Sibling Cases of Leber’s Hereditary Optic Neuropathy with the m.4171C>A Mutation

While 90% of Leber’s hereditary optic neuropathy (LHON) cases are caused by three primary mutations, rare variants like m.4171C>A also exist, but their clinical profiles are not yet well-defined. We report two Japanese sibling cases with the m.4171C>A mutation. Case 1 (a 20-year-old male) presented with a progressive decline in right eye (RE) Best-Corrected Visual Acuity (BCVA) to 0.07, accompanied by subtle funduscopic findings. BCVA later declined to less than 0.1 bilaterally with no recovery. Case 2 (a 24-year-old male) experienced a rapid bilateral decline in BCVA to 0.01 within two weeks, worsening to counting fingers, again with minimal acute signs and no recovery. Both tested negative for primary mutations but positive for m.4171C>A. A review of 18 published cases suggests that m.4171C>A often has a younger onset and potentially a better prognosis (61% achieving a better than 0.1 BCVA) than primary mutations, yet rapid deterioration can still occur. Our cases, the first Japanese siblings reported, highlight a rapid decline in BCVA, poor prognosis, and subtle acute optic disc findings. This clinical diversity underscores the need to consider m.4171C>A in LHON diagnosis, even in atypical presentations. Age, haplogroup, and other variants may influence prognosis.