Zonisamide‐responsive myoclonus in SEMA6B‐associated progressive myoclonic epilepsy

Herzog, Rebecca; Hellenbroich, Yorck; Brüggemann, Norbert; Lohmann, Katja; Grimmel, Mona; Haack, Tobias B.; Spiczak, Sarah von; Münchau, Alexander

doi:10.1002/acn3.51403

Cited by 11 publications

(10 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The author suggested that the gene was dominant-negative or had gain-of-function effects rather than showing haploid deficiency. Upon searching for reported cases of SEMA6B variants, we found seven other variants reported in the literature ( 6 – 8 , 13 – 15 ). All of the variants are summarized in Table 1 and Figure 3 .…”

Section: Discussionmentioning

confidence: 99%

“…Clonazepam is useful but often leads to considerable sedation and increasing tolerance. Due to the partial response to clonazepam and the short-term improvement after treatment with valproic acid and levetiracetam, myoclonus tends to persist after treatment ( 8 ). Some newer ASMs are reportedly effective, such as piracetam ( 17 ), topiramate ( 18 ), zonisamide ( 19 ), clobazam ( 20 ), and perampanel ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

“…The small number of mutations observed in SEMA6B in patients with PME has limited our understanding of how SEMA6B plays a role in the pathogenesis of PME. In addition, the treatment experience is also very limited ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Non-convulsive Status Epilepticus in SEMA6B-Related Progressive Myoclonic Epilepsy: A Case Report With Literature Review

Duan

Chen

et al. 2022

Front. Pediatr.

View full text Add to dashboard Cite

Progressive myoclonic epilepsy (PME) is a group of rare diseases characterized by progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. PME has high genetic heterogeneity, and more than 40 genes are reportedly associated with this disorder. SEMA6B encodes a member of the semaphorin family and was first reported to cause PME in 2020. Herein, we present a rare case of PME due to a novel SEMA6B gene mutation in a 6-year-old boy born to healthy non-consanguineous Chinese parents. His developmental milestones were delayed, and he developed recurrent atonic seizures and myoclonic seizures without fever at 3 years and 11 months of age. He experienced recurrent myoclonic seizures, non-convulsive status epilepticus (NCSE), atonic seizures, and atypical absence seizures during the last 2 years. At different time points since onset, valproic acid, levetiracetam, piracetam, and clobazam were used to control the intractable seizures. Notably, NCSE was controlled by a combination of piracetam with clobazam and valproic acid instead of intravenous infusion of midazolam and phenobarbital. Due to the limited number of cases reported to date, the clinical description of our case provides a better understanding of the genotype–phenotype correlations associated with PME and indicate that piracetam may be effective against NCSE in patients with SEMA6B-related PME.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Non-convulsive Status Epilepticus in SEMA6B-Related Progressive Myoclonic Epilepsy: A Case Report With Literature Review

Duan

Chen

et al. 2022

Front. Pediatr.

View full text Add to dashboard Cite

show abstract

“…With 14 variants, of which 11 are novel, added to those already reported in the literature, (10)(11)(12)(13)(14)(15) our study leads to a total of 22 heterozygous variants currently identified in SEMA6B in 28 unrelated patients. In all patients for whom DNA of the two parents was available (22/28), these variants had occurred de novo.…”

Section: Discussionmentioning

confidence: 90%

“…Until now, SEMA6B variants have been identified in individuals with epilepsy, including (1) 10 truncating variants in the last exon of SEMA6B in 10 patients with progressive myoclonic epilepsy (PME, MIM #618876), (10)(11)(12)(13)(14) and in one individual with global developmental delay and recurrent febrile seizures, (15) and ( 2) one missense variant in exon 14 in an individual with epilepsy without intellectual disability (Supplementary Table 1). ( 13) Here, we broaden the phenotypic spectrum and the role of SEMA6B by reporting 14 heterozygous variants, of which 11 are novel, identified in 16 unrelated patients with moderate to severe intellectual disability, as well as variable neurological features and seizures in some cases.…”

Section: Introductionmentioning

confidence: 99%

SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance

Cordovado

Schaettin

Jeanne

et al. 2022

Human Molecular Genetics

View full text Add to dashboard Cite

Intellectual disability is a neurodevelopmental disorder frequently caused by monogenic defects. In this study, we collected 14 SEMA6B heterozygous variants in 16 unrelated patients referred for intellectual disability to different centres. Whereas until now SEMA6B variants have mainly been reported in patients with progressive myoclonic epilepsy, our study indicates that the clinical spectrum is wider, and also includes non-syndromic intellectual disability without epilepsy or myoclonus. To assess the pathogenicity of these variants, selected mutated forms of Sema6b were overexpressed in HEK293T cells and in primary neuronal cultures. shRNAs targeting Sema6b were also used in neuronal cultures to measure the impact of the decreased Sema6b expression on morphogenesis and synaptogenesis. The overexpression of some variants leads to a subcellular mislocalisation of SEMA6B protein in HEK293T cells and to a reduced spine density due to loss of mature spines in neuronal cultures. Sema6b knock-down also impairs spine density and spine maturation. In addition, we conducted in vivo rescue experiments in chicken embryos with the selected mutated forms of Sema6b expressed in commissural neurons after knock-down of endogenous SEMA6B. We observed that expression of these variants in commissural neurons fails to rescue the normal axon pathway. In conclusion, identification of SEMA6B variants in patients presenting with an overlapping phenotype with intellectual disability, and functional studies highlight the important role of SEMA6B in neuronal development, notably in spine formation and maturation, and in axon guidance. This study adds SEMA6B to the list of intellectual disability-related genes.

show abstract

Progressive myoclonus epilepsies due to SEMA6B mutations. New variants and appraisal of published phenotypes

et al. 2023

View full text Add to dashboard Cite

Variants of SEMA6B have been identified in an increasing number of patients, often presenting with progressive myoclonus epilepsy (PME), and to lesser extent developmental encephalopathy, with or without epilepsy. The exon 17 is mainly involved, with truncating mutations causing the production of aberrant proteins with toxic gain of function. Herein, we describe three adjunctive patients carrying de novo truncating SEMA6B variants in this exon (c.1976delC and c.2086C > T novel; c.1978delC previously reported). These subjects presented with PME preceded by developmental delay, motor and cognitive impairment, worsening myoclonus, and epilepsy with polymorphic features, including focal to bilateral seizures in two, and non-convulsive status epilepticus in one. The evidence of developmental delay in these cases suggests their inclusion in the "PME plus developmental delay" nosological group. This work further expands our knowledge of SEMA6B variants causing PMEs. However, the data to date available confirms that phenotypic features do not correlate with the type or location of variants, aspects that need to be further clarified by future studies.

show abstract

Zonisamide‐responsive myoclonus in SEMA6B‐associated progressive myoclonic epilepsy

Cited by 11 publications

References 9 publications

Non-convulsive Status Epilepticus in SEMA6B-Related Progressive Myoclonic Epilepsy: A Case Report With Literature Review

Non-convulsive Status Epilepticus in SEMA6B-Related Progressive Myoclonic Epilepsy: A Case Report With Literature Review

SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance

Progressive myoclonus epilepsies due to SEMA6B mutations. New variants and appraisal of published phenotypes

Contact Info

Product

Resources

About