• Journal of Genetic Medicine
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• v.7 no.2
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• pp.111-118
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• 2010

Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.

• Clinical and Experimental Pediatrics
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• v.64 no.4
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• pp.141-148
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• 2021

There are very scant data on the epidemiology of primary immunodeficiency diseases (PIDs) in Korea. Here we attempted to estimate the PID epidemiology and disease burden in Korea. A systematic review was performed of studies retrieved from the PubMed, KoreaMed, and Google Scholar databases. Studies on PIDs published in Korean or English between January 2001 and November 2018 were analyzed. The number of PID patients and the healthcare costs were estimated from Health Insurance Review and Assessment Service (HIRA) Korea data for 2017. A total of 398 PID patients were identified from 101 reports. Immunodeficiencies affecting cellular and humoral immunity were reported in 11 patients, combined immunodeficiency with associated or syndromic features in 40, predominantly antibody deficiencies in 144, diseases of immune dysregulation in 58, congenital defects of phagocytes in 104, defects in the intrinsic and innate immunity in 1, auto-inflammatory disorders in 4, complement deficiencies in 36, and phenocopies of PID in none. From the HIRA reimbursement data, a total of 1,162 outpatients and 306 inpatients were treated for 8,166 and 6,149 days, respectively. In addition, reimbursement was requested for 8,200 outpatient and 1,090 inpatient cases and $1,924,000 and $4,715,000 were reimbursed in 2017, respectively. This study systematically reviewed published studies on PID and analyzed the national open data system of the HIRA to estimate the disease burden of PID, for the first time in Korea.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.64-69
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• 2021

Primary cilium has a signal transduction function that is essential for brain development, and also determines cell polarity and acts as a mediator for important signaling systems, especially the Sonic Hedgehog (SHH) pathway. TBC1D32 is a ciliary protein, implicated in SHH signaling. Biallelic mutations in the TBC1D32 gene causes a kind of ciliopathy, heterogeneous developmental or degenerative disorders that affect multiple organs, including the brain. Here we report a boy who carried compound heterozygous variants in TBC1D32. The patient showed hypotonia, respiratory difficulty, and multiple anomalies at his birth. He was diagnosed with congenital hypopituitarism and treated with T4, hydrocortisone, and growth hormone. Despite the hormonal replacement, the patient needed long-term respiratory support with tracheostomy and nutritional support with a feeding tube. His developmental milestones were severely retarded. Hydrocephalus and strabismus developed and both required surgery, during the outpatient follow-up. Whole-exome sequencing indicated compound heterozygous variants, c.2200C>T (p.Arg734^*) and c.156-1G>T, in TBC1D32 gene. This is the first Korean case of TBC1D32-related ciliopathy and we reported detailed and sequential clinical features. This case demonstrated the utility of whole-exome sequencing and provided valuable clinical data on ultra-rare disease.

• Journal of Korean Neurosurgical Society
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• v.64 no.3
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• pp.386-405
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• 2021

Recent advancements in basic research on the process of secondary neurulation and increased clinical experience with caudal spinal anomalies with associated abnormalities in the surrounding and distal structures shed light on further understanding of the pathoembryogenesis of the lesions and led to the new classification of these dysraphic entities. We summarized the changing concepts of lesions developed from the disordered secondary neurulation shown during the last decade. In addition, we suggested our new pathoembryogenetic explanations for a few entities based on the literature and the data from our previous animal research. Disordered secondary neurulation at each phase of development may cause corresponding lesions, such as failed junction with the primary neural tube (junctional neural tube defect and segmental spinal dysgenesis), dysgenesis or duplication of the caudal cell mass associated with disturbed activity of caudal mesenchymal tissue (caudal agenesis and caudal duplication syndrome), failed ingression of the primitive streak to the caudal cell mass (myelomeningocele), focal limited dorsal neuro-cutaneous nondisjunction (limited dorsal myeloschisis and congenital dermal sinus), neuro-mesenchymal adhesion (lumbosacral lipomatous malformation), and regression failure spectrum of the medullary cord (thickened filum and filar cyst, low-lying conus, retained medullary cord, terminal myelocele and terminal myelocystocele). It seems that almost every anomalous entity of the primary neural tube may occur in the area of secondary neurulation. Furthermore, the close association with the activity of caudal mesenchymal tissue in secondary neurulation involves a wider range of surrounding structures than in primary neurulation. Although the majority of the data are from animals, not from humans and many theories are still conjectural, these changing concepts of normal and disordered secondary neurulation will provoke further advancements in our management strategies as well as in the pathoembryogenetic understanding of anomalous lesions in this area.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.4
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• pp.201-212
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• 2023

