Madelung lipomatosis presenting as a manifestation of. The signs and symptoms of this disorder appear at an early age, generally. Myoclonus epilepsy with ragged red fibers and multiple. Cognitive functions in myoclonic epilepsy with ragged red. Merrf syndrome nord national organization for rare disorders. Common findings are hearing loss, short stature, optic atrophy, and cardiomyopathy with wolffparkinsonwhite wpw. Merrf syndrome or myoclonic epilepsy with ragged red fibers is a mitochondrial disease. Myoclonic epilepsy with raggedred fibers merrf the winnower. The atog mutation at nucleotide 8344 accounts for 80 to 90% of merrf cases shoffner and wallace, 1992. Its caused by the presence of clusters of ragged red fibers in the mitochondria in muscle tissue. These symptoms often worsen over time and can be fatal. This rare inherited disorder affects muscles cells. Myoclonic epilepsy associated with ragged red fibers is one of the mitochondrial encephalomyopathies.
The features of merrf vary widely among affected individuals, even among members of the same family merrf is characterized by muscle twitches. 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. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for myoclonic epilepsy with. 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. 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. Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and raggedred fibres merrf were studied. A specific mutation in mitochondrial dna was first demonstrated by shoffner et al. The appearance of madelung lipomatosis should prompt physicians to. Conventional brain mr imaging showed atrophy of the superior cerebellar peduncles and the cerebellum in all patients and brain stem atrophy in 2 patients. Myoclonus epilepsy associated with raggedred fibers merrf. 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. 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.
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 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 with epilepsy with ragged red fibers symptoms. Characteristics of myoclonic epilepsy associated with raggedred fibers include myoclonic epilepsy, generalized epilepsy, hearing loss, exercise intolerance. Two other mutations, 8356ttoc and 8363gtoa, have been found in the same gene but occur infrequently. This case further illustrates the heterogeneity observed with mtdna mutations. Myoclonus is a brief jerk that often happens first thing in the morning and can be a run of jerks. Its common clinical features include myoclonic and tonicclonic seizures, ataxia, and myopathy, but other features have also been reported, including lipoma, diabetes. 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.
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. Jun 03, 2003 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. Cerebellar ataxia was the first symptom in all patients. Clinical and brain mr imaging features focusing on the. Cognitive functions in myoclonic epilepsy with ragged red fibres a case report martyna domanska 1,2, emilia j.
Characteristics of myoclonic epilepsy associated with ragged red fibers include myoclonic epilepsy, generalized epilepsy, hearing loss, exercise intolerance. We report 3 patients with myoclonic epilepsy with raggedred fibers merrf diagnosed by mitochondrial a8344g mutation. Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged red fibres merrf were studied. Over time, the symptoms progress to recurrent seizures epilepsy, difficulty walking ataxia, muscle weakness, and progressive cognitive decline dementia. 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. 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. 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 present study reports the case of a 25 yearold male who presented with paroxysmal left upper limb tics and weak.
The first symptom of myoclonic epilepsy associated with ragged red fibers merrf is often muscle spasms known as myoclonus. 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. Merrf syndrome is also known as myoclonic epilepsy with ragged red fibers. Myoclonic epilepsy with ragged red fibers merrf has mitochondrial or maternal inheritance. 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 syndrome nord national organization for rare.
Magnetic resonance spectroscopy study in basal ganglia of. Although the trna lys mutation does not alter recognition sequences for commercially available restriction enzymes, we have successfully changed two nucleotides flanking. Biochemically, the mutation produces multiple deficiencies in the enzyme complexes of the respiratory chain, most prominently involving nadhcoq reductase complex i in cytochrome. 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. Myoclonic epilepsy with raggedred fibers merrf is a disorder that affects many parts of the body, particularly the muscles and nervous system. In these circumstances, merrf can only be diagnosed using genetic analyses.
The probands had the typical clinical characteristics of merrf. Myoclonus epilepsy with ragged red fibers and multiple mtdna. There was considerable heterogeneity in the age of onset, severity and associated clinical features. This pdf is available for free download from a site hosted by medknow. Several members of a threegeneration kindred from sardinia were affected by a maternally inherited syndrome characterized by features of both myoclonus epilepsy with ragged red fibers merrf and.
