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