scholarly journals Focal epilepsy-intellectual disability-cerebro-cerebellar malformation

2020 ◽  
Author(s):  
Keyword(s):  
Intellectual Disability ◽  
Focal Epilepsy ◽  
Cerebellar Malformation

scholarly journals GRIN2Bmutations in west syndrome and intellectual disability with focal epilepsy

2014 ◽  
Vol 75 (1) ◽  
pp. 147-154 ◽  
Author(s):  
Johannes R. Lemke ◽  
Rik Hendrickx ◽  
Kirsten Geider ◽  
Bodo Laube ◽  
Michael Schwake ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Focal Epilepsy ◽  
West Syndrome

scholarly journals Clinical features and outcome of 6 new patients carrying de novo KCNB1 gene mutations

2017 ◽  
Vol 3 (6) ◽  
pp. e206 ◽  
Author(s):  
Carla Marini ◽  
Michele Romoli ◽  
Elena Parrini ◽  
Cinzia Costa ◽  
Davide Mei ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Focal Epilepsy ◽  
Brain Mri ◽  
Somatic Mosaicism ◽  
Epileptic Encephalopathy ◽  
Seizure Onset ◽  
Severe Intellectual Disability ◽  
The Mean

Objective:To describe electroclinical features and outcome of 6 patients harboring KCNB1 mutations.Methods:Clinical, EEG, neuropsychological, and brain MRI data analysis. Targeted next-generation sequencing of a 95 epilepsy gene panel.Results:The mean age at seizure onset was 11 months. The mean follow-up of 11.3 years documented that 4 patients following an infantile phase of frequent seizures became seizure free; the mean age at seizure offset was 4.25 years. Epilepsy phenotypes comprised West syndrome in 2 patients, infantile-onset unspecified generalized epilepsy, myoclonic and photosensitive eyelid myoclonia epilepsy resembling Jeavons syndrome, Lennox-Gastaut syndrome, and focal epilepsy with prolonged occipital or clonic seizures in each and every one. Five patients had developmental delay prior to seizure onset evolving into severe intellectual disability with absent speech and autistic traits in one and stereotypic hand movements with impulse control disorder in another. The patient with Jeavons syndrome evolved into moderate intellectual disability. Mutations were de novo, 4 missense and 2 nonsense, 5 were novel, and 1 resulted from somatic mosaicism.Conclusions:KCNB1-related manifestations include a spectrum of infantile-onset generalized or focal seizures whose combination leads to early infantile epileptic encephalopathy including West, Lennox-Gastaut, and Jeavons syndromes. Long-term follow-up highlights that following a stormy phase, seizures subside or cease and treatment may be eased or withdrawn. Cognitive and motor functions are almost always delayed prior to seizure onset and evolve into severe, persistent impairment. Thus, KCNB1 mutations are associated with diffuse brain dysfunction combining seizures, motor, and cognitive impairment.

scholarly journals Voltage-independent GluN2A-type NMDA receptor Ca2+ signaling promotes audiogenic seizures, attentional and cognitive deficits in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ilaria Bertocchi ◽  
Ahmed Eltokhi ◽  
Andrey Rozov ◽  
Vivan Nguyễn Chi ◽  
Vidar Jensen ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Focal Epilepsy ◽  
Mechanistic Explanation ◽  
Audiogenic Seizures ◽  
Coincidence Detection ◽  
Oscillatory Activity ◽  
Sensory Stimuli ◽  
Inherent Voltage