Purpose: The gastrointestinal system is the most commonly affected organ, followed by the lungs, in patients with primary immunodeficiency disease (PID). Hence, it is common for children with PIDs to present with gastrointestinal symptoms. We aimed to analyze the clinical and histopathological findings of patients who were initially admitted to pediatric gastroenterology/hepatology clinics and subsequently diagnosed with PIDs to identify the clinical clues for PIDs. Methods: The demographic, laboratory, and histopathological findings, treatment modality, and outcomes of patients initially admitted to the pediatric gastroenterology/hepatology unit and subsequently diagnosed with PIDs were recorded. Results: The study included 24 patients (58.3% male; median age [range]: 29 [0.5-204] months). Common clinical presentations included chronic diarrhea (n=8), colitis (n=6), acute hepatitis (n=4), and acute liver failure (n=2). The association of autoimmune diseases, development of malignant diseases, and severe progression of viral diseases was observed in 20.8%, 8.3%, and 16.6% of the patients, respectively. Antibody deficiency was predominantly diagnosed in 29.2% of patients, combined immunodeficiency in 20.8%, immune dysregulation in 12.5%, defects in intrinsic and innate immunity in 4.2%, autoinflammatory disorders in 8.3%, and congenital defects of phagocytes in 4.2%. Five patients remained unclassified (20.8%). Conclusion: Patients with PIDs may initially experience gastrointestinal or liver problems. It is recommended that the association of autoimmune or malignant diseases or severe progression of viral diseases provide pediatric gastroenterologists some suspicion of PIDs. After screening using basic laboratory tests, genetic analysis is mandatory for a definitive diagnosis.

• Journal of Genetic Medicine
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• v.21 no.1
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• pp.31-35
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• 2024

Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked neurodevelopmental disorder with abnormal thyroid function caused by mutation in the solute carrier family 16 member 2 (SLC16A2) gene. Clinical manifestations of AHDS are global or axial hypotonia, a variety of movement disorders, severe intellectual disability, quadriplegia or spastic diplegia, growth failure, and seizures. A 10-year-old boy visited our hospital with the chief complaint of newly onset generalized tonic seizures with vocalization of weekly to daily frequency. He showed early infantile hypotonia, severe intellectual disability, and frequent respiratory infections. He could not walk independently and was non-verbal. Electroencephalogram revealed generalized slow spike and waves with multifocal spikes and slow background rhythms. His tonic seizures were controlled with more than two anti-seizure medications (ASMs). At 11 years of age, he was evaluated for thyroid function as part of regular screening for ASM maintenance and was found to have abnormal thyroid function. We performed whole exome sequencing for severe global developmental delay, drug-resistant epilepsy, and abnormal thyroid function. The hemizygous c.940C>T (p.Arg314Ter) variant in the SLC16A2 gene (NM_006517.5) was identified and confirmed based on Sanger sequencing. Herein, we describe a case of an AHDS patient with late-onset drug-resistant epilepsy combined with congenital hypotonia, global developmental delay, and abnormal thyroid function results. To the best of our knowledge, this is the oldest adolescent among AHDS cases reported in Korea. In this report, clinical characteristics of a mid-adolescence patient with AHDS were presented.

• Journal of the Korean Society of Radiology
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• v.81 no.4
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• pp.770-793
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• 2020

Newborn gastrointestinal tract emergency diseases include various disorders that occur anywhere along the digestive tract. Most of them are congenital malformations, not acquired diseases. Many of them cannot be confirmed on prenatal examination, and consequently, postnatal evaluation is required. Unlike adults, in newborn babies, detailed evaluations with computed tomography (CT) and magnetic resonance imaging (MRI) are often limited, so making the diagnosis based on early abdominal radiography is most important. Therefore, it is necessary to be familiar with the radiologic findings that may be seen on imaging studies. In addition, it is important to understand abdominal ultrasound and fluoroscopy findings, which can be used in addition to simple radiography and indications that can be used for further diagnosis and appropriate treatment. Therefore, this study describes and organizes the various imaging findings that may occur in neonatal gastrointestinal emergencies.

