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

  • Andres Berardo
  • Valentina Emmanuele
  • Wendy Vargas
  • Kurenai Tanji
  • Ali Naini
  • Michio HiranoEmail author
Original Communication


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.


Leber hereditary optic neuropathy Transverse myelitis Dystonia Mitochondrial DNA Mutation 


Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Informed consent

We have obtained the patient’s permission and informed consent for the publishing of his information and images.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, H. Houston Merritt Neuromuscular Research CenterColumbia University Medical CenterNew YorkUSA
  2. 2.Department of Pathology and Cell BiologyColumbia UniversityNew YorkUSA

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