Article Text

This article has a correction. Please see:

Download PDFPDF
Leber hereditary optic neuropathy
  1. P Y W Man,
  2. D M Turnbull,
  3. P F Chinnery
  1. Department of Neurology, School of Neurosciences and Psychiatry, The Medical School, University of Newcastle Upon Tyne, UK
  1. Correspondence to:
 Dr P F Chinnery, Department of Neurology, School of Neurosciences and Psychiatry, The Medical School, University of Newcastle Upon Tyne, Newcastle upon Tyne, UK;


Leber hereditary optic neuropathy (LHON) is a mitochondrial genetic disease that preferentially causes blindness in young adult males, affecting about 1 in 25 000 of the British population. It is characterised by bilateral subacute loss of central vision owing to focal degeneration of the retinal ganglion cell layer and optic nerve. Over 95% of LHON cases are primarily the result of one of three mitochondrial DNA (mtDNA) point mutations, G3460A, G11778A, and T14484C, which all involve genes encoding complex I subunits of the respiratory chain. An intriguing feature of LHON is that only ∼50% of males and ∼10% of females who harbour a pathogenic mtDNA mutation actually develop the optic neuropathy. This marked incomplete penetrance and gender bias imply that additional mitochondrial and/or nuclear genetic factors must be modulating the phenotypic expression of LHON. It is also likely that environmental factors contribute to the onset of visual failure. However, these secondary precipitating factors remain poorly defined at present. In this review, we describe the natural history of this optic nerve disorder and highlight issues relating to clinical diagnosis, management, and genetic counselling. We also discuss the findings of recently published studies and the light they shed on the complex aetiology and pathophysiology of LHON.

  • mitochondrial DNA
  • optic atrophy
  • optic nerve
  • Leber hereditary optic neuropathy
  • Leber optic atrophy
  • LHON, Leber hereditary optic neuropathy
  • mtDNA, mitochondrial DNA
  • MS, multiple sclerosis
  • MHC, major histocompatibility complex
  • VEPs, visual evoked potentials
  • ADOA, autosomal dominant optic atrophy

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Correction
    BMJ Publishing Group Ltd