May 04, 2015 after the first patients were diagnosed with merrf in 1973, researchers have been working to understand the pathology and cause of the disease. Myoclonic epilepsy with ragged red fibers merrf devin nellis. Myoclonus epilepsy associated with ragged red fibers mitochondrial abnormalities. Myoclonic epilepsy with ragged red fibers merrf free download as powerpoint presentation.
Merrf syndrome is also known as myoclonic epilepsy with ragged red fibers. Causes of myoclonus with epilepsy with ragged red fibers. Myoclonic epilepsy with raggedred fibers merrf syndrome is a rare syndromic mitochondrial disorder mid with a broad range of clinical manifestations. Myoclonic epilepsy and ragged red fibers syndrome condition and symptoms.
Ragged red fibers consist of a large collection of abnormalappearing mitochondria 4. Abstract myoclonic epilepsy associated with ragged red fibers merrf is a rare mitochondrial disorder. Introduction myoclonic epilepsy and ragged red fiber disease merrf has been shown to fulfill all of the criteria for a mitochondria dna mtdna mutation. Myoclonus with epilepsy with ragged red fibers is a genetic disease caused by a mutation in a mitochondrial gene, including mttk, mttl1, mtth, mtts1, mtts2, and mttf. Myoclonus epilepsy with raggedred fibers merrfs, an inherited mitochondrial disorder, has characteristic morphological changes of. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production. Over 80% of individuals with merrf syndrome carry the 8344ag mutation in the lysine transfer rna trna.
Dr lal pathlabs offers test service for merrf myoclonic epilepsy associated with ragged red fibres mutation detection test for checking neurologic disorder. The winnower myoclonic epilepsy with raggedred fibers merrf. Myoclonic epilepsy with raggedred fibers merrf is a multisystem disorder in which the cardinal symptoms of pme are associated with typical myopathy with. However, both leigh syndrome and merrf exhibit considerable clinical and genetic heterogeneity. Merrf syndrome myoclonic epilepsy with ragged red fibres. These abnormal muscle cells are called raggedred fibers. The merrf diagnostic criteria described in 1980 by fukuhara et al included as typical manifestations of the dis. Myoclonic epilepsy with ragged red fibers is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular weakness. The acronym, merrf, or myoclonus epilepsy and ragged red fiber disease, represents one of the early mitochondrial syndromes, whose molecular genetic basis was first established in 1990 by shoffner and coworkers. Myoclonic epilepsy with raggedred fibers merrf genedx. Pathogenic mutations in the mitochondrial trna lys may cause the merrf syndrome. The disease is maternally inherited as is the mtdna. Myoclonic epilepsy with ragged red fibers merrf is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia.
Pdf myoclonic epilepsy with raggedred fibers merrf clinical. In addition to the mitochondrial myopathy, both patients had consistent lesions in the central and peripheral nervous systems. When should merrf myoclonus epilepsy associated with ragged. Myoclonic epilepsy with ragged red fibers archives. Myoclonic epilepsy and ragged red fibers merrf syndrome. These jerks are sudden in onset and not necessarily associated with a loss of consciousness. Merrf myoclonic epilepsy with ragged red fibers syndrome is a mitochondrial. Myoclonic seizures are brief but can happen in clusters many happening close together in time and often happen shortly after waking. Management of epilepsy in merrf syndrome seizure european.
Patients exhibit myoclonus epilepsy involuntary muscle contractions and show signs of ragged red fibers in muscle biopsy. Myoclonic epilepsy with ragged red fibers merrf is a disorder that affects many parts of the body, particularly the muscles and nervous system. Patients with merrf can additionally exhibit recurrent seizures, difficulty coordinating movements, peripheral neuropathy and the slow deterioration of intellectual function 1. Two other mutations, 8356ttoc and 8363gtoa, have been found in the same gene but occur infrequently. Other features of merrf include recurrent seizures epilepsy, difficulty coordinating movements ataxia, a loss of sensation in the extremities peripheral neuropathy, and slow deterioration of intellectual function dementia. In myoclonic seizures the person is conscious, but they are classified as. This rare inherited disorder affects muscles cells. Sep 29, 2017 myoclonus epilepsy with ragged red fibers merrfs, an inherited mitochondrial disorder, has characteristic morphological changes of ragged red fibers rrfs in muscle biopsy, in the absence of which mitochondrial etiology is usually not considered in patients with phenotypes suggestive of merrf. The clinical features that patients experience with this mutation are predominantly neurological.
This means that myoclonus with epilepsy with ragged red fibers, or a subtype of myoclonus with epilepsy with ragged red fibers, affects less than 200,000 people in the us population. View details of cost of test, pretest information and report availability on dr lal pathlabs. When muscle is stained with gomori trichrome, characteristic ragged red fibers are visible under the microscope. Myoclonic epilepsy with ragged red fibers genetic and. Overlapping leigh syndromemyoclonic epilepsy with ragged red. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. Mar 16, 2016 myoclonic epilepsy with ragged red fibers merrf is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. Myoclonic epilepsy with ragged red fibers merrf youtube. In these circumstances, merrf can only be diagnosed using genetic analyses.
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. Less prevalent symptoms include deafness, exercise intolerance, dementia, and. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Myoclonic epilepsy and ragged red fibers merrf is caused in 80% of cases by an atog mutation in the trna lys gene mttk at position nt8344 of the mtdna. Myoclonus epilepsy associated with raggedred fibers merrf. Progressive myoclonus epilepsy is a disease associated with myoclonus, epileptic seizures, and other problems with walking or speaking. Myoclonus epilepsy and raggedred fibres merrf brain. The distinguishing feature in merrf is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. Other features of merrf include recurrent seizures epilepsy, difficulty coordinating. When should merrf myoclonus epilepsy associated with. Merrf myoclonic epilepsy associated with ragged red fibres. A typical case of myoclonic epilepsy with ragged red fibers.
