• mitochondrial DNA
• single deletion
• identical twins

• CPEO, chronic progressive external ophthalmoplegia
• KSS, Kearns-Sayre syndrome
• PS, Pearson’s syndrome

Defects of mitochondrial DNA (mtDNA) are an important cause of genetic disease in humans.¹ The defect may take the form of a deletion or point mutation, and clinical features range from severe neonatal illness to mild muscle weakness later in life.² In a recent epidemiology study, single large scale mtDNA deletion disorders represented approximately 25% of adult patients with mtDNA disease.³ The three main syndromes observed in these patients are Pearson’s syndrome (PS), a severe systemic illness of childhood associated with sideroblastic anaemia; Kearns-Sayre syndrome (KSS) which is also associated with multiple system involvement; and chronic progressive external ophthalmoplegia (CPEO) in which the predominant clinical problem relates to an eye movement disturbance and ptosis. In both KSS and PS the mtDNA deletion is present in many tissues,^4–6 whereas in CPEO, the mtDNA deletion is found in muscle but not other tissues.^5,7

In patients with single large scale mtDNA deletions, it is not established at which stage in development the mtDNA deletion occurs. For the vast majority of cases, there is no family history and as described above, the mtDNA deletion may be limited to a single tissue. Recently, we had the opportunity to study 31 year old twin brothers who were genetically identical in terms of nuclear markers, but one had developed CPEO whereas the other was completely asymptomatic. We hoped that by studying these brothers we might gain further insight into the origin of the mtDNA deletion.