Phenotypic heterogeneity of the 8344A>G mtDNA "MERRF" mutation

Michelangelo Mancuso, Daniele Orsucci, Corrado Angelini, Enrico Bertini, Valerio Carelli, Giacomo Pietro Comi, Carlo Minetti, Maurizio Moggio, Tiziana Mongini, Serenella Servidei, Paola Toninc, Antonio Toscano, Graziella Uziel, Claudio Bruno, Elena Caldarazzo Ienco, Massimiliano Filosto, Costanza Lamperti, Diego Martinelli, Isabella Moroni, Olimpia MusumeciElena Pegoraro, Dario Ronchi, Filippo Maria Santorelli, Donato Sauchelli, Mauro Scarpelli, Monica Sciacco, Marco Spinazzi, Maria Lucia Valentino, Liliana Vercelli, Massimo Zeviani, Gabriele Siciliano

Research output: Contribution to journalArticlepeer-review


Objectives: Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial syndrome, mostly caused by the 8344A>G mitochondrial DNA mutation. Most of the previous studies have been based on single case/family reports or series with few patients. The primary aim of this study was the characterization of a large cohort of patients with the 8344A>G mutation. The secondary aim was revision of the previously published data. Methods: Retrospective, database-based study (Nation-wide Italian Collaborative Network of Mitochondrial Diseases) and systematic revision. Results: Forty-two patients carrying the mutation were identified. The great majority did not have full-blown MERRF syndrome. Myoclonus was present in 1 of 5 patients, whereas myopathic signs and symptoms, generalized seizures, hearing loss, eyelid ptosis, and multiple lipomatosis represented the most common clinical features. Some asymptomatic mutation carriers have also been observed. Myoclonus was more strictly associated with ataxia than generalized seizures in adult 8344A.G subjects. Considering all of the 321 patients so far available, including our dataset and previously published cases, at the mean age of approximately 35 years, the clinical picture was characterized by the following signs/symptoms, in descending order: myoclonus, muscle weakness, ataxia (35%-45% of patients); generalized seizures, hearing loss (25%-34.9%); cognitive impairment, multiple lipomatosis, neuropathy, exercise intolerance (15%-24.9%); and increased creatine kinase levels, ptosis/ophthalmoparesis, optic atrophy, cardiomyopathy, muscle wasting, respiratory impairment, diabetes, muscle pain, tremor, migraine (5%-14.9%). Conclusions: Our results showed higher clinical heterogeneity than commonly thought. Moreover, MERRF could be better defined as a myoclonic ataxia rather than a myoclonic epilepsy.

Original languageEnglish
Pages (from-to)2049-2054
Number of pages6
Issue number22
Publication statusPublished - May 28 2013

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)


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