• Clinical and Experimental Pediatrics
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• v.45 no.12
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• pp.1503-1511
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• 2002

Purpose : Although the short- and long-term outcomes of low birth weight(LBW) neonatal intensive care unit(NICU) survivors have been extensively studied, much less information is available for normal birth weight(NBW) infants(greater than 2,500 gm) who require NICU care. Methods : We retrospectively examined the neonatal hospitalizations and one year health status of 302 NBW and 131 LBW admissions to our NICU. Information on the neonatal hospitalization was obtained from a review of medical records. Postdischarge health status was collected by using telephone surveys and medical records. Results : After initial discharge, 21.2% of the NBW infants and 23% of the LBW infants required rehospitalization during the first year of life and there was no significant difference between the two groups. The reasons for rehospitalization of the NBW infants included respiratory disorders (32.1%), G-I problems(26.2%), genitourinary problems(11.9%), surgery(10.7%), cardiac problems(7.1%), and congenital/developmental problems(1.2%). For the LBW infants, the order of frequency was the same, with the percentages slightly different. Neonatal risk factors related to the rehospitalization of the NBW infants included mechanical ventilation, duration of mechanical ventilation, and congenital anomaly. But no positive significant correlation of neonatal risk factors with rehospitalization of LBW infants was found. Conclusion : Low and normal birthweight NICU survivors were rehospitalized at similar rates. The most common cause of rehospitalization was respiratory problems. Neonatal risk factors related to rehospitalization of NBW infants were mechanical ventilation, duration of mechanical ventilation, and congenital anomaly. However, no positive significant correlation of neonatal risk factors with rehospitalization of LBW infants was found. The data suggests that NBW infant survivors, as well as LBW infant NICU survivors, require close follow up.

• Childhood Kidney Diseases
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• v.11 no.2
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• pp.280-287
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• 2007

Purpose : Urinary lithiasis is uncommon in children, however, it may lead to chronic renal insufficiency and even end stage renal disease. The etiology of stone formation in children is largely unknown; although the most common causes are known to be associated with congenital anomalies of the genito-urinary(G-U) tract, urinary tract infections(UTI), and metabolic diseases. Methods : A total of 73 children(male:female=42:31, mean age $6.6{\pm}5.3$ years) presented with urinary lithiasis between Sep. 1998 and Jul. 2007 at Seoul National University Children's Hospital. The medical records were reviewed retrospectively. Results : The most common presenting symptoms were gross hematuria(28/73, 38%) and flank or abdominal pain(23/73, 32%). The stones were located in the upper urinary tract in 48 patients(66%), in the bladder in 18(24%), and in both the bladder and upper urinary tract in 2 (3%). Congenital anomalies of the G-U tract with/without UTI were detected in 30 children (41%), hypercalciuria with/without hypercalcemia in 15(20%), and other metabolic diseases in 8(11%). In 17 patients(23%), no underlying cause of stone formation was detected. The majority of stones were infected stones(24/36, 67%), which were followed by calcium stones(8/36, 22%), uric acid stones(3/36, 8%). and cystine stones(1/36, 3%). Thirty-four patients(46%) underwent surgical procedures and/or extracorporeal shockwave lithotripsy for stone removal, and 13(18%) passed stones spontaneously with/without medical management. Stones recurred in 6 patients(8%): 4 with neurogenic bladder augmented by ileocystoplasty, 1 with cystinuria, and 1 with unknown etiology. Conclusion : The common causes of urinary lithiasis in children were congenital anomalies of the G-U tract with/without UTI and metabolic disorders including hypercalciuria/hypercalcemia. For the management of stones, minimally invasive procedures should be chosen on the basis of accompanying symptoms and the composition, locations and etiology of stones.

• Journal of the korean academy of Pediatric Dentistry
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• v.40 no.1
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• pp.66-71
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• 2013

Muscular dystrophy is a genetically heterogeneous group of disorders characterized by progressive muscle weakness of variable distribution and severity. Fukuyama type congenital muscular dystrophy (FCMD) is an unusual form of muscular dystrophy with autosomal recessive inheritance and is clinically characterized by an early age of onset, severe central nervous system involvement, facial muscle weakness, and multiple joint contractures. Muscular dystrophy is susceptible to perioperative respiratory, cardiac and other complications. Patients with FCMD have upper airway muscle weakness, therefore general anesthesia is preferred to sedation regarding maintaining the airway when treating these patients. The development of malignant hyperthermia in general anesthesia for patients with muscular dystrophy is a concern. Total intravenous anesthesia should be used instead of inhaled anesthetics because of the risk of malignant hyperthermia. A 3-year-9-month old, 13kg girl with Fukuyama type congenital muscular dystrophy was scheduled for dental treatment under general anesthesia. She had multiple caries and 14 primary teeth needed caries treatment. Prior to general anesthesia, oral premedication with 9 mg midazolam was given. General anesthesia was induced and maintained with target controlled infusion of propofol $3{\sim}3.5{\mu}g/mL$. The patient with progressive muscular dystrophy was successfully treated under total intravenous anesthesia with a target controlled infusion of propofol. There were no complications related to anesthesia and dental treatment during or after the operation. This case suggests that target controlled infusion of propofol is a safe and appropriate anesthetic technique in FCMD patients for dental treatment.