infantile epilepsy

Miller-Dieker syndrome (MDS) is characterized by facial abnormalities and lissencephaly and is caused by a microdeletion in the region containing the LIS1 gene at chromosome 17p13.3. We report a case in which postnatal neuroimaging revealed severe lissencephaly. A 9-month-old boy presented with infantile spasms syndrome. Because of the refractory course of seizures and continued poor vitality, total corpus callosotomy was performed at 28 months of age. Intraoperative electroencephalogram (EEG) showed that the bilateral synchronous epileptiform discharges disappeared immediately after the disconnection...

Heterozygous de novo mutations in Munc18-1, which is essential for neurotransmitter release, cause early infantile epileptic encephalopathy. Munc18-1-linked epilepsy is currently an untreatable disorder and its precise disease mechanism remains elusive. Here, we investigated how Munc18-1 pathogenic variants affect inhibitory neurons using Caenorhabditis elegans . Expression analysis revealed that three missense mutant proteins form aggregates in the cell body of gamma-aminobutyric-acid (GABA)-ergic motoneurons, resulting in a strong reduction of their expression in axons...

Children with developmental and epileptic encephalopathies often present with co-occurring dyskinesias. Pathogenic variants in ARX cause a pleomorphic syndrome that includes infantile epilepsy with a variety of movement disorders ranging from focal hand dystonia to generalized dystonia with frequent status dystonicus. In this report, we present three patients with severe movement disorders as part of ARX-associated epilepsy-dyskinesia syndrome, including a patient with a novel pathogenic missense variant (p...

CACNA1A-related disorders are rare neurodevelopmental disorders linked to variants in the CACNA1A gene. This gene encodes the α1 subunit of the P/Q-type calcium channel Cav2.1, which is globally expressed in the brain and crucial for fast synaptic neurotransmission. The broad spectrum of CACNA1A-related neurological disorders includes developmental and epileptic encephalopathies, familial hemiplegic migraine type 1, episodic ataxia type 2, spinocerebellar ataxia type 6, together with unclassified presentations with developmental delay, ataxia, intellectual disability, autism spectrum disorder, and language impairment...

AIMS: Vigabatrin is an antiepileptic drug used to treat some forms of severe epilepsy in children. The main adverse effect is ocular toxicity, which is related to the cumulative dose. The aim of the study is to identify an acceptable exposure range, both through the development of a population pharmacokinetic model of vigabatrin in children enabling us to calculate patient exposure and through the study of therapeutic response. METHODS: We performed a retrospective study including children with epilepsy followed at Necker-Enfants Malades hospital who had a vigabatrin assay between January 2019 and January 2022...

Type 1 lissencephaly is a brain malformation characterized by agyria and pachygyria and is known to be caused by congenital infections and genetic variations. Here we present a case of a 4-month-old female with new onset infantile epileptic spasms syndrome (IESS) with initial etiology concerned for congenital cytomegalovirus (cCMV) due to a positive urine CMV PCR and maternal viral syndrome during pregnancy. Her brain MRI was significant for type 1 lissencephaly without other radiographical features of cCMV...

BACKGROUND AND OBJECTIVES: Hexokinase 1 (encoded by HK1 ) catalyzes the first step of glycolysis, the adenosine triphosphate-dependent phosphorylation of glucose to glucose-6-phosphate. Monoallelic HK1 variants causing a neurodevelopmental disorder (NDD) have been reported in 12 individuals. METHODS: We investigated clinical phenotypes, brain MRIs, and the CSF of 15 previously unpublished individuals with monoallelic HK1 variants and an NDD phenotype. RESULTS: All individuals had recurrent variants likely causing gain-of-function, representing mutational hot spots...

OBJECTIVE: Relapse of epileptic spasms after initial treatment of infantile epileptic spasms syndrome (IESS) is common. However, past studies of small cohorts have inconsistently linked relapse risk to etiology, treatment modality, and EEG features upon response. Using a large single-center IESS cohort, we set out to quantify the risk of epileptic spasms relapse and identify specific risk factors. METHODS: We identified all children with epileptic spasms at our center using a clinical EEG database...

