Are duplications of mitochondrial DNA characteristic of Kearns--Sayre syndrome?

The phenotypes of Kearns–Sayre syndrome (KSS) and chronicprogressive external ophthalmoplegia (CPEO) are closely associatedwith deletions of mitochondrial DNA (mtDNA). Recent evidencesuggesting that more than one type of rearrangement may be presentin KSS led us to reinvestigate 18 patients with KSS or CPEOfor the presence of mtDNA rearrangements other than deletion.mtDNA duplication was detectable in 10 of 10 patients with KSS,while deletion monomers were the only recombinant mtDNA easilydetectable in eight of eight patients with CPEO. Deletion dimerswere found only in cases having duplications. Thus, duplicationsof mtDNA seem to be a hallmark of KSS, including a patient wherePearson's syndrome was the first manifestation. We suggest thatduplication of mtDNA is characteristic of the early-onset diseaseKSS, and that the balance of mtDNA rearrangements may be centralto the pathogenesis of this unique group of disorders.