Optic Atrophy Type 1

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: Optic atrophy type 1 (OPA1, or Kjer type optic atrophy) is characterized by bilateral and symmetric optic nerve pallor associated with insidious decrease in visual acuity (usually between ages 4 and 6 years), visual field defects, and color vision defects. Visual impairment is usually moderate (6/10 to 2/10), but ranges from mild or even insignificant to severe (legal blindness with acuity <1/20). The visual field defect is typically centrocecal, central, or paracentral; it is often large in those with severe disease. The color vision defect is often described as acquired blue-yellow loss (tritanopia). Other findings can include auditory neuropathy resulting in sensorineural hearing loss that ranges from severe and congenital to subclinical (i.e., identified by specific audiologic testing only).

Visual evoked potentials are typically absent or delayed; pattern electroretinogram shows an abnormal N95:P50 ratio. Tritanopia is the classic feature of color vision defect, but more diffuse nonspecific dyschromatopsia is not uncommon. Ophthalmoscopic examination discloses temporal or diffuse pallor of the optic discs, sometimes associated with optic disc excavation. The neuroretinal rim shows some pallor in most cases, sometimes associated with a temporal pigmentary gray crescent.

Diagnosis: The diagnosis of OPA1 is made based on a combination of clinical findings, electrophysiologic studies, and family history and/or by the identification of a heterozygous pathogenic variant in OPA1, the only gene known to be associated with OPA1, by molecular genetic testing.

Management: Treatment of manifestations: Low-vision aids for decreased visual acuity.

Surveillance: Annual ophthalmologic evaluations (including measurement of visual acuity, visual fields, and optical coherence tomography) and hearing evaluations.

Agents/circumstances to avoid: Smoking, excessive alcohol intake, medications (antibiotics, antivirals) that interfere with mitochondrial metabolism.

Genetic counseling: OPA1 is inherited in an autosomal dominant manner. Most individuals diagnosed with OPA1 have an affected parent; however, de novo pathogenic variants have been reported. Each child of an individual with OPA1 has a 50% chance of inheriting the pathogenic variant. Prenatal testing for a pregnancy at increased risk is possible if the pathogenic variant has been identified in an affected family member, but genetic counseling remains complicated by the incomplete penetrance and the markedly variable inter- and intrafamilial expressivity of the disease.

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