TY - JOUR
T1 - Phenotypic heterogeneity of the 8344A>G mtDNA "MERRF" mutation
AU - Mancuso, Michelangelo
AU - Orsucci, Daniele
AU - Angelini, Corrado
AU - Bertini, Enrico
AU - Carelli, Valerio
AU - Comi, Giacomo Pietro
AU - Minetti, Carlo
AU - Moggio, Maurizio
AU - Mongini, Tiziana
AU - Servidei, Serenella
AU - Toninc, Paola
AU - Toscano, Antonio
AU - Uziel, Graziella
AU - Bruno, Claudio
AU - Ienco, Elena Caldarazzo
AU - Filosto, Massimiliano
AU - Lamperti, Costanza
AU - Martinelli, Diego
AU - Moroni, Isabella
AU - Musumeci, Olimpia
AU - Pegoraro, Elena
AU - Ronchi, Dario
AU - Santorelli, Filippo Maria
AU - Sauchelli, Donato
AU - Scarpelli, Mauro
AU - Sciacco, Monica
AU - Spinazzi, Marco
AU - Valentino, Maria Lucia
AU - Vercelli, Liliana
AU - Zeviani, Massimo
AU - Siciliano, Gabriele
PY - 2013/5/28
Y1 - 2013/5/28
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0b013e318294b44c
DO - 10.1212/WNL.0b013e318294b44c
M3 - Article
C2 - 23635963
AN - SCOPUS:84879495511
VL - 80
SP - 2049
EP - 2054
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 22
ER -