Meiotic breakpoint mapping of a proposed X linked visual loss susceptibility locus in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a rare, maternally transmitted disease that most commonly causes acute or subacute visual loss in young men, typically between the ages of 17 and 24 years (although perhaps 14% of affected individuals are women), which may be associated with systemic disorders, eg, cardiac dysrhythmias and neurologic problems.1 Onset is usually asymmetric, but intervals between involvement of the two eyes are usually less than a few months. A definitive diagnosis rested on a family history, age of onset, and the characteristic circumpapillary microangiopathy of the optic disc in the acute phase. However, recent demonstration of point mutations of mitochondrial DNA in affected individuals means that confirmation of the diagnosis can now be obtained in atypical or sporadic cases.2

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Antiretroviral therapy-induced Leber’s hereditary optic neuropathy

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v15i2.24 ◽

2014 ◽

Vol 15 (2) ◽

pp. 69-71 ◽

Cited By ~ 2

Author(s):

Anand Moodley ◽

Sudika Bhola ◽

Fierdoz Omar ◽

Jade Mogambery

Keyword(s):

Antiretroviral Therapy ◽

Optic Neuropathy ◽

Visual Loss ◽

Opportunistic Infections ◽

Genetic Disorders ◽

Mitochondrial Disorder ◽

Phenotypic Expression ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Hereditary Optic Neuropathy

Optic neuropathy in HIV-infected patients results from the HIV infection itself, post-infectious auto-immune disease, opportunistic infections and drugs. Nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber’s hereditary optic neuropathy (LHON), a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking. We report on two HIV-infected patients with LHON mutations (m.14484T>C and m.11778G>A) who developed profound visual loss with antiretroviral therapy. We postulate that the phenotypic expression of LHON in these genetically predisposed individuals was triggered by NRTI drugs lamivudine and tenofovir when used in combination, despite their relatively weak mitochondrial toxic effects.

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Leber’s hereditary optic neuropathy following unilateral painful optic neuritis: a case report

BMC Ophthalmology ◽

10.1186/s12886-020-01461-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Chaeyeon Lee ◽

Kyung-Ah Park ◽

Ga-In Lee ◽

Sei Yeul Oh ◽

Ju-Hong Min ◽

...

Keyword(s):

Visual Acuity ◽

Optic Neuritis ◽

Optic Neuropathy ◽

Visual Loss ◽

Early Stage ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Intravenous Methylprednisolone ◽

The Right ◽

Hereditary Optic Neuropathy

Abstract Background Leber’s hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease, characterized by acute or subacute, painless, bilateral visual loss. LHON is often misdiagnosed as optic neuritis at an early stage because of the similarity of their clinical presentation. To date, there has been no reported case of actual optic neuritis and LHON in one patient. Case presentation A 40-year-old, healthy man was referred to our clinic with acute painful visual loss in the right eye for 2 weeks. In the right eye, visual acuity decreased to 20/40, and the Ishihara colour test score was 8/14 with a relative afferent pupillary defect. Optic disc swelling was found only in the right eye, and magnetic resonance imaging revealed enhancement of the the right optic nerve, consistent with optic neuritis. After receiving 1 g of intravenous methylprednisolone daily for three days, his ocular pain resolved, and visual acuity improved to 20/20 within 2 weeks. Seven months later, the patient developed acute painless visual loss in the right eye. Visual acuity decreased to 20/200 in the right eye. There was no response to the intravenous methylprednisolone therapy at that time. Eight months later, he developed subacute painless visual loss in the left eye. Genetic testing for LHON was performed and revealed the pathologic mtDNA 11778 point mutation. Conclusions We report a case with painful unilateral optic neuritis preceding the onset of LHON. Even if a typical optic neuritis patient has completely recovered from steroid treatment once in the past, it is advisable to keep in mind the possibility of LHON if acute or subacute loss of vision subsequently or simultaneously occurs in both eyes and does not respond to steroids.

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048 Harding’s disease: an important MS mimic

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-anzan.43 ◽

2019 ◽

Vol 90 (e7) ◽

pp. A16.2-A16

Author(s):

Stuti Joshi ◽

Allan Kermode

Keyword(s):

Multiple Sclerosis ◽

Genetic Testing ◽

Optic Neuropathy ◽

Visual Loss ◽

List Type ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Leber Hereditary Optic Neuropathy ◽

Mtdna Mutations ◽

Hereditary Optic Neuropathy

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.

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Severe sequential visual loss in MS co-diagnosis of Leber's hereditary optic neuropathy

Canadian Journal of Ophthalmology ◽

10.1016/j.jcjo.2018.06.020 ◽

2019 ◽

Vol 54 (2) ◽

pp. e69-e70

Author(s):

Patricia M. Riccio ◽

J. Alexander Fraser ◽

Donald H. Lee ◽

Sarah A. Morrow

Keyword(s):

Optic Neuropathy ◽

Visual Loss ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Hereditary Optic Neuropathy

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Leber’s hereditary optic neuropathy - case report

Journal of Health Sciences ◽

10.17532/jhsci.2012.54 ◽

2012 ◽

Vol 2 (2) ◽

pp. 148-152

Author(s):

Mirjana A. Janicijevic Petrovic ◽

Tatjana Sarenac Vulovic ◽

Nenad Petrovic ◽

Suncica Sreckovic ◽

Svetlana Paunovic ◽

...

