Pathogenic mutations in the mitochondrial trna lys may cause the merrf syndrome. Progressive myoclonus epilepsy pme may develop in adult life. How is myoclonic epilepsy with ragged red fibers merrf. Clinical and histological study of sixty patients with ragged red fibers sundaram challa, meena a. Myoclonic epilepsy with ragged red fibers merrf free download as powerpoint presentation. 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. 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.
Myoclonus epilepsy and ragged red fiber merrf oxford. Myoclonic epilepsy and ragged red fibers syndrome condition and symptoms. Merrf is characterized by myoclonic seizures brief, sudden twitching muscle spasms, weakness myopathy, cerebellar ataxia, progressive spasticity and dementia. If a mother has a mutation in her mitochondrial dna, all of her children will inherit the mutation and may or may not have symptoms. Onset is usually in childhood, occurring after normal early development. The disease was so named because the patients all had myoclonus epilepsy and mitochondrialdysfunction wasfound uponmuscle biopsy2. Myoclonic epilepsy and ragged red fibers syndrome, or merrf, is a rare, genetic disease, affecting only about one in every 400,000 people. A typical case of myoclonic epilepsy with ragged red fibers merrf and the lessons learned. Merff myoclonic epilepsy with raggedred fibers inheritance.
Progressive myoclonus epilepsy in young adults with. Symptoms of myoclonus with epilepsy with ragged red fibers including 9 medical symptoms and signs of myoclonus with epilepsy with ragged red fibers, alternative diagnoses, misdiagnosis, and correct diagnosis for myoclonus with epilepsy with ragged red fibers signs or myoclonus with epilepsy with ragged red fibers symptoms. He was 1 of 3 affected siblings and the offspring of an affected mother, suggesting maternal transmission. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged red fibres merrf were studied.
However, classification of such syndromes is often difficult because the terminology used to describe seizures can be confusing and inconsistent. Cognitive functions in myoclonic epilepsy with ragged red fibres a case report article pdf available in journal of epileptology 231. People may have strange sensations and emotions or behave strangely. Patients exhibit myoclonus epilepsy involuntary muscle contractions and show signs of ragged red fibers in muscle biopsy. Rare condition or disease genetic, mitochondrial pediatric onset behavioral and mental health disorders. The present study reports the case of a 25yearold male who presented with paroxysmal left upper limb tics and weakness for two years. Merrf myoclonic epilepsy with ragged red fibers syndrome is a mitochondrial encephalomyopathy characterized by myoclonic seizures. Mitochondrially transmitted diseases are no exception. A new mitochondrial transfer rnapro gene mutation associated with myoclonic epilepsy with ragged red fibers and other neurological features.
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. Myoclonic seizures are brief but can happen in clusters many happening close together in time and often happen shortly after waking. It is called maternal inheritance because mitochondrial dna are inherited from maternally inherited egg cells, but not from paternally inherited sperm cells. Myoclonus epilepsy with ragged red fibers and multiple. In 1980 fukuhara and colleagues reported 2 patients with a syndrome that they named myoclonus epilepsy associated with raggedred fibers fukuhara et al 1980. Myoclonic epilepsy with ragged red fibers merrf youtube. Diagnosis of the pme syndrome can be more difficult in. Myoclonic epilepsy and raggedred fiber merrf rare disorder that affects neuromuscular systems.
Myoclonus epilepsy with raggedred fibers merrfs, an inherited mitochondrial disorder, has characteristic morphological changes of raggedred fibers rrfs in muscle biopsy, in the absence of which mitochondrial etiology is usually not considered in patients with phenotypes suggestive of merrf. Epilepsy is a brain disorder that causes people to have recurring seizures. In these circumstances, merrf can only be diagnosed using genetic analyses. In its fully developed form with florid, unremitting myoclonic seizures and progressive neurologic deterioration, the syndrome can hardly be missed. 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 involuntary muscle twitches, generalized epilepsy, and cerebellar ataxia these symptoms are typically indicative of a mitochondrial myopathy.
