Coffin-Siris syndrome with bilateral macular dysplasia caused by a novel exonic deletion in ARID1B.

Coffin-Siris syndrome (CSS) is a congenital anomaly syndrome characterized by developmental delay, coarse facial features, and hypoplasia of the fifth digit's nail or phalanges. Herein, we report a case of the 8-year-old female patient who showed developmental delay associated with dysplasia in the macular and large toe area. Comprehensive genomic analysis showed no possible candidate variants, but the subsequent genomic copy number analysis revealed a novel exonic deletion in the coding region of AT-rich interactive domain-containing protein 1B (ARID1B), a gene responsible for CSS.

MeCP2_e2 partially compensates for lack of MeCP2_e1: A male case of Rett syndrome.

Background: Rett syndrome (RTT) is a neurodevelopmental disorder that predominantly affects girls. Its causative gene is the X-linked MECP2 encoding the methyl-CpG-binding protein 2 (MeCP2). The gene comprises four exons and generates two isoforms, namely MECP2_e1 and MECP2_e2.

Abnormal γ-aminobutyric acid neurotransmission in a Kcnq2 model of early onset epilepsy.

Objective: Mutations of the KCNQ2 gene, which encodes the K 7.2 subunit of voltage-gated M-type potassium channels, have been associated with epilepsy in the neonatal period. This developmental stage is unique in that the neurotransmitter gamma aminobutyric acid (GABA), which is inhibitory in adults, triggers excitatory action due to a reversed chloride gradient.

Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain.

Missense mutations in sodium channel SCN1A and SCN2A predispose children to encephalopathy with severe febrile seizures.

Objective: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood encephalopathy following severe febrile seizures. The pathogenesis of AESD is considered to be fever-induced seizure susceptibility and excitotoxicity, which may be caused by sodium channel dysfunction in some cases. Here we studied whether mutations in genes encoding sodium channels, SCN1A and SCN2A, predispose children to AESD.

A case of recurrent encephalopathy with SCN2A missense mutation.

Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A, which encodes the Na(+) channel Nav1.2, cause epilepsy syndromes and predispose children to acute encephalopathy.

Clinical and genetic features of acute encephalopathy in children taking theophylline.

Background: Theophylline has recently been suspected as a risk factor of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), although there has been no systematic study on the relationship between acute encephalopathy in children taking theophylline (AET) and AESD.

Methods: We recruited 16 Japanese patients (11 male and 5 female, median age of 2 years and 7 months) with AET from 2008 to 2013. We evaluated their clinical features, such as the duration of first seizure, biphasic clinical course and cranial CT/MRI imaging and compared them with those of AESD.

Exacerbation of benign familial neonatal epilepsy induced by massive doses of phenobarbital and midazolam.

Background: Barbiturates and benzodiazepines are the first-line anticonvulsants for neonatal seizures. However, in immature brains, those drugs may lead to paradoxical neuronal excitation.

Patient: A patient with benign familial neonatal epilepsy developed epileptic encephalopathy after massive doses of phenobarbital that were followed by a continuous infusion of midazolam on postnatal day 3.

A novel SCN1A mutation in a cytoplasmic loop in intractable juvenile myoclonic epilepsy without febrile seizures.

Generalised (genetic) epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with various phenotypes. The majority of individuals with GEFS+ have generalised seizure types, in addition to febrile seizures (FS) or febrile seizures plus (FS+), defined as either continued FS after 6 years of age or afebrile seizures following FS. A 27-year-old man with no history of FS/FS+ experienced intractable generalised convulsive seizures.

Effect of CYP2C19 polymorphisms on stiripentol administration in Japanese cases of Dravet syndrome.

Objective: The objective of this study was to investigate stiripentol (STP) administration in cases of Dravet syndrome (DS) by comparing CYP2C19 allelic polymorphisms with the clinical effects of STP, including plasma concentrations of concomitant drugs and adverse effects of STP.

Materials And Methods: Eleven cases of DS cases were included. Demographic and clinical characteristics of the cases (age at the study period, body weight, mean dose and plasma concentration of valproate acid (VPA)/clobazam (CLB) off and on STP, mean plasma concentration of norclobazam (N-CLB) off and on STP, degree of seizure reduction, and adverse effects of STP) were examined with each CYP2C19 polymorphism.

Genetic analysis of PRRT2 for benign infantile epilepsy, infantile convulsions with choreoathetosis syndrome, and benign convulsions with mild gastroenteritis.

Purpose: PRRT2 mutations were recently identified in benign familial infantile epilepsy (BFIE) and infantile convulsions with paroxysmal choreoathetosis (ICCA) but no abnormalities have so far been identified in their phenotypically similar seizure disorder of benign convulsions with mild gastroenteritis (CwG), while mutations in KCNQ2 and KCNQ3 have been recognized in benign familial neonatal epilepsy (BFNE). The aim of this study was to identify PRRT2 mutations in infantile convulsions in Asian families with BFIE and ICCA, CwG and BFNE.

Methods: We recruited 26 unrelated Japanese affected with either BFIE or non-familial benign infantile seizures and their families, including three families with ICCA.