AbstractThe NMDA receptor-mediated Ca2+ signaling during simultaneous pre- and postsynaptic activity is critically involved in synaptic plasticity and thus has a key role in the nervous system. In GRIN2-variant patients alterations of this coincidence detection provoked complex clinical phenotypes, ranging from reduced muscle strength to epileptic seizures and intellectual disability. By using our gene-targeted mouse line (Grin2aN615S), we show that voltage-independent glutamate-gated signaling of GluN2A-containing NMDA receptors is associated with NMDAR-dependent audiogenic seizures due to hyperexcitable midbrain circuits. In contrast, the NMDAR antagonist MK-801-induced c-Fos expression is reduced in the hippocampus. Likewise, the synchronization of theta- and gamma oscillatory activity is lowered during exploration, demonstrating reduced hippocampal activity. This is associated with exploratory hyperactivity and aberrantly increased and dysregulated levels of attention that can interfere with associative learning, in particular when relevant cues and reward outcomes are disconnected in space and time. Together, our findings provide (i) experimental evidence that the inherent voltage-dependent Ca2+ signaling of NMDA receptors is essential for maintaining appropriate responses to sensory stimuli and (ii) a mechanistic explanation for the neurological manifestations seen in the NMDAR-related human disorders with GRIN2 variant-meidiated intellectual disability and focal epilepsy.

scholarly journals A Focal Epilepsy and Intellectual Disability Syndrome Is Due to a Mutation in TBC1D24

2010 ◽  
Vol 87 (3) ◽  
pp. 371-375 ◽  
Author(s):  
Mark A. Corbett ◽  
Melanie Bahlo ◽  
Lachlan Jolly ◽  
Zaid Afawi ◽  
Alison E. Gardner ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Focal Epilepsy

scholarly journals Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders

2018 ◽  
Author(s):  
Claudio Toma ◽  
Kerrie D. Pierce ◽  
Alex D. Shaw ◽  
Anna Heath ◽  
Philip B. Mitchell ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Intellectual Disability ◽  
Candidate Gene ◽  
Psychiatric Disorders ◽  
Rare Variants ◽  
Focal Epilepsy ◽  
Psychiatric Diseases ◽  
Risk Gene ◽  
Functional Snps ◽  
Sequence Variations

ABSTRACTThe contactin-associated protein-like 2 (CNTNAP2) gene is a member of the neurexin superfamily. CNTNAP2 was implicated in the cortical dysplasia-focal epilepsy (CDFE) syndrome, a recessive disease characterized by intellectual disability, epilepsy, language impairments and autistic features. Associated SNPs and heterozygous deletions in CNTNAP2 have also frequently been reported in autism, schizophrenia and other psychiatric or neurological disorders. We aim here to gain conclusive evidence for the role of CNTNAP2 in susceptibility to psychiatric disorders by the comprehensive analysis of large genomic datasets. In this study we used: i) summary statistics from the Psychiatric Genomics Consortium (PGC) GWAS; ii) examined all reported CNTNAP2 structural variants in patients and controls; iii) performed cross-disorder analysis of functional or previously associated SNPs; iv) and conducted burden tests for pathogenic rare variants using sequencing data (4,483 ASD and 6,135 schizophrenia cases, and 13,042 controls).In a CNV mircroarray study, we previously identified a 131kb deletion in CNTNAP2 intron 1, removing a FOXP2 transcription factor binding site in an extended BD family. Here we perform a quantitative-PCR validation showing imperfect segregation with disease (5 bipolar disorder relatives). The distribution of CNVs across CNTNAP2 in psychiatric cases from previous reports was no different from controls of the database of genomic variants. Gene-based association testing did not implicate common variants in autism, schizophrenia or other psychiatric phenotypes. The association of proposed functional SNPs rs7794745 and rs2710102, reported to influence brain connectivity, was not replicated; nor did functional SNPs yield significant results in meta-analysis across psychiatric disorders. Disrupting CNTNAP2 rare variant burden was not higher in autism or schizophrenia compared to controls. This large comprehensive candidate gene study indicates that CNTNAP2 may not be a robust risk gene for psychiatric phenotypes.AUTHOR SUMMARYGenetic mutations that disrupt both copies of the CNTNAP2 gene lead to severe disease, characterized by profound intellectual disability, epilepsy, language difficulties and autistic traits. Researchers hypothesized that this gene may also be involved in autism given some overlapping clinical features with this disease. Indeed, several large DNA deletions affecting one of the two copies of CNTNAP2 were found in some patients with autism, and later also in patients with schizophrenia, bipolar disorder, ADHD and epilepsy, suggesting that this gene was involved in several psychiatric or neurologic diseases. Other studies considered genetic sequence variations that are common in the general population, and suggested that two such sequence variations in CNTNAP2 predispose to psychiatric diseases by influencing the functionality and connectivity of the brain. In the current study, we report the deletion of one copy of CNTNAP2 in a patient with bipolar disorder from an extended family where five relatives were affected with this condition. To better understand the involvement of CNTNAP2 in risk of mental illness, we performed several genetic analyses using a series of large publically available or in-house datasets, comprising many thousands of patients and controls. Despite the previous consideration of CNTNAP2 as a strong candidate gene for autism or schizophrenia, we show that neither common, deletion nor ultra-rare variants in CNTNAP2 are likely to play a major role in risk of psychiatric diseases.

