NORD gratefully acknowledges Salvatore DiMauro, MD, Lucy G. Moses Professor of Neurology, Columbia University Medical Center, for assistance in the preparation of this report.
MERRF (Myoclonus Epilepsy with Ragged-Red Fibers) syndrome is an extremely rare disorder that begins in childhood and affects the nervous system and skeletal muscle as well as other body systems. The distinguishing feature in MERRF is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. In addition, individuals with MERRF syndrome may have muscle weakness (myopathy), an impaired ability to coordinate movements (ataxia), seizures, and a slow deterioration of intellectual function (dementia). Short stature, degeneration of the optic nerve (optic atrophy), hearing loss, cardiomyopathy and abnormal sensation from nerve damage (peripheral neuropathy) are also common symptoms. Abnormal muscle cells are present and appear as ragged red fibers (RRF) when stained with the modified Gomori trichrome and viewed microscopically. MERRF is caused by mutations in mitochondrial DNA (mtDNA).
Symptoms of MERRF syndrome can begin in childhood, adolescence or early adulthood after a period of normal development. Symptoms and physical findings associated with MERRF syndrome vary greatly between affected individuals in the same family and between different families. Myoclonus is usually the first symptom followed by seizures, ataxia, muscle weakness and dementia. Short stature, degeneration of the optic nerve (optic atrophy), hearing loss, and altered sensation (pins-and-needles or pain) from nerve damage (peripheral neuropathy) are also common symptoms. Cardiomyopathy and the heart rhythm abnormality known as Wolff-Parkinson-White syndrome are frequently present. Occasional symptoms include benign fat cell tumors (lipomas), especially around the neck, and eye abnormalities involving melanin in the retina (pigmentary retinopathy).
People with MERRF syndrome have an accumulation of lactic acid in the blood (lactic acidosis) and often complain of vomiting, abdominal pain, fatigue, muscle weakness and difficulty breathing.
MERRF syndrome is caused by mutations in mitochondrial DNA (mtDNA).
Mutations affecting the genes of mtDNA are inherited from the mother. MtDNA in sperm cells is typically lost during fertilization and as a result, all human mtDNA comes from the mother. An affected mother will pass on the mutation to all her children, but only her daughters will pass it on to their children. Mitochondria, which are found by the hundreds or thousands in the cells of the body, carry the blueprints for regulating energy production.
Both normal and mutated mtDNA can exist in the same cell, a situation known as heteroplasmy. The number of defective mtDNAs may be out-numbered by the number of normal mtDNAs. Symptoms may not appear in any given generation until the mutation affects a significant proportion of mtDNAs. The uneven distribution of normal and mutant mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of symptoms in affected family members.
Mutations in the mtDNA gene MT-TK are associated with MERRF in approximately 90% of cases. One particular MT-TK mutation, m.8344A>G, accounts for 80% of cases. Mutations in MT-TL1, MT-TH, MT-TS1, MT-TS2 and MT-TF have also been associated with MERRF.
A few cases of MERRF syndrome appear to occur as the result of a new spontaneous mutation in a mitochondrial gene and are not inherited.
MERRF syndrome is a rare disorder that affects males and females in equal numbers. Some researchers believe that mitochondrial myopathies may go unrecognized and underdiagnosed in the general population, making it difficult to determine the true frequency of disorders like MERRF syndrome.
MERRF is diagnosed based on clinical findings and molecular genetic testing.
Clinical testing may include measurement of lactate and pyruvate concentrations in blood and CSF. CSF protein may also be elevated in MERRF syndrome. Brain imaging techniques such as magnetic resonance imaging (MRI) may be used to look for stroke-like lesions and magnetic resonance spectroscopy (MRS) is used to look for lactate in the brain. Electrocardiogram may be used to diagnose heart rhythm abnormalities. Muscle biopsy will usually show ragged red fibers.
The mtDNA mutations associated with MELAS can usually be detected in white blood cells, but due to heteroplasmy (see Causes), other tissue samples may be necessary such as skin, saliva, hair follicles, urinary sediment and skeletal muscle.
No specific treatment is available for MERRF syndrome. Anti-convulsant drugs are used to help prevent and control seizures associated with MERRF syndrome. Levetiracetam has been effective in controlling myoclonus in a small number of patients. Therapies are sometimes used to increase energy production by the mitochondria and slow the effects of the condition. Coenzyme Q10 and L-carnitine have been beneficial in some patients.
Physical therapy and aerobic exercise may help to improve muscle weakness, stiffness and motor function.
Genetic counseling is recommended for affected individuals and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Contact for additional information about MERRF syndrome:
Salvatore DiMauro, MD
Lucy G. Moses Professor of Neurology
4-424B College of Physicians & Surgeons
630 West 168th Street
New York, NY 10032
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FROM THE INTERNET
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