Autosomal Dominant Optic Atrophy (ADOA), also known as Kjer’s optic atrophy [1], is a rare mitochondrial disease characterized by wasting of the optic nerve called optic atrophy, resulting in vision loss [2]. Other syndromic forms of ADOA include ADOA and deafness (ADOAD), ADOA plus, and ADOA and cataract (ADOAC). Patients with ADOAD experience sensorineural hearing loss in addition to vision loss. Patients with ADOA plus experience neurological symptoms like muscle weakness, pain, or stiffness, stroke, or multiple sclerosis in addition to vision loss. Patients with ADOAC experience cataracts in addition to vision loss [3]. About 20% of ADOA patients experience symptoms other than vision loss [4].

Though disease onset later in life is possible, ADOA symptoms typically manifest in childhood in the first decade of life [3, 5]. The penetrance of ADOA, or the likelihood that a person with a pathogenic mutation will experience symptoms of the disease, is approximately 70%, though ADOA penetrance is known to vary, even within families [3]. The prevalence of the disease is estimated to be 1 in 35,000 individuals in the North of England, and this can likely be extrapolated to the general population [6]. Others estimate the prevalence to be 1 in 30,000 individuals in the general population [3]. The prevalence is higher in Denmark, approximately 1 in 10,000 people, though this could be explained by the founder effect (which is a decrease in genetic diversity when a population grows from a small group) and the fact that the estimate was made without molecular diagnoses [3, 5, 6]. The vision loss caused by ADOA, while irreversible, is typically milder than other diseases like LHON and does not impact lifespan, though the vision loss may progress over time [3, 5].

The most common cause of ADOA is the presence of a disease-causing mutation, or “pathogenic variant”, in the gene OPA1. Hundreds of disease-causing OPA1 mutations have been identified [1, 4, 6]. The OPA1 protein is a GTPase, which is a type of molecular switch, that resides in the inner membrane of the mitochondria. Mitochondria constantly divide (called fission) and come back together (called fusion). OPA1 is one of the proteins responsible for mitochondrial fusion and has been implicated in maintaining mitochondrial structure, mitochondrial DNA, and energy production and protecting from cell death [3, 4]. Most mutations in OPA1 cause degradation of its mRNA, or the blueprint that is translated into the OPA1 protein, making it difficult to match specific mutations with disease severity. However, some mutations located where the chemical reaction of the molecular switch occurs in OPA1 are known to cause more severe disease, with symptoms in addition to vision loss. While less common, ADOA can also be caused by mutations in other OPA genes, including OPA2, OPA3, OPA4, OPA5, OPA6, OPA7/TMEM126A, and OPA8 [3].

It is unclear why retinal ganglion cells (RGCs) are more affected than other cells. It is possible that OPA1 mutations cause a decrease in energy production in the mitochondria, and RGCs are uniquely vulnerable to this loss in energy due to their high demands [1, 4]. Another possibility is that mitochondrial dynamics and distribution in RGCs are particularly important. RGCs could also be more susceptible to oxidative damage due to light exposure [3]. Further research is required [1].

ADOA is an autosomal dominant disease. This means that a mutation in one of two copies of a gene, called an allele, is sufficient to cause the disease. Most OPA1 mutations are haploinsufficient, meaning that the one normal, non-mutated allele is unable to make up for the mutated, non-functional allele [4, 7]. Other OPA1 mutations are dominant negative, meaning that the mutated, non-functional allele prevents the normal, non-mutated allele from functioning normally [4]. Mutations in other ADOA-related genes vary in their mode of inheritance, including X-linked inheritance (OPA2), dominant (OPA4, OPA5), recessive (OPA6, OPA7/TMEM126A), and dominant or recessive forms (OPA3, OPA8). However, 50% of ADOA patients have no family history of disease and have sporadic mutations that are not inherited from either parent [3].

While some patients are asymptomatic, the main symptom of ADOA is vision loss, which is typically identified in children due to reading problems. However, vision loss may also begin in adulthood. The vision loss is usually slowly progressive, though rapid decline is possible in adults. It is irreversible but moderate compared to other diseases like LHON, though the degree of severity is highly variable, even within families [3].

