Hereditary optic neuropathies include dominant optic atrophy and Leber hereditary optic neuropathy, which are both mitochondrial cytopathies (1 General reference Hereditary optic neuropathies result from genetic defects that cause vision loss and occasionally cardiac or neurologic abnormalities. There is no effective treatment. Hereditary optic neuropathies... read more ). These disorders typically manifest in childhood or adolescence with bilateral, symmetric central vision loss. Optic nerve damage is usually permanent and in some cases progressive. By the time optic atrophy is detected, substantial optic nerve injury has already occurred.
Dominant optic atrophy is inherited in an autosomal dominant fashion. It is believed to be the most common of the hereditary optic neuropathies, with prevalence in the range of 1:10,000 to 1:50,000. It is thought to be optic abiotrophy, premature degeneration of the optic nerve leading to progressive vision loss. Onset is in the 1st decade of life.
Leber hereditary optic neuropathy involves a mitochondrial DNA abnormality Mitochondrial Oxidative Phosphorylation Disorders Impairment of oxidative phosphorylation often, but not always, causes lactic acidosis, particularly affecting the central nervous system, retina, and muscle. See also Approach to the Patient... read more that affects cellular respiration. Although mitochondrial DNA throughout the body is affected, vision loss is the primary manifestation. Most cases (80 to 90%) occur in males. The disease is inherited with a maternal inheritance pattern, meaning that all offspring of a woman with the abnormality inherit the abnormality, but only females can pass on the abnormality because the zygote receives mitochondria only from the mother.
Most patients with dominant optic atrophy have no associated neurologic abnormalities, although nystagmus and hearing loss have been reported. The only symptom is slowly progressive bilateral vision loss, usually mild until late in life. The entire optic disk or, at times, only the temporal portion is pale without visible vessels. A blue-yellow color vision deficit is characteristic.
Vision loss in patients with Leber hereditary optic neuropathy typically begins between 15 and 35 years (range, 1 to 80 years). Painless central vision loss in one eye is usually followed weeks to months later by loss in the other eye. Simultaneous vision loss has been reported. Most patients lose vision and develop worse than 20/200 acuity. Ophthalmoscopic examination may show telangiectatic microangiopathy, swelling of the nerve fiber layer around the optic disk, and an absence of leakage on fluorescein angiography. Eventually, optic atrophy supervenes.
Some patients with Leber hereditary optic neuropathy have cardiac conduction defects. Other patients have minor neurologic abnormalities, such as a postural tremor, loss of ankle reflexes, dystonia, spasticity, or a multiple sclerosis–like illness.
Diagnosis of dominant optic atrophy and Leber hereditary optic atrophy is mainly clinical. Molecular genetic testing is available to confirm many mutations responsible for both disorders. However, results can be falsely negative because mutations may exist for which molecular testing does not yet test.
If Leber hereditary optic neuropathy is suspected, electrocardiography (ECG) should be done to diagnose occult cardiac conduction defects.
There is no effective treatment for the hereditary optic neuropathies. Low-vision aids (eg, magnifiers, large-print devices, talking watches) may be helpful. Genetic counseling is suggested.
In patients with Leber hereditary optic neuropathy, corticosteroids, vitamin supplements, and antioxidants have been tried without success. A small study found benefits from quinone analogs (ubiquinone and idebenone) during the early phase (1 Treatment reference Hereditary optic neuropathies result from genetic defects that cause vision loss and occasionally cardiac or neurologic abnormalities. There is no effective treatment. Hereditary optic neuropathies... read more ). Suggestions to avoid agents that might stress mitochondrial energy production (eg, tobacco, alcohol, particularly if excessive) have no proven benefit but are theoretically reasonable. Patients with cardiac and neurologic abnormalities should be referred to a specialist.