Keyword(s):

Visual Acuity ◽

Optic Neuropathy ◽

Visual Loss ◽

Positive Family History ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Inheritance Pattern ◽

Visual Improvement ◽

Hereditary Optic Neuropathy ◽

Biochemical Abnormalities

Leber’s hereditary optic neuropathy is a neuro-ophthalmological entity characterized by acute or subacute bilateral, not simultaneous visual loss with centro cekal scotoma and occasional further visual improvement. This rare ophthalmological disease can be accompanied with dyschromatopsia. It is associated with a matrilineal inheritance pattern. Its diagnosis used to be solely clini¬cal, aided by imaging and neuro-physiological studies, until the advent of descriptions of mitochondrial biochemical abnormalities and genetic testing. We describe a case of 24 year old male with progressive painless deterioration of visual acuity and positive family history.

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A pedigree of Leber's hereditary optic neuropathy with visual loss in childhood, primarily in girls

Graefe s Archive for Clinical and Experimental Ophthalmology ◽

10.1007/s004170050301 ◽

1999 ◽

Vol 237 (9) ◽

pp. 714-719 ◽

Cited By ~ 12

Author(s):

Hagen Thieme ◽

Bernd Wissinger ◽

Claudia Jandeck ◽

Margot Christ-Adler ◽

Hannelore Kraus ◽

...

Keyword(s):

Optic Neuropathy ◽

Visual Loss ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Hereditary Optic Neuropathy

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Leber's hereditary optic neuropathy: case report and literature review

Sao Paulo Medical Journal ◽

10.1590/s1516-31802004000600010 ◽

2004 ◽

Vol 122 (6) ◽

pp. 276-279 ◽

Cited By ~ 2

Author(s):

Hélio Afonso Ghizoni Teive ◽

André Ribeiro Troiano ◽

Salmo Raskin ◽

Lineu César Werneck

Keyword(s):

Case Report ◽

Optic Neuropathy ◽

Visual Loss ◽

Young Male ◽

Ophthalmological Examination ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Conduction Disturbances ◽

Testing Case ◽

Hereditary Optic Neuropathy

CONTEXT: Leber's hereditary optic neuropathy is an important cause of progressive painless visual loss among young male patients. OBJECTIVE: To report on a case of a young patient with a clinical and neurophysiological condition suggestive of Leber's hereditary optic neuropathy, confirmed by genetic testing. CASE REPORT: We describe a 17-year-old male with progressive bilateral visual loss. Two maternal uncles had had similar patterns of visual loss. The patient had a history of smoking and alcohol abuse. Neuro-ophthalmological examination revealed visual acuity of 20/800 in both eyes, with decreased direct and consensual pupillary light reflexes. Fundus examination demonstrated pale optic discs. The visual evoked potential test showed signs of conduction disturbances in both optic nerves and campimetric study showed complete visual loss in all fields of both eyes. A diagnosis of bilateral optic neuropathy with a clinical suspicion of Leber's hereditary optic neuropathy was made. A blood sample was submitted to genetic analysis in relation to the principal mutations of this disorder, and homoplasmic mutation in 11778 was detected, thereby confirming the diagnosis of Leber's hereditary optic neuropathy.

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Ladies with Leber's Hereditary Optic Neuropathy: An Atypical Disease

European Journal of Ophthalmology ◽

10.1177/112067210201200615 ◽

2002 ◽

Vol 12 (6) ◽

pp. 537-541 ◽

Cited By ~ 13

Author(s):

S.S. Dandekar ◽

E.M. Graham ◽

G.T. Plant

Keyword(s):

Optic Neuropathy ◽

Visual Loss ◽

Dna Analysis ◽

Past History ◽

Case Reports ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Increased Risk ◽

History Of ◽

Hereditary Optic Neuropathy

Purpose Leber's Hereditary Optic Neuropathy (LHON) is considered to be a disease predominantly affecting young males. The risk of women becoming symptomatic if they are carriers of a primary mutation is 1/5 of that in males. The disease however appears to behave differently in women in some instances. We describe three cases of ladies with LHON and discuss the importance of making the diagnosis. Case Reports A 28-year-old female presented with blurring of vision in her left eye with bilateral small hyperemic discs and telangiectatic vessels adjacent to them. DNA analysis confirmed the 11778 mutation and the second eye remains unaffected 10 years later. The second case was 49 years old and presented with bilateral visual loss developing over 3 months. She had no family history of visual loss but had a past history of Wolf Parkinson White syndrome and 3460 mutation was confirmed. The last case was diagnosed with multiple sclerosis at age 24 and went on to develop visual loss with poor recovery. DNA analysis demonstrated the 11778 mutation and confirmed LHON. Conclusions All three cases, although not unique, posed considerable diagnostic difficulties over a long period of time. The authors have highlighted important associations of the disease and stress the importance of making the diagnosis in women. They are at increased risk of having affected children, unlike the affected males, especially if they are affected themselves and may wish to seek further genetic advice.

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Emerging Treatments for Leber's Hereditary Optic Neuropathy and Other Genetic Causes of Visual Loss

Seminars in Neurology ◽

10.1055/s-0039-3399504 ◽

2019 ◽

Vol 39 (06) ◽

pp. 732-738

Author(s):

Tatiana Bakaeva ◽

Robert Mallery ◽

Sashank Prasad

Keyword(s):

Optic Neuropathy ◽

Visual Loss ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Ethical Challenges ◽

Genetic Causes ◽

Gene Therapies ◽

Emerging Treatments ◽

New Treatments ◽

Hereditary Optic Neuropathy

AbstractLeber's hereditary optic neuropathy (LHON) and other genetic causes of visual loss are important clinical entities that can cause profound visual loss. To date, therapeutic options have been quite limited, but insights into the genetic basis of these diseases and advances in the ability to deliver effective and safe gene therapy have opened the door for new therapeutics that may revolutionize the approach to treating these conditions. This article reviews emerging gene therapies of LHON and other inherited ophthalmological diseases, addressing the technical, clinical, and ethical challenges that researchers and clinicians will encounter as new treatments become available for these conditions.

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