Open AccessLeber hereditary optic neuropathy plus dystonia, and transverse myelitis due to double mutations in MT-ND4 and MT-ND6
Author(s) -
Andrés Berardo,
Valentina Emmanuele,
Wendy Vargas,
Kurenai Tanji,
Ali Naini,
Michio Hirano
Publication year - 2019
Publication title -
journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 136
eISSN - 1432-1459
pISSN - 0340-5354
DOI - 10.1007/s00415-019-09619-z
Subject(s) - optic neuropathy , leber's hereditary optic neuropathy , point mutation , penetrance , external ophthalmoplegia , ataxia , mitochondrial disease , mitochondrial dna , acute transverse myelitis , genetics , medicine , fatal familial insomnia , mutation , transverse myelitis , biology , pathology , optic nerve , phenotype , ophthalmology , neuroscience , gene , disease , immunology , prion protein , multiple sclerosis
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.