title: Phenotypic heterogeneity of the 8344A>G mtDNA "MERRF" mutation.
abstract: OBJECTIVE
  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.
authors: Neurological Clinic, University of Pisa, Pisa, Italy. mancusomichelangelo@gmail.com
authors: Michelangelo
authors: M
authors: Mancuso
authors: Daniele
authors: D
authors: Orsucci
authors: Corrado
authors: C
authors: Angelini
authors: Enrico
authors: E
authors: Bertini
authors: Valerio
authors: V
authors: Carelli
authors: Giacomo Pietro
authors: GP
authors: Comi
authors: Carlo
authors: C
authors: Minetti
authors: Maurizio
authors: M
authors: Moggio
authors: Tiziana
authors: T
authors: Mongini
authors: Serenella
authors: S
authors: Servidei
authors: Paola
authors: P
authors: Tonin
authors: Antonio
authors: A
authors: Toscano
authors: Graziella
authors: G
authors: Uziel
authors: Claudio
authors: C
authors: Bruno
authors: Elena
authors: E
authors: Caldarazzo Ienco
authors: Massimiliano
authors: M
authors: Filosto
authors: Costanza
authors: C
authors: Lamperti
authors: Diego
authors: D
authors: Martinelli
authors: Isabella
authors: I
authors: Moroni
authors: Olimpia
authors: O
authors: Musumeci
authors: Elena
authors: E
authors: Pegoraro
authors: Dario
authors: D
authors: Ronchi
authors: Filippo Maria
authors: FM
authors: Santorelli
authors: Donato
authors: D
authors: Sauchelli
authors: Mauro
authors: M
authors: Scarpelli
authors: Monica
authors: M
authors: Sciacco
authors: Marco
authors: M
authors: Spinazzi
authors: Maria Lucia
authors: ML
authors: Valentino
authors: Liliana
authors: L
authors: Vercelli
authors: Massimo
authors: M
authors: Zeviani
authors: Gabriele
authors: G
authors: Siciliano
mesh_terms: D000328:Adult; D017668:Age of Onset; D004272:DNA, Mitochondrial / Q000235:genetics*; D030541:Databases, Genetic; D018450:Disease Progression; D005260:Female; D006801:Humans; D017243:MERRF Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: D004272:DNA, Mitochondrial