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Early infantile epileptic encephalopathy type 4: clinical, neurophysiological and therapeutic aspects

https://doi.org/10.17749/2077-8333.2019.11.2.164-174

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Abstract

Objective. Study the clinical and neurophysiological evolution of early infantile epileptic encephalopathy type 4 (EIEE4) caused by a STXBP1 gene mutation.

Material and methods. During 2016-2019, we conducted dynamic observation and treatment of a girl with EIEE4 combined with a mutation in the STXBP1 gene. DNA sequencing was performed using the "Hereditary epilepsies" panel (Next Generation Sequencing on the platform of Illumina HiSeq 2500, USA). Dynamic video-EEG monitoring was performed with an “Encephalan-Video" RM-19/26 ("Medicom MTD“, Russia).

Results. In this 3.5 y.o. patient with infantile epileptic encephalopathy, a heterozygous autosomal dominant de novo mutation in the STXBP1 gene was found. This mutation (not described previously) is located in chromosome 9, specifically, in the 20th exon with genome coordinates Chr9:130453 (C.*96T>A). This child suffered from severe neonatal hypoxic-ischemic encephalopathy, which led to spastic cerebral palsy. In addition, she developed seizures as early as at the age of 6 month; the seizures (flexor tonic spasms) were paralleled with EEG changes similar to the Mar-kand-Blume-Ohtahara syndrome, namely, multiple independent spike-wave foci in combination with the partial attenuation pattern (kind of the "burst-suppression" pattern). Valproate monotherapy had little effect, and hormonal treatment caused a temporary improvement. Permanent clinical remission with no seizures was achieved by including leveti-racetam in the therapeutic combination. A number of studies demonstrated a high efficacy of levetiracetam in cases of STXBP1 gene mutations. At the age of 2,5years, the girl demonstrated changes in her EEG records toward the continuous spike-wave during sleep (CSWS) pattern with the morphology of "benign epileptiform discharges of childhood" ("BEDC").

Conclusions. In spite of the aggravated perinatal anamnesis, children with epileptic encephalopathy need genetic examination using the Next Generation Sequencing (NGS) methods (such as "Hereditary epilepsies" panel), combined with full exome sequencing. Such genetic examinations are helpful for establishing the exact etiology of epilepsy and developing a personalized approach to antiepileptic therapy.

About the Authors

A. A. Kholin
Pirogov Russian National Research Medical University
Russian Federation

Alexey A. Kholin - MD, PhD, Professor at the Department of Neurology, Neurosurgery and Medical Genetics n.a. Badalyan, Faculty of Pediatrics.

1 Ostrovityanova Str., Moscow 117997



N. N. Zavadenko
Pirogov Russian National Research Medical University
Russian Federation

Nikolay N. Zavadenko - MD, PhD, Professor & Head, Department of Neurology, Neurosurgery and Medical Genetics n.a. Badalyan, Faculty of Pediatrics.

1 Ostrovityanova Str., Moscow 117997



L. M. Kolpakchi
Pirogov Russian National Research Medical University
Russian Federation

Larisa M. Kolpakchi- MD, PhD, Neurologist at the Department of Psychoneurology №2, Children's Clinical Hospital affiliated with.

1 Ostrovityanova Str., Moscow 117997



I. D. Fedonyuk
Pirogov Russian National Research Medical University
Russian Federation

Inessa D. Fedonyuk- MD, PhD, Neurologist at the Department of Psychoneurology №2, Children's Clinical Hospital affiliated with.

1 Ostrovityanova Str., Moscow 117997



A. S. Papikyan
Pirogov Russian National Research Medical University
Russian Federation

Andrey S. Papikyan - MD, PhD, Neurophysiologist at the Department of Psychoneurology №2, Children's Clinical Hospital affiliated with.

1 Ostrovityanova Str., Moscow 117997



А. N. Zavadenko
Pirogov Russian National Research Medical University
Russian Federation

Alexandra N. Zavadenko - MD, PhD, Assistant Professor, Department of Neonatology, Faculty of Pediatrics.

1 Ostrovityanova Str., Moscow 117997



E. S. Ilina
Pirogov Russian National Research Medical University
Russian Federation

Elena S. Ilina - MD, PhD, Head of the Department of Psychoneurology №2, Children's Clinical Hospital affiliated with.

1 Ostrovityanova Str., Moscow 117997



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For citation:


Kholin A.A., Zavadenko N.N., Kolpakchi L.M., Fedonyuk I.D., Papikyan A.S., Zavadenko А.N., Ilina E.S. Early infantile epileptic encephalopathy type 4: clinical, neurophysiological and therapeutic aspects. Epilepsy and paroxysmal conditions. 2019;11(2):164-174. (In Russ.) https://doi.org/10.17749/2077-8333.2019.11.2.164-174

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ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)