Myoclonus epilepsy and raggedred fibres merrf brain. 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. Merrf is a highly variable disorder that affects energy metabolism in multiple tissues. Neuropathology of myoclonus epilepsy associated with ragged. 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. Myoclonus epilepsy with raggedred fibers merrfs, an inherited mitochondrial disorder, has characteristic morphological changes of.
Myoclonic epilepsy and raggedred fibers with cytochrome. 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. Merrf typically begins in childhood, but adultonset has been reported hirano 2008. Pubmed is a searchable database of medical literature and lists journal articles that discuss myoclonic epilepsy with ragged red fibers. The myoclonic epilepsy and raggedred fiber mutation. What is myoclonus with epilepsy and with ragged red fibers. Merrf syndrome affects different parts of the body, particularly the muscles and nervous system. Specifically, testing for unverrichtlundborg disease, lafora disease, myoclonic epilepsy with ragged red fibers and other mitochondrial disorders, and action myoclonusrenal failure syndrome had unrevealing results. Up to 4,000 children per year in the us are born with a type of mitochondrial disease. The features of merrf vary widely among affected individuals, even among members of the same family. Yes are approved or conditionally approved by new york state and do not require an nys npl exemption. Myoclonic epilepsy with ragged red fibers archives. Disease support groups 1 general support groups 19 support services.
Muscle histopathology in myoclonus epilepsy with raggedred. Transgenomic myoclonus epilepsy with ragged red fibers. In addition, we examine her cognitive decline over a 9year period, demonstrating a. Myoclonus epilepsy with raggedred fibers springerlink. Less prevalent symptoms include deafness, exercise intolerance, dementia, and. Mitochondrial diseases have a special predilection to involve the brain in view of its high metabolic demand. If myoclonic epilepsy with ragged red fibers merrf syndrome is caused by at least one of four point mutations in mitochondrial dna, then curing the disease should be as. Myoclonic epilepsy with ragged red fibers merrf genetic. Postmortem studies in 3 patients from the one family showed a particular system degeneration. The signs and symptoms of this disorder appear at an early age, generally childhood or adolescence. Merrf syndrome nord national organization for rare disorders. Myoclonus with epilepsy with ragged red fibers disease. A 29yearold female with progressive myoclonus and cognitive.
Myoclonic epilepsy with ragged red fibers merrf devin nellis. Myoclonus with epilepsy with ragged red fibers symptoms. 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. In this study cns tissues from a patient with myoclonus epilepsy and ragged red fibers merrf syndrome. Myoclonic epilepsy with raggedred fibers merrf the winnower. Myoclonic epilepsy with ragged red fibers merff is a progressive myoclonic epileptic syndrome characterized by myoclonus, tonicclonic seizures. Objectives to describe a patient with typical als and the finding of ragged red fibers in muscle biopsy.
Myoclonic epilepsy with ragged red fibers genetic and rare. Myoclonic epilepsy with ragged red fibers merrf syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers rrfs in the muscle. There was considerable heterogeneity in the age of onset, severity and associated clinical features. This case further illustrates the heterogeneity observed with mtdna mutations. Myoclonic epilepsy with raggedred fibers merrf genedx. Classification of the myoclonic epilepsies leppik 2003. Myoclonic epilepsy with raggedred fibers merrf is a disorder that affects many parts of the body, particularly the muscles and nervous system. They may have violent muscle spasms or lose consciousness. Enable javascript to view the expandcollapse boxes. 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 definition of epilepsy requires the occurrence of at. Abnormal muscle cells are present and appear as ragged red fibers rrf. Frontiers molecular diagnosis of myoclonus epilepsy. Juvenile myoclonic epilepsy jme is a familial disorder that typically begins in the second decade of life and is characterized by mild myoclonic seizures, generalized tonicclonic or clonictonicclonic seizures clonictonicclonic seizures are a variation of gtc seizures in which there is an initial clonic phase, and occasionally absence seizures. About 1 in 4,000 children in the united states will develop mitochondrial disease by the age of 10 years. Myoclonic epilepsy with raggedred fibers is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular weakness. Mar 29, 2017 a muscle biopsy had revealed numerous ragged red fibers. The signs and symptoms of this disorder appear at an early age, generally. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy. 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.
