Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review

Ende, Tom van den; Sharifi, Sarvi; Salm, Sandra; Rootselaar, Anne-Fleur van

doi:10.7916/d85155wj

Cited by 17 publications

(14 citation statements)

References 94 publications

(445 reference statements)

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“…FAME has a broad range of age at onset from 10 to 60 years; onset in the second decade of life overlaps with both the milder phenotype of IGE and the more severe group of PMEs. 1,3,6 GTCSs in FAME are occasionally preceded by myoclonic seizures or provoked by intermittent light stimulation (ILS), 1,3,4 which may also occur in…”

Section: Juvenile Myoclonic Epilepsy and Other Idiopathic Generalized...mentioning

confidence: 99%

“…7 On EEG recordings, a photoparoxysmal response is observed in both FAME and JME, with generalized spike-wave activity often seen during ILS. 1,3 Despite the possible overlap between seizure types and EEG patterns in JME and FAME, the insidiously progressive course of FAME indicates the need for an accurate disease diagnosis, which is essential for patient care. Moreover, although in JME cortical myoclonus occurs spontaneously in association with polyspike waves, 8 in FAME, cortical myoclonus is typically elicited by motor activation and the EEG correlate occurs in the contralateral sensorimotor area, revealed by averaging procedures.…”

Section: Key Pointsmentioning

confidence: 99%

“…1 It presents in adolescence or adult life with a movement disorder that was originally considered a "cortical" tremor. [1][2][3] Electrophysiological studies have revealed polygraphic patterns of "cortical myoclonus" and associated signs of cortical hyperexcitability, indicating a cortical origin of the movement disorder. [2][3][4] In FAME, generalized tonic-clonic seizures (GTCSs) and myoclonic seizures, together with a photoparoxysmal response on electroencephalography (EEG), overlap with the classical features of the idiopathic generalized epilepsy (IGE) syndrome of juvenile myoclonic epilepsy (JME).…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] Electrophysiological studies have revealed polygraphic patterns of "cortical myoclonus" and associated signs of cortical hyperexcitability, indicating a cortical origin of the movement disorder. [2][3][4] In FAME, generalized tonic-clonic seizures (GTCSs) and myoclonic seizures, together with a photoparoxysmal response on electroencephalography (EEG), overlap with the classical features of the idiopathic generalized epilepsy (IGE) syndrome of juvenile myoclonic epilepsy (JME). 4 Additional clinical features, such as abnormal eye movements, dysarthria, cerebellar ataxia, and progressive cognitive impairment may occur, such that FAME may need to be distinguished from progressive myoclonus epilepsies (PMEs), although FAME has milder symptoms and less obvious progression.…”

Section: Introductionmentioning

confidence: 99%

“…4 Additional clinical features, such as abnormal eye movements, dysarthria, cerebellar ataxia, and progressive cognitive impairment may occur, such that FAME may need to be distinguished from progressive myoclonus epilepsies (PMEs), although FAME has milder symptoms and less obvious progression. 3,5 The First International Workshop on FAME was held in Naples in 2022. The discussions highlighted the challenges of differential diagnoses and that the global prevalence of FAME is probably underestimated.…”

Section: Introductionmentioning

confidence: 99%

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Differential diagnosis of familial adult myoclonic epilepsy

et al. 2023

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Objective Familial adult myoclonic epilepsy (FAME) is an under‐recognized disorder characterized by cortical myoclonus, generalized tonic–clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes. FAME should be distinguished from a range of differential diagnoses. Methods The differential diagnoses and frequent presentations leading to misdiagnosis of FAME were investigated from the available literature and reported based on an expert opinion survey. Results The phenotypic features of FAME, including generalized tonic–clonic and myoclonic seizures, are also seen in other epilepsy syndromes, such as juvenile myoclonic epilepsy, with a resultant risk of misdiagnosis and lack of identification of the underlying cause. Cortical myoclonus may mimic essential tremor or drug‐induced tremor. In younger individuals, the differential diagnosis includes progressive myoclonus epilepsies (PMEs), such as Unverricht‐Lundborg disease, whereas, in adulthood, late‐onset variants of PMEs, such as sialidoses, myoclonus epilepsy, and ataxia due to potassium channel pathogenic variants should be considered. PMEs may also be suggested by cognitive impairment, cerebellar signs, or psychiatric disorders. Electroencephalography (EEG) may show similarities to other idiopathic generalized epilepsies or PMEs, with generalized spike–wave activity. Signs of cortical hyperexcitability may be seen, such as an increased amplitude of somatosensory evoked potentials or enhanced cortical reflex to sensory stimuli, together with the neurophysiological pattern of the movement disorder. Significance Recognition of FAME will inform prognostic and genetic counseling and diagnosis of the insidious progression, which may occur in older individuals who show mild cognitive deterioration. Distinguishing FAME from other disorders in individuals or families with this constellation of symptoms is essential to allow the identification of underlying etiology.

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Section: Juvenile Myoclonic Epilepsy and Other Idiopathic Generalized...mentioning

confidence: 99%

Section: Key Pointsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential diagnosis of familial adult myoclonic epilepsy

et al. 2023

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Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and SAMD12 intronic repeat expansion

et al. 2021

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Objective Our goal was to perform detailed clinical and genomic analysis of a large multigenerational Chinese family with 21 individuals showing symptoms of Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE) that we have followed for over 20 years. Methods Patients were subjected to clinical evaluation, routine EEG, and structural magnetic resonance imaging. Whole exome sequencing, repeat‐primed PCR, long‐range PCR, and PacBio sequencing were performed to characterize the disease‐causing mutation in this family. Results All evaluated patients manifested adult‐onset seizures and presented with progressive myoclonic postural tremors starting after the third or fourth decade of life. Seizures typically diminished markedly in frequency with implementation of antiseizure medications but did not completely cease. The electroencephalogram of affected individuals showed generalized or multifocal spikes and slow wave complexes. An expansion of TTTTA motifs with addition of TTTCA motifs in intron 4 of SAMD12 was identified to segregate with the disease phenotype in this family. Furthermore, we found that the mutant allele is unstable and can undergo both contraction and expansion by changes in the number of repeat motifs each time it is passed to the next generation. The size of mutant allele varied from 5 to 5.5 kb with 549‐603 copies of TTTTA and 287‐343 copies of TTTCA repeat motifs in this family. Significance Our study provides a detailed description of clinical progression of FCMTE symptoms and its management with antiseizure medications. Our method of repeat analysis by PacBio sequencing of long‐range PCR products does not require high‐quality DNA and hence can be easily applied to other families to elucidate any correlation between the repeat size and phenotypic variables, such as, age of onset, and severity of symptoms.

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Phenomenology of Myoclonus

Frucht

Termsarasab

2020

Movement Disorders Phenomenology

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Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review

Cited by 17 publications

References 94 publications

Differential diagnosis of familial adult myoclonic epilepsy

Differential diagnosis of familial adult myoclonic epilepsy

Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and SAMD12 intronic repeat expansion

Phenomenology of Myoclonus

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