Faculty Opinions recommendation of Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.

2018 ◽  
Author(s):  
John Paul Leach
Keyword(s):  
Genetic Testing ◽  
Neurodevelopmental Disorders ◽  
Patients With Epilepsy ◽  
Diagnostic Outcomes

scholarly journals Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders

Epilepsia ◽  
2018 ◽  
Vol 59 (5) ◽  
pp. 1062-1071 ◽  
Author(s):  
Amanda S. Lindy ◽  
Mary Beth Stosser ◽  
Elizabeth Butler ◽  
Courtney Downtain‐Pickersgill ◽  
Anita Shanmugham ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Neurodevelopmental Disorders ◽  
Patients With Epilepsy ◽  
Diagnostic Outcomes

Genetic Testing in Epilepsy

2020 ◽  
Vol 40 (06) ◽  
pp. 730-738
Author(s):  
David M. Ritter ◽  
Katherine Holland
Keyword(s):  
Genetic Testing ◽  
Metabolic Disorders ◽  
Chromosomal Abnormalities ◽  
Cost Effective ◽  
Resonance Imaging ◽  
Seizure Onset ◽  
Brain Malformations ◽  
Genetic Epilepsies ◽  
Patients With Epilepsy ◽  
Generation Sequencing

AbstractBecause 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.

scholarly journals When Should Genetic Testing be Performed in Epilepsy Patients?

2017 ◽  
Vol 17 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Annapurna Poduri
Keyword(s):  
Genetic Testing ◽  
Annual Meeting ◽  
Genomic Medicine ◽  
Rational Approach ◽  
Society Annual ◽  
Patients With Epilepsy

This review is a summary of a talk presented at the 2015 American Epilepsy Society Annual Meeting. Its purposes are 1) to review developments in epilepsy genetics, 2) to discuss which groups of patients with epilepsy might benefit from genetic testing, and 3) to present a rational approach to genetic testing in epilepsy in the rapidly evolving era of genomic medicine.

Genetic Testing in Children with Epilepsy: Report of a Single-Center Experience

2020 ◽  
pp. 1-12
Author(s):  
So Lee ◽  
Natalya Karp ◽  
Eugenio Zapata-Aldana ◽  
Bekim Sadikovic ◽  
Ping Yang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Diagnostic Yield ◽  
Single Gene ◽  
Medication Management ◽  
Genetic Diagnosis ◽  
Single Center Experience ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Testing ◽  
Patients With Epilepsy

ABSTRACT: Background: Retrospective observational study to determine diagnostic yield and utility of genetic testing in children with epilepsy attending the Epilepsy Clinic at Children’s Hospital, London, Ontario, Canada. Methods: Children (birth–18 years) with epilepsy, who were seen in a 10-year period (January 1, 2008–March 31, 2018), were selected using defined inclusion criteria and by combining clinic datasets and laboratory records. Results: In total, 105 children (52.38% male and 47.61% female) with a variety of seizures were included in the analysis. Developmental delay was documented in the majority (83; 79.04%). Overall, a genetic diagnosis was established in 24 (22.85%) children. The diagnostic yield was highest for whole-exome sequencing (WES), at 35.71%. The yield from microarray was 8.33%. Yields of single-gene testing (18.60%) and targeted multigene panel testing (19.23%) were very similar. Several likely pathogenic and pathogenic variants not previously reported were identified and categorized using ACMG criteria. All diagnosed patients underwent a review of anti-seizure medication management and received counseling on natural history of their disease, possible complications, recurrence risks, and possibilities of preimplantation or prenatal genetic diagnosis. Conclusions: Our study confirms the multiple benefits of detecting a genetic etiology in children with epilepsy. Similar yields in single versus multigene testing underscore the importance of accurate clinical phenotyping. Patients with epilepsy and their caregivers in Ontario would undoubtedly benefit from repatriation of multigene panels and WES to the province.

scholarly journals Chromosomal microarray detects genetic risks of neurodevelopmental disorders in newborns with congenital heart disease

2021 ◽  
pp. 1-8
Author(s):  
Kamalvir Gill ◽  
Jun Sasaki ◽  
Parul Jayakar ◽  
Lisa Sosa ◽  
Elizabeth Welch
Keyword(s):  
Genetic Testing ◽  
Neurodevelopmental Disorders ◽  
In Situ Hybridisation ◽  
Multidisciplinary Care ◽  
Chromosomal Microarray ◽  
Fluorescence In Situ Hybridisation ◽  
Genetic Abnormalities ◽  
Common Diagnosis ◽  
Hybridisation Analysis

