Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G)

Am J Med Genet. 1994 Apr 15;50(3):265-71. doi: 10.1002/ajmg.1320500310.


Mutation of mitochondrial (mt) DNA at nucleotide (nt) 8993 has been reported to cause neurogenic weakness, ataxia, retinitis pigmentosa (NARP), or Leigh syndrome (LS). We report a family in whom the mutation was expressed clinically as LS and hypertrophic cardiomyopathy (CMP) in a boy who presented with a history of developmental delay and hypotonia, and who had recurrent lactic acidosis. The mother's first pregnancy resulted in the birth of a stillborn female; an apparently healthy older brother had died suddenly (SIDS) at age 2 months. MtDNA analysis identified the presence of the T8993G point mutation, which was found to be heteroplasmic in the patient's skeletal muscle (90%) and fibroblasts (90%). The identical mutation was present in leukocytes (38%) isolated from the mother, but not from the father or maternal grandmother. Our findings expand the clinical phenotype of the nt 8993 mtDNA mutation to include hypertrophic cardiomyopathy and confirm its cause of LS.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Acidosis, Lactic / genetics*
  • Adult
  • Base Sequence
  • Brain Diseases, Metabolic / genetics*
  • Cardiomyopathy, Hypertrophic / genetics*
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Fatal Outcome
  • Female
  • Fetal Death / genetics
  • Humans
  • Infant
  • Male
  • Mitochondrial Myopathies / genetics*
  • Molecular Sequence Data
  • Muscle Hypotonia / genetics*
  • Pedigree
  • Point Mutation*
  • Recurrence
  • Sudden Infant Death / genetics
  • Syndrome


  • DNA, Mitochondrial