Epilepsy With Myoclonic Atonic Seizures: An Electroclinical Study of 69 Patients

Caraballo, Roberto; Chamorro, Noelia; Darra, Francesca; Fortini, Sebastián; Arroyo, H

doi:10.1016/j.pediatrneurol.2012.12.022

Cited by 29 publications

(18 citation statements)

References 33 publications

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“…Although the most frequent seizure types in MAE are as expected (myoclonic atonic or atonic seizure, 100%; GTCS, 72.7%; and myoclonic seizures, 68.2%), 3,5,6,41 a minority of MAE patients have focal seizures, some (6.9%) with additional focal epileptiform activity on EEG. Focal EEG features have been reported in up to 39% of MAE cohorts 40 and have been proposed as a marker of poor prognosis in MAE 42 .…”

Section: Discussionsupporting

confidence: 50%

“…These neurodevelopmental comorbidities may be a primary feature of the genetic disease rather than secondary to disturbance of brain function due to excessive epileptiform activity (an epileptic encephalopathy). Abnormal neurological findings were reported in 21 of 92 patients, higher than the 12% in previous smaller MAE series 2,41 . Ataxia and tremor have been recognized in MAE patients with pathogenic variants in SLC2A1 , 11 STX1B , 15 and SLC6A1 16 and occurred in our probands with pathogenic variants in SYNGAP1 (n = 3) and MECP2 (n = 1).…”

Section: Discussionmentioning

confidence: 42%

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Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures

et al. 2020

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Objective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE). Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies. Results: We analyzed 101 patients with MAE (70% male). The median age of seizure onset was 34 months (range = 6-72 months). The main seizure types were myoclonic atonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absence in 60%, and tonic seizures in 19% of patients. We observed intellectual disability in 62% of patients, with extremely low adaptive behavioral scores in 69%. In addition, 24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivity symptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, including five previously published patients. These were pathogenic genetic variants in SYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2, SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three new candidate genes, ASH1L, CHD4, and SMARCA2 in one patient each. Significance: MAE is associated with significant neurodevelopmental impairment.MAE is genetically heterogeneous, and we identified a pathogenic genetic etiology in 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestation of several etiologies rather than a discrete syndromic entity. K E Y W O R D S Doose syndrome, epilepsy/seizures, genetics, myoclonic astatic epilepsy SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section. How to cite this article: Tang S, Addis L, Smith A, et al; EuroEPINOMICS-RES Consortium. Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. Epilepsia. 2020;61:995-1007. https://

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 42%

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures

et al. 2020

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“…It is of interest that these appear to have the inverse sequence of classic myoclonic-atonic seizures whereby a single myoclonic jerk heralds the onset of the seizure followed by atonia. 6 Patient 8 had a history of seizures that was suspicious of the atonic-myoclonic-absence seizure type at age 2.5 years, but video was not captured.…”

Section: Resultsmentioning

confidence: 99%

CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures

et al. 2015

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Objective: To delineate the phenotype of early childhood epileptic encephalopathy due to de novo mutations of CHD2, which encodes the chromodomain helicase DNA binding protein 2. Methods:We analyzed the medical history, MRI, and video-EEG recordings of 9 individuals with de novo CHD2 mutations and one with a de novo 15q26 deletion encompassing CHD2.Results: Seizures began at a mean of 26 months (12-42) with myoclonic seizures in all 10 cases.Seven exhibited exquisite clinical photosensitivity; 6 self-induced with the television. Absence seizures occurred in 9 patients including typical (4), atypical (2), and absence seizures with eyelid myoclonias (4). Generalized tonic-clonic seizures occurred in 9 of 10 cases with a mean onset of 5.8 years. Convulsive and nonconvulsive status epilepticus were later features (6/10, mean onset 9 years). Tonic (40%) and atonic (30%) seizures also occurred. In 3 cases, an unusual seizure type, the atonic-myoclonic-absence was captured on video. A phenotypic spectrum was identified with 7 cases having moderate to severe intellectual disability and refractory seizures including tonic attacks. Their mean age at onset was 23 months. Three cases had a later age at onset (34 months) with relative preservation of intellect and an initial response to antiepileptic medication. Conclusion:The phenotypic spectrum of CHD2 encephalopathy has distinctive features of myoclonic epilepsy, marked clinical photosensitivity, atonic-myoclonic-absence, and intellectual disability ranging from mild to severe. Recognition of this genetic entity will permit earlier diagnosis and enable the development of targeted therapies. Neurology ® 2015;84:951-958 GLOSSARY ASD 5 autism spectrum disorder; CHD2 5 chromodomain helicase DNA binding protein 2; GSW 5 generalized spike wave; MAE 5 epilepsy with myoclonic-atonic seizures.The epileptic encephalopathies are severe epilepsy syndromes characterized by multiple seizure types and developmental slowing, often associated with regression; many begin in infancy or childhood. The etiology of these disorders is increasingly being recognized as due to de novo genetic mutations with a recent explosion in the number of causative genes identified.

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“…Although sodium valproate (VPA), ethosuximide (ESM), benzodiazepines (BZPs), lamotrigine (LTG), and a ketogenic diet (KD) have been found to be effective in the treatment of MAE, seizure prognosis varies by case. Between 50% and 80% of patients respond to treatment, and their seizures disappear within 3 years from the start of treatment, while other patients exhibit intractable seizures and depressed intellectual development 4,5 …”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic characteristics of patients with Doose syndrome

et al. 2020

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Objective To elucidate the genetic background and genotype‐phenotype correlations for epilepsy with myoclonic‐atonic seizures, also known as myoclonic‐astatic epilepsy (MAE) or Doose syndrome. Methods We collected clinical information and blood samples from 29 patients with MAE. We performed whole‐exome sequencing for all except one MAE case in whom custom capture sequencing identified a variant. Results We newly identified four variants: SLC6A1 and HNRNPU missense variants and microdeletions at 2q24.2 involving SCN1A and Xp22.31 involving STS. Febrile seizures preceded epileptic or afebrile seizures in four patients, of which two patients had gene variants. Myoclonic‐atonic seizures occurred at onset in four patients, of which two had variants, and during the course of disease in three patients. Variants were more commonly identified in patients with a developmental delay or intellectual disability (DD/ID), but genetic status was not associated with the severity of DD/ID. Attention‐deficit/hyperactivity disorder and autistic spectrum disorder were less frequently observed in patients with variants than in those with unknown etiology. Significance MAE patients had genetic heterogeneity, and HNRNPU and STS emerged as possible candidate causative genes. Febrile seizures prior to epileptic seizures and myoclonic‐atonic seizure at onset indicate a genetic predisposition to MAE. Comorbid conditions were not related to genetic predisposition to MAE.

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Epilepsy With Myoclonic Atonic Seizures: An Electroclinical Study of 69 Patients

Cited by 29 publications

References 33 publications

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures

CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures

Clinical and genetic characteristics of patients with Doose syndrome

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