High genetic burden in 163 Chinese children with status epilepticus

Wang, Tianqi; Wang, Ji; Ma, Yu; Zhou, Hao; Ding, Ding; Li, Chunpei; Du, Xinyue; Jiang, Yong‐Hui; Wang, Yi; Long, Shasha; Li, Shuang; Li, Guoping; Chen, Wei-Ming; Zhou, Yuanfeng; Zhou, Shuizhen

doi:10.1016/j.seizure.2020.10.032

Cited by 9 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When considering whom to test, providers should exercise clinical judgment based on the outcomes outlined above. Individuals with neonatal or infantile-onset seizures, those with DEE or epilepsy plus other neurodevelopmental comorbidities have the highest diagnostic yield to date (Costain et al, 2019;Sheidley et al, 2022;Stefanski et al, 2021;Symonds et al, 2019;Wang et al, 2021) Note: For CGH/CMA's, single-exon CNV detection is laboratory and gene dependent. For MGPs, laboratories may include analysis for recurrent intronic variants for specific genes, and/or repeat expansions for genes in which those are common.…”

Section: Indications For Testingmentioning

confidence: 99%

“…When considering whom to test, providers should exercise clinical judgment based on the outcomes outlined above. Individuals with neonatal or infantile‐onset seizures, those with DEE or epilepsy plus other neurodevelopmental comorbidities have the highest diagnostic yield to date (Costain et al, 2019; Sheidley et al, 2022; Stefanski et al, 2021; Symonds et al, 2019; Wang et al, 2021). Diagnostic yields remain significant among other age groups (Helbig et al, 2016; Stefanski et al, 2021), and among individuals with generalized and focal epilepsies in the absence of other reported clinical features (Sheidley et al, 2022).…”

Section: Rationalementioning

confidence: 99%

See 1 more Smart Citation

Genetic testing and counseling for the unexplained epilepsies: An evidence‐based practice guideline of the National Society of Genetic Counselors

Smith

Malinowski²,

Ceulemans

et al. 2022

Journal of Genetic Counseling

View full text Add to dashboard Cite

Epilepsy, defined by the occurrence of two or more unprovoked seizures or one unprovoked seizure with a propensity for others, affects 0.64% of the population and can lead to significant morbidity and mortality. A majority of unexplained epilepsy (seizures not attributed to an acquired etiology, such as trauma or infection) is estimated to have an underlying genetic etiology. Despite rapid progress in understanding of the genetic underpinnings of the epilepsies, there are no recent evidence-based guidelines for genetic testing and counseling for this population. This practice guideline provides evidence-based recommendations for approaching genetic testing in the epilepsies using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework. We used evidence from a recent systematic evidence review and meta-analysis of diagnostic yield of genetic tests in patients with epilepsy. We also compiled data from other sources, including recently submitted conference abstracts and peer-reviewed journal articles. We identified and prioritized outcomes of genetic testing as critical, important or not important and based our recommendations on outcomes deemed critical and important. We considered the desirable and undesirable effects, value and acceptability to relevant stakeholders, impact on health equity, cost-effectiveness, certainty of evidence, and feasibility of the interventions in individuals with epilepsy. Taken together, we generated two clinical recommendations: (1) Genetic testing is strongly recommended for all individuals with unexplained epilepsy, without limitation of age, with exome/genome sequencing and/or a multi-gene panel (>25 genes) as first-tier testing followed by chromosomal microarray, with exome/genome sequencing conditionally recommended over multi-gene panel. (2) It is strongly recommended that genetic tests be selected, ordered, and interpreted by a qualified healthcare provider in the setting of appropriate pre-test and post-test genetic counseling. Incorporation of genetic counselors into neurology practices and/or referral to genetics specialists are both useful models for supporting providers without genetics expertise to implement these recommendations.

show abstract

Section: Indications For Testingmentioning

confidence: 99%

Section: Rationalementioning

confidence: 99%

Genetic testing and counseling for the unexplained epilepsies: An evidence‐based practice guideline of the National Society of Genetic Counselors

Smith

Malinowski²,

Ceulemans

et al. 2022

Journal of Genetic Counseling

View full text Add to dashboard Cite

show abstract

“…Similarly, a Korean center reported two patients with SCN1A , c.2589+3A>T, and it was the only recurrent variant found in their study 24 . Several other studies have reported one case each with the c.2589+3A>T variant 25–29 . However, the total number of reported patients with the c.2589+3A>T variant remains limited.…”

Section: Discussionmentioning

confidence: 98%

“…24 Several other studies have reported one case each with the c.2589+3A>T variant. [25][26][27][28][29] However, the total number of reported patients with the c.2589+3A>T variant remains limited. Similarly, another recurrent variant, c.2837G>A, has been reported in previous studies but was never identified as a predominant variant.…”

Section: Discussionmentioning

confidence: 99%

Common genes and recurrent causative variants in 957 Asian patients with pediatric epilepsy

