Early‐onset epileptic encephalopathy with myoclonic seizures related to 9q33.3‐q34.11 deletion involving <i>STXBP1</i> and <i>SPTAN1</i> genes

Aravindhan, Akilandeswari; Shah, Kinal; Pak, Jayoung; Veerapandiyan, Aravindhan

doi:10.1684/epd.2018.0969

Cited by 10 publications

(10 citation statements)

References 12 publications

(39 reference statements)

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“…GABAergic more than glutamatergic neurons seem impaired, probably resulting in an imbalanced excitability in the neocortex, responsible for an abnormal epileptic activity [34,35]. The phenotype of patients with a STXBP1 pathogenic variant ranges [25] from the generic early onset epilepsy encephalopathy, to Ohathara syndrome [36,37], EME [38], West syndrome [39,40], Dravet syndrome [41], but also includes intellectual disability (ID) in the absence of epilepsy [42,43,44], classic MECP 2-negative RTT and atypical RTT [45]. As the degree of ID does not appear to correlate with the severity of the seizures and/or the age of onset of epilepsy, STXBP1 -EE is not thought to be a simple Early Onset Epileptic Encephalopaty-EOEE, but a more complex neurodevelopmental disorder (DEE, Developmental and Epileptic Encephalopaty), where both ID (often occurring before the onset of epilepsy) and epilepsy play a synergic role in the phenotype evolution [25,26,27].…”

Section: Discussionmentioning

confidence: 99%

Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes

Cogliati

Giorgini

Masciadri

et al. 2019

IJMS

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Rett syndrome (RTT) is a neurodevelopmental disorder, affecting 1 in 10,000 girls. Intellectual disability, loss of speech and hand skills with stereotypies, seizures and ataxia are recurrent features. Stringent diagnostic criteria distinguish classical Rett, caused by a MECP2 pathogenic variant in 95% of cases, from atypical girls, 40–73% carrying MECP2 variants, and rarely CDKL5 and FOXG1 alterations. A large fraction of atypical and RTT-like patients remain without genetic cause. Next Generation Sequencing (NGS) targeted to multigene panels/Whole Exome Sequencing (WES) in 137 girls suspected for RTT led to the identification of a de novo variant in STXBP1 gene in four atypical RTT and two RTT-like girls. De novo pathogenic variants—one in GABRB2 and, for first time, one in GABRG2—were disclosed in classic and atypical RTT patients. Interestingly, the GABRG2 variant occurred at low rate percentage in blood and buccal swabs, reinforcing the relevance of mosaicism in neurological disorders. We confirm the role of STXBP1 in atypical RTT/RTT-like patients if early psychomotor delay and epilepsy before 2 years of age are observed, indicating its inclusion in the RTT diagnostic panel. Lastly, we report pathogenic variants in Gamma-aminobutyric acid-A (GABAa) receptors as a cause of atypical/classic RTT phenotype, in accordance with the deregulation of GABAergic pathway observed in MECP2 defective in vitro and in vivo models.

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Section: Discussionmentioning

confidence: 99%

Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes

Cogliati

Giorgini

Masciadri

et al. 2019

IJMS

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“…The deletion (9q33.3 to 9q34.11), which involves eight genes including STXBP1 gene was reported twice in the literature to be associated with epileptic encephalopathy and intellectual disability [19].…”

Section: Genes Responsible For the Synapsis Neurotransmitters And Receptorsmentioning

confidence: 99%

The landscape of early infantile epileptic encephalopathy in a consanguineous population

Nashabat

Qahtani

Almakdob

et al. 2019

Seizure

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Epileptic encephalopathies (EE), are a group of age-related disorders characterized by intractable seizures and electroencephalogram (EEG) abnormalities that may result in cognitive and motor delay. Early infantile epileptic encephalopathies (EIEE) manifest in the first year of life. EIEE are highly heterogeneous genetically but a genetic etiology is only identified in half of the cases, typically in the form of de novo dominant mutations. Method: This is a descriptive retrospective study of a consecutive series of patients diagnosed with EIEE from the participating hospitals. A chart review was performed for all patients. The diagnosis of epileptic encephalopathy was confirmed by molecular investigations in commercial labs. In silico study was done for all novel mutations. A systematic search was done for all the types of EIEE and their correlated genes in the literature using the Online Mendelian Inheritance In Man and PubMed databases. Results: In this case series, we report 72 molecularly characterized EIEE from a highly consanguineous population, and review their clinical course. We identified 50 variants, 26 of which are novel, causing 26 different types of EIEE. Unlike outbred populations, autosomal recessive EIEE accounted for half the cases. The phenotypes ranged from self-limiting and drug-responsive to severe refractory seizures or even death. Conclusions: We reported the largest EIEE case series in the region with confirmed molecular testing and detailed clinical phenotyping. The number autosomal recessive predominance could be explained by the society's high consanguinity. We reviewed all the EIEE registered causative genes in the literature and proposed a functional classification. IntroductionEpileptic encephalopathies (EE), are disorders of the developing brain characterized by intractable seizures and electroencephalogram (EEG) abnormalities, that typically result in cognitive and motor delay, regression, and sometimes death. [1,2] Forty percent of seizures in children aged three years or less can be classified as EE [3]. Early infantile epileptic encephalopathy (EIEE) have their onset during infancy and are highly variable in etiology and natural history. While seizure is the core symptom for all EIEE syndromes often accompanied by

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“…92 The EEG findings in SPTAN1 encephalopathy include hypsarrhythmia, diffuse slowing of the background, and multifocal discharges, whereas neuroimaging may show brainstem and cerebellar atrophy, hypomyelination, cortical atrophy, and a thin corpus callosum. [90][91][92] Some seizure improvement has been observed with vigabatrin, adrenocorticotropic hormone, valproic acid, topiramate, levetiracetam, and the ketogenic diet. 91 However, there is no targeted therapy for SPTAN1 encephalopathy.…”

Section: Sptan1mentioning

confidence: 99%

Early-Onset Developmental and Epileptic Encephalopathies of Infancy: An Overview of the Genetic Basis and Clinical Features

Morrison‐Levy

Borlot

Jain

et al. 2021

Pediatric Neurology

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Early‐onset epileptic encephalopathy with myoclonic seizures related to 9q33.3‐q34.11 deletion involving STXBP1 and SPTAN1 genes

Cited by 10 publications

References 12 publications

Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes

Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes

The landscape of early infantile epileptic encephalopathy in a consanguineous population

Early-Onset Developmental and Epileptic Encephalopathies of Infancy: An Overview of the Genetic Basis and Clinical Features

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