Pericallosal lipoma in an infant with fetal alcohol syndrome: a case report

In this article we report a case of pericallosal lipoma in a newborn with fetal alcohol syndrome, brain malformation (agenesis of the corpus callosum), and intrauterine infection (meningitis) diagnosed in a perinatal center.

The hypothesis of the functional disintegration of the brain due to the persistence of benign epileptiform patterns on the electroencephalogram

In this work, we have analyzed the results of observation of 200 children aged from 3 to 15 years old, who had various neuropsychiatric disorders in combination with benign childhood epileptiform patterns on the electroencephalogram. A hypothesis has been put forward about functional disorders of the developing nervous system with prolonged persistence of benign focal epileptiform discharge of childhood on electroencephalogram, mainly in slow-wave sleep. The possibilities of therapeutic correction of these disorders are discussed.

Leukoencephalopathy with vanishing white matter caused by EIF2B5 gene mutations: a case report

Leukoencephalopathy with vanishing white matter (VWM disease) is a progressive neurodegenerative disease with a specific magnetic resonance pattern characterized by diffuse lesions to the white matter and cystic degeneration. In this article, we report a case VWM disease in a boy with white matter lesions, in whom early onset and neurological symptoms suggested infantile form of the disease. The diagnosis was confirmed by the detection of biallelic mutations c.1688G>A (p.Arg563Gln) and c.1309G>A (p.Val437Met) in the EIF2B5 gene. The c.1309G>A mutation (p.Val437Met) was detected for the first time; it caused the development of severe disease.

Clinical and genetic parallels in congenital brain lesions without epilepsy

Background. The problem of preventing the development of gross congenital brain lesions and their successful treatment is more than relevant now. It is known that approximately in every third case of the development of congenital cerebral palsy (CP), it is impossible to identify the main pathogenetic factor. This determines the activity of the search for gene mechanisms for the formation of this phenotype. G. McMichael et al. were among the first to identify the most relevant directions of the influence of genes on the formation of the CP phenotype.Objective: to study the influence of gene determinants on the formation of the phenotype of CP, which is not accompanied by epilepsy.Materials and methods. Gene abnormalities in 18 patients with CP were divided into groups of determinable physiological processes. Genetic mutations were confirmed by next generation sequencing (NGS) and Sanger trio methods. For the study, samples of the patients' venous blood were taken.Results and discussion. The analysis showed that genes from different groups by determinants are to varying degrees associated with the formation of the CP phenotype. The “map of determinants” in the pathogenesis of CP is specific. The pathogenesis involves genetically determined disorders of cell division and neuroontogenesis (neuronal migration, sprouting, myelination, partly apoptosis), cell metabolism, including those whose disturbance leads to the formation of storage diseases, transmembrane transport, the exchange of neurotransmitters and the functioning of synapses, the formation of and the functioning of the cytoskeleton, as well as the regulation of immunity and oncogenesis. Malformations of the brain are more often associated with determinants of the regulation of the formation and functioning of the cytoskeleton, neuroontogenesis, as well as the processes of cell division (chromatin modification, transcription, replication). The pathogenesis of congenital cerebral palsy does not involve (according to our data) the determinants of canalopathy, energy supply of the cell, intracellular synthesis with the Golgi complex, and ribosomal synthesis.Conclusions. Genetically determined CP is a universal phenotype that implements the multidirectional effect of the genome. The influence of the genome does not apply to the energy supply of the cell, ribosomal synthesis and the functioning of the Golgi complex. In the absence of epilepsy in the phenotype, there is no influence of the genes of canalopathies.

Experience with the use of a ketogenic diet with type 1 glucose transporter deficiency (De Vivo disease)

De Vivo disease is characterized by early epileptic encephalopathy, delayed psychomotor development, spasticity, the formation of microcephaly, ataxia, dysarthria, alternating hemiplegia, and a decrease in glucose and lactate levels in the cerebrospinal fluid. Epilepsy is pharmacoresistant and the therapy for this syndrome is the ketogenic diet (until the time when will development of genetic targeted therapy). In GLUT1 deficiency syndrome, mutations are found in the SLC2A1 gene that lead to a decrease in glucose transport across the cell membrane. The “classic” ketogenic diet is a special high-fat, low-carbohydrate diet that helps to control seizures in some people with epilepsy. It is prescribed by a physician and carefully monitored by a dietitian. It is usually used in children with seizures that do not respond to medications. It is stricter than the modified Atkins diet, requiring careful measurements of calories, fluids, and proteins. Foods are weighed and measured. Normal dietary fats, which are used predominantly in the classical ketogenic diet, consist of a mixture of mainly long chain triglyceride (LCT) fats with a small amount of short and medium chain triglyceride (MCT) fats. The MCT ketogenic diet uses a fat supplement that consists only of MCT fats (MCT oil).

