Clinical review of genetic epileptic encephalopathies

Noh, Grace; Asher, Yael; Graham, John M.

doi:10.1016/j.ejmg.2011.12.010

Cited by 45 publications

(47 citation statements)

References 190 publications

(226 reference statements)

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“…Epileptic encephalopathies could be classified in different ways based on age of onset, underlying pathophysiologic mechanism, and associated manifestations . While neurological deterioration is typically viewed as secondary to epileptic activity, there are patients with mutations in epileptic encephalopathies‐associated genes who present with encephalopathy without epilepsy, indicating that pathophysiology of neurological manifestations in these patients is more complex.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic characterization of KCTD3‐related developmental epileptic encephalopathy

Faqeih¹,

Almannai²,

Saleh³

et al. 2018

Clinical Genetics

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The association between KCTD3 gene and neurogenetic disorders has only been published recently. In this report, we describe the clinical phenotype associated with 2 pathogenic variants in KCTD3 gene. Seven individuals (including one set of monozygotic twin) from 4 consanguineous families presented with developmental epileptic encephalopathy, global developmental delay, central hypotonia, progressive peripheral hypertonia, and variable dysmorphic facial features. Posterior fossa abnormalities (ranging from Dandy-Walker malformation to isolated hypoplasia of the cerebellar vermis) were consistently observed in addition to other variable neuroradiological abnormalities such as hydrocephalus and abnormal brain myelination. One patient also had a multicystic kidney. Whole exome sequencing revealed 2 probably pathogenic homozygous variants in KCTD3 gene that fully segregated with the disease. KCTD3 gene belongs to a family of accessory subunits that regulate the biophysical properties of ion channels, and is highly expressed in the kidney and brain. In this largest series to date on KCTD3-mutated patients, we show that biallelic loss of function mutations in KCTD3 lead to a consistent phenotype of developmental epileptic encephalopathy and abnormal cerebellum on brain imaging.

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Section: Discussionmentioning

confidence: 99%

Phenotypic characterization of KCTD3‐related developmental epileptic encephalopathy

Faqeih¹,

Almannai²,

Saleh³

et al. 2018

Clinical Genetics

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“…81 A detailed discussion of these syndromes is beyond the scope of this review. Table 5 summarizes some common syndromic epilepsy syndromes and Fig.…”

Section: Syndromic Genetic Epilepsiesmentioning

confidence: 98%

Genetics of Pediatric Epilepsy

Hani

Mikati

2015

Pediatric Clinics of North America

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“…Clinical features of epileptic encephalopathies have been extensively reviewed elsewhere (Noh et al . ; McTague et al . ; Shbarou and Mikati ), and we will only introduce a few examples of well‐established syndromes, such as Ohtahara, West, Lennox‐Gastaut, and Dravet syndrome.…”

Section: Epileptic Encephalopathymentioning

confidence: 99%

Models for discovery of targeted therapy in genetic epileptic encephalopathies

Maljevic

Reid

Petrou

2017

Journal of Neurochemistry

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Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms, the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies. We focus on ion channels as the best-studied group of epilepsy genes. Given the clinical and genetic heterogeneity of epileptic encephalopathy disorders, experimental models that can reflect this complexity are critical for the development of disease mechanisms-based targeted therapy. The convergence of technological advances in gene sequencing, stem cell biology, genome editing, and high throughput functional screening together with massive unmet clinical needs provides unprecedented opportunities and imperatives for precision medicine in epileptic encephalopathies.

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Clinical review of genetic epileptic encephalopathies

Cited by 45 publications

References 190 publications

Phenotypic characterization of KCTD3‐related developmental epileptic encephalopathy

Phenotypic characterization of KCTD3‐related developmental epileptic encephalopathy

Genetics of Pediatric Epilepsy

Models for discovery of targeted therapy in genetic epileptic encephalopathies

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