Eye examination may reveal [3]:

• • • Loss of RGC fibers in the optic nerve, which connects the retina and brain
    • Atrophy or wasting of the optic nerve rim
    • Temporal gray crescent
    • Decreased thickness of the peripapillary retinal nerve fiber layer
    • Blind spot, or scotoma, in the center or near the center of the eye
    • Blue-yellow color confusion called tritanopia
    • Cataracts (in ADOAC)

The most common additional symptom for ADOAD and ADOA plus patients is sensorineural hearing loss. ADOA plus patients may experience neurological symptoms such as skeletal muscle disease called myopathy and peripheral nerve damage called neuropathy, which may result in [3]:

• • • Muscle weakness, stiffness, or pain
    • Stroke
    • Multiple sclerosis
    • Loss of reflexes or sensation
    • Lack of coordination or balance

To determine if your loved one has ADOA, your healthcare provider will evaluate their symptoms and family history, particularly looking for affected individuals in consecutive generations, as this is suggestive of the dominant inheritance observed with ADOA. Your healthcare provider may perform ophthalmological examination, visual evoked potential testing, and molecular genetic testing. For symptoms other than vision loss, affected individuals should consult a multidisciplinary team and diagnostic centers that specialize in mitochondrial disease [3].

There are currently no FDA-approved treatments for ADOA. Visual aids and cochlear implants are beneficial to patients with vision loss and hearing loss, respectively. Affected individuals are recommended to avoid tobacco, alcohol, and medications that impair mitochondrial function [3].

Are there any clinical trials for ADOA?

To see what trials you may qualify for, visit our Clinical Trials page – which also included a Clinical Trials Finder Tool. We also highly encourage you to join our patient registry, mitoSHARE, where we are actively recruiting ADOA families.

We are here to help. UMDF serves a number of families coping with ADOA. We suggest you reach out to our Support & Education Team – online, via email at  support@umdf.org or phone at (888) 900-6486 – who can suggest a host of resources including doctors, disease specific support meetings, and more. They’ll also connect you with a UMDF ambassador, likely a fellow ADOA patient or family member, who can help support and guide you through your questions.

• Get Support
  Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.

• Check our clinical trials finder
  Use our Clinical Trials Finder tool to see if you qualify for any clinical trials.

• Join our patient registry, mitoSHARE
  We are actively recruiting ADOA families to participate in our patient registry, mitoSHARE. Patient registries like mitoSHARE are an integral part in charting a course toward treatments and cures for ADOA and other mitochondrial diseases. There are currently over 30 active mitochondrial disease clinical trials. Next generation patient registries like mitoSHARE are an integral part of expanding that number.

• Become an advocate
  Ask your representatives to prioritize mitochondrial disease research and support via the UMDF Advocacy Center. We’ll send regular action items where you – and your friends and family – can let Congress know we need their support. Click here to sign up.

• Join the conversation online
  – UMDF Social Media Support Groups: Facebook Support Group
  – UMDF News & Updates: Facebook | Twitter | Instagram | YouTube

• Get involved
  Join the fight by giving your voice, generosity, time, or energy. Click here to see how you can help.

UMDF is helping chart a path toward treatments and eventual cure of mitochondrial diseases like ADOA through:

• Research & Funding: UMDF has provided more than $18 million in research funding to find treatments for diseases like ADOA. UMDF advocacy has helped secure an additional $80 million in federal funding via the Department of Defense and National Institutes of Health.
• Data: Over two decades ago, UMDF pioneered patient registries for the mitochondrial disease community. Today, our next generation patient registry, mitoSHARE, is helping chart a path toward the treatment and eventual cure of mitochondrial diseases.
• Patient Support: Thousands of families just like you depend upon UMDF for support and education. Attendance at our support meetings annually tops 7,000, including disease specific support meetings for families.
• Clinician Support: To help educate clinicians on diseases like ADOA, we feature monthly Bench to Bedside clinician seminars, host the annual Mitochondrial Medicine Symposium, support the Mitochondrial Care Network, and educate clinicians on our Mito U platform.

• • • Autosomal Dominant Optic Atrophy Association
    • National Institutes of Health Genetic and Rare Diseases Information Center: Autosomal dominant optic atrophy classic form
    • National Institutes of Health Genetic and Rare Diseases Information Center: Autosomal dominant optic atrophy plus syndrome
    • Online Mendelian Inheritance in Man: Optic Atrophy 1; OPA1

UMDF is here to help. Contact the Support Line at (888) 900-6486 weekdays from 8:00am to 5:00pm EST to connect with our Patient Concierge. Or, via email contact at support@umdf.org.

1. Amati-Bonneau et al., 2009. OPA1-associated disorders: Phenotypes and pathophysiology.
2. National Institutes of Health Genetic and Rare Diseases Information Center, last updated 2026. Autosomal dominant optic atrophy classic form.
3. Lenaers et al., 2012. Dominant optic atrophy.
4. Wong et al., 2023. OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.
5. Orphanet, last updated 2020. Autosomal dominant optic atrophy, classic form.
6. Yu-Wai-Man, et al., 2010. The Prevalence and Natural History of Dominant Optic Atrophy Due to OPA1 Mutations.
7. Alexander et al., 2000. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28.