Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations

Pfeffer, Gerald; Burke, Ailbhe; Yu‐Wai‐Man, Patrick; Compston, D. A. S.; Chinnery, Patrick F.

doi:10.1212/01.wnl.0000437308.22603.43

Cited by 107 publications

(92 citation statements)

References 40 publications

(29 reference statements)

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“…It's due to mutation in the mitochondrial genome (mtDNA) and occasionally associated with neurological, cardiac, and skeletal changes [18,19]. This disease may have a clinical features that mimics a multiple sclerosis (sclerosis-like syndrome) [20] or be associated with an authentic multiple sclerosis defining the "Harding's syndrome" making the diagnosis even more challenging for the clinician [21,22]. Moreover, LHON can mimic not only MS, but also neuromyelitis optica [23] or Susac syndrome [19].…”

Section: Discussionmentioning

confidence: 99%

Bilateral and Simultaneous Retrobulbar Optic Neuritis Revealing Multiple Sclerosis

Bouomrani¹,

Belgacem²,

Rekik³

et al. 2017

J Mult Scler

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Optic neuritis is a common manifestation of multiple sclerosis. It occurs in two thirds of patients at some point in the course of this disease and is usually unilateral, acute and often recurrent. However, optic neuritis can be the first manifestation of this demyelinating disease in 15 to 20% of cases.Bilateral, simultaneous and retrobulbar forms of optic neuritis inaugurating multiple sclerosis remain exceptional and unusual. They represent a real diagnostic challenge and require special attention from the clinician Herein we report the case of bilateral simultaneous and isolated retrobulbar optic neuritis inaugurating multiple sclerosis in a 24 year old woman.

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Section: Discussionmentioning

confidence: 99%

Bilateral and Simultaneous Retrobulbar Optic Neuritis Revealing Multiple Sclerosis

Bouomrani¹,

Belgacem²,

Rekik³

et al. 2017

J Mult Scler

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“…Some patients with LHON also present with clinical and MRI features suggesting multiple sclerosis. The disorder resulting from the co-occurrence of LHON and multiple sclerosis (‘Harding's disease’) has a distinct phenotype, suggesting a mechanistic interaction between these two diseases39 (figure 4). OPA1 encodes a dynamin-related GTPase-like OPA1 protein that is involved in mitochondrial dynamics.…”

Section: Optic Neuropathy and Pigmentary Retinopathymentioning

confidence: 99%

Mitochondrial disease: mimics and chameleons

Martikainen

Chinnery

2015

Pract Neurol

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Mitochondrial diseases are inherited disorders of oxidative phosphorylation that present with a multitude of clinical features in different combinations and with various inheritance patterns. To complicate the issue further, the clinical features of mitochondrial disorders overlap with common neurological and non-neurological diseases. This presents a diagnostic challenge: when is a rare mitochondrial disease responsible for a more 'common or garden' neurological presentation, and how often are neurologists missing them in routine clinical practice? Here, we briefly review some common clinical features associated with mitochondrial disease, and provide some clues as to how patients with these mitochondrial disorders might be identified. We discuss both 'chameleons'-mitochondrial disorders that may look like something else, and 'mimics'-other conditions that may clinically resemble mitochondrial disease. The diagnosis sometimes needs highly specialised tests, but the advent of 'next generation' sequencing will simplify the clinical approach over the next few years.

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“…Optic atrophy can be isolated or associated with multi-systemic involvement (syndromic; Allen et al, 2015) such as in Costeff's syndrome (methyl-glutaconic aciduria type 3; OMIM 258501; Ho et al, 2008), Behr's syndrome (OMIM 210000; Pyle et al, 2014) or Wolfram syndrome (OMIM 598500;Safarpour et al, 2016). While multiple modes of inheritance have been reported, autosomal dominant optic atrophy (ADOA) and mitochondrial inherited Leber's hereditary optic neuropathy (LHON) are the most common forms (Pfeffer et al, 2013;Skidd et al, 2013). Optic atrophy type 1, caused by mutations in the OPA1 gene is believed to be the most common hereditary optic neuropathy, and most patients inherit a mutation from an affected parent.…”

Section: Introductionmentioning

confidence: 99%

Exome sequencing identified a novelde novo OPA1mutation in a consanguineous family presenting with optic atrophy

et al. 2016

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SummaryInherited optic neuropathies are a heterogeneous group of disorders characterized by mild to severe visual loss, colour vision deficit, central or paracentral visual field defects and optic disc pallor. Optic atrophies can be classified into isolated or non-syndromic and syndromic forms. While multiple modes of inheritance have been reported, autosomal dominant optic atrophy and mitochondrial inherited Leber's hereditary optic neuropathy are the most common forms. Optic atrophy type 1, caused by mutations in the OPA1 gene is believed to be the most common hereditary optic neuropathy, and most patients inherit a mutation from an affected parent. In this study we used whole-exome sequencing to investigate the genetic aetiology in a patient affected with isolated optic atrophy. Since the proband was the only affected individual in his extended family, and was a product of consanguineous marriage, homozygosity mapping followed by whole-exome sequencing were pursued. Exome results identified a novel de novo OPA1 mutation in the proband. We conclude, that though de novo OPA1 mutations are uncommon, testing of common optic atrophy-associated genes such as mitochondrial mutations and OPA1 gene sequencing should be performed first in single individuals presenting with optic neuropathy, even when dominant inheritance is not apparent.

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Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations

Cited by 107 publications

References 40 publications

Bilateral and Simultaneous Retrobulbar Optic Neuritis Revealing Multiple Sclerosis

Bilateral and Simultaneous Retrobulbar Optic Neuritis Revealing Multiple Sclerosis

Mitochondrial disease: mimics and chameleons

Exome sequencing identified a novelde novo OPA1mutation in a consanguineous family presenting with optic atrophy

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