GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy.

Objective: Rett syndrome (RTT) and epileptic encephalopathy (EE) are devastating neurodevelopmental disorders with distinct diagnostic criteria. However, highly heterogeneous and overlapping clinical features often allocate patients into the boundary of the two conditions, complicating accurate diagnosis and appropriate medical interventions. Therefore, we investigated the specific molecular mechanism that allows an understanding of the pathogenesis and relationship of these two conditions.

Painful legs and moving toes syndrome in a 16-year-old girl.

Painful legs and moving toes (PLMT) syndrome is characterized by spontaneous movements of the digits and pain in one or both lower extremities. Of the reported cases, a majority of the patients was female, and the mean age of onset was 58 years. Only one pediatric case has been reported so far.

Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome.

Background And Purpose: Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome.

Methods: Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included.

Alpha-thalassemia X-linked intellectual disability syndrome identified by whole exome sequencing in two boys with white matter changes and developmental retardation.

Alpha-thalassemia X-linked intellectual disability (ATRX) syndrome is a genetic syndrome caused by mutation of the ATRX gene associated with chromatin remodeling. Recently, a wide spectrum of brain MRI abnormalities and clinical manifestations has been recognized. We describe two male patients with genetically confirmed ATRX syndrome, both presented with developmental delay and white matter changes without typical clinical characteristics of ATRX.

Noninvasive prenatal diagnosis of duchenne muscular dystrophy: comprehensive genetic diagnosis in carrier, proband, and fetus.

Background: Noninvasive prenatal diagnosis of monogenic disorders using maternal plasma and targeted massively parallel sequencing is being investigated actively. We previously demonstrated that comprehensive genetic diagnosis of a Duchenne muscular dystrophy (DMD) patient is feasible using a single targeted sequencing platform. Here we demonstrate the applicability of this approach to carrier detection and noninvasive prenatal diagnosis.

Mutation is a Low-Incidence Genetic Cause in Atypical Rett Syndrome.

Due to the genetic and clinical heterogeneity of Rett syndrome, patients with nonclassic phenotypes are classified as an atypical Rett syndrome, that is, preserved speech variant, early seizure variant, and congenital variant. Respectively, , , and have been found to be the causative genes, but variants are the rarest and least studied. We performed mutational analyses for on 11 unrelated patients without and mutations, who were diagnosed with atypical Rett syndrome.

Screening Autoimmune Anti-neuronal Antibodies in Pediatric Patients with Suspected Autoimmune Encephalitis.

Background And Purpose: The aim of this study was to identify and describe the pediatric autoimmune encephalitis cases positive for anti-neuronal antibody tests.

Methods: Screening of six anti-neuronal antibodies in 23 children with suspected autoimmune encephalitis was performed by cell-based indirect immunofluorescence test with patients' serum or cerebrospinal fluid.

Results: Among the 23 cases enrolled here, eight patients (35%) were positive for the anti-N-methyl-d-aspartate (NMDA) receptor antibody and one patient (4%) was positive for the anti-contactin-associated protein-like 2 (CASPR2) antibody.

Epilepsy phenotype associated with a chromosome 2q24.3 deletion involving SCN1A: Migrating partial seizures of infancy or atypical Dravet syndrome?

The deletion of a sodium channel gene cluster located on chromosome 2q24.3 is associated with variable epilepsy phenotypes, including Dravet syndrome and migrating partial seizures of infancy. Although SCN1A is considered as the major contributor to the epilepsy phenotype, the role of other sodium channel genes that map within this cluster has not been delineated.

Rare coincidence of familial central core disease and hemophagocytic lymphohistiocytosis.

Central core disease is a congenital myopathy caused by mutations in RYR1. A 6-year-old girl was admitted due to difficulty in running and climbing stairs. Another 13 members through the four generations had similar symptoms, indicating autosomal dominant inheritance.

Mutational analysis of paediatric patients with tuberous sclerosis complex in Korea: genotype and epilepsy.

To date, only a few studies have reported that, in tuberous sclerosis, TSC2 mutations are more frequently associated with infantile spasms and cognitive impairment compared to TSC1 mutations. We analyzed the mutational spectrum of patients with tuberous sclerosis in Korea and attempted to explore the associations between genotype and seizure type/outcome. We performed mutational analyses on 70 unrelated patients with clinically confirmed tuberous sclerosis by using direct DNA sequencing and/or multiplex ligation-dependent probe amplification.

Clinical and mutational spectrum in Korean patients with Rubinstein-Taybi syndrome: the spectrum of brain MRI abnormalities.

Objective: Rubinstein-Taybi syndrome (RSTS) is one of the neurodevelopmental disorders caused by mutations of epigenetic genes. The CREBBP gene is the most common causative gene, encoding the CREB-binding protein with histone acetyltransferase (HAT) activity, an epigenetic modulator. To date, there have been few reports on the structural abnormalities of the brain in RSTS patients.

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

Objectives: Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE.

Methods: We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE.

Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole-exome sequencing.

Background: Hoyeraal-Hreidarsson syndrome is a severe multisystem disorder that is characterized by bone-marrow failure, intrauterine growth retardation, microcephaly, immunodeficiency, and cerebellar atrophy. This rare disease shares clinical features with dyskeratosis congenita and, together, they are recognized as a group of disorders caused by telomere dysfunction. As the genetic background of dyskeratosis congenita or Hoyeraal-Hreidarsson syndrome has expanded rapidly, multiple causative genes and inheritance patterns pose a great challenge to their genetic diagnosis.

