoms other than vision loss have autosomal dominant optic atrophy plus syndrome. Some people with the disease may have hearing loss that is caused by damage to the nerves in the ears (sensorineural hearing loss). In severe cases, the hearing loss may be present from birth (congenital), but in other cases it may not be noticeable until a person undergoes a hearing evaluation. Other signs and symptoms of the disease may include difficulty coordinating movements (ataxia) and muscle disease (myopathy).

The signs and symptoms of optic atrophy type 1 can vary widely, even among people in the same family. For example, some people may have severe vision loss, hearing loss, and muscle weakness, while other people may only have mild vision loss. This wide variation of signs and symptoms of the disease is called variable expressivity. In some cases, people with a genetic change (pathogenic variant or mutation) in the OPA1 gene may not have any signs of optic atrophy type 1 at all. This is called reduced penetrance.

OPA1 gene. This gene provides instructions to the body to make a protein that helps the mitochondria function correctly. Mitochondria are the parts of the cell that help the cell produce energy. The protein that is created by the OPA1 gene helps the mitochondria maintain a normal shape and structure. Therefore, this protein is important in helping mitochondria create energy for the cells to use. The protein also has a role in the process called programmed cell death (apoptosis).

When there is a pathogenic variant in the OPA1 gene, there is not enough functioning protein to help the mitochondria maintain the normal shape and structure. This causes the mitochondria to not produce enough energy for cells. It also causes cells to undergo cell death earlier than they should. When cells of the eyes do not receive enough energy and undergo cell death earlier than they should, it causes loss of tissue in parts of the eye called the retina and the optic nerve. These parts of the eye transmit signals from the eyes to the brain so that we can see. Loss of cells in the retina and optic nerve cause the signs and symptoms of optic atrophy type 1.

In some cases, people with optic atrophy type 1 do not have a pathogenic variant in the OPA1 gene that is found on genetic testing. In these cases, the exact cause of the disease is unknown.

OPA1 gene can cause the signs and symptoms of optic atrophy type 1. We inherit one copy of the OPA1 gene from our mother and the other from our father. When a person with a pathogenic variant in OPA1 has children, for each child there is a:

• 50% chance to inherit the changed copy of OPA1
• 50% chance to inherit the working copy of OPA1

When a person has a pathogenic variant in the OPA1 gene, it can be difficult to predict the signs and symptoms that the person may have. This is because the signs and symptoms of optic atrophy type 1 can vary, even among members of the same family (variable expressivity). In addition, some people with pathogenic variants in OPA1 do not have any signs or symptoms of optic atrophy type 1 at all (reduced penetrance).

In most cases, people with optic atrophy type 1 inherit the pathogenic variant in OPA1 from one of their parents. This parent may have different signs and symptoms of the disease than other family members, or the parent may not have any signs or symptoms of the disease at all. It is not known why there is such a wide variation of signs and symptoms that can be associated with optic atrophy type 1. It may be that there are genetic and environmental factors that influence the signs and symptoms of the disease.

In some cases, a pathogenic variant in the OPA1 gene occurs for the first time in the person diagnosed with optic atrophy type 1, and it was not inherited from either parent. Pathogenic variants that are occurring for the first time are called de novo.

People who have questions about the chances for other family members to have optic atrophy type 1 may wish to speak with a genetic counselor.

OPA1 gene.

People with optic atrophy type 1 may be recommended to avoid alcohol intake and certain medications, as these can impact the function of mitochondria in the cells.

The long-term outlook for people with optic atrophy type 1 may depend on the severity of vision loss and if there are any other symptoms, such as hearing loss or muscle weakness. About 20% of people with a genetic change (pathogenic variant or mutation) in the OPA1 gene have symptoms other than vision loss.

In some cases, people with optic atrophy type 1 may experience anxiety and depression due to the symptoms of the disease. It is important to contact your doctor if you have concerns that you or a family member is suffering from anxiety or depression.