IMPORTANCE: Mitochondrial DNA (mtDNA) disorders have emerged as major causes of 
inherited neurologic disease. Despite being well recognized for more than 2 
decades, the clinical presentation continues to broaden. The phenotypic 
heterogeneity is partly owing to different percentage levels of mutant mtDNA 
heteroplasmy in different tissues, but the factors influencing this are poorly 
understood.
OBSERVATIONS: This case report describes monozygotic male twins with ptosis, 
optic atrophy, and recent-onset intractable myoclonic epilepsy. The assessment 
of respiratory chain enzyme activities in the muscle from 1 twin revealed a 
severe and isolated defect involving mitochondrial complex I. Mitochondrial DNA 
sequencing revealed a pathogenic m.14487T>C MTND6 mutation, which was present at 
very high levels of heteroplasmy in muscle (84%) and lower levels in blood 
(15%), urinary epithelium (75%), and buccal mucosa (58%). Of particular 
interest, his identical twin was found to harbor very similar levels of the 
m.14487T>C mutation in his blood, urine, buccal mucosa, and hair follicle DNA 
samples, while the presence of low levels in the mother's tissues confirmed 
maternal transmission.
CONCLUSIONS AND RELEVANCE: It was shown that m14487T>C can also cause the 
unusual combination of optic atrophy, ptosis, and encephalomyopathy leading to 
intractable seizures. Near-identical heteroplasmy levels in different tissues in 
both siblings support a nuclear genetic mechanism controlling the tissue 
segregation of mtDNA mutations.