Myoclonic epilepsy with ragged red fibers merrf free download as powerpoint presentation. Cerebellar ataxia was the first symptom in all patients. Myoclonus with epilepsy with ragged red fibers conditions. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Patients also often have generalized seizures and decline cognitively in the course of the disease. Myoclonic epilepsy with ragged red fibers merrf genetic. The distinguishing feature in merrf is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. 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.
Myoclonus epilepsy with ragged red fibers and multiple mtdna. We report 3 patients with myoclonic epilepsy with raggedred fibers merrf diagnosed by mitochondrial a8344g mutation. 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. Myoclonus epilepsy associated with raggedred fibres mitochondrial abnormalities. The wellcome trust centre for mitochondrial research is built on our long standing clinical and scientific expertise in mitochondrial disease. Less prevalent symptoms include deafness, exercise intolerance, dementia, and. Myoclonic epilepsy with ragged red fibers genetic and. Myoclonus epilepsy associated with raggedred fibers merrf diagnosis discussed by researchers myoclonic epilepsy with ragged red fibers. Apr 24, 2020 myoclonic epilepsy with ragged red fibers merrf is characterized by myoclonus, seizures, and ataxia. Patients exhibit myoclonus epilepsy involuntary muscle contractions and show signs of ragged red fibers in muscle biopsy.
Molecular diagnosis of myoclonus epilepsy associated. Myoclonic epilepsy and ragged red fibres merrf 8344 ag home patient and. The merrf diagnostic criteria described in 1980 by fukuhara et al included as typical manifestations of the dis. When should merrf myoclonus epilepsy associated with. The first symptom of myoclonic epilepsy associated with ragged red fibers merrf is often muscle spasms known as myoclonus. Myoclonic epilepsy and ragged red fibers merrf syndrome. We discuss the etiology of merrf syndrome and its link with madelung lipomatosis via a common mitochondrial mutation that can be present in both diseases. Selective vulnerability of subpopulations of neurons is a striking feature of neurodegeneration.
Although the trnalys mutation does not alter recognition sequences for commercially available restriction enzymes, we have successfully changed two nucleotides flanking the a to g mutation at. Myoclonic epilepsy with ragged red fibers merrf evicore. Common findings are hearing loss, short stature, optic atrophy, and cardiomyopathy with wolffparkinsonwhite wpw. Myoclonus epilepsy and raggedred fibres merrf oup academic.
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. Its caused by the presence of clusters of ragged red fibers in the mitochondria in muscle tissue. Myoclonus epilepsy and ragged red fiber merrf oxford medicine. We developed a simple method for the detection of a trnalys mutation in myoclonus epilepsy associated with ragged red fibers merrf by polymerase chain reaction with use of a mismatched primer. Diagnostic criteria for merrf include typical manifestations of the disease. Involuntary muscle twitches, generalized epilepsy, and cerebellar ataxia these symptoms are typically indicative of a mitochondrial myopathy. Myoclonus epilepsy associated with raggedred fibers. Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and raggedred fibres merrf were studied. This may be in the form of myoclonic jerks or myoclonic seizures. The probands had the typical clinical characteristics of merrf. We report 3 patients with myoclonic epilepsy with ragged red fibers merrf diagnosed by mitochondrial a8344g mutation. A rare disorder of mitochondrial metabolism characterized by myoclonic epilepsy and raggedred muscle fibers.
Myoclonic epilepsy with ragged red fibers genetic and rare. Conventional brain mr imaging showed atrophy of the superior cerebellar peduncles and the cerebellum in all patients and brain stem atrophy in 2 patients. An a to g transition mutation at nucleotide pair 8344 in human mitochondrial dna mtdna has been identified as the cause of merrf. Although the trnalys mutation does not alter recognition sequences for commercially available restriction enzymes, we have successfully changed two nucleotides flanking. Selective vulnerability of cns neurons does not correlate with the level of mitochondrial trnalys mutation in individual neuronal isolates li zhou,1 anne chomyn,2 giuseppe attardi,2 and carol a. Myoclonic epilepsy with ragged red fibers merrf youtube. 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. Myoclonic epilepsy and ragged red fibers syndrome condition and symptoms. Muscle biopsies showed many raggedred fibers and abnormal mitochondria with concentric cristae. The diagnosis of merrf syndrome relies on the demonstration of abnormal lactate accumulation in blood or, more often, in the cerebrospinal fluid, and on the muscle biopsy, which reveals the presence of cytochrome c oxidase negative muscle fibers and ragged red fibers. This is a unique case of a patient with a history of myoclonic epilepsy with ragged red fibers merrf syndrome presenting with madelung or multiple symmetric lipomatosis. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy. After the first patients were diagnosed with merrf in 1973, researchers have been working to understand the pathology and cause of the disease. Electrophysiological studies eeg, evoked potentials, nerve conduction and emg in patients with myoclonus epilepsy with ragged red fibres merrf are presented the most notable findings are the presence of atypical irregular generalized spike and wave discharges arising from an abnormal eeg background 9 patients, focal epileptiform abnormalities 6 patients most commonly.