The postmortem findings are reported of two patients with myoclonus epilepsy associated with ragged red fibers merrf, fukuharas disease, whose clinical findings have been described in detail previously. Myoclonic epilepsy with ragged red fibers merrf is a rare inherited neurometabolic disorder that affects the central nervous system, skeletal muscles, and other body systems. Red ragged fibers diseases of the mitochondria can be caused by defects in nuclear or mitochondrial dna and result in decreased energy availability for cell processes. The disease was so named because the patients all had myoclonus epilepsy and mitochondrialdysfunction wasfound uponmuscle biopsy2.
Pdf myoclonic epilepsy with raggedred fibers merr f is an ultrarare mitochondrial disease, typically associated with a point mutation of. Diagnostic criteria for merrf include typical manifestations of. Myoclonus epilepsy associated with raggedred fibers merrf diagnosis discussed by researchers myoclonic epilepsy with ragged red fibers involuntary muscle twitches, generalized epilepsy, and cerebellar ataxia these symptoms are typically indicative of a mitochondrial myopathy. Yes are approved or conditionally approved by new york state and do not require an nys npl exemption. Merrf syndrome nord national organization for rare disorders. Merrf syndrome myoclonic epilepsy with ragged red fibres presenting with cervicothoracic. In 80% of cases, merrf is caused by a single base pair mutation a changes to g in mitochondrial dna mtdna, at location 8344. Symptoms usually first appear in childhood or adolescence after normal early development. Postmortem studies in 3 patients from the one family showed a particular system degeneration. Merrf myoclonic epilepsy with ragged red fibers is a multisystem disorder characterized by myoclonus often the first symptom followed by generalized epilepsy, ataxia, weakness, and dementia. Jul 01, 2009 read myoclonic epilepsy with ragged red fibers without increased lactate levels, pediatric neurology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. The present study reports the case of a 25 yearold male who presented with paroxysmal left upper limb tics and weak ness for two years. Merrf syndrome affects different parts of the body, particularly the muscles and nervous system.
Pdf when should merrf myoclonus epilepsy associated. The features of merrf vary widely among affected individuals, even among members of the same family. Jun 15, 2016 cases of the month merrf and kearnssayre overlap syndrome due to the mitochondrial dna m. Myoclonic epilepsy and ragged red fibers syndrome, or merrf, is a rare, genetic disease, affecting only about one in every 400,000 people. Complex i deficiency status and myoclonic epilepsy with ragged red fibers merrf result from several trna mutations in the gene for lysine which includes m8344ag, m8356tc and then m8361ga. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy. The first symptom of myoclonic epilepsy associated with ragged red fibers merrf is often muscle spasms known as myoclonus. Myoclonus with epilepsy with ragged red fibers is listed as a rare disease by the office of rare diseases ord of the national institutes of health nih. Myoclonic epilepsy associated with ragged red fibers merrf is a rare mitochondrial disorder. Sep, 2018 myoclonus, generalized seizures, ataxia, and the presence of ragged red fibers rrf upon muscular biopsy characterize merrf 57. Myoclonic epilepsy with raggedred fibers merrf is a neurological disorder that is characterized by muscle twitches, weakness and progressive stiffness that affects numerous muscles of the body.
Myoclonic epilepsy with ragged red fibers genetic and rare. Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged red fibres merrf were studied. Myoclonus epilepsy with raggedred fibers merrf is a multisytemic mitochondrial syndrome fukuhara 1991. Myoclonus with epilepsy with ragged red fibers symptoms. Onset is usually in childhood, occurring after normal early development. Merrf syndrome or myoclonic epilepsy with ragged red fibers is a mitochondrial disease. Its caused by the presence of clusters of ragged red fibers in the mitochondria in muscle tissue.
Diagnostic criteria for merrf include typical manifestations of the disease. Merrf is characterized by myoclonic seizures brief, sudden twitching muscle spasms, weakness myopathy, cerebellar ataxia, progressive spasticity and dementia. Myoclonic epilepsy with raggedred fibers is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular weakness. The full text of this article is available in pdf format. Neuropathology of myoclonus epilepsy associated with ragged. Myoclonic epilepsy an overview sciencedirect topics. People with this condition may also develop hearing loss or optic atrophy, which is the degeneration atrophy of nerve cells that carry visual information from the eyes to the brain. The winnower myoclonic epilepsy with raggedred fibers. These symptoms often worsen over time and can be fatal. Myoclonic epilepsy with raggedred fibers genetics home reference.
Frontiers molecular diagnosis of myoclonus epilepsy. Myoclonic epilepsy and ragged red fibres merrf 8344 ag. In this study cns tissues from a patient with myoclonus epilepsy and ragged red fibers merrf syn drome, which results from an a to g transition of nucleotide. The probands had the typical clinical characteristics of merrf. Myoclonus is a brief jerk that often happens first thing in the morning and can be a run of jerks. The present study reports the case of a 25yearold male who presented with paroxysmal left upper limb tics and weakness for two years. This may be in the form of myoclonic jerks or myoclonic seizures. A point mutation at nucleotide 8363 in two japanese families. Myoclonic epilepsy with raggedred fibers merrf new york clients tests displaying the status new york approved. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for myoclonic epilepsy with.