Rare Ophthalmology News

Disease Profile

Optic atrophy 1

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Childhood

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ICD-10

H47.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

OPA1; Optic atrophy, juvenile; Kjer-type optic atrophy;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders

Summary

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.[1]

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.[1]

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.[1][2]

Symptoms

The signs and symptoms of optic atrophy type 1 include changes in vision. People with the disease typically have vision loss that begins between 4-6 years-old. The vision loss typically affects both eyes and can cause a person to have a range of vision loss from mild to being legally blind. People with optic atrophy type 1 may experience narrowing of the visual field (tunnel vision).[1][2] Vision loss may worsen as people with the disease get older. Optic atrophy type 1 can also cause a change in color vision, making it difficult to distinguish between blue and yellow colors (tritanopia).[1]

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).[1]

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.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Optic atrophy
0000648
30%-79% of people have these symptoms
Color vision defect
Abnormal color vision
Abnormality of color vision

[ more ]

0000551
Moderately reduced visual acuity
Moderate visual impairment
0030515
Morning glory anomaly
0025514
Ophthalmoplegia
Eye muscle paralysis
0000602
Sensorimotor neuropathy
Nerve damage causing decreased feeling and movement
0007141
Sensorineural hearing impairment
0000407
Temporal optic disc pallor
0012511
5%-29% of people have these symptoms
Ataxia
0001251
Central scotoma
Central blind spot
0000603
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Myopathy
Muscle tissue disease
0003198
Ptosis
Drooping upper eyelid
0000508
1%-4% of people have these symptoms
Abnormality of the periventricular white matter
0002518
Areflexia
Absent tendon reflexes
0001284
Atrophy/Degeneration affecting the brainstem
0007366
Basal ganglia calcification
0002135
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cerebellar atrophy
Degeneration of cerebellum
0001272
Corpus callosum atrophy
0007371
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Diabetes mellitus
0000819
Duane anomaly
0009921
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Fatigue
Tired
Tiredness

[ more ]

0012378
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Global developmental delay
0001263
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hemiparesis
Weakness of one side of body
0001269
Horizontal nystagmus
0000666
Hypogonadism
Decreased activity of gonads
0000135
Hypothyroidism
Underactive thyroid
0000821
Macrocytic anemia
0001972
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Pes cavus
High-arched foot
0001761
Progressive external ophthalmoplegia
0000590
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Scapular winging
Winged shoulder blade
0003691
Seizure
0001250
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Spastic paraplegia
0001258
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Weakness of facial musculature
Decreased facial muscle strength
Decreased strength of facial muscles
Face weakness
Facial muscle weakness
Facial weakness
Reduced facial muscle strength
Weakness of face

[ more ]

0030319
Percent of people who have these symptoms is not available through HPO
Abnormal amplitude of pattern reversal visual evoked potentials
0000650
Autosomal dominant inheritance
0000006
Centrocecal scotoma
0000576
Incomplete penetrance
0003829
Insidious onset
Gradual onset
0003587
Pallor
0000980
Red-green dyschromatopsia
Red green color blindness
0000642
Reduced visual acuity
Decreased clarity of vision
0007663

Cause

Optic atrophy type 1 is caused by a change (pathogenic variant or mutation) in the 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).[2]

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.[2]

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.[3]

Diagnosis

Optic atrophy type 1 may be suspected when a person has signs and symptoms of the disease including vision loss beginning in childhood, loss of color vision affecting blue and yellow colors (tritanopia), and findings of loss of tissue of the optic nerve (optic atrophy) on an exam by an ophthalmologist. A doctor may take a medical history and family history, as people with optic atrophy type 1 may have other signs and symptoms of the disease or other family members with signs and symptoms. The diagnosis can be confirmed with genetic testing of the OPA1 gene.[1]

Treatment

Treatment for optic atrophy type 1 typically includes regular exams by an ophthalmologist, including measuring vision and color vision, and regular evaluation by an audiologist. Vision aids such as glasses, contact lenses, and magnifiers may be used to help treat vision loss. Cochlear implants may help improve hearing in people who have sensorineural hearing loss.[1] Some people with optic atrophy type 1 have shown improvement in vision after being treated with idebenone. However, more research is needed to determine how effective this medication is in treating the disease.[3][5]

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.[1]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Optic atrophy 1. Click on the link to view a sample search on this topic.

          References

          1. Delettre-Cribaillet C, Hamel CP, and Lenaers G. Optic Atrophy Type 1. GeneReviews. November 12, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1248/.
          2. Optic atrophy type 1. Genetics Home Reference. August 2017; https://ghr.nlm.nih.gov/condition/optic-atrophy-type-1.
          3. Milea D and Procaccio V. Autosomal dominant optic atrophy, classic form. Orphanet. August 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=98673.
          4. Yu-Wai-Man P, et al. Multi-system neurological disease is common in patients with OPA1 mutations. Brain. March 2010; 133(Pt 3):771-786. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842512/.
          5. Barboni P. et al. Idebenone treatment in patients with OPA1-mutant dominant optic atrophy. Brain. February 2013; 136(Pt 2):e231. https://www.ncbi.nlm.nih.gov/pubmed/23388408.

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