Reduction of seizure frequency after epilepsy surgery in a patient with <scp><i>STXBP1</i></scp> encephalopathy and clinical description of six novel mutation carriers

Weckhuysen, Sarah; Holmgren, Philip; Hendrickx, Rik; Jansen, Anna; Hasaerts, Danielle; Dielman, Charlotte; Bellescize, Julitta de; Boutry‐Kryza, Nadia; Lesca, Gaëtan; Spiczak, Sarah von; Helbig, Ingo; Gill, Deepak; Yendle, Simone C.; Møller, Rikke S.; Klitten, Laura L.; Korff, Christian; Godfraind, Catherine; Rijckevorsel, Kenou van; Jonghe, Peter De; Hjalgrim, Helle; Scheffer, Ingrid E.; Suls, Arvid

doi:10.1111/epi.12124

Cited by 62 publications

(77 citation statements)

References 12 publications

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“…Of the .50 patients with STXBP1 encephalopathy described, the majority present by 3 months of age, with Ohtahara syndrome or other early-onset epileptic encephalopathies. [22][23][24][25][26][27][28][29][30][31][32] Our patients had onset from 6 to 12 months, which is later than usually seen in STXBP1 encephalopathy. It is typically associated with epileptic spasms, and notably these were not observed in our patients with Dravet syndrome.…”

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confidence: 53%

GABRA1 and STXBP1 : Novel genetic causes of Dravet syndrome

et al. 2014

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Objective: To determine the genes underlying Dravet syndrome in patients who do not have an SCN1A mutation on routine testing. Methods:We performed whole-exome sequencing in 13 SCN1A-negative patients with Dravet syndrome and targeted resequencing in 67 additional patients to identify new genes for this disorder.Results: We detected disease-causing mutations in 2 novel genes for Dravet syndrome, with mutations in GABRA1 in 4 cases and STXBP1 in 3. Furthermore, we identified 3 patients with previously undetected SCN1A mutations, suggesting that SCN1A mutations occur in even more than the currently accepted ;75% of cases. Conclusions:We show that GABRA1 and STXBP1 make a significant contribution to Dravet syndrome after SCN1A abnormalities have been excluded. Our results have important implications for diagnostic testing, clinical management, and genetic counseling of patients with this devastating disorder and their families. Neurology ® 2014;82:1245-1253 GLOSSARY cDNA 5 complementary DNA; dHPLC 5 denaturing high-performance liquid chromatography; FS 5 febrile seizures; GABA 5 g-aminobutyric acid; GEFS1 5 genetic epilepsy with febrile seizures plus; WES 5 whole-exome sequencing; WT 5 wild-type.

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confidence: 53%

GABRA1 and STXBP1 : Novel genetic causes of Dravet syndrome

et al. 2014

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“…7, 8, 30-35 Two of the 4 patients had burst suppression identified at approximately 2 months, resolving by 4 months and 13 months, respectively. Two patients did not have burst suppression after careful review of EEGs.…”

Section: Resultsmentioning

confidence: 99%

Genetics and genotype–phenotype correlations in early onset epileptic encephalopathy with burst suppression

Olson

Kelly

LaCoursiere

et al. 2017

Annals of Neurology

117

112

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Objective We sought to identify genetic causes of early onset epileptic encephalopathies with burst suppression (Ohtahara syndrome and early myoclonic encephalopathy) and evaluate genotype-phenotype correlations. Methods We enrolled 33 patients with a referral diagnosis of Ohtahara syndrome or early myoclonic encephalopathy without malformations of cortical development. We performed detailed phenotypic assessment including seizure presentation, EEG, and MRI. We confirmed burst suppression in 28 out of 33 patients. Research-based exome sequencing was performed for patients without a previously identified molecular diagnosis from clinical evaluation or research-based epilepsy gene panel. Results In 17/28 (61%) patients with confirmed early burst suppression, we identified variants predicted to be pathogenic in KCNQ2 (n=10), STXBP1 (n=2), SCN2A (n=2), PNPO (n=1), PIGA (n=1), and SEPSECS (n=1). In 3/5 (60%) patients without confirmed early burst suppression, we identified variants predicted to be pathogenic in STXBP1 (n=2) and SCN2A (n=1). The patient with the homozygous PNPO variant had a low CSF pyridoxal-5-phosphate level. Otherwise, no early laboratory or clinical features distinguished the cases associated with pathogenic variants in specific genes from each other or from those with no prior genetic cause identified. Interpretation We characterize the genetic landscape of epileptic encephalopathy with burst suppression, without brain malformations, and demonstrate feasibility of genetic diagnosis with clinically available testing in over 60% of our cohort with KCNQ2 implicated in one third. This electroclinical syndrome is associated with pathogenic variation in SEPSECS.

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“…One study discovered a mutation in the SCN1A gene in a patient with some clinical features resembling, but without pathological confirmation of, RE [59]. Interestingly, the association of gene mutations in STXBP1 (MUNC-18-1) with some epileptic syndromes and childhood encephalopathies, and the presence of autoantibodies against Munc-18 in a subset of patients with RE [38,[60][61][62] may raise the possibility that mutations in STXBP1 may be present in patients with RE. Although the rarity of RE makes it difficult to perform genetic studies, a potential approach should focus on the assessment of genetic susceptibility to immunological responses as a potential predisposing factor in patients with RE.…”

Section: Genetics Factors and "Double Pathology" In Rementioning

confidence: 99%

Mechanisms of Epileptogenesis in Pediatric Epileptic Syndromes: Rasmussen Encephalitis, Infantile Spasms, and Febrile Infection-related Epilepsy Syndrome (FIRES)

2014

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The mechanisms of epileptogenesis in pediatric epileptic syndromes are diverse, and may involve disturbances of neurodevelopmental trajectories, synaptic homeostasis, and cortical connectivity, which may occur during brain development, early infancy, or childhood. Although genetic or structural/metabolic factors are frequently associated with agespecific epileptic syndromes, such as infantile spasms and West syndrome, other syndromes may be determined by the effect of immunopathogenic mechanisms or energy-dependent processes in response to environmental challenges, such as infections or fever in normally-developed children during early or late childhood. Immune-mediated mechanisms have been suggested in selected pediatric epileptic syndromes in which acute and rapidly progressive encephalopathies preceded by fever and/or infections, such as febrile infection-related epilepsy syndrome, or in chronic progressive encephalopathies, such as Rasmussen encephalitis. A definite involvement of adaptive and innate immune mechanisms driven by cytotoxic CD8 +

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Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers

Cited by 62 publications

References 12 publications

GABRA1 and STXBP1 : Novel genetic causes of Dravet syndrome

GABRA1 and STXBP1 : Novel genetic causes of Dravet syndrome

Genetics and genotype–phenotype correlations in early onset epileptic encephalopathy with burst suppression

Mechanisms of Epileptogenesis in Pediatric Epileptic Syndromes: Rasmussen Encephalitis, Infantile Spasms, and Febrile Infection-related Epilepsy Syndrome (FIRES)

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