Autosomal dominant optic atrophy and peripheral neuropathy

Autosomal dominant optic atrophy and peripheral neuropathy (also known as optic atrophy plus syndrome or Kjer disease plus) is a rare inherited neurological condition that combines progressive vision loss due to optic nerve degeneration with peripheral nerve damage. This condition is most commonly caused by mutations in the OPA1 gene, which encodes a mitochondrial dynamin-like GTPase essential for mitochondrial fusion and maintenance. It represents a more severe, syndromic form of autosomal dominant optic atrophy (Kjer disease, ADOA), sometimes referred to as ADOA plus or DOA plus. The disease primarily affects the visual system and the peripheral nervous system. Patients typically experience progressive bilateral visual impairment beginning in childhood or early adulthood due to degeneration of retinal ganglion cells and the optic nerve, leading to central visual field defects, color vision abnormalities (particularly blue-yellow dyschromatopsia), and optic disc pallor. In addition, patients develop a peripheral neuropathy that may be sensorimotor in nature, causing weakness, numbness, and tingling in the extremities. Some patients may also develop additional neurological features including sensorineural hearing loss, ataxia, progressive external ophthalmoplegia (PEO), myopathy, and mitochondrial myopathy with cytochrome c oxidase-negative fibers on muscle biopsy. There is currently no cure or disease-modifying treatment for autosomal dominant optic atrophy and peripheral neuropathy. Management is supportive and multidisciplinary, involving regular ophthalmological monitoring, low-vision aids, neurological assessment for peripheral neuropathy and other neurological complications, audiological evaluation, and physical rehabilitation as needed. Genetic counseling is recommended for affected families. Research into potential therapies, including gene therapy and agents targeting mitochondrial function such as idebenone, is ongoing but no specific treatment has yet been proven effective in clinical trials for this condition.

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