We report 3 patients with myoclonic epilepsy with ragged red fibers merrf diagnosed by mitochondrial a8344g mutation. Onset is usually in childhood, occurring after normal early development. Alice wong phd, gino cortopassi phd, in neurobiology of disease, 2007. 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. The features of merrf vary widely among affected individuals, even among members of the same family. Mediterranean myoclonus versus mitochondrial encephalomyopathy with ragged red fibers and baltic myoclonus. Myoclonus epilepsy with raggedred fibers merrf is an inherited mitochondrial disorder characterized by myoclonus epilepsy, ataxia, generalized seizures, and myopathy. Myoclonic epilepsy with raggedred fibers without increased. A typical case of myoclonic epilepsy with ragged red. Less prevalent symptoms include deafness, exercise intolerance, dementia, and. Myoclonic epilepsy and ragged red fibres merrf 8344 ag.
Shen c, xian w, zhou h, li x, liang x and chen l 2018 overlapping leigh syndromemyoclonic epilepsy with ragged red fibres in an adolescent patient with a mitochondrial dna a8344g mutation. Pdf when should merrf myoclonus epilepsy associated with. It is called maternal inheritance because mitochondrial dna are inherited from maternally inherited egg cells, but not from paternally inherited sperm cells. Myoclonus epilepsy and raggedred fibres merrf brain.
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. Myoclonus epilepsy associated with raggedred fibers. Case report chinsan liu department of neurology, changhua christian hospital, 5 nanhsiao street, changhua, taiwan 500. Myoclonic epilepsy and ragged red fibers syndrome, or merrf, is a rare, genetic disease, affecting only about one in every 400,000 people. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy.
Pathogenic mitochondrial dna mutations have been identified in the mitochondrial transfer rna trnalys at positions 8344 and 8356. Its estimated prevalence is about 1400,000 in northern europe, although its prevalence in asia is not established. Pdf myoclonic epilepsy associated with ragged red fibers merrf is a rare mitochondrial disorder. In diffusion tensor analysis, fractional anisotropy of. Myoclonic epilepsy and ragged red fibers merrf syndrome. Myoclonic epilepsy with ragged red fibers merrf free download as powerpoint presentation.
Mitochondrially transmitted diseases are no exception. Simple detection of trnalys mutation in myoclonus epilepsy. Myoclonus epilepsy associated with ragged red fibers mitochondrial abnormalities. Merrf syndrome myoclonic epilepsy with ragged red fibres. In 80% of cases, merrf is caused by a single base pair mutation a changes to g in mitochondrial dna mtdna, at location 8344.
Epidemiology of the mitochondrial dna 8344ag mutation for. A merrfmelas overlap syndrome associated with a new point. Pdf myoclonic epilepsy with raggedred fibers merr f is an ultrarare mitochondrial disease, typically associated with a point. Progressive myoclonus epilepsy is a disease associated with myoclonus, epileptic seizures, and other problems with walking or speaking. Common findings are hearing loss, short stature, optic atrophy, and cardiomyopathy with wolffparkinsonwhite wpw syndrome.
Myoclonic epilepsy and ragged red fibers syndrome condition and symptoms. Histopathologic findings were examined in skeletal muscle biopsies from 6 patients with myoclonus epilepsy with raggedred fibers merrf who had an a to g. Pdf myoclonic epilepsy with raggedred fibers merrf clinical. Myoclonic epilepsy associated with raggedred fibers is one of the mitochondrial encephalomyopathies. Refer to the specific health plans procedure code list for management requirements. 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. This disorder is an encephalomyopathy characterized by myoclonic. Molecular diagnosis of myoclonus epilepsy associated. The myoclonic epilepsy and raggedred fiber mutation.
