Optic Atrophy (Autosomal Dominant)

Definition

Definition of Optic Atrophy (Autosomal Dominant)
Autosomal dominant optic atrophy (ADOA) is genetically heterogeneous, with OPA1 on 3q28 being the most prevalently mutated gene. Additional loci are OPA3, OPA4, and OPA5, located at 19q13.2, 18q12.2, and 22q12.1-q13.1, respectively. Mutations in the WFS1 gene, at 4p16.3, are associated with either optic atrophy (OA) as part of the autosomal recessive Wolfram syndrome or with autosomal dominant progressive low frequency sensorineural hearing loss (LFSNHL) without any ophthalmological abnormalities. Linkage and sequence mutation analyses of the ADOA candidate genes OPA1, OPA3, OPA4, and OPA5, including the genes WFS1, GJB2, and GJB6 associated with recessive inherited OA or dominant LFSNHL, were performed. We identified one novel WFS1 missense mutation E864K, c.2590G-->A in exon 8 that co-segregates with ADOA combined with hearing impairment and impaired glucose regulation. This is the first example of autosomal dominant optic atrophy and hearing loss associated with a WFS1 mutation, supporting the notion that mutations in WFS1 as well as in OPA1 may lead to ADOA combined with impaired hearing.

Symptoms

Symptoms of Optic Atrophy (Autosomal Dominant)
Symptoms of autosomal dominant optic atrophy are a change in the optic disc and a decrease in visual function. This change in visual function can be a decrease in sharpness and clarity of vision (visual acuity) or decreases in side (peripheral) vision. Color vision and contrast sensitivity can also be affected.

Causes

Causes of Optic Atrophy (Autosomal Dominant)
There are many possible causes of autosomal dominant optic atrophy. The causes can range from trauma to systemic disorders. Some possible causes of autosomal dominant optic atrophy include:

1. Optic neuritis: Optic neuritis is an inflammation of the optic nerve. It may be associated with eye pain worsened by eye movement. It is more common in young to middle-aged women. Some patients with optic neuritis may develop multiple sclerosis later on in life.
2. Leber's hereditary optic neuropathy: This is a disease of young men (late teens, early 20s), characterized by an onset over a few weeks of painless, severe, central visual loss in one eye, followed weeks or months later by the same process in the other eye. At first the optic disc may be slightly swollen, but eventually there is optic atrophy. The visual loss is generally permanent. -This condition is hereditary: If a patient knows that Leber's runs in the family, genetic counseling should be considered.
3. Toxic optic neuropathy: Nutritional deficiencies and poisons can be associated with gradual vision loss and optic atrophy, or with sudden vision loss and optic disc swelling. Toxic and nutritional optic neuropathies are uncommon in the United States, but took on epidemic proportions in Cuba in 1992–1993. The most common toxic optic neuropathy is known as tobacco-alcohol amblyopia, thought to be caused by exposure to cyanide from tobacco smoking, and by low levels of vitamin B12 because of poor nutrition and poor absorption associated with drinking alcohol. Other possible toxins included ethambutol, methyl alcohol (moonshine), ethylene glycol (antifreeze), cyanide, lead, and carbon monoxide. Certain medications have also been implicated. Nutritional optic neuropathy may be caused by deficiencies of protein, or of the B vitamins and folate, associated with starvation, malabsorption, or alcoholism.
4. Glaucoma: Glaucoma may be caused by an increase of pressure inside the eye. This increased pressure may eventually affect the optic nerve if left untreated.
5. Compressive optic neuropathy: This is the result of a tumor or other lesion putting pressure on the optic nerve. Another possible cause is enlargement of muscles involved in eye movement seen in hyperthyroidism (Graves' disease).
6. Retinitis pigmentosa: This is a hereditary ocular disorder.
7. Syphilis: Left untreated, this disease may result in optic atrophy.

Diagnosis

Diagnosis of Optic Atrophy (Autosomal Dominant)
Diagnosis involves recognizing the characteristic changes in the optic disc with an ophthalmoscope, and measuring visual acuity, usually with an eye chart. Visual field testing can test peripheral vision. Color vision and contrast sensitivity can also be tested. Family history is important in the diagnosis of inherited conditions. Exposure to poisons, drugs, and even medications should be determined. Suspected poisoning can be confirmed through blood and urine analysis, as can vitamin deficiency.

Brain magnetic resonance imaging (MRI) may show a tumor or other structure putting pressure on the optic nerve, or may show plaques characteristic of multiple sclerosis, which is frequently associated with optic neuritis. However, similar MRI lesions may appear in Leber's hereditary optic neuropathy. Mitochondrial DNA testing can be done on a blood sample, and can identify the mutation responsible for Leber's.
Visual evoked potentials (VEP), which measure speed of conduction over the nerve pathways involved in sight, may detect abnormalities in the clinically unaffected eye in early cases of Leber's. Fluorescein angiography gives more detail about blood vessels in the retina.

Treatment

Treatment of Optic Atrophy (Autosomal Dominant)
Treatment of optic neuritis with steroids is controversial. As of mid-1998, there is no known treatment for Leber's hereditary optic neuropathy. Treatment of other causes of optic atrophy varies depending upon the underlying disease.

Prognosis

Prognosis of Optic Atrophy (Autosomal Dominant)
Many patients with optic neuritis eventually develop multiple sclerosis. Most patients have a gradual recovery of vision after a single episode of optic neuritis, even without treatment. Prognosis for visual improvement in Leber's hereditary optic neuropathy is poor, with the specific rate highly dependent on which mitochondrial DNA mutation is present. If the cause of toxic or nutritional deficiency optic neuropathy can be found and treated early, such as stopping smoking and taking vitamins in tobacco-alcohol amblyopia, vision generally returns to near normal over several months' time. However, visual loss is often permanent in cases of long-standing toxic or nutritional deficiency optic neuropathy.

Prevention

Prevention of Optic Atrophy (Autosomal Dominant)
People noticing a decrease in vision (central and/or side vision) should ask their eye care practitioner for a check up. Patients should also go for regular vision exams. Patients should ask their doctor how often that should be, as certain conditons may warrant more frequent exams. Early detection of inflammations or other problems lessens the chance of developing optic atrophy.