Hereditary Diseases and Syndromes Accompanied by Febrile Convulsions: Clinical and Genetic Characteristics and Diagnostic Procedures

Дадали, Е. Л.; Sharkov, Artem; Шаркова, И. В.; Канивец, И. В.; Коновалов, Ф. А.; Акимова, И. А.

doi:10.17650/2073-8803-2016-11-2-33-41

Cited by 6 publications

(4 citation statements)

References 17 publications

(21 reference statements)

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“…After the third febrile seizure, the risk of additional episodes is approaching 50% and the risk of epilepsy formation is up to 15.8% ( Bertelsen et al, 2016 ). Recent studies showed the contribution of genetic causes in the development of febrile-associated epilepsy including inborn errors of metabolism (mitochondrial, peroxisomal, lysosomal diseases, organic acidurias, aminoacidopathies, glycosylation, and urea cycle disorders), monogenic early-onset epileptic encephalopathies, and epilepsy phenotype caused by copy number variations (CNVs) such as the Cornelia de Lange, Seckel, and Rubinstein–Taybi syndromes ( Dadali et al, 2016 ; Wang et al, 2017 ; Deng et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Phenotype-Driven Diagnosis of Atypical Dravet-Like Syndrome Caused by a Novel Splicing Variant in the SCN2A Gene

et al. 2022

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Febrile-associated epileptic encephalopathy is a large genetically heterogeneous group that is associated with pathogenic variants in SCN1A, PCDH19, SCN2A, SCN8A, and other genes. The disease onset ranges from neonatal or early-onset epileptic encephalopathy to late-onset epilepsy after 18 months. Some etiology-specific epileptic encephalopathies have target therapy which can serve as a clue for the correct genetic diagnosis. We present genetic, clinical, electroencephalographic, and behavioral features of a 4-year-old girl with epileptic encephalopathy related to a de novo intronic variant in the SCN2A gene. Initial NGS analysis revealed a frameshift variant in the KDM6A gene and a previously reported missense variant in SCN1A. Due to lack of typical clinical signs of Kabuki syndrome, we performed X-chromosome inactivation that revealed nearly complete skewed inactivation. Segregation analysis showed that the SCN1A variant was inherited from a healthy father. The proband had resistance to multiple antiseizure medications but responded well to sodium channel inhibitor Carbamazepine. Reanalysis of NGS data by a neurogeneticist revealed a previously uncharacterized heterozygous variant c.1035–7A>G in the SCN2A gene. Minigene assay showed that the c.1035–7A>G variant activates a cryptic intronic acceptor site which leads to 6-nucleotide extension of exon 9 (NP_066287.2:p.(Gly345_Gln346insTyrSer). SCN2A encephalopathy is a recognizable severe phenotype. Its electro-clinical and treatment response features can serve as a hallmark. In such a patient, reanalysis of genetic data is strongly recommended in case of negative or conflicting results of DNA analysis.

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Section: Introductionmentioning

confidence: 99%

Case Report: Phenotype-Driven Diagnosis of Atypical Dravet-Like Syndrome Caused by a Novel Splicing Variant in the SCN2A Gene

et al. 2022

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“…3 From a practical point of view, on-time diagnosis can limit the diagnostic search, the duration of which often provokes parental anxiety and unnecessary financial expenditures, it is necessary for calculating the risk of giving birth to a sick child in a burdened family and planning of preventive measures, improves the prognosis accuracy and can lead to targeted therapy. 4,5,6 The interpretation of the results is believed to be carried out in collaboration with geneticists, only if the treating neurologist doesn't have the sufficient experience and understanding of genetics.3 Russian practice shows that the management of these patients, including the selection and interpretation of genetic testing, often falls on the shoulders of neurologists-epileptologists. Therefore, it is important for the practitioner to evaluate progress in this area and prepare for the use of genetic testing in clinical practice .9 The aim of the study was to describe the spectrum of detectable gene mutations in patients with epilepsy or epileptic encephalopathy in everyday clinical practice, including analysis of diagnosed epileptic syndromes, characteristics of seizures, timing of the genetic diagnosis, treatment options and efficacy.…”

Section: Introductionmentioning

confidence: 99%

Identification and Analysis of Genetic Epilepsy and Epileptic Encephalopathies in the Outpatient Practice of Epilepsy Specialists

