SUMMARY:

• Optic atrophy is vision loss due to abnormalities of the optic nerve.
• Autosomal dominant optic atrophy type 1 and Leber’s hereditary optic neuropathy (both related to OPA1 gene) are the most common hereditary optic neuropathies.
• Wolfram syndrome is a progressive neurodegenerative disorder that is also associated with optic atrophy as well as sensorineural hearing loss, progressive neurologic abnormalities, and endocrine abnormalities.
• Optic atrophy has been associated with pathogenic/likely pathogenic (P/LP) variants in several genes including: OPA1, OPA3, TMEM126A, WFS1, as well as common point mutations in mitochondrial DNA.

CLINICAL SCENARIOS FOR MOLECULAR TESTING:

Patient Considerations

• The following scenarios are reasonable based on published guidelines and/or current clinical understanding:
  • Patients with a diagnosis of optic atrophy with or without additional features. 

Additional Considerations 

• Are any tests required prior to molecular testing? No
• If the patient has a clinical diagnosis, is molecular testing ever indicated? Yes
• Is repeat testing ever warranted? No
• If the indication for testing is reproductive carrier screening, please see this reference library: Reproductive Carrier Screening

Medical Management

• Are results expected to lead to a change in medical management? Yes
  • Molecular testing has demonstrated an impact to clinical care in this setting for most individuals by:
    • Guiding the selection of additional procedures (laboratory, radiology, etc.)
    • Informing the need for additional surveillance and/or specialty referral for management/monitoring of symptoms, e.g. ophthalmology, ENT, gastroenterology, cardiology, neurology
    • Anticipatory guidance regarding long-term vision loss
    • Directing treatment decisions
    • Informing reproductive decision-making
    • Identifying at-risk family members

TEST CONSIDERATIONS:

• Single gene test or multi-gene panels targeted to the associated genes have clinical utility. 
  • Based on the current commercial laboratory offerings, such panels are commonly available.
• Note, there are rare genetic syndromes with optic atrophy as a feature; most of these syndromes have other distinguishing features that would allow for testing to be targeted to the gene/syndrome highest on the list of differential diagnoses.

Published Guidelines and/or Key Reference Articles:

Published Guidelines

• N/A

Key Reference Articles

• N/A

GeneReviews

• Barrett T, Tranebjærg L, Gupta R, et al. WFS1 Spectrum Disorder. 2009 Feb 24 [Updated 2022 Dec 1]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK4144/

Related Content:

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