TBC1D24 mutation associated with focal epilepsy, cognitive impairment and a distinctive cerebro-cerebellar malformation

2013 ◽  
Vol 105 (1-2) ◽  
pp. 240-244 ◽  
Author(s):  
Zaid Afawi ◽  
Simone Mandelstam ◽  
Amos D. Korczyn ◽  
Sara Kivity ◽  
Simri Walid ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Focal Epilepsy ◽  
Cerebellar Malformation

The phenotypic spectrum of ARHGEF9 includes intellectual disability, focal epilepsy and febrile seizures

2017 ◽  
Vol 264 (7) ◽  
pp. 1421-1425 ◽  
Author(s):  
Karl Martin Klein ◽  
◽  
Manuela Pendziwiat ◽  
Anda Eilam ◽  
Ronit Gilad ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Focal Epilepsy ◽  
Febrile Seizures ◽  
Phenotypic Spectrum

scholarly journals Structural mapping of GABRB3 variants reveals genotype-phenotype correlation

2021 ◽  
Author(s):  
Katrine M Johannesen ◽  
Sumaiya Iqbal ◽  
Milena Guazzi ◽  
Nazanin A Mohammadi ◽  
Eduardo Perez-Palma ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Disorders ◽  
Transmembrane Domain ◽  
Focal Epilepsy ◽  
Wide Spectrum ◽  
Age At Onset ◽  
3D Structure ◽  
Mild Intellectual Disability ◽  
Pathogenic Variants ◽  
Severe Intellectual Disability

Objective: Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability. In the present study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype-phenotype correlations. Methods: Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3 and we reviewed previously published cases. All missense variants were mapped onto the 3D structure of the GABRB3 subunit and clinical phenotypes associated with the different key structural domains were investigated. Results: We characterize 71 individuals with GABRB3 variants, including 22 novel subjects, expressing a wide spectrum of phenotypes. Interestingly, phenotypes correlated with structural locations of the variants. Generalized epilepsy, with a median age at onset of 10.5 months, and mild-to-moderate intellectual disability were associated with variants in the extracellular domain. Focal epilepsy with early onset (median: 2.75 months of age) and severe intellectual disability were associated with variants in the pore-lining helical transmembrane domain. Significance: These genotype/phenotype correlations will aid the genetic counseling and treatment of individuals affected by GABRB3-related disorders. Future studies may reveal whether functional differences underlie the phenotypic differences.

Normocentric biases taint cognitive neuroscience and intervention of autism

2019 ◽  
Vol 42 ◽  
Author(s):  
Laurent Mottron
Keyword(s):  
Intellectual Disability ◽  
Cognitive Neuroscience ◽  
Social Motivation ◽  
Repetitive Behaviors ◽  
Restricted Interests ◽  
Autistic People

Abstract Stepping away from a normocentric understanding of autism goes beyond questioning the supposed lack of social motivation of autistic people. It evokes subversion of the prevalence of intellectual disability even in non-verbal autism. It also challenges the perceived purposelessness of some restricted interests and repetitive behaviors, and instead interprets them as legitimate exploratory and learning-associated manifestations.

Receipt of psychotropic medication by people with intellectual disability in residential settings

2000 ◽  
Vol 44 (6) ◽  
pp. 666-676 ◽  
Author(s):  
J. Robertson ◽  
E. Emerson ◽  
N. Gregory ◽  
C. Hatton ◽  
S. Kessissoglou ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Psychotropic Medication ◽  
Residential Settings
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