By: Catherine Joachin
Myoclonic Epilepsy with Ragged-Red Fibers (MERRF)
What is MERRF?
Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare condition of the central nervous system caused by genetic mutations in the mitochondrial genetic material (mtDNA) (National Organization for Rare Disorders, 2021). MERRF can result from various maternally inherited pathogenic mtDNA variants, including the m.8344A>G, m.8356T>C and m.8363G>A variants (Finsterer, 2025).
This disorder typically presents with predominant progressive myoclonus (muscle jerks) and seizures; however other core clinical features such as impaired muscle movement coordination (ataxia), short stature, muscle weakness (myopathy), vision problems (optic atrophy), hearing loss, cardiac arrhythmia and decline in cognitive abilities (dementia) may manifest as well (Hameed & Tadi, 2023; NORD, 2021).
Diagnosis
Patients with MERRF display a broad range of clinically recognizable symptoms and variations in genetic makeup; so, myoclonic epilepsy is the distinguishing feature that sets it apart from other mitochondrial diseases (Finsterer, Zarrouk-Mahjoub & Shoffner, 2018).
Generally, MERRF diagnosis is informed by both clinical presentation and molecular findings, meaning that tests need to be conducted in order to determine the genetic basis for the disease (NORD, 2021; Finsterer, Zarrouk-Mahjoub & Shoffner, 2018).
In view of specific symptoms such as exercise intolerance and muscle weakness, laboratory tests may be performed to detect elevated levels of creatine kinase (CK) or lactic acid in the blood and cerebrospinal fluid (CSF) (Hameed & Tadi, 2023). Brain imaging scans may be used to expose signs of atrophy, changes in red nucleus and grey and white matter changes, as well as seizure activity, which is recorded via electroencephalogram (EEG) (Hameed & Tadi, 2023).
Genetic testing can identify specific mitochondrial gene mutations that are linked to the condition, the most common one being m.8344A>G pathogenic variant of the MT-TK gene, which accounts for more than 90% of MERRF cases (NORD, 2021). This supports not only disease monitoring, treatment and clinical trial design, but also screening of family members at risk (NORD, 2021).
Muscle biopsy, which involves removing a small piece of muscle tissue for examination, is crucial to identify ragged red fibers, a hallmark of MERFF found in more than 90% of patients (Hameed & Tadi, 2023). When stained and placed under a microscope, those fibers, which are abnormal muscle cells caused by the accumulation of defective mitochondria, appear to have a red rim and speckled interior (Genetic and Rare Diseases Information Center, n.d.).
Treatment
As with other mitochondrial disorders, MERRF has neither specific treatment nor cure (Hameed & Tadi, 2023). Rather, each symptom is addressed separately. Recent scientific developments suggest that levetiracetam, benzodiazepines and potentially zonisamide are the most effective options for managing myoclonic epilepsy in MERRF (Firsterer, 2025). Patients with drug-resistant epilepsy are advised to look into alternative treatment avenues including a low carb diet, surgery, vagus nerve stimulation or deep brain stimulation (Firsterer, 2025).
Additionally, symptomatic management for other related complications such arrhythmia, optic atrophy or height problems should be overseen by specialists (i.e., cardiologists, ophthalmologists and endocrinologists, etc.) (Hameed & Tadi, 2023).
References
Finsterer, J. (2025). A Review of the Advances in the Medical Management of Epilepsy Associated With Myoclonic Epilepsy With Ragged-Red Fibers (MERRF) Syndrome. Curēus (Palo Alto, CA), 17(4), e82875. https://doi.org/10.7759/cureus.82875
Finsterer, J., Zarrouk-Mahjoub, S., & Shoffner, J. M. (2018). MERRF Classification: Implications for Diagnosis and Clinical Trials. Pediatric Neurology, 80, 8–23. https://doi.org/10.1016/j.pediatrneurol.2017.12.005
Genetic and Rare Diseases Information Center. (n.d.). Myoclonic epilepsy with ragged-red fibers. National Center for Advancing Translational Sciences, National Institutes of Health. Retrieved [November 8, 2025], from https://rarediseases.info.nih.gov/diseases/7144/myoclonic-epilepsy-with-ragged-red-fibers
Hameed, S., & Tadi, P. (2023, July 16). Myoclonic epilepsy and ragged red fibers. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK555923/
National Organization for Rare Disorders (2021, June 14). MERRF syndrome. https://rarediseases.org/rare-diseases/merrf-syndrome/
