В последние десятилетия достижения в области применения полноэкзомных и полногеномных технологий секвенирования позволили идентифицировать большое количество генов, связанных с умственной отсталостью, включая редкие формы, в частности, ассоциированные с мутациями в гене QRICH1. Синдром Вервери-Брэди (СВБ; MIM# 617982) - редкий синдром с аутосомно-доминантным типом наследования, характеризуется нарушением интеллекта, задержкой речи и легкими дисморфическими чертами лица. Впервые в России представлено клиническое и молекулярное описание двух пациентов с эпилепсией, задержкой развития и речи, мягкими дисморфическими чертами лица. При полноэкзомном секвенировании выявлены варианты нуклеотидной последовательность в гене QRICH1 -миссенс-мутация (c.1711G>A; p. Asp571Asn) и мутация сдвига рамки считывания (c.1963_1964insT; p.Lys655IlefsTer). На сегодняшний день в мире зарегистрировано 38 пациентов с мутациями в гене QRICH1. Recent advances in sequencing technologies have enabled identification of multiple genes associated with intellectual disability disorders, including QRICH1 gene. Ververi-Brady syndrome (VBS; MIM: #617982) is a rare developmental disorder, characterized by mild developmental delay, mildly impaired intellectual development and speech delay and mild dysmorphic facial features. For the first time in Russia, clinical and molecular description of two patients with epilepsy, developmental and speech delay, and mild dysmorphic facial features is presented. The variants nucleotide sequence in QRICH1 gene - missense mutation (c.1711G>A; p. Asp571Asn) and frameshift mutations (c.1963_1964insT; p.Lys655IlefsTer) were detected by whole exome sequencing. To date, thirty-eight individuals have been reported with QRICH1 mutations in the world.

Синдром Хельсмуртел-Ван дер Аа (OMIM #615873) - аутосомно-доминантная умственная отсталость, тип 28, которая характеризуется наличием черепно-лицевых дисморфий, нарушением поведения и расстройствами аутистического спектра. Развитие редкого синдрома связано с мутациями в гене ADNP. В статье представляется клиническое наблюдение пациентки с задержкой психомоторного и речевого развития, специфическими лицевыми дисморфиями, нарушением поведения и выявленной мутацией в гене ADNP. При проведении таргетного экзомного секвенирования выявлен ранее неописанный вариант нуклеотидной последовательности в гене ADNP (p.Ala1017fs). Мутации в гене ADNP в гетерозиготном состоянии описаны у пациентов с синдромом Хельсмуртел-Ван дер Аа (Helsmoortel-van der Aa syndrome; MIM:#615873). Мутации в гене ADNP могут быть генетической причиной расстройств аутистического спектра у 0,17% пациентов. Целесообразно при интерпретации данных NGS у пациентов с эпилептической энцефалопатией, расстройством аутистического спектра и характерным фенотипом учитывать, что ген ADNP относится к ключевым генам эмбрионального развития нервной системы. Helsmoortel-van der Aa syndrome (OMIM # 615873) is an autosomal dominant mental retardation 28 type, which is characterized by dysmorphic craniofacial features, impaired behavior and autism spectrum disorders. The development of a rare syndrome is associated with mutations in the ADNP gene. The clinical case is presented in patient with a development delay (psychomotor and speech), characteristic facial dysmorphia, impaired behavior and a detected mutation in the ADNP gene. Previously undescribed variant of the nucleotide sequence in the ADNP gene (p.Ala1017fs) was detected by targeted exome sequencing. Heterozygous mutations in the ADNP gene have been described in patients with Helsmoortel-van der Aa syndrome (MIM: # 615873). Mutations in the ADNP gene can be a genetic cause of autism spectrum disorders in 0,17% of patients. It is advisable to take into account that the ADNP gene is one of the key genes for embryonic neurodevelopment when interpreting NGS data in patients with epileptic encephalopathy, autism spectrum disorder and characteristic facial dysmorphia.

X-linked mental retardation, Cantagrel type ((MIM #300912; ORPHA:85277) is characterised by marked neonatal hypotonia, severely delayed developmental milestones, gastroesophageal reflux, stereotypic movements of the hands, esotropia and infantile autism. The article describes the case of mutation in the KIAA2022 gene in a 5-year-old girl with epilepsy, psychomotor, speech and intellectual development delay, behavioral disorders and autistic characters. Previously unknown heterozygous mutation in KIAA2022 gene , 3 exon (p.Asp451fs) was detected by targeted sequencing. Mutation was validated by the Sanger sequencing. The mutation was not found in parents of the child. Skewed X-inactivation was not detected in the study of CAG-repeat, AR gene, 1 exon in the proband. Mutations in the KIAA2022 gene can cause epileptic encephalopathy and intellectual disability in both boys and girls. It is important for genetic testing, medical management and genetic counseling.

