A patient with early myoclonic encephalopathy (EME) with a de novo KCNQ2 mutation.

Background: The potassium voltage-gated channel subfamily Q member 2 (KCNQ2) gene has been reported to be associated with various types of epilepsy, including benign familial neonatal seizure (BFNS), early infantile epileptic encephalopathy (EIEE), and unclassified early onset encephalopathies. We herein report a patient with early myoclonic encephalopathy (EME) caused by a KCNQ2 mutation.

Case Report: A male infant started to exhibit erratic myoclonus several days after birth and apnea attacks lasting for seconds with desaturation.

Rare variants of small effect size in neuronal excitability genes influence clinical outcome in Japanese cases of SCN1A truncation-positive Dravet syndrome.

Dravet syndrome (DS) is a rare, devastating form of childhood epilepsy that is often associated with mutations in the voltage-gated sodium channel gene, SCN1A. There is considerable variability in expressivity within families, as well as among individuals carrying the same primary mutation, suggesting that clinical outcome is modulated by variants at other genes. To identify modifier gene variants that contribute to clinical outcome, we sequenced the exomes of 22 individuals at both ends of a phenotype distribution (i.

Variable expressivity of a likely pathogenic variant in KCNQ2 in a three-generation pedigree presenting with intellectual disability with childhood onset seizures.

KCNQ2 has been reported as a frequent cause of autosomal dominant benign familial neonatal seizures. De novo likely pathogenic variants in KCNQ2 have been described in neonatal or early infantile onset epileptic encephalopathy patients. Here, we report a three-generation family with six affected patients with a novel likely pathogenic variant (c.

Benign infantile seizures followed by autistic regression in a boy with 16p11.2 deletion.

Benign infantile seizures (BIS) are usually a self-limiting condition, which may be associated with heterozygous mutations in the PRRT2 gene at chromosome 16p11.2. Here, we report a boy with a deletion in 16p11.

Association of a synonymous SCN1B variant affecting splicing efficiency with Benign Familial Infantile Epilepsy (BFIE).

Benign Familial Infantile Epilepsy (BFIE) is clinically characterized by clusters of brief partial seizures progressing to secondarily generalized seizures with onset at the age of 3-7 months and with favorable outcome. PRRT2 mutations are the most common cause of BFIE, and found in about 80% of BFIE families. In this study, we analyzed a large multiplex BFIE family by linkage and whole exome sequencing (WES) analyses.

Two Novel Mutations in 2 Families With Benign Familial Neonatal Convulsions.

Benign familial neonatal convulsion is a rare autosomal dominant inherited epilepsy syndrome characterized by unprovoked seizures in the first few days of life, normal psychomotor development, and a positive intergenerational family history of neonatal seizures. Over 90% of the affected individuals have inherited causal mutations in , which encodes for the potassium voltage-gated channel subfamily Q, member 2. Mutations in are also associated with a severe neonatal encephalopathy phenotype associated with poor seizure control and neurodevelopmental deficits.

Core outcome sets in women's and newborn health: a systematic review.

Background: Variation in outcome collection and reporting is a serious hindrance to progress in our specialty; therefore, over 80 journals have come together to support the development, dissemination, and implementation of core outcome sets.

Objective: This study systematically reviewed and characterised registered, progressing, or completed core outcome sets relevant to women's and newborn health.

Search Strategy: Systematic search using the Core Outcome Measures in Effectiveness Trial initiative and the Core Outcomes in Women's and Newborn Health initiative databases.

Endoplasmic reticulum retention of KCNQ2 potassium channel mutants following temperature elevation.

Background: KCNQ2 plays a key role in the regulation of neuronal excitability. The R214W and Y284C mutants of KCNQ2 channels, which are associated with BFNC, can decrease channel function to cause neuronal hyperexcitability and promote seizures. Previous studies revealed that elevated temperature caused up-regulation of KCNQ2 expression.

Opposing Effects on Na1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures.

Background: Variants in the SCN2A gene that disrupt the encoded neuronal sodium channel Na1.2 are important risk factors for autism spectrum disorder (ASD), developmental delay, and infantile seizures. Variants observed in infantile seizures are predominantly missense, leading to a gain of function and increased neuronal excitability.

Corticokinematic coherence as a new marker for somatosensory afference in newborns.

Objective: Somatosensory evoked potentials have high prognostic value in neonatal intensive care, but their recording from infants is challenging. Here, we studied the possibility to elicit cortical responses in newborns by simple passive hand movements.

Methods: We examined 13 newborns (postnatal age 1-46days) during clinically indicated 19-channel electroencephalography (EEG) recordings in the neonatal intensive care unit; EEG indications included birth asphyxia and suspected epileptic seizures.

Exploring temporal information in neonatal seizures using a dynamic time warping based SVM kernel.

Seizure events in newborns change in frequency, morphology, and propagation. This contextual information is explored at the classifier level in the proposed patient-independent neonatal seizure detection system. The system is based on the combination of a static and a sequential SVM classifier.

