Myoclonus epilepsy with ragged-red fibers

Michelangelo Mancuso MD PhD (Dr. Mancuso received research grants and consultation fees from Shire, Actelion, Valeas, and Stealth.)
Salvatore DiMauro MD, editor. (Dr. DiMauro, Director Emeritus of H Houston Merritt Clinical Center for the Study of Muscular Dystrophy and Related Diseases at Columbia University, has no relevant financial relationships to disclose.)
Originally released September 6, 1993; last updated August 24, 2016; expires August 24, 2019

This article includes discussion of myoclonus epilepsy with ragged-red fibers and MERRF. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Myoclonus epilepsy with ragged-red fibers (MERRF) is a multisystem mitochondrial disorder defined by myoclonus, generalized epilepsy, ataxia, and myopathy with ragged-red fibers detected in muscle biopsy. MERRF is a clinical syndrome that has been associated with at least 6 different point mutations of mitochondrial DNA; however, about 80% of MERRF patients harbor an A-to-G transition at nucleotide 8344 (m.8344A>G) of the MT-TK gene that is a hot spot for MERRF mutations. The pathogenesis of the disease is incompletely understood. In this article, the authors refer to reports from Italian and German cohorts that the great majority of 8344A>G patients do not have myoclonus and that myoclonus, if present, is not inextricably linked to epilepsy but, at least in the Italian population, is linked with cerebellar ataxia. Hence, the term “myoclonic epilepsy” seems inadequate, and the acronym MERRF could better be read as myoclonic encephalomyopathy with ragged-red fibers.

Key points

 

• Myoclonus epilepsy with ragged-red fibers (MERRF) is clinically defined by: myoclonus, generalized epilepsy, ataxia, and myopathy with ragged-red fibers.

 

• In addition, MERRF patients often have sensorineural hearing loss, cognitive impairment, multiple lipomatosis, peripheral neuropathy, exercise intolerance, ptosis, ophthalmoparesis, optic atrophy, cardiomyopathy, muscle wasting, respiratory impairment, diabetes, muscle pain, tremor, and migraine.

 

• About 80% of patients with MERRF have a pathogenic m.8344A>G mutation in the MT-TK gene encoding tRNALys.

 

• The term “myoclonic epilepsy” seems inadequate, and the acronym MERRF could better be read as myoclonic encephalomyopathy with ragged-red fibers.

Historical note and terminology

In 1921 Ramsay Hunt described 6 patients with a disorder resembling Friedreich ataxia characterized by ataxia, myoclonus, and epilepsy, which he called "dyssynergia cerebellaris myoclonica" (Hunt 1921). Several different disorders have been associated with this clinical triad; however, over 50 years passed before mitochondrial abnormalities were described in 1 family with these clinical features (Tsairis et al 1973). In 1980 Fukuhara and colleagues reported 2 patients with a syndrome that they named "myoclonus epilepsy associated with ragged-red fibers" (Fukuhara et al 1980). Eight years later, Shoffner and colleagues identified a mitochondrial DNA point mutation in myoclonus epilepsy with ragged-red fibers pedigrees (Shoffner et al 1990).

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