This article describes 4 clinical cases of glucose transporter type 1 deficiency syndrome (GLUT1, De Vivo disease) in children admitted to the neuropsychiatric department of Scientific and Practical Center of children medical care. The drug-resistant epilepsy, movement disorders, psychomotor and intellectual disabilities, decrease of glucose levels in the cerebrospinal fluid (CSF) were diagnosed in children. The different types of mutations in the SLC2A1 gene, responded for the development of GLUT1 deficiency syndrome were detected by targeted sequencing in all patients. De Vivo disease is characterized by the infantile-onset encephalopathy, symptomatic drug-resistant epilepsy, microcephaly, delayed psychomotor development with spasticity, ataxia, dysarthria and alternating hemiplegia and decrease the level of glucose in the CSF. Currently, the ketogenic diet is highly effective method of pathogenesis therapy, which can reduce the clinical manifestations: controlling the seizures, improving the movement disorder and speech.

AIM:To study mutations and polymorphisms in the sodium channels genes, determining the development of idiopathic epilepsy (IE).MATERIAL AND METHODS:The study of SCN1A gene by direct Sanger sequencing in 53 patients and targeted resequencing of the regions of 34 genes in 40 patients with different clinical forms of IE was performed.RESULTS:Seven mutations (c.3022G>T, c.3637C>T, c.1144G>T, c.80G>C, c.1603C>T, c.2427G>A and c.1131A>C) were detected among 53 patients by direct Sanger sequencing of SCN1A gene. The mutations of SCN1A gene (2 - nonsense mutation, 5 - missense mutation) were identified in 7/40 (17.5%) patients with epilepsy using high-performance sequencing, Mutations in sodium channel genes encoding other subunits: SCN1B, SCN2A, SCN9A were identified in 6 patients.CONCLUSION:As epileptic encephalopathy is polygenic, it is important to conduct genetic testing of more genes (primarily sodium channel genes - SCN1B, SCN2A, SCN9A etc.) using special gene panels to find the molecular defect in DNA.

We present the experience of applying the methods of nondrug treatment drugresistant epilepsy in children. These include surgery, ketogenic diet and chronic vagus nerve stimulation (VNS therapy). Methods. We observed 118 patients with refractory epilepsy. As a result of a comprehensive survey 46 patients became candidates for surgical treatment, VNS stimulator implanted in 17 patients, and the ketogenic diet recommended for 50 patients. Results. Surgical treatment showed the highest efficiency: the complete elimination of seizures (100%) was observed in 28 (61%) patients, reducing the number of seizures of >75% was observed in 1 (2%), >50% in 5 (11%) and 75% in 10 (20%), >50 % in 4 (8%) and 75% in 2 (12%), >50 % in 17 (15%) and

UNLABELLED:Aims of the study include diagnosis of focal epilepsy, determination of localization of interictal and ictal epileptiform activity. 785 patients (age range -- 1 month-21 year) with admission diagnosis "epilepsy" were analyzed. Video-EEG-monitoring using a 21-chanel EEG system with duration 9-96 hours (mean -- 10 hours) was applied. The diagnosis of epilepsy was confirmed in 634 patients (80.8%) while in 151 patient (19.2%) non-epileptic paroxysms were diagnosed. Generalized epilepsy (GE) was diagnoses in 47 cases (7.4%), focal (FE) -- in 587 (92.6%) cases. According to localization, distribution was the following: frontal -- 48.2%, temporal -- 30.8%, occipital -- 10%, parietal -- 5.5%, multifocal -- 5.5%. 45% of patients with FE younger than 3 years had marked generalized seizures known as infantile spasms. Among 587 patients with FE discrepancy of localization of interictal focus and zone of seizure onset was found in 41 cases (7%), mainly in younger patients. In 14 cases (2.4%) we observed more than one zone of seizure onset: 2 -- in 13, 3 -- in 1, both in frontal and left temporal areas (all specified patients are from the younger group).CONCLUSIONS:1) every fifth patients with primarily diagnosed epilepsy does not suffer from this disease; 2) 92.6% of patients in pediatric epileptologic clinic have FE, about half of them have frontal localization of the focus; 3) presence of generalized types of seizures mimicking GE is an important feature of FE in younger patients; 4) In some patients with FE, especially in younger ones, discrepancy of localization of interictal epileptiform activity and zone of seizure onset is found, we also observed that more than one zone was producing attacks. The specified features are necessary for consideration during preoperative assessment.

Ketogenic diet (KD) is one of the most effective methods of epilepsy non-drug therapy. Ten patients with pharmacoresistant epilepsy, aged 1,5-18 years, were treated with individually matched and strictly controlled KD with high fat content and restricted amount of proteins and carbohydrates. After 1 year, only 4 patients kept the diet. Factors of efficacy, causes of withdrawal and side effects of KD are discussed.

Gelastic seizures (laughing seizures) are a rare type of epileptic seizure in which laugh in a main and dominating manifestation of the seizure. As a rule, the seizures are caused by organic cerebral pathology and are often reported as a specific epilepsy marker related to hypothalamic hamartoma. The interictal EEG frequently shows a focal activity. Based on examination of 2 patients with gelastic seizures and hypothalamic hamartoma, clinical features, EEG characteristics and therapeutic perspectives for the disorder are discussed.