Phenotype of Relapsing Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease in Children.

Background And Purpose: To determine the clinical phenotypes, relapse timing, treatment responses, and outcomes of children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Methods: We collected the demographic, clinical, laboratory, and radiological data of patients aged <18 years who had been diagnosed with MOGAD at Seoul National University Children's Hospital between January 2010 and January 2022; 100 were identified as positive for MOG antibodies, 43 of whom experienced relapse.

Results: The median age at onset was 7 years (range 2-16 years).

Exploring the Clinical Utility of Targeted MECP2 Testing in Real-World Practice.

Background: This study aimed to explore the clinical utility of targeted MECP2 testing in a large cohort of females with neurodevelopmental delays. Our aim was to identify suitable candidates for testing based on prevailing diagnostic criteria.

Methods: Eligible participants with global developmental delay/arrest or regression before age 36 months underwent MECP2 testing.

Discovery of novel disease-causing mutation in and its correction using adenine base editor to improve mitochondrial function.

Mutations in nuclear genes regulating mitochondrial DNA (mtDNA) replication are associated with mtDNA depletion syndromes. Using whole-genome sequencing, we identified a heterozygous mutation (c.272G>A:p.

De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder.

Histone deacetylase 3 (HDAC3) is a crucial epigenetic modulator essential for various developmental and physiological functions. Although its dysfunction is increasingly recognized in abnormal phenotypes, to our knowledge, there have been no established reports of human diseases directly linked to HDAC3 dysfunction. Using trio exome sequencing and extensive phenotypic analysis, we correlated heterozygous de novo variants in HDAC3 with a neurodevelopmental disorder having variable clinical presentations, frequently associated with intellectual disability, developmental delay, epilepsy, and musculoskeletal abnormalities.

Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity.

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected.

SYNGAP1-related developmental and epileptic encephalopathy: Genotypic and phenotypic characteristics and longitudinal insights.

The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined.

Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies.

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12).

Clinical Characteristics of Diabetes in People with Mitochondrial DNA 3243A>G Mutation in Korea.

Maternally inherited diabetes and deafness (MIDD) is a rare mitochondrial disorder primarily resulting from m.3243A>G mutation. The clinical characteristics of MIDD exhibit significant heterogeneity.

Nusinersen demonstrates effectiveness in treating spinal muscular atrophy: findings from a three-year nationwide study in Korea.

Introduction: Nusinersen is the first drug approved for spinal muscular atrophy (SMA) treatment. In this study, we aimed to evaluate the long-term safety and efficacy of nusinersen, assess the therapeutic effects based on the treatment initiation timing and baseline motor function, and explore the perception of functional improvement from either parents or patients, utilizing 3-year nationwide follow-up data in South Korea.

Methods: We enrolled patients with SMA who were treated with nusinersen under the National Health Insurance coverage, with complete motor score records available and a minimum treatment duration of 6 months.

Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation.

WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities.

Interaction of interictal epileptiform activity with sleep spindles is associated with cognitive deficits and adverse surgical outcome in pediatric focal epilepsy.

Objective: Temporal coordination between oscillations enables intercortical communication and is implicated in cognition. Focal epileptic activity can affect distributed neural networks and interfere with these interactions. Refractory pediatric epilepsies are often accompanied by substantial cognitive comorbidity, but mechanisms and predictors remain mostly unknown.

Epilepsy phenotype and gene ontology analysis of the 129 genes in a large neurodevelopmental disorders cohort.

Objective: Although pediatric epilepsy is an independent disease entity, it is often observed in pediatric neurodevelopmental disorders (NDDs) as a major or minor clinical feature, which might provide diagnostic clues. This study aimed to identify the clinical and genetic characteristics of patients with epilepsy in an NDD cohort and demonstrate the importance of genetic testing.

Methods: We retrospectively analyzed the detailed clinical differences of pediatric NDD patients with epilepsy according to their genetic etiology.

Impact of nusinersen on the health-related quality of life and caregiver burden of patients with spinal muscular atrophy with symptom onset after age 6 months.

Introduction/aims: Novel disease-modifying approaches for spinal muscular atrophy (SMA) have highlighted the patient's perspective on functional changes over time. In this study, we evaluated the impact of nusinersen on the health-related quality of life (HRQoL) of patients with later-onset SMA and the caregiver burden.

Methods: We assessed the changes in HRQoL using the Pediatric Quality of Life Inventory 4.

Broad spectrum of phenotype and genotype in Korean α-dystroglycan related muscular dystrophy presenting to a tertiary pediatric neuromuscular center.

α-Dystroglycanopathies are a clinically and genetically heterogeneous group of muscular dystrophies associated with the defective glycosylation of α-dystroglycan (α-DG). Eighteen genes associated with α-dystroglycanopathies have been identified, and the relative prevalence of genetic subtypes varies with ethnicity. Here, we investigated the clinical and genetic characteristics of α-DG-related muscular dystrophy in the Korean pediatric population.

A case of pediatric anti-leucine-rich glioma inactivated 1 encephalitis with faciobrachial dystonic seizure.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare type of autoimmune encephalitis. A characteristic faciobrachial dystonic seizure (FBDS) is also frequently associated with this disease. Although primarily reported in the adult population, reports of its occurrence in the pediatric population are rare.

Seizure Evolution and Outcome in Pediatric Autoimmune Encephalitis.

Background: Our study aimed to characterize seizure incidence and seizure outcome of pediatric autoimmune encephalitis (AE) focusing on subgroup analysis based on antibody (Ab).

Methods: Among 110 pediatric patients with AE, we compared seizure characteristics and outcomes in 68 patients with seizure, who satisfied the proposed criteria of pediatric AE. Accordingly, patients were classified into three groups, anti-myelin oligodendrocyte glycoprotein (anti-MOG) AE, anti-N-methyl-D-aspartic acid receptor (anti-NMDAR) AE, and Ab-negative AE.

A database of 5305 healthy Korean individuals reveals genetic and clinical implications for an East Asian population.

Despite substantial advances in disease genetics, studies to date have largely focused on individuals of European descent. This limits further discoveries of novel functional genetic variants in other ethnic groups. To alleviate the paucity of East Asian population genome resources, we established the Korean Variant Archive 2 (KOVA 2), which is composed of 1896 whole-genome sequences and 3409 whole-exome sequences from healthy individuals of Korean ethnicity.