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01-03-2020 | Dystonia | Original Communication

Leber hereditary optic neuropathy plus dystonia, and transverse myelitis due to double mutations in MT-ND4 and MT-ND6

Authors: Andres Berardo, Valentina Emmanuele, Wendy Vargas, Kurenai Tanji, Ali Naini, Michio Hirano

Published in: Journal of Neurology | Issue 3/2020

Abstract

Leber hereditary optic neuropathy (LHON) typically presents as painless central or centrocecal scotoma and is due to maternally inherited mitochondrial DNA (mtDNA) mutations. Over 95% of LHON cases are caused by one of three mtDNA “common” point mutations: m.3460G>A, m.11778G>A, or m.14484T>C, which are all in genes encoding structural subunits of complex I of the respiratory chain. Intriguing features of LHON include: incomplete penetrance, tissue specificity, and male predominance, indicating that additional genetic or environmental factors are modulating the phenotypic expression of the pathogenic mtDNA mutations. However, since its original description as a purely ophthalmological disorder, LHON has also been linked to multisystemic conditions with variable neurological, cardiac, and skeletal abnormalities. Although double “common” mutations have been reported to cause LHON and LHON-plus, they are extremely rare. Here, we present a patient with an unusual double point mutation (m.11778 G>A and m.14484T>C) with a multisystemic LHON-plus phenotype characterized by: optic neuropathy, ptosis, ataxia, dystonia, dysarthria, and recurrent extensive transverse myelitis.

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Title: Leber hereditary optic neuropathy plus dystonia, and transverse myelitis due to double mutations in MT-ND4 and MT-ND6
Authors: Andres Berardo
Valentina Emmanuele
Wendy Vargas
Kurenai Tanji
Ali Naini
Michio Hirano
Publication date: 01-03-2020
Publisher: Springer Berlin Heidelberg
Keywords: Dystonia
Neuromyelitis Optica Spectrum Disease
Ptosis
Published in: Journal of Neurology / Issue 3/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-019-09619-z

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Leber hereditary optic neuropathy plus dystonia, and transverse myelitis due to double mutations in MT-ND4 and MT-ND6

Abstract

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Abstract

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