IntroductionLeber’s hereditary optic neuropathy is a mitochondrially-inherited disorder characterized by bilateral, painless visual loss, which leads to severe optic atrophy.1 LHON can be associated with an MS-like illness referred to as Harding’s disease.2We report two siblings, who both harbour the 11778 mtDNA mutation, but manifest markedly different clinical phenotypes; a male with classical LHON and a female with Harding’s disease.Methods and ResultsA 61-year-old female, who was diagnosed with MS 22 years ago was referred to our service for a second opinion. She developed unilateral painless visual loss in her 20’s, was diagnosed with optic neuritis and treated with corticosteroids with some recovery. A second episode of more severe visual loss at age 39 left her with visual impairment to less than finger counting. 4 years later, she had an episode of dysarthria and gait ataxia. MRI showed multifocal white matter lesions involving the juxta-cortical and periventricular regions, cerebellar peduncle and cervical cord. Targeted views of the optic pathways showed hyperintensity of the left optic nerve, with involvement extending into the optic canal.The patient has one brother who was diagnosed with LHON at age 37 after presenting with severe painless bilateral sequential visual loss. Genetic testing of the index patient confirmed the presence of the same mutation identified in her brother. ConclusionLHON and Harding’s disease demonstrate a great degree of variability in clinical phenotype and penetrance between males and females as well as individuals within the same family.3 While there is no evidence for screening MS cohorts for the LHON, consider genetic testing in patients with severe and persistent bilateral visual loss or with a suggestive family history.4ReferencesHarding AE, Sweeney MG, Miller DH, Mumford CJ, Kellar-Wood H, Menard D,McDonald WI, Compston DA. Occurrence of a multiple sclerosis-like illness in women who have a Leber’s hereditary optic neuropathy mitochondrial DNA mutation. Brain. 1992 August;115 ( Pt 4):979–89.Palace J. Multiple sclerosis associated with Leber’s Hereditary Optic Neuropathy. J Neurol Sci. 2009 November 15;286(1–2):24–7. Review.Pfeffer G, Burke A, Yu-Wai-Man P, Compston DAS, Chinnery PF. Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations. Neurology. 2013;81(24):2073–2081.Yu-Wai-Man P, Chinnery PF. Leber hereditary optic neuropathy. In: Pagon RA MP, Adam Ardinger HH eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 2013. Accessed May 7, 2018.
A Typical Case Presentation with Spontaneous Visual Recovery in Patient Diagnosed with Leber Hereditary Optic Neuropathy due to Rare Point Mutation in MT-ND4 Gene (m.11253T>C) and Literature Review