Kim,

Seo,

Kwon

et al. 2023

Epilepsia

View full text Add to dashboard Cite

ObjectiveWe aimed to identify common genes and recurrent causative variants in a large group of Asian patients with different epilepsy syndromes and subgroups.MethodsPatients with unexplained pediatric‐onset epilepsy were identified from the in‐house Severance Neurodevelopmental Disorders and Epilepsy Database. All patients underwent either exome sequencing or multigene panels from January 2017 to December 2019, at Severance Children's Hospital in Korea. Clinical data were extracted from the medical records.ResultsOf the 957 patients studied, 947 (99.0%) were Korean and 570 were male (59.6%). The median age at testing was 4.91 years (interquartile range, 1.53–9.39). The overall diagnostic yield was 32.4% (310/957). Clinical exome sequencing yielded a diagnostic rate of 36.9% (134/363), whereas the epilepsy panel yielded a diagnostic rate of 29.9% (170/569). Diagnostic yield differed across epilepsy syndromes. It was high in Dravet syndrome (87.2%, 41/47) and early infantile developmental epileptic encephalopathy (60.7%, 17/28), but low in West syndrome (21.8%, 34/156) and myoclonic‐atonic epilepsy (4.8%, 1/21). The most frequently implicated genes were SCN1A (n = 49), STXBP1 (n = 15), SCN2A (n = 14), KCNQ2 (n = 13), CDKL5 (n = 11), CHD2 (n = 9), SLC2A1 (n = 9), PCDH19 (n = 8), MECP2 (n = 6), SCN8A (n = 6), and PRRT2 (n = 5). The recurrent genetic abnormalities included 15q11.2 deletion/duplication (n = 9), Xq28 duplication (n = 5), PRRT2 deletion (n = 4), MECP2 duplication (n = 3), SCN1A, c.2556+3A>T (n = 3), and 2q24.3 deletion (n = 3).SignificanceHere we present the results of a large‐scale study conducted in East Asia, where we identified several common genes and recurrent variants that varied depending on specific epilepsy syndromes. The overall genetic landscape of the Asian population aligns with findings from other populations of varying ethnicities.

show abstract

“…The lack of genetic explanation in FIRES stands in stark contrast to the genetic landscape of epilepsy more broadly in which the genetic yield is up to 33% with different forms of genetic testing ( 9 , 10 ). Studies exploring genetic etiologies of SE and RSE indicate a subset of various genes that are associated with SE ( 11 , 12 ). However, there are fewer recognized genes and validated variants associated with RSE ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Investigating the genetic contribution in febrile infection-related epilepsy syndrome and refractory status epilepticus

et al. 2023

View full text Add to dashboard Cite

IntroductionFebrile infection-related epilepsy syndrome (FIRES) is a severe childhood epilepsy with refractory status epilepticus after a typically mild febrile infection. The etiology of FIRES is largely unknown, and outcomes in most individuals with FIRES are poor.MethodsHere, we reviewed the current state-of-the art genetic testing strategies in individuals with FIRES. We performed a systematic computational analysis to identify individuals with FIRES and characterize the clinical landscape using the Electronic Medical Records (EMR). Among 25 individuals with a confirmed FIRES diagnosis over the last decade, we performed a comprehensive review of genetic testing and other diagnostic testing.ResultsManagement included use of steroids and intravenous immunoglobulin (IVIG) in most individuals, with an increased use of immunomodulatory agents, including IVIG, plasma exchange (PLEX) and immunosuppressants such as cytokine inhibitors, and the ketogenic diet after 2014. Genetic testing was performed on a clinical basis in almost all individuals and was non-diagnostic in all patients. We compared FIRES with both status epilepticus (SE) and refractory status epilepticus (RSE) as a broader comparison cohort and identified genetic causes in 36% of patients with RSE. The difference in genetic signatures between FIRES and RSE suggest distinct underlying etiologies. In summary, despite the absence of any identifiable etiologies in FIRES, we performed an unbiased analysis of the clinical landscape, identifying a heterogeneous range of treatment strategies and characterized real-world clinical practice.DiscussionFIRES remains one of the most enigmatic conditions in child neurology without any known etiologies to date despite significant efforts in the field, suggesting a clear need for further studies and novel diagnostic and treatment approaches.

show abstract

High genetic burden in 163 Chinese children with status epilepticus

Cited by 9 publications

References 36 publications

Genetic testing and counseling for the unexplained epilepsies: An evidence‐based practice guideline of the National Society of Genetic Counselors

Genetic testing and counseling for the unexplained epilepsies: An evidence‐based practice guideline of the National Society of Genetic Counselors

Common genes and recurrent causative variants in 957 Asian patients with pediatric epilepsy

Investigating the genetic contribution in febrile infection-related epilepsy syndrome and refractory status epilepticus

Contact Info

Product

Resources

About