Overview
Dominant optic atrophy (DOA), also known as Kjer disease, is the most common hereditary optic neuropathy, affecting approximately 1 in 12,000–50,000 individuals. It is caused by mutations in OPA1, encoding a mitochondrial dynamin-like GTPase essential for mitochondrial fusion and cristae remodeling. DOA presents with insidious bilateral central vision loss beginning in the first decade of life, temporal disc pallor, and tritanopia (blue-yellow color vision defect). A subset (~20%) develops additional neurological features (DOA-plus syndrome).
Genetics
OPA1 mutations account for ~60–70% of DOA. OPA3 mutations cause a rare autosomal recessive form with cataracts and neuropathy. Autosomal dominant.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| OPA1 | 3q29 | AD | Mitochondrial dynamin-like GTPase; most common cause (60–70%) |
| OPA3 | 19q13.32 | AR | Rare; Costeff syndrome (3-methylglutaconic aciduria type III) |
Clinical Presentation
Childhood (1st decade)
- Insidious bilateral visual acuity reduction
- Tritanopia (blue-yellow color vision defect)
- Central or cecocentral scotoma
Progressive
- Slow progression over decades
- Temporal optic disc pallor
- Visual acuity typically 20/30–20/200
DOA-plus (subset ~20%)
- Sensorineural hearing loss
- Ataxia, myopathy
- Peripheral neuropathy, ptosis
Diagnosis
- OCT: Retinal nerve fiber layer (RNFL) thinning, especially temporal sector
- Visual field: Central or cecocentral scotoma
- Color vision: Tritanopia
- Fundus: Temporal disc pallor
- Genetic testing: OPA1 sequencing
Current Research & Treatment
No approved treatments. Idebenone is used off-label. OPA1 gene therapy and mitochondria-targeted antioxidants are in preclinical development. The DOA-plus phenotype has increased research interest in mitochondrial dynamics as a therapeutic target.
Active Clinical Trials
The following active clinical trials are investigating treatments for Dominant Optic Atrophy. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.