BACKGROUND: Pathogenic variants of PCDH19, located on the X-chromosome (Xq22.1), cause a rare epileptic encephalopathy with speech and development delay, seizures, behavioral and psychiatric problems. The specific underlying pathogenic mechanism is known as "cellular interference" that results in affected heterozygous females, normal hemizygous males and affected mosaic males but its functioning is not yet clear. OBJECTIVES: Reporting new cases of affected males is considered useful to a deeper insight...

OBJECTIVE: Infantile epileptic spasms syndrome (IESS) is a common and urgent diagnosis with seizure and nonseizure mimics. Evaluation with prolonged video-electroencephalography (EEG) can be time-consuming and costly. This study investigated the use of EEG review of a single sleep-wake cycle to exclude IESS. METHODS: We retrospectively reviewed video-EEG studies to rule out IESS in children between the ages of 2 months and 2 years in the period from January 2019 through June 2020...

We identified the PACS2 gene responsible for the multifunctional sorting protein that play a role in nuclear gene expression as well as pathway traffic regulation. Diseases associated with PACS2 include early infantile epileptic encephalopathy (EIEE66), alacrima, achalasia, and mental retardation syndrome. Whole exome sequencing (WES) technique was used for the identification of variants that may lead to the disease. We identified a consanguineous Saudi family segregating developmental delay, mental retardation and epilepsy...

We summarize the copy number variations (CNVs) and phenotype spectrum of infantile epileptic spasms syndrome (IESS) in a Chinese cohort. The CNVs were identified by genomic copy number variation sequencing. The CNVs and clinical data were analyzed. 74 IESS children with CNVs were enrolled. 35 kinds of CNVs were identified. There were 11 deletions and 5 duplications not reported previously in IESS, including 2 CNVs not reported in epilepsy. 87.8% were de novo, 9.5% were inherited from mother and 2.7% from father...

INTRODUCTION: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by GFAP mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis, and seizures as the most characteristic features. In this case report, we provide a detailed clinical description of the neonatal type of AxD. METHOD: Next-Generation Sequencing (NGS), including a panel of 49 genes related to Early Infantile Epileptic Encephalopathy (EIEE), was carried out, and then Whole Exome Sequencing (WES) was performed on the proband's DNA extracted from blood...

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date...

Myoclonic-tonic (MT) and spasm-tonic (ST) seizures represent distinctive features in late infantile epileptic encephalopathy (LIEE). This commentary aims to delineate the electroclinical characteristics of MT and ST seizures, setting them apart from other seizure types. Our analysis encompasses 211 ST and MT seizures observed in 31 patients diagnosed with LIEE, providing a comprehensive overview of video-EEG features and polygraphic signatures. In MT seizures, EEG findings reveal a high-voltage diffuse spike/polyspike and wave discharge, often succeeded by diffuse electrodecrements...

Motor proteins, encoded by Kinesin superfamily ( KIF ) genes, are critical for brain development and plasticity. Increasing studies reported KIF 's roles in neurodevelopmental disorders. Here, a 6 years and 3 months-old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease-related family history. Whole exome sequencing identified a novel heterozygous in-frame deletion (c...

OBJECTIVE: Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE. METHODS: Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed...

BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases...

Hypothalamic hamartomas (HHs) are rare, benign brain tumors or lesions of the hypothalamus that are predominantly identified in cases of epilepsy and central precocious puberty (CPP), whereas isolated manifestations of infantile obesity are atypical. We herein report an 8-month-old boy with severe obesity (Kaup index 26.4 [>100th percentile]) and uncontrollable hyperphagia. His growth chart demonstrated remarkable weight gain that exceeded the length gain in magnitude. Brain magnetic resonance imaging identified a lesion consistent with HH...

BACKGROUND: Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients. METHODS: The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using 'metachromatic leukodystrophy' as a keyword...