Redefining phenotypes associated with mitochondrial DNA single deletion

Michelangelo Mancuso, Daniele Orsucci, Corrado Angelini, Enrico Bertini, Valerio Carelli, Giacomo Pietro Comi, Maria Alice Donati, Antonio Federico, Carlo Minetti, Maurizio Moggio, Tiziana Mongini, Filippo Maria Santorelli, Serenella Servidei, Paola Tonin, Antonio Toscano, Claudio Bruno, Luca Bello, Elena Caldarazzo Ienco, Elena Cardaioli, Michela CatterucciaPaola Da Pozzo, Massimiliano Filosto, Costanza Lamperti, Isabella Moroni, Olimpia Musumeci, Elena Pegoraro, Dario Ronchi, Donato Sauchelli, Mauro Scarpelli, Monica Sciacco, Maria Lucia Valentino, Liliana Vercelli, Massimo Zeviani, Gabriele Siciliano

Research output: Contribution to journalArticlepeer-review


Progressive external ophthalmoplegia (PEO), Kearns–Sayre syndrome (KSS) and Pearson syndrome are the three sporadic clinical syndromes classically associated with single large-scale deletions of mitochondrial DNA (mtDNA). PEO plus is a term frequently utilized in the clinical setting to identify patients with PEO and some degree of multisystem involvement, but a precise definition is not available. The purpose of the present study is to better define the clinical phenotypes associated with a single mtDNA deletion, by a retrospective study on a large cohort of 228 patients from the database of the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”. In our database, single deletions account for about a third of all patients with mtDNA-related disease, more than previously recognized. We elaborated new criteria for the definition of PEO and “KSS spectrum” (a category of which classic KSS represents the most severe extreme). The criteria for “KSS spectrum” include the resulting multisystem clinical features associated with the KSS features, and which therefore can predict their presence or subsequent development. With the new criteria, we were able to classify nearly all our single-deletion patients: 64.5 % PEO, 31.6 % KSS spectrum (including classic KSS 6.6 %) and 2.6 % Pearson syndrome. The deletion length was greater in KSS spectrum than in PEO, whereas heteroplasmy was inversely related with age at onset. We believe that the new phenotype definitions implemented here may contribute to a more homogeneous patient categorization, which will be useful in future cohort studies of natural history and clinical trials.

Original languageEnglish
Pages (from-to)1301-1309
Number of pages9
JournalJournal of Neurology
Issue number5
Publication statusPublished - Mar 26 2015


  • CPEO
  • KSS
  • Mitochondrial disorders
  • mtDNA
  • Pearson syndrome
  • Single deletion

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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