Myoclonus with epilepsy and with ragged red fibers explanation free. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production. Myoclonus with epilepsy with ragged red fibers conditions. Myoclonic epilepsy and raggedred fiber disease merrf is. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. When should merrf myoclonus epilepsy associated with. 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. This disorder is an encephalomyopathy characterized by myoclonic.
The postmortem findings are reported of two patients with myoclonus epilepsy associated with raggedred fibers merrf, fukuharas disease, whose clinical findings have been described in detail previously. Symptoms usually first appear in childhood or adolescence after normal early development. Post gardasil heart failure, ragged red fibers and thiamine. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, and by the neurobiologic, cognitive, psychological, and social consequences of this condition.
Myoclonic epilepsy with raggedred fibers merrf is a disorder that affects many parts of the body, particularly muscles and the nervous system. People with epilepsy may be classified into different syndromes based on specific clinical features. Clinical presentation patients usually present in late adolescence or early adulthood with myoclonus epilepsy cerebellar ataxia intellectu. Introduction myoclonic epilepsy and ragged red fiber disease merrf has been shown to fulfill all of the criteria for a mitochondria dna mtdna mutation. The myoclonic epilepsies are a collection of syndromes in which myoclonic seizures are a prominent feature. Under the terms of the licence agreement, an individual user may print out a pdf of a single chapter of a title in oxford medicine. 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. Mar 16, 2016 access to this database is free of charge. Merrf is a diagnosis based on the presence of four canonical phenotypic features, which are myoclonic, generalized. Myoclonic epilepsy with ragged red fibers merrf syndrome is a disabling condition on the compassionate allowance list, which qualifies an individual for an expedited approval process. Its caused by the presence of clusters of ragged red fibers in the mitochondria in muscle tissue.
Myoclonic epilepsy with raggedred fibers genetics home reference. Berkovic introduction progressive myoclonus epilepsy pme is an uncommon epilepsy syndrome caused by a large number of rare specific disorders. 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. Myoclonus epilepsy associated with raggedred fibers merrf. Identifying an epilepsy syndrome is useful as it helps determine the underlying causes as well as deciding what antiseizure medication should be tried. Neuropathology of myoclonus epilepsy associated with. Merrf syndrome or myoclonic epilepsy with ragged red fibers is a mitochondrial disease. The prevalence of mitochondrial disease is 1 in 10,000 and seizures and. Ragged red fibers definition of ragged red fibers by. Myoclonic epilepsy with red ragged fibres merrf is a rare, multisystem mitochondrial disorder. Myoclonic epilepsy and ragged red fibres merrf 8344 ag.
Muscle weakness is variable and muscle biopsy often, but not always, shows characteristic raggedred fibers. The wellcome trust centre for mitochondrial research is built on our long standing clinical and scientific expertise in mitochondrial disease myoclonic epilepsy and ragged red fibres merrf 8344 ag wellcome trust centre for mitochondrial research. In myoclonic seizures the person is conscious, but they are classified as. Myoclonic epilepsy with ragged red fibers merrf syndrome.
Myoclonic epilepsy with raggedred fibers due tothe. 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. A novel mutation of mitochondrial t14709c causes myoclonic epilepsy with ragged red fibers syndrome in a chinese patient. To provide free information, advice and advocacy services to patients with chronic illnesses, in areas including health and disability insurance, social. Myoclonic epilepsy with ragged red fibers merrf is a multisystem disorder characterized by four common features. Because mitochondrial disorders contain many variations and subsets, some particular mitochondrial disorders are very rare. Myoclonic epilepsy with ragged red fibers merrf is characterized by myoclonus, seizures, and ataxia. Neurofibromatosis a genetic condition that can cause growths on the nerves. Myoclonic epilepsy with raggedred fibers merrf new york clients tests displaying the status new york approved. Here, the authors present a case of a 29yearold lady presenting with myoclonus and describe the subsequent investigations that led to a diagnosis of merrf.