Rakhmanina

Volkov²,

Shestakova

et al. 2020

MNJ

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Background: Given the significant share of gene mutations in the etiology of epilepsy, it is important for the practitioners to evaluate progress in this area. Objective: To describe the spectrum of being detected gene mutations in patients with epilepsy or epileptic encephalopathy in clinical practice of neurologists specializing in epilepsy with an analysis of diagnosed epileptic syndromes, the characteristics of seizures, the timing of a genetic diagnosis, options and treatment efficacy. Methods: The study included 100 patients (40 boys, 60 girls) with epilepsy/epileptic encephalopathy and a gene mutation identified. The average age was 6.9±5.1 years. Through remote access, epilepsy specialists filled out a specially designed unified table containing information from outpatient case history. Results: In the outpatient practice of epilepsy specialists, there are patients with a wide range of gene mutations, the leading of which is a mutation in the SCN1A gene (15%). Nowadays, the main method (85%) of detection remains the next generation sequencing in the "Hereditary Epilepsy" panel. Years pass from the onset of the disease to the genetic diagnosis (Me-3 years). In most cases, patients with severe (52% have epileptic encephalopathy, 88% have developmental disorders) and pharmacoresistant (mean amount of anti-epileptic drugs-3,8±2,2, multitherapy-70%) syndromes have undergone genetic testing. In the treatment of these patients epileptologists are increasingly (52%) use alternative methods: steroids, ketogenic diet and others. The absence of seizures was observed only in 46% of patients. Conclusion: Thus, in the outpatient practice of epileptologists of Russia, patients with a wide range of gene mutations are found. As a rule, these are patients with severe, therapy-resistant epileptic syndromes.

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“…Продуктами двох із цих генів є субодиниці натрієвих каналів, а одного -рецептор ГАМК, який виконує роль субстрат залежного каналу. Про дуктами двох інших генів є активатор шляхів сигнальної трансдукції клітини й фермент кар бопептидаза, який бере участь у біосинтезі ней рональних білків [13,42].…”

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“…Усі гени, відповідальні за виникнення захво рювань цієї групи, картовані, однак ідентифі ковано лише п'ять. Виявлено, що продукти цих генів є окремими субодиницями іонних і ГАМК залежних каналів мембран нейронів [13,42].…”

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On the study of seizures in newborns and early age children (features of diagnosis and clinical and genetic characteristics of epileptic encephalopathies)

Martyniuk¹,

Znamenska²,

Shveikina³

et al. 2021

MPU

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The article is devoted to the urgent problem of neonatology and pediatric neurology — seizures in newborns and young children. In the work, a short review of the clinical and genetic characteristics of monogenic epilepsy is presented, in particular, the main attention is paid to the variants that begin in neonatal and early childhood. It has been shown that a significant number of epileptic encephalopathies are caused by mutations in genes whose protein products form voltage-dependent (sodium and potassium), ligan(dependent (γ-aminobutyric acid — GABA) channels, the functioning of which ensures the passage of a nerve impulse in neurons of the cerebral cortex. The necessity of including the molecular genetic methods into the algorithm for examining a child with epilepsy, in particular with epileptic encephalopathy, is emphasized. It is noted that congenital metabolic disorders are one of the etiological reasons for the development of epileptic seizures in children, in particular in newborns and young children. It was shown that congenital metabolic disorders have phenotypic manifestations of epileptic encephalopathy. Some curable metabolic defects that are accompanied by seizures, their diagnosis and timely treatment are described. No conflict of interest was declared by the authors. Key words: newborn, epilepsy, epileptic encephalopathy, diagnosis, genetic examination, metabolic defects, review.

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Hereditary Diseases and Syndromes Accompanied by Febrile Convulsions: Clinical and Genetic Characteristics and Diagnostic Procedures

Cited by 6 publications

References 17 publications

Case Report: Phenotype-Driven Diagnosis of Atypical Dravet-Like Syndrome Caused by a Novel Splicing Variant in the SCN2A Gene

Case Report: Phenotype-Driven Diagnosis of Atypical Dravet-Like Syndrome Caused by a Novel Splicing Variant in the SCN2A Gene

Identification and Analysis of Genetic Epilepsy and Epileptic Encephalopathies in the Outpatient Practice of Epilepsy Specialists

On the study of seizures in newborns and early age children (features of diagnosis and clinical and genetic characteristics of epileptic encephalopathies)

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