Childhood epilepsies: What should a pediatrician know?

Seizures in children are among the most common neurological disorders. A pediatrician should know how to approach a child who presents with a seizure. This review will focus on points that are important in the evaluation of children who have experienced seizures.

A KCNQ2 E515D mutation associated with benign familial neonatal seizures and continuous spike and waves during slow-wave sleep syndrome in Taiwan.

Background/purpose: Pediatric epilepsy caused by a KCNQ2 gene mutation usually manifests as benign familial neonatal seizures (BFNS) during the 1 week of life. However, the exact mechanism, phenotype, and genotype of the KCNQ2 mutation are unclear.

Methods: We studied the KCNQ2 genotype from 75 nonconsanguineous patients with childhood epilepsy without an identified cause (age range: from 2 days to 18 years) and from 55 healthy adult controls without epilepsy.

Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate.

Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP).

Rapid and safe response to low-dose carbamazepine in neonatal epilepsy.

Objective: To evaluate treatment responses in benign familial neonatal epilepsy (BFNE).

Methods: We recruited patients with BFNE through a multicenter international collaboration and reviewed electroclinical and genetic details, and treatment response. All patients were tested at minimum for mutations/deletions in the KCNQ2, KCNQ3, and SCN2A genes.

Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to Oral Mexiletine.

Background: Genetic alterations are significant causes of epilepsy syndromes; especially early-onset epileptic encephalopathies and voltage-gated sodium channelopathies are among the best described. Mutations in the SCN2A subunit of voltage-gated sodium channels have been associated with benign familial neonatal-infantile seizures, generalized epilepsy febrile seizures plus, and an early-onset infantile epileptic encephalopathy.

Method: We describe two infants with medically refractory seizures due to a de novo SCN2A mutation.

Regulation of KCNQ/Kv7 family voltage-gated K channels by lipids.

Many years of studies have established that lipids can impact membrane protein structure and function through bulk membrane effects, by direct but transient annular interactions with the bilayer-exposed surface of protein transmembrane domains, and by specific binding to protein sites. Here, we focus on how phosphatidylinositol 4,5-bisphosphate (PIP) and polyunsaturated fatty acids (PUFAs) impact ion channel function and how the structural details of the interactions of these lipids with ion channels are beginning to emerge. We focus on the Kv7 (KCNQ) subfamily of voltage-gated K channels, which are regulated by both PIP and PUFAs and play a variety of important roles in human health and disease.

Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies.

In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood.

Novel Mutation in a Large Family with Benign Familial Neonatal Epilepsy: A Rare Cause of Neonatal Seizures.

Benign familial neonatal seizures (BFNS) present a rare familial epilepsy syndrome caused by genetic alterations in the voltage-gated potassium channels Kv7.2 and Kv7.3, encoded by and While most BFNS families carry alterations in , mutations in appear to be less common.

Phenotypic Variability from Benign Infantile Epilepsy to Ohtahara Syndrome Associated with a Novel Mutation in .

Mutations in have been associated with benign familial neonatal-infantile seizures (BFNIS) as well as infantile-onset epileptic encephalopathy, such as Ohtahara syndrome (OS). We describe a family with 3 affected individuals carrying the novel missense variant c.1147C>G, p.

In other RCNi journals.

'Healthcare professionals need greater awareness of the features of benign neonatal sleep myoclonus to reduce the number of neonates undergoing unnecessary investigations and avoid misdiagnosis of the condition as epilepsy.'

Avoiding mistaken epilepsy diagnosis in newborns.

Parents of newborns can be reassured if healthcare professionals are aware of benign neonatal sleep myoclonus (BNSM) so it is not mistaken for epilepsy.

Pharmacophore modeling, 3D-QSAR, and in silico ADME prediction of N-pyridyl and pyrimidine benzamides as potent antiepileptic agents.

Biological mechanism attributing mutations in KCNQ2/Q3 results in benign familial neonatal epilepsy (BFNE), a rare form of epilepsy and thus neglected. It offers a potential target for antiepileptic drug discovery. In the present work, a pharmacophore-based 3D-QSAR model was generated for a series of N-pyridyl and pyrimidine benzamides possessing KCNQ2/Q3 opening activity.

Clinical and genetic features of 13 Spanish patients with KCNQ2 mutations.

The KCNQ2 gene codifies a subunit of the voltage-gated potassium M channel underlying the neuronal M-current. Classically, mutations in this gene have been associated with benign familial neonatal seizures, however, in recent years KCNQ2 mutations have been reported associated to early-onset epileptic encephalopathy. In this work, detailed familiar, clinical and genetic data were collected for 13 KCNQ2-positive patients revealed among a cohort of 80 epileptic pediatric probands from Spain who were analyzed through a targeted next-generation sequencing assay for 155 epilepsy-associated genes.