Genetic testing in a cohort of patients with potential epilepsy with myoclonic-atonic seizures

Angione, Katie; Eschbach, Krista; Smith, Garnett; Joshi, Charuta; Demarest, Scott

doi:10.1016/j.eplepsyres.2019.01.008

Cited by 18 publications

(12 citation statements)

References 25 publications

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“…Fourteen percent of the participants in this study had gene variants (4/29). While this ratio varies from 3% to 41% in similar studies for MAE (in which the original definition by Doose was applied), 10,29 the frequency of gene variants identified in the present study is comparable to that in a recent study of 77 patients with MAE (in which the recent ILAE definition was applied), in which a molecular diagnosis was determined for six of 59 patients (10%) 30 . Variants of SLC6A1, SLC2A1, and SCN1A are relatively common in patients with MAE, with reported variant rates of 4% (6/160), 11 4.8% (4/84), 9 and 5% (1/20), 31 respectively.…”

Section: Discussionsupporting

confidence: 71%

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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Section: Discussionsupporting

confidence: 71%

Clinical and genetic characteristics of patients with Doose syndrome

et al. 2020

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“…55 Epilepsy with myoclonic-atonic seizures has a genetic diagnosis in 14% of patients, but this may be limited by testing sent. 56 Interestingly, in the largest study of infantile spasms and Lennox-Gastaut patients, only 17% received a genetic diagnosis through whole exome sequencing. 2 Besides providing positive diagnoses, clinicians cannot underestimate the psychological impact that testing patients brings to families.…”

Section: Providing a Diagnosismentioning

confidence: 99%

Genetic Testing in Epilepsy

Ritter

Holland

2020

Semin Neurol

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Because of next-generation sequencing and the discovery of many new causative genes, genetic testing in epilepsy patients has become widespread. Pathologic variants resulting in epilepsy cause a variety of changes that can be broadly classified into syndromic disorders (i.e., chromosomal abnormalities), metabolic disorders, brain malformations, and abnormal cellular signaling. Here, we review the available genetic testing, reasons to pursue genetic testing, common genetic causes of epilepsy, the data behind what patients are found to have genetic epilepsies based on current testing, and discussing these results with patients. We propose an algorithm for testing patients with epilepsy to maximize yield and limit costs based on their phenotype (including electroencephalography and magnetic resonance imaging findings), age of seizure onset, and presence of other neurologic comorbidities. Being able to discern which type of genetic testing to order, using that information to give targeted and cost-effective patient care, and interpreting results accurately will be a crucial skill for the modern neurologist.

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“…This low rate was partially attributed to the need for updated testing, including wider use of whole exome/genome sequencing. 6 However, in a recent study of 101 patients with EMAS who underwent whole exome sequencing, a pathogenic etiology was identified in only 14%. It is suggested that this is due to multifactorial inheritance.…”

Section: Commentarymentioning

confidence: 99%

“…Despite the high rate of positive family history in patients with EMAS, even higher than the “presumed genetic” idiopathic generalized epilepsy syndromes, the yield of genetic testing thus far has been quite low. 6 In a study of 77 patients with EMAS, 59 of whom had at least one genetic test performed, a definitive molecular diagnosis was identified in only 10%. This low rate was partially attributed to the need for updated testing, including wider use of whole exome/genome sequencing.…”

Section: Commentarymentioning

confidence: 99%