This study aimed to implement genome sequencing using an automated pipeline for critically ill pediatric patients within a real-world healthcare system. Twenty patients under 36 months of age, admitted to the NICU/PICU or suspected of having rapidly progressive genetic disorders, were enrolled. Trio-based genome sequencing was performed using an optimized processing pipeline, which automatically performed mapping, variant calling, annotation, and in silico pathogenicity assessment. Among 20 enrolled patients, 11 (55%) were from the NICU, and 16 (80%) presented with neurological manifestations as their chief complaint. The median time from symptom onset to study enrollment was 73 days for 18 patients referred from other hospitals and less than a week for 2 in-hospital patients. The median turnaround time (TAT) for rWGS was 10 days, with the shortest being 5 days. A definite or presumed genetic diagnosis was made in 11 patients (55%), including 10 of 16 with neurological symptoms (62.5%) and 1 of 4 with non-neurologic symptoms (25%). Management plans were modified for 8 of the 11 patients (72.7%), including medication changes, diet modifications, and preimplantation genetic testing for future pregnancies. This study highlights the feasibility and clinical utility of WGS in critically ill pediatric patients in Korea, demonstrating a high diagnostic yield and significant impact on patient management, particularly among those presenting with neurologic symptoms. Establishing a nationwide fast-track system and providing detailed testing indications are required for effective implementation. Further automation and resource optimization could reduce the TAT and improve the efficacy of rWGS in critical care settings.
This study investigated the seizure recurrence rate and potential predictors of seizure recurrence following antiepileptic drug (AED) withdrawal after resective epilepsy surgery in children with focal cortical dysplasia (FCD).We retrospectively analyzed the records of 70 children and adolescents with FCD types I, II, and IIIa who underwent resective epilepsy surgery between 2004 and 2015 and were followed for at least 2 years after surgery.We attempted AED withdrawal in 40 patients. The median time of starting the AED reduction was 10.8 months after surgery. Of these 40 patients, 14 patients (35%) experienced seizure recurrence during AED reduction or after AED withdrawal. Half of the 14 patients who experienced recurrence regained seizure freedom after AED reintroduction and optimization. Compared with their preoperative status, the AED dose or number was decreased in 57.1% of patients, and remained unchanged in 14.3% after surgery. A multivariate analysis found that incomplete resection (p=0.004) and epileptic discharges on the postoperative EEG (p=0.025) were important predictors of seizure recurrence after AED withdrawal. Over the mean follow-up duration of 4.5 years after surgery, 34 patients (48.6% of the entire cohort) were seizure-free with and without AEDs.Children with incomplete resection and epileptic discharges on postoperative EEG are at a high risk of seizure recurrence after drug withdrawal. Complete resection of FCD may lead to a favorable surgical outcome and successful AED withdrawal after surgery.
Purpose: X-linked myotubular myopathy (XLMTM) is a rare condition of centronuclear myopathy caused by myotubularin 1 (MTM1) mutations. Patients with XLMTM show different neurodevelopmental outcomes after the neonatal period depending on age and acquired hypoxic damage. We aim to evaluate the clinical characteristics and neurodevelopmental outcomes of patients with XLMTM who were followed up at a single center. It is essential to understand the volume and conditions to prepare for being a candidate for new therapeutic strategies. Methods: Patients diagnosed with centronuclear myopathy by muscle pathology and MTM1 mutation analysis were included. We retrospectively investigated motor milestones, communication skills, and bulbar and respiratory function in the patients. The patients were categorized into two groups: with and without hypoxic insults (HI). Results: All 13 patients were severely affected by neonatal hypotonia and required respiratory support and a feeding tube during the neonatal period. The follow-up duration was 4.4 years (range, 0.3 to 8.9). In the non-HI group, developmental milestones were delayed but were slowly achieved. Some patients underwent training in oral feeding with thickened foods and weaning from ventilation. Patients with HI showed poor motor function catch-up and communication skills. Three deaths were associated with acute respiratory failure.Conclusion: Patients with XLMTM without HI can survive long-term with the slow achievement of motor milestones and bulbar and respiratory function. However, hypoxic brain damage following acute respiratory failure negatively influences their developmental potential or even lead to death. Therefore, parental education for proper respiratory management is necessary, especially for young children.
The aim of the present study was to evaluate the role of comorbid psychiatric symptoms on quantitative electroencephalogram (QEEG) activities in boys with the attention deficit/hyperactivity disorder (ADHD).All participants were male students in the second, third or fourth grade in elementary school. Therefore, there were no significant differences in age or sex. Participants with ADHD were assigned to one of three groups: pure ADHD (n=22), ADHD with depressive symptoms (n=11), or ADHD with problematic internet use (n=19). The Korean version of the Children's Depression Inventory and the Korean Internet Addiction Self-scale were used to assess depressive symptoms and problematic internet use, respectively. Resting-state EEG during eyes closed was recorded, and the absolute power of five frequency bands was analyzed: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), and gamma (30-50 Hz).The ADHD with problematic internet use group showed decreased absolute theta power at the central and posterior region compared with the pure ADHD group. However, The ADHD with depressive symptoms group showed no significant differences compared with the other groups.These findings will contribute to a better understanding of brain-based electrophysiological changes in children with ADHD in accordance with comorbid psychiatric symptoms.
The Shprintzen-Goldberg syndrome (SGS) is an extremely rare genetic disorder caused by heterozygous variant in SKI.SGS is characterized by neurodevelopmental impairment with skeletal anomaly.Recognition of SGS is sometimes quite challenging in practice because it has diverse clinical features involving skeletal, neurological, and cardiovascular system.Here we report a case of a 6-month-old boy who initially presented with developmental delay and marfanoid facial features including prominent forehead, hypertelorism, high arched palate and retrognathia.He showed motor developmental delay since birth and could not control his head at the time of first evaluation.His height was above 2 standard deviation score.Arachnodactyly, hypermobility of joints, skin laxity, and pectus excavatum were also noted.Sequencing for FBN1 was negative, however, a novel missense variant, c.350G>A in SKI was identified by sequential whole exome sequencing.To our knowledge, this is the first case with SGS with phenotypic features of SGS overlapping with those of the Marfan syndrome, diagnosed by next generation sequencing in Korea.
The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOG-antibody-positive demyelinating diseases in children.This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay.The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4-169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p=0.011).MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.
The aim of this study was to expand the understanding of the genotype-phenotype spectrum of ATP1A3-related disorders and to evaluate the therapeutic effect of a ketogenic diet in patients with alternating hemiplegia of childhood (AHC).The clinical information of 13 patients with ATP1A3 mutations was analyzed by performing retrospective chart reviews. Patients with the AHC phenotype who consented to ketogenic diet were included in the trial.Ten patients presented with the clinical phenotype of AHC, two patients presented with rapid-onset dystonia parkinsonism, and one patient presented with cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Two novel mutations of the AHC phenotype were identified: p.Ile363Thr and p.Asn743Ser. The clinical phenotypes of three mutations differed from those in previous reports: p.Arg597Pro, p.Thr769Pro, and p.Arg756Cys. One of the two patients who started a ketogenic diet experienced seizure provocation and so immediate stopped consuming the diet, while the other patient continued the ketogenic diet for 1 year, but this produced no clear benefit such as reduction of paroxysmal symptoms.Our study is the first case series of ATP1A3-related disorders to be described in Korea and which further expands the understanding of its genotype-phenotype spectrum. A ketogenic diet showed no clear benefit for the patients with AHC.
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