Symptoms usually first appear in childhood or adolescence after normal early development. Myoclonic epilepsy an overview sciencedirect topics. The myoclonus epilepsy and ragged red fibres merrf syndrome is a maternally inherited progressive mitochondrial encephalomyopathy caused by a 8344ag mutation in the mttk gene that encodes mitochondrial trna for lysine. When muscle is stained with gomori trichrome, characteristic raggedred fibers are visible under the microscope.
Patients exhibit myoclonus epilepsy involuntary muscle contractions and show signs of ragged red fibers in muscle biopsy. When should merrf myoclonus epilepsy associated with ragged. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. Frontiers molecular diagnosis of myoclonus epilepsy.
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. 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. Myoclonic epilepsy with ragged red fibers merrf youtube. The signs and symptoms of this disorder appear at an early age, generally childhood or adolescence. Merrf is characterized by myoclonic seizures brief, sudden twitching muscle spasms, weakness myopathy, cerebellar ataxia, progressive spasticity and dementia. Postmortem studies in 3 patients from the one family showed a particular system degeneration. Several members of a threegeneration kindred from sardinia were affected by a maternally inherited syndrome characterized by features of both myoclonus epilepsy with raggedred fibers merrf and. The clinical features that patients experience with this mutation are predominantly neurological. 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. Merrf syndrome myoclonic epilepsy with ragged red fibres presenting with.
Muscle histopathology in myoclonus epilepsy with raggedred fibers. 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. 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. Myoclonic epilepsy with raggedred fibers is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular weakness.
Clinical and brain mr imaging features focusing on the brain. Its common clinical features include myoclonic and tonicclonic seizures, ataxia, and myopathy, but other features have also been reported, including. 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. Myoclonus is a possible manifestation of mitochondrial disorders, and its presence is considered, in association with epilepsy and the ragged red fibers, pivotal for the syndromic diagnosis of merrf myoclonic epilepsy with ragged red fibers. We developed a simple method for the detection of a trna lys mutation in myoclonus epilepsy associated with raggedred fibers merrf by polymerase chain reaction with use of a mismatched primer. A point mutation at nucleotide 8363 in two japanese families. Myoclonic epilepsy with ragged red fibers is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular weakness. It is known that the myoclonus epilepsy with raggedred fibers merrf is characterized by cerebellar ataxia and myoclonus epilepsy, while that the mitochondrial encephalopathy, lactic acidosis, and strokelike episodes melas is characterized by recurrent strokelike episodes, migrainelike headaches, and elevated resting lactate blood level. Merrf affects the nervous system and skeletal muscles and is a genetically. Myoclonus is usually the first symptom it is later followed by epilepsy, ataxia, physical weakness, and dementia. The features of merrf vary widely from individual to individual, even within families. Overlapping leigh syndromemyoclonic epilepsy with ragged red. Myoclonic epilepsy with ragged red fibers merrf is a disorder that affects many parts of the body, particularly the muscles and nervous system.
This may be in the form of myoclonic jerks or myoclonic seizures. Sitek 2,3, michal schinwelski 2, maria mazurkiewiczbeldzinska 1. However, another condition with optional ophthalmological symptoms, sialidosis, was only clearly identified in the s rapin et al. Myoclonus epilepsy with raggedred fibers merrfs, an inherited mitochondrial disorder, has characteristic morphological changes of. Generalized anxiety disorder understanding the nature of worry and anxiety duration. 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 over. Myoclonic epilepsy with raggedred fibers is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular. The features of merrf vary widely among affected individuals, even among members of the same family merrf is characterized by muscle twitches myoclonus.
Merrf syndrome affects different parts of the body, particularly the muscles and nervous system. Merrf syndrome is also known as myoclonic epilepsy with raggedred fibers. Selective vulnerability of subpopulations of neurons is a striking feature of neurodegeneration. Tiziana granata, in handbook of clinical neurology, 2012. 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. 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. 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. Pathogenic mutations in the mitochondrial trna lys may cause the merrf syndrome. Patients exhibit myoclonus epilepsy involuntary muscle contractions and show signs of raggedred fibers in muscle biopsy. 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. A typical case of myoclonic epilepsy with ragged red fibers. Myoclonic epilepsy with ragged red fibers genetic and rare.
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