Acute optic neuropathy associated with a novel MFN2 mutation

Area of Science:

• Genetics
• Neurology
• Ophthalmology

Background:

• Mutations in the mitofusin 2 (MFN2) gene are the primary cause of Charcot-Marie-Tooth disease type 2A (CMT2A), an autosomal dominant axonal neuropathy.
• MFN2 mutations also cause Hereditary Motor Sensory Neuropathy type VI (HMSN VI), a rare early-onset axonal CMT associated with optic neuropathy, typically presenting sub-acutely.

Observation:

• A 40-year-old male with slowly progressive gait disturbance and lower limb weakness was diagnosed with CMT2.
• Genetic analysis revealed a novel heterozygous c.775C>T (p.Arg259Cys) mutation in MFN2.
• The patient experienced sudden, severe bilateral visual deterioration, indicative of acute optic neuropathy.

Findings:

• This case presents a CMT2A patient with a rapidly progressing, severe optic neuropathy, a manifestation not typically seen in this form.
• The identified MFN2 mutation expands the genotypic spectrum associated with MFN2-related neuropathies.
• The optic neuropathy in this patient occurred later in the disease course, challenging the notion of it being exclusively an early-onset feature.

Implications:

• This report broadens the differential diagnosis for acute-onset bilateral optic neuropathies, suggesting MFN2-related disorders should be considered.
• Clinicians evaluating patients with unexplained acute optic neuropathy, especially when accompanied by axonal neuropathy, should consider MFN2 mutations.
• Understanding the varied clinical presentations of MFN2 mutations is crucial for accurate diagnosis and patient management.