Menkes disease in Korea: ATP7A mutation and epilepsy phenotype.

Objective: Menkes disease (MD) is an X-linked recessive disorder characterized by progressive neuro-degeneration. There are few reports of epilepsy and electroencephalography (EEG) findings and few reports of MD patients in Korea. We explored MD genotypes and phenotypes, including epilepsy, in Korean patients.

Involuntary movement in pediatric moyamoya disease patients: consideration of pathogenetic mechanism using neuroimaging studies.

Purpose: Involuntary movement is a rare symptom of moyamoya disease (MMD). No consensus has been reached regarding its clinical features and pathogenetic mechanism. Therefore, pediatric MMD patients presenting with involuntary movement were retrospectively analyzed, focusing on the image findings.

Lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy.

Purpose: To evaluate the efficacy and safety of lacosamide in pediatric patients with refractory focal epilepsy.

Methods: We reviewed retrospectively the medical records of children younger than 18 years of age treated at Seoul National University Bundang Hospital, in whom oral lacosamide was used as an adjunctive treatment for refractory focal epilepsy. Clinical information regarding the patients' epilepsy and the outcome of lacosamide treatment was gathered and analyzed.

Electroencephalography in pediatric moyamoya disease: reappraisal of clinical value.

Purpose: The clinical value of electroencephalography (EEG) in pediatric moyamoya disease has been underestimated, though the characteristic patterns are well known. We undertook this study to evaluate the clinical value of EEG as a diagnostic and postoperative follow-up modality in pediatric moyamoya disease.

Methods: We retrospectively reviewed the pre and postoperative EEG with effective hyperventilation in 127 pediatric moyamoya patients and compared their patterns with hemodynamic images.

Clinical and EEG risk factors for subsequent epilepsy in patients with complex febrile seizures.

Purpose: To identify the risk factors for subsequent epilepsy in patients with complex febrile seizures from a single-center retrospective cohort.

Methods: The medical records of 1091 patients discharged with a diagnosis of febrile seizures from the Seoul National University Bundang Hospital from February 2004 to October 2009 were reviewed. One hundred eighty-three patients (107 boys and 76 girls) with complex febrile seizures who showed normal neurocognitive development were included in the analysis.

A unique phenotype of 2q24.3-2q32.1 duplication: early infantile epileptic encephalopathy without mesomelic dysplasia.

The voltage-gated sodium channel genes and HOXD genes are clustered on chromosome 2q, and duplication of this region is associated with 2 clinical phenotypes: early-onset epilepsy and mesomelic dysplasia Kantaputra type, respectively. We report a case involving 2q24.3-2q32.

Molecular diagnosis of congenital muscular dystrophies with defective glycosylation of alpha-dystroglycan using next-generation sequencing technology.

Targeted resequencing using next-generation sequencing technology is being rapidly applied to the molecular diagnosis of human genetic diseases. The group of muscular dystrophies may be an appropriate candidate for this approach because these diseases exhibit genotype-phenotype heterogeneity. To perform a proof-of-concept study, we selected four patients with congenital muscular dystrophies with defective glycosylation of alpha-dystroglycan.

Distinct neurological features in a patient with Schinzel-Giedion syndrome caused by a recurrent SETBP1 mutation.

Introduction: Schinzel-Giedion syndrome (SGS) is a rare multiple congenital malformation syndrome defined by characteristic facial features, profound developmental delay, severe growth failure, and multiple congenital anomalies. Most individuals affected by SGS die in early childhood mainly because of progressive neurodegeneration and respiratory failure. The causative gene of SGS, SETBP1, was identified, but there are few reports of SGS with molecular confirmation worldwide.

A case of isodicentric chromosome 15 presented with epilepsy and developmental delay.

We report a case of isodicentric chromosome 15 (idic(15) chromosome), the presence of which resulted in uncontrolled seizures, including epileptic spasms, tonic seizures, and global developmental delay. A 10-month-old female infant was referred to our pediatric neurology clinic because of uncontrolled seizures and global developmental delay. She had generalized tonic-clonic seizures since 7 months of age.

Comparison of flunarizine and topiramate for the prophylaxis of pediatric migraines.

The purpose of this study was to compare the efficacy and tolerability of topiramate and flunarizine for the prophylaxis of pediatric migraines. A retrospective medical-record review of patients who underwent prophylaxis after receiving a diagnosis of migraine with aura and without aura was performed. Only patients who completed at least 3 months of treatment were included in the analysis.

A case of Becker muscular dystrophy with early manifestation of cardiomyopathy.

An 18-year-old boy was admitted with chest discomfort, nausea, and dyspnea at rest. At the age of 3 years, he underwent muscle biopsy and dystrophin gene analysis owing to an enlarged calf muscle and elevated serum kinase level (6,378 U/L) without overt weakness; based on the results, Becker muscular dystrophy (BMD) was diagnosed. The dystrophin gene showed deletion of exons 45 to 49.

Magnetoencephalography in pediatric lesional epilepsy surgery.

This study was performed to assess the usefulness of magnetoencephalography (MEG) as a presurgical evaluation modality in Korean pediatric patients with lesional localization-related epilepsy. The medical records and MEG findings of 13 pediatric patients (6 boys and 7 girls) with localization-related epilepsy, who underwent epilepsy surgery at Seoul National University Children's Hospital, were retrospectively reviewed. The hemispheric concordance rate was 100% (13/13 patients).