Abstract Objective: To compare the genetic testing results of neonates with CHD by chromosomal microarray to karyotyping and fluorescence in situ hybridisation analysis. Methods: This was a single-centre retrospective comparative study of patients with CHD and available genetic testing results admitted to the cardiac ICU between January, 2004 and December, 2017. Patients from 2004 to 2010 were tested by karyotyping and fluorescence in situ hybridisation analysis, while patients from 2012 to 2017 were analysed by chromosomal microarray. Results: Eight-hundred and forty-nine neonates with CHD underwent genetic testing, 482 by karyotyping and fluorescence in situ hybridization, and 367 by chromosomal microarray. In the karyotyping and fluorescence in situ hybridisation analysis group, 86/482 (17.8%) had genetic abnormalities detected, while in the chromosomal microarray group, 135/367 (36.8%) had genetic abnormalities detected (p < 0.00001). Of patients with abnormal chromosomal microarray results, 41/135 (30.4%) had genetic abnormality associated with neurodevelopmental disorders that were exclusively identified by chromosomal microarray. Conotruncal abnormalities were the most common diagnosis in both groups, with karyotyping and fluorescence in situ hybridisation analysis detecting genetic abnormalities in 26/160 (16.3%) patients and chromosomal microarray detecting abnormalities in 41/135 (30.4%) patients (p = 0.004). In patients with d-transposition of the great arteries, 0/68 (0%) were found to have genetic abnormalities by karyotyping and fluorescence in situ hybridisation compared to 7/54 (13.0%) by chromosomal microarray. Conclusions: Chromosomal microarray identified patients with CHD at genetic risk of neurodevelopmental disorders, allowing earlier intervention with multidisciplinary care and more accurate pre-surgical prognostic counselling.

scholarly journals De novo Variants in Neurodevelopmental Disorders with Epilepsy

2017 ◽  
Author(s):  
Henrike O. Heyne ◽  
Tarjinder Singh ◽  
Hannah Stamberger ◽  
Rami Abou Jamra ◽  
Hande Caglayan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Genetic Testing ◽  
Neurodevelopmental Disorders ◽  
Disease Gene ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Disease Association ◽  
Joint Analysis ◽  
Limited Evidence ◽  
Significant Excess

AbstractEpilepsy is a frequent feature of neurodevelopmental disorders (NDD) but little is known about genetic differences between NDD with and without epilepsy. We analyzed de novo variants (DNV) in 6753 parent-offspring trios ascertained for different NDD. In the subset of 1942 individuals with NDD with epilepsy, we identified 33 genes with a significant excess of DNV, of which SNAP25 and GABRB2 had previously only limited evidence for disease association. Joint analysis of all individuals with NDD also implicated CACNA1E as a novel disease gene. Comparing NDD with and without epilepsy, we found missense DNV, DNV in specific genes, age of recruitment and severity of intellectual disability to be associated with epilepsy. We further demonstrate to what extent our results impact current genetic testing as well as treatment, emphasizing the benefit of accurate genetic diagnosis in NDD with epilepsy.

scholarly journals Polygenic burden in focal and generalized epilepsies

Brain ◽  
2019 ◽  
Vol 142 (11) ◽  
pp. 3473-3481 ◽  
Author(s):  
Costin Leu ◽  
Remi Stevelink ◽  
Alexander W Smith ◽  
Slavina B Goleva ◽  
Masahiro Kanai ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Focal Epilepsy ◽  
Common Variant ◽  
European Ancestry ◽  
Uk Biobank ◽  
Clinical Biomarkers ◽  
Generalized Epilepsy ◽  
Patients With Epilepsy ◽  
Japanese Ancestry ◽  
Population Controls

Abstract Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10−15; Cleveland: P = 2.85×10−4; Finnish-ancestry Epi25: P = 1.80×10−4) or population controls (Epi25: P = 2.35×10−70; Cleveland: P = 1.43×10−7; Finnish-ancestry Epi25: P = 3.11×10−4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10−4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10−19; Cleveland: P = 1.69×10−6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10−15; Cleveland: P = 1.39×10−2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls—in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment.

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