Myoclonic epilepsy with ragged red fibers merr f is an ultrarare mitochondrial disease, typically associated with a point mutation of nucleotide 8344 of the mitochondrial dna. 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. Selective vulnerability of subpopulations of neurons is a striking feature of neurodegeneration. Background motor neuron diseases amyotrophic lateral sclerosis als and spinal muscular atrophy sma have been rarely associated with mitochondrial respiratory chain defects. Myoclonic epilepsy with ragged red fibers merrf is a disorder that affects many parts of the body, particularly the muscles and nervous system. Description for this condition is not yet available. Patients exhibit myoclonus epilepsy involuntary muscle contractions and show signs of raggedred fibers in muscle biopsy. Amyotrophic lateral sclerosis with raggedred fibers. Myoclonus epilepsy associated with raggedred fibers. This diagnosis must be considered in addition to possible kufs disease or myoclonic epilepsy with ragged red fibers merrf when pme develops in young adults. Common findings are hearing loss, short stature, optic atrophy, and cardiomyopathy with wolffparkinsonwhite wpw syndrome.
Bhoompally, mohandas surath departmetns of pathology and neurology, nizams institute of medical sciences, hyderabad. Tuberous sclerosis a rare condition that causes growths in organs including the brain. In addition to the mitochondrial myopathy, both patients had consistent lesions in the central and peripheral nervous systems. Engage your students during remote learning with video readalouds. Myoclonus epilepsy an overview sciencedirect topics. Yet with the different types of mitochondrial myopathies, it may be difficult. She had tremor, fatigue and developmental delay for more than 2 years. Symptoms of myoclonus with epilepsy with ragged red fibers. Histopathologic findings were examined in skeletal muscle biopsies from 6 patients with myoclonus epilepsy with ragged red fibers merrf who had an a to g base substitution at mitochondrial dna mtdna nucleotide pair 8344. A typical case of myoclonic epilepsy with ragged red fibers merrf. Myoclonus with epilepsy and with ragged red fibers. 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.
The myoclonic epilepsy and raggedred fiber mutation provides new insights into human mitochondrial function and genetics. The distinguishing feature in merrf is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. The merrf diagnostic criteria described in 1980 by fukuhara et al included as typical manifestations of the dis. Myoclonus epilepsy with raggedred fibers merrf is a multisytemic mitochondrial syndrome fukuhara 1991. Muscle jerks are not always due to epilepsy for example, some people have them as they fall asleep. Proper classification of a patients syndrome is critical for appropriate treatment and prognosis. Of these, perhaps the beststudied is the ag transition at position 8344 in the trnalys gene, the mutation that causes myoclonic epilepsy and raggedred fiber syndrome merrf. Eight years later, shoffner and colleagues identified a mitochondrial dna point mutation in myoclonus epilepsy with raggedred fibers pedigrees shoffner et al 1990. 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. Mutation in mttk gene encoding mitochondrial trna lysine. Pdf myoclonic epilepsy with raggedred fibers merrf.
Additionally, patients may display sensorineural hearing loss, myopathy, peripheral neuropathy, dementia, short stature, exercise intolerance or optic atrophy. 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. The winnower myoclonic epilepsy with raggedred fibers. Click on the link to view a sample search on this topic. Some researchers now believe that the chance of developing epilepsy is probably always genetic to some extent, in that any person who starts having seizures has always had some level of genetic likelihood to do so.
Cognitive functions in myoclonic epilepsy with ragged red. Merrf myoclonus epilepsy with raggedred fibers syndrome is an extremely. The present study reports the case of a 25yearold male who presented with paroxysmal left. When should merrf myoclonus epilepsy associated with ragged. 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 and ragged red fibers merrf syndrome. Causes of myoclonus with epilepsy with ragged red fibers. Merrf results from a mutation in mitochondrial dna mtdna that impairs protein synthesis, oxygen consumption, and energy production. Looking for online definition of myoclonus with epilepsy and with ragged red fibers in the medical dictionary. The disease is maternally inherited as is the mtdna. We present two patients with pme appearing around the age of 30 years in whom the disorder represented a manifestation of alzheimers disease. When muscle is stained with gomori trichrome, characteristic ragged red fibers are visible under the microscope. Myoclonic epilepsy with ragged red fibers genetic and.
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