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

J Neurol. 2020 Mar;267(3):823-829. doi: 10.1007/s00415-019-09619-z. Epub 2019 Nov 27.


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.

Keywords: Dystonia; Leber hereditary optic neuropathy; Mitochondrial DNA; Mutation; Transverse myelitis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Dystonia / genetics*
  • Dystonia / pathology*
  • Humans
  • Male
  • Myelitis, Transverse / etiology
  • Myelitis, Transverse / pathology*
  • NADH Dehydrogenase / genetics*
  • Optic Atrophy, Hereditary, Leber / genetics*
  • Optic Atrophy, Hereditary, Leber / pathology*
  • Point Mutation


  • NADH dehydrogenase subunit 4
  • MT-ND6 protein, human
  • NADH Dehydrogenase

Supplementary concepts

  • Marsden syndrome