Myoclonus epilepsy with raggedred fibers merff is manifested by myoclonus, ataxia and seizures. Merrf myoclonic epilepsy with ragged red fibers syndrome is a mitochondrial encephalomyopathy characterized by myoclonic seizures. Myoclonic epilepsy an overview sciencedirect topics. Mitochondria are the part of the body cells that produce energy. Merrf affects the nervous system and skeletal muscles and is a genetically. In this study cns tissues from a patient with myoclonus epilepsy and ragged red fibers merrf syndrome, which results from an a to g transition of nucleotide nt 8344 in the mitochondrial trnalys gene, were examined for the proportion of. 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. Myoclonus epilepsy and ragged red fibers sciencedirect. These abnormal muscle cells are called raggedred fibers. Pathogenic mutations in the mitochondrial trna lys may cause the merrf syndrome. The appearance of madelung lipomatosis should prompt physicians to. 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. Myoclonus epilepsy with ragged red fibers merrf is a multisytemic mitochondrial syndrome fukuhara 1991.
Myoclonus epilepsy and ragged red fiber merrf oxford. Myoclonus epilepsy with ragged red fibers merrf symptoms, causes, diagnosis, and treatment information for myoclonus epilepsy with ragged red fibers merrf mitochondrial diseases with alternative diagnoses, fulltext book chapters, misdiagnosis, research treatments, prevention, and prognosis. Progressive myoclonus epilepsy is a disease associated with myoclonus, epileptic seizures, and other problems with walking or speaking. Pdf myoclonic epilepsy with raggedred fibers merr f is an ultrarare mitochondrial disease, typically associated with a point mutation of. Myoclonus with epilepsy with ragged red fibers symptoms. Myoclonic epilepsy associated with ragged red fibers merrf is a rare mitochondrial disorder. Myoclonic epilepsy with ragged red fibers merrf is a disorder that affects many parts of the body, particularly the muscles and nervous system. Myoclonus is a brief jerk that often happens first thing in the morning and. Myoclonus epilepsy and raggedred fibres merrf brain. When should merrf myoclonus epilepsy associated with raggedred fibers be the diagnosis. Merrf at a glance maternal inheritance paternal mitochondrial dna is destroyed during fertilization.
The features of merrf vary widely among affected individuals, even among members of the same family. The mother was a 55yearold woman who had myoclonic jerks of the arms and generalized seizures since the age of 37 years. Myoclonic epilepsy with ragged red fibers merrf is a multisystem disorder in which the cardinal symptoms of pme are associated with typical myopathy with ragged red fibers seen on muscle biopsy, indicating dysfunction of the mitochondrial respiratory chain. Tiziana granata, in handbook of clinical neurology, 2012. Frontiers molecular diagnosis of myoclonus epilepsy. A point mutation at nucleotide 8363 in two japanese families. Myoclonic epilepsy with raggedred fibers is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular weakness. Patients exhibit myoclonus epilepsy involuntary muscle contractions and show signs of raggedred fibers in muscle biopsy. This rare inherited disorder affects muscles cells. Enable javascript to view the expandcollapse boxes. They can be caused by mutation of genes encoded by either nuclear dna or mitochondrial dna mtdna. Simple detection of trnalys mutation in myoclonus epilepsy.
In diffusion tensor analysis, fractional anisotropy of. Myoclonic epilepsy with ragged red fibers is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular weakness. 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. Myoclonus appears to be intractable, and some antiepileptic drugs may change the. She had tremor, fatigue and developmental delay for more than 2 years. The present study reports the case of a 25yearold male who presented with paroxysmal left upper limb tics and weakness for two years. Myoclonic epilepsy and ragged red fibres merrf 8344 ag.
Myoclonic epilepsy and ragged red fibers syndrome, or merrf, is a rare, genetic disease, affecting only about one in every 400,000 people. Myoclonus epilepsy with raggedred fibers springerlink. 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. Merrf syndrome or myoclonic epilepsy with ragged red fibers is a mitochondrial disease.
Merrf myoclonus epilepsy with raggedred 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. Myoclonic epilepsy with ragged red fibers archives. Merrf syndrome nord national organization for rare. Muscle weakness is variable and muscle biopsy often, but not always, shows characteristic raggedred fibers. Merrf typically begins in childhood, but adultonset has been reported hirano 2008. Antiepileptic treatment and blood lactate level alteration in. Myoclonus epilepsy associated with ragged red fibers mitochondrial abnormalities. In these circumstances, merrf can only be diagnosed using genetic analyses. Myoclonus epilepsy associated with raggedred fibers merrf. Merrf is characterized by myoclonic seizures brief, sudden twitching muscle spasms, weakness myopathy, cerebellar ataxia, progressive spasticity and dementia. Myoclonus and ataxia are characteristic and often presenting features.
