Three Presentations of Female Relatives Affected by 11778 Mutation of Leber's Hereditary Optic Neuropathy (LHON)

Three female cousins presented with unexplained vision loss. The first (19-year-old) developed acutely blurred vision OD; she kept missing the ball during soccer practices. The second (34-year-old in her second pregnancy) reported a history of optic neuritis OS after painless vision loss during her first pregnancy. She had periventricular plaques characteristic of multiple sclerosis (MS). The third (37-year-old) described debilitating headaches and decreased vision OD; she had previously been diagnosed as malingering.

Poster 8 Three Presentations of Female Relatives Affected by 11778 Mutation of Leber's Hereditary Optic Neuropathy (LHON) Sudip Thakar1, Sudip Thakar1, Nicholas Volpe1, Shira Simon1 1 Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA Introduction: Three female cousins presented with unexplained vision loss. The first (19-year-old) developed acutely blurred vision OD; she kept missing the ball during soccer practices. The second (34-year-old in her second pregnancy) reported a history of optic neuritis OS after painless vision loss during her first pregnancy. She had periventricular plaques characteristic of multiple sclerosis (MS). The third (37-year-old) described debilitating headaches and decreased vision OD; she had previously been diagnosed as malingering. Description of Case(s): All three cousins separately reported having four male relatives with severely decreased vision from LHON; they all tested positive for the 11778 mutation. 19-year-old presented with best corrected visual acuity (BCVA) of 20/20 OU and mildly hyperemic discs. Neuroimaging was normal. She started idebenone and her latest BCVA was 20/50 OD, 20/30 OS. 34-year-old presented with BCVA of 20/20 OD, CF 6' OS with segmental pallor OS. Patient had presumed Harding's syndrome (MS-LHON). Idebenone was deferred during pregnancy, and she delivered her second child (26 months after first episode) with stable vision. 37-year-old presented with BCVA of 20/60 OD, 20/20 OS. Neuroimaging was normal. She was enrolled in the GenSIGHT/REFLECT study. Her most recent BCVA is CF 3' OD, 20/200 OS. Conclusions, including unique features of the case(s): LHON is an inherited mitochondrial disorder classically presenting (80-90% of cases) in males during their second-third decade with acute, painless visual deterioration. It remains unclear how and with what severity this affects females. To our knowledge, this is one of only a few reported case-series of three female relatives with LHON with the 11778 mutation in the US. It is prudent that we continue to publicly report these cases to understand common trends and more rapidly detect this disease. Ideally this will help us collaboratively identify therapeutic options for these challenging cases. References: Harding AE, Sweeney MG, Govan GG, Riordan-eva P. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am J Hum Genet. 1995;57(1):77-86. Newman NJ. Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol. 2005;140:517-523 Newman NJ, Lott MT, Wallace DC. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am J Ophthalmol. 1991;111(6):750-62. Ortiz RG, Newman NJ, Manoukian SV, Diesenhouse MC, Lott MT, et al. Optic disk cupping and electrocardiographic abnormalities in an American pedigree with Leber's hereditary optic neuropathy. Am J Ophthalmol. 1992;113(5):561-6. Qu J, Wang Y, Tong Y, Zhou X, Zhao F, et al. Leber's hereditary optic neuropathy affects only female matrilineal relatives in two Chinese families. Invest Ophthalmol Vis Sci. 2010;51(10):4906-12. Thieme H, Wissinger B, Jandeck C, Christ-Adler M, Kraus H, et al. A pedigree of Leber's hereditary optic neuropathy with visual loss in childhood, primarily in girls. Graefes Arch Clin Exp Ophthalmol. 1999;237(9):714-9. Keywords: Optic neuropathy, Genetic disease Financial Disclosures: The authors had no disclosures. Grant Support: None. Contact Information: Shira Simon- [e-mail] 66 | North American Neuro-Ophthalmology Society