Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C

J Neurol Neurosurg Psychiatry. 2010 Jan;81(1):90-3. doi: 10.1136/jnnp.2008.157354.


Background: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported.

Objectives: To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family.

Methods: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies.

Results: Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue.

Interpretation: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Belgium
  • Child
  • DNA, Mitochondrial / genetics
  • Dystonic Disorders / genetics
  • Family
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Leigh Disease / genetics*
  • Male
  • Middle Aged
  • Muscle, Skeletal / pathology
  • Mutation, Missense / genetics
  • Myoclonic Epilepsies, Progressive / genetics*
  • NADH Dehydrogenase / genetics*
  • Pedigree
  • Phenotype
  • Young Adult


  • DNA, Mitochondrial
  • MT-ND6 protein, human
  • NADH Dehydrogenase