Mowat-Wilson syndrome: literature review and case series

Mowat-Wilson syndrome (MWS) is a rare genetic disorder characterized by a combination of the following signs: 1) facial dysmorphism (wide nose, broad medial eyebrows, pronounced chin, and open mouth); 2) mental retardation; 3) abnormalities of internal organs (congenital heart defects, Hirschsprung's disease, hypospadias/cryptorchidism). The disease is associated with a heterozygous pathogenic mutation in the ZEB2 gene. More than 80 % of MWS patients are diagnosed with epilepsy, the onset of which is usually observed in infancy. Patents have focal motor seizures, atypical absence seizures, generalized convulsive seizures. Epileptic seizures are often triggered by fever; some children are resistant to therapy. MWS patients have a specific phenotype (blue eyes, fair hair, wide-based gait, frequent laughter, limited or absent expressive language) that requires differential diagnosis with Angelman syndrome (caused by a mutation in the UBE3A gene). MWS was described in 1998, but there have been no case reports in the Russian literature yet. We report 4 cases of MWS in children aged 2 to 13 years treated in the Svt. Luka's Institute of Neurology and Epilepsy. In all of these patients, we identified a heterozygous de novo deletion in the ZEB2 gene. Epilepsy was observed in all patients. Mean age at onset was 13 months. All children had focal motor seizures and atypical absence seizures. None of them had tonic-clonic seizures or status epilepticus. The analysis of electroencephalograms showed that patients with a lower index of epileptiform activity tend to have better development and vice versa: children with a high index of epileptiform activity during sleep had more severe developmental delay.

EEG findings in patients with angelman syndrome. Notched slow waves and age-specific characteristics of the main EEG patterns

Angelman syndrome (AS) is a genetic disorder caused by a mutation in the maternal copy of the UBE3A gene and characterized by typical clinical manifestations (such as mental retardation, difficulty walking, and laughter) and specific changes on the electroencephalogram (EEG).The aim of this study was to analyze age-specific characteristics of the main EEG patterns, including high-amplitude frontal delta activity with spikes, slow-wave delta-theta activity with spikes in the posterior regions, and diffuse continuous rhythmic theta activity. In addition to that, we assessed the frequency of a rare and highly specific for AS EEG pattern: notched slow waves.We have identified and described additional criteria for EEG during sleep: high index of pathological slow-wave activity and the ratio of pathological slow-wave activity index to epileptiform activity index during sleep. We also analyzed all EEG patterns at the age most significant for the detection of this syndrome (up to 3 years) and their age-specific dynamics.We covered the frequency and characteristics of EEG patterns rare in AS patients, such as three-phase bifrontal delta waves, reactive pathological activity in the posterior areas, EEG patterns of focal seizures originating from the posterior areas, benign epileptiform discharges of childhood, and migrating continuous slow-wave activity.We analyzed the differences between main EEG patterns in AS and frontal and occipital intermittent rhythmic delta activity (fIRDA and OIRDA patterns).

Juvenile form of alexander disease caused by a previously undescribed mutation in the GFAP gene. a case report

Alexander disease is a form of leukoencephalopathy caused by mutations in the GFAP gene. There are three forms of the disease: infant, juvenile and adult. We present the clinical case of a patient born in 2004 (16 years old) with a debut of the disease at the age of 4 years with complex ticks. further neurological symptoms progressed and appeared atactic gait, intention tremor by performing coordination tests, muscle hypotension, decreased tendon reflexes, nasal voices, and behavior changes.Magnetic resonance imaging revealed changes in the white matter of both frontal lobes. An analysis was made of 59 genes of the panel “Leukodystrophy/leukoencephalopathy” by the method of mass parallel sequencing on the Ion S5. A mutation of the GFAP gene (Nm_002055), 4 exon c.758C>A, p.ALA253Asp in a heterozygous state, not described in Human Gene mutation Database, was detected. The patient was confirmed to have a diagnosis of Alexander disease. According to tractography, a decrease in the number of fibers in the frontal lobes was found.The patient is currently receiving symptomatic treatment.

Genetic epilepsy caused by CDKL5 gene mutations as an example of epileptic encephalopathy and developmental encephalopathy: literature review and own observations

The disease caused by mutations in the CDKL5 gene (encoding cyclin-dependent kinase 5, CDK5) belongs to the group of early (infantile) epileptic encephalopathies caused by alterations in the genome. Currently, the disease is called “developmental encephalopathy and epileptic encephalopathy type 2”. This disorder is a complex combination of symptoms that develop due to deficiency or absence of the CDKL5 gene product, which is serine/threonine kinase. The CDKL5 gene is located on X chromosome; the disease has an X-linked dominant inheritance pattern. This literature review summarizes relevant studies analyzing the disease caused by CDKL5 gene mutations, including its genetic and epidemiological aspects, clinical manifestations, characteristics of epilepsy, principles of diagnosis, and therapeutic approaches. We present a case series of several patients with genetic disorders involving the CDKL5 gene.

Continuous spike-and-wave activity during slow-wave sleep in patients with rett syndrome

The article presents a description of a clinical case of a child 3 years 8 months old with Rett syndrome caused by the mutation of p.Val485fs in the MECP2 gene. According to electroencephalography data at the age of 1 year and 6 months, diffuse continued epileptiform activity in the form of high-amplitude (up to 300 μV) acute – slow wave complexes (continuous spike-waves during slow-wave sleep, CSWS) with an index of 90–100 % was revealed. At the control examination at the age of 2 years and 10 months diffuse epileptiform activity was replaced by multifocal activity with an index of up to 70–80 % at certain epochs, in general, not exceeding 50–60 %. During the entire observation period there were no epileptic seizures. It remains unknown whether the presence of CSWS at such an early age is a predictor of a more severe course of Rett syndrome – in our observation the girl did not acquire walking skills and a delay in psychic and speech development was evident already before the 12 month of life. more research is needed on the frequency of the CSWS phenomenon and its role in the development of clinical features in Rett syndrome.