Clinical and brain mr imaging features focusing on the brain. Myoclonic epilepsy with ragged red fibers merrf is characterized by myoclonus, seizures, and ataxia. Myoclonus epilepsy with raggedred fibers merrf is an inherited mitochondrial disorder characterized by myoclonus epilepsy, ataxia, generalized seizures, and myopathy. Merrf syndrome is also known as myoclonic epilepsy with raggedred fibers. Electrophysiological studies eeg, evoked potentials, nerve conduction and emg in patients with myoclonus epilepsy with ragged red fibres merrf are presented the most notable findings are the presence of atypical irregular generalized spike and wave discharges arising from an abnormal eeg background 9 patients, focal epileptiform. Myoclonic epilepsy with raggedred fibers merrf syndrome is a rare syndromic mitochondrial disorder mid with a broad phenotypic but narrow genotypic. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. We developed a simple method for the detection of a trnalys mutation in myoclonus epilepsy associated with raggedred fibers merrf by polymerase chain reaction with use of a mismatched primer. This case further illustrates the heterogeneity observed with mtdna mutations. 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. In this study cns tissues from a patient with myoclonus epilepsy and ragged red fibers merrf syndrome, which results from an a to g transition of nucleotide nt 8344 in the mitochondrial trnalys gene, were examined for the. 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.
Pdf when should merrf myoclonus epilepsy associated. Myoclonus epilepsy with raggedred fibers merrf symptoms, causes, diagnosis, and treatment information for myoclonus epilepsy with raggedred fibers merrf mitochondrial diseases with alternative diagnoses, fulltext book chapters, misdiagnosis, research. Myoclonic epilepsy and raggedred fiber disease merrf is. 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. Overlapping leigh syndromemyoclonic epilepsy with ragged. Myoclonus epilepsy with ragged red fibers and multiple.
Many individuals with a mutation of mtdna display a cluster of clinical features that fall into a discrete clinical syndrome, such as the kearnssayre syndrome kss, chronic progressive external ophthalmoplegia cpeo, mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes melas, myoclonic epilepsy with ragged red. Myoclonic epilepsy with ragged red fibers merrf is a multisystem mitochondrial disease. These symptoms often worsen over time and can be fatal. In 80% of cases, merrf is caused by a single base pair mutation a changes to g in mitochondrial dna mtdna, at location 8344. If myoclonic epilepsy with ragged red fibers merrf. Myoclonic epilepsy with ragged red fibers merrf devin. The winnower myoclonic epilepsy with raggedred fibers merrf. Mitochondrially transmitted diseases are no exception. Myoclonic epilepsy with raggedred fibers genetics home reference. Rowland had already published on the mitochondrial origin of kearnssayre syndrome, 1, 2 and dr. Onset is usually in childhood, occurring after normal early development.
Madelung lipomatosis presenting as a manifestation of. While some mitochondrial disorders only affect a single organ e. Myoclonic epilepsy with raggedred fibers merrf is a multisystem disorder in which the cardinal symptoms of pme are associated with typical myopathy with raggedred fibers seen on muscle biopsy, indicating dysfunction of the mitochondrial respiratory chain. Myoclonus epilepsy with raggedred fibers merrfs, an inherited mitochondrial disorder, has characteristic morphological changes of. Myoclonus appears to be intractable, and some antiepileptic drugs may change the blood lactate level. Fukuhara had already proposed the name merrf for a syndrome comprising myoclonic epilepsy and ragged red fibers on muscle biopsy. Merrf syndrome nord national organization for rare disorders. Its estimated prevalence is about 1400,000 in northern europe, although its prevalence in asia is not established.
When should merrf myoclonus epilepsy associated with ragged. Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged red fibres merrf were studied. Myoclonus epilepsy associated with raggedred fibers mitochondrial abnormalities. 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. Management of epilepsy in merrf syndrome seizure european. Merrf syndrome affects different parts of the body, particularly the muscles and nervous system. In a patient with clinical features of myoclonus epilepsy with ragged red fibers merff, molecular genetic analysis of mitochondrial dna did not show either of the two point mutations typically associated with merrf but did show multiple deletions by southern blot. How is myoclonic epilepsy with ragged red fibers merrf. Pdf myoclonic epilepsy with raggedred fibers merrf clinical. Abstract myoclonic epilepsy associated with ragged red fibers merrf is a rare mitochondrial disorder. Antiepileptic treatment and blood lactate level alteration. Clinical and brain mr imaging features focusing on the. Over time, the symptoms progress to recurrent seizures epilepsy, difficulty walking ataxia, muscle weakness, and progressive cognitive decline dementia.
Biol 1406 genetic disorder myoclonic epilepsy ragged red. The present study reports the case of a 25 yearold male who presented with paroxysmal left upper limb tics and weak. A clinical, pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study. The disease was so named because the patients all had myoclonus epilepsy and mitochondrialdysfunction wasfound uponmuscle biopsy2.
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