• Journal of Korean Neurosurgical Society
• /
• v.64 no.2
• /
• pp.151-188
• /
• 2021

Spinal dysraphic lesions due to focal nondisjunction in primary neurulation are commonly encountered in paediatric neurosurgery, but the "fog-of-war" on these conditions was only gradually dispersed in the past 10 years by the works of the groups led by the senior author and Prof. Kyu-Chang Wang. It is now clear that limited dorsal myeloschisis and congenital spinal dermal sinus tract are conditions at the two ends of a spectrum; and mixed lesions of them with various configurations exist. This review article summarizes the current understanding of these conditions' embryogenetic mechanisms, pathological anatomy and clinical manifestations, and their management strategy and surgical techniques.

• Neonatal Medicine
• /
• v.18 no.1
• /
• pp.14-22
• /
• 2011

Neonatal bleeding is a common problem encountered in nursery rooms or neonatal intensive care units, especially among premature infants. Furthermore, owing to recent remarkable improvement of neonatology, survival rates of preterm neonates have increased; hence, neonatal bleeding cannot be emphasized enough. Since the total blood volume of neonates is small, bleeding can be one of the causes of morbidities and mortalities. Therefore, rapid diagnosis and immediate therapy is urgently needed. The patient's medical history including a familial history of a bleeding disorder or of a previously affected infant who suffered from bleeding along with maternal and neonatal drugs can provide important diagnostic clues. Presence of bleeding with or without petechiae and ecchymoses in a healthy term or late preterm infant with thrombocytopenia but normal prothrombin time and activated partial thromboplastin time strongly suggests a congenital bleeding disorder. For a sick infant who is bleeding from multiple sites, an acquired disorder such as disseminated intravascular coagulation is suspected. Intracranial hemorrhage in term or late preterm infants without a history of birth trauma is highly suggestive of coagulation disorders. The purpose of this review is to summarize recent advances in diagnostic methods is as well as basic concepts of neonatal hemostatic disorders. First, an outline of background information will be presented followed by a discussion of primary and secondary hemostatic disorders as well as inherited and acquired disorders.

• Proceedings of the Korean Society for Bioinformatics Conference
• /
• 2006.02a
• /
• pp.125-126
• /
• 2006

NimbleGen has developed strategies to use its high-density oligonucleotide microarray platform (385,000 probes per array) to map both promoter binding sites and copy number variation at very high-resolution in the human genome. Here we describe a genome-wide map of active promoters determined by experimentally locating the sites of transcription imitation complex binding throughout the human genome using microarrays combined with chromatin immunoprecipitation. This map defines 10,567 active promoters corresponding to 6,763 known genes and at least 1,196 un-annotated transcriptional units. Microarray-based comparative genomic hybridisation (CGH) is animportant research tool for investigating chromosomal aberrations frequently associated with complex diseases such as cancer, neuropsychiatric disorders, and congenital developmental disorders. NimbleGen array CGH is an ultra-high resolution (0.5-50 Kb) oligo array platform that can be used to detect amplifications and deletions and map the associated breakpoints on the whole-genome level or with custom fine-tiling arrays. For whole-genome array CGH, probes are tiled through genic and intergenic regions with a median probe spacing of 6 Kb, which provides a comprehensive, unbiased analysis of the genome.

• Annals of Clinical Neurophysiology
• /
• v.22 no.2
• /
• pp.51-60
• /
• 2020

Muscle pathology findings may guide the diagnosis of neuromuscular disorders since they are helpful for understanding the pathological processes causing muscle weakness and also provide significant clues for the diagnosis of muscle diseases. Recent advances in molecular genetics mean that a muscle biopsy can be omitted when diagnosing inherited muscle diseases. However, the muscle pathology can still play a role in those cases and its findings are also required when diagnosing inflammatory myopathies.

• Journal of Interdisciplinary Genomics
• /
• v.3 no.2
• /
• pp.41-46
• /
• 2021

Inherited platelet function disorders (IPFDs) are a disease group of heterogeneous bleeding disorders associated with congenital defects of platelet functions. Normal platelets essential role for primary hemostasis by adhesion, activation, secretion of granules, aggregation, and procoagulant activity of platelets. The accurate diagnosis of IPFDs is challenging due to unavailability of important testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. Among several IPFDs, Glanzmann thrombasthenia (GT) is a most representative IPFD and is relatively frequently found compare to the other types of rarer IPFDs. GT is an autosomal recessive disorder caused by mutations of ITGA2B or ITGB3. There are quantitative or qualitative defects of the GPIIb/IIIa complex in platelet, which is the binding receptor for fibrinogen, von Willbrand factor, and fibronectin in GT patients. Therefore, patients with GT have normal platelet count and normal platelet morphology, but they have severely decreased platelet aggregation. Thus, GT patients have a very severe hemorrhagic phenotypes that begins at a very early age and persists throughout life. In this article, the general contents about platelet functions and respective IPFDs, the overall contents of GT, and the current status of genetic diagnosis of GT in Korea will be reviewed.

• Journal of Preventive Medicine and Public Health
• /
• v.50 no.6
• /
• pp.347-360
• /
• 2017

Objectives: This meta-analysis aimed to evaluate congenital malformations in infants conceived by assisted reproductive techniques (ART), compared with infants conceived spontaneously. Methods: In this study, available resources searched to find relevant articles included PubMed, ScienceDirect, Scopus, Google Scholar, Cochrane, ProQuest, Iranmedex, Magiran, and Scientific Information Database. After extracting the necessary information from evaluated articles, meta-analysis on the articles' data was performed using Stata version 11.2. Results: In this study, from a total of 339 articles, extracted from the initial investigation, ultimately 30 articles were selected for meta-analysis that assessed the use of ART on the risk of congenital abnormalities and some birth complications on 5 470 181 infants (315 402 cases and 5 154 779 controls). The odds ratio (95% confidence interval [CI]) for low birth weight was 1.89 (95% CI, 1.36 to 2.62), preterm labor 1.79 (95% CI, 1.21 to 2.63), cardiac abnormalities 1.43 (95% CI, 1.27 to 1.62), central nervous system abnormalities 1.36 (95% CI, 1.10 to 1.70), urogenital system abnormalities 1.58 (95% CI, 1.28 to 1.94), musculoskeletal disorders 1.35 (95% CI, 1.12 to 1.64), and chromosomal abnormalities in infants conceived by ART was 1.14 (95% CI, 0.90 to 1.44), which were all statistically significant, except chromosomal abnormalities. Conclusions: The risk of congenital abnormalities and some birth complications were significantly higher in ART than normal conception, while chromosomal abnormalities were not; therefore, the application of ART should be selected individually for patients by detailed assessment to reduce such risks in the population.

• Clinical and Experimental Pediatrics
• /
• v.49 no.7
• /
• pp.796-799
• /
• 2006

Multicystic dysplastic kidney and congenital cystic adenomatoid malformation of the lung are independent disorders, but both result from abnormal morphogenesis during embryogenesis. Congenital cystic adenomatoid malformation of the lung is associated with renal anomalies as well as other extrapulmonary anomalies and almost all cases with these anomalies are stillborn. We report a case of a 21-month-old male who was admitted with the impression of acute infectious gastroenteritis; multicystic dysplastic kidney with congenital cystic adenomatoid malformation of the lung was detected incidentally during evaluation.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.25 no.6
• /
• pp.441-452
• /
• 2022

Congenital diarrheal disorders (CDDs) with genetic etiology are uncommon hereditary intestinal diseases characterized by chronic, life-threatening, intractable watery diarrhea that starts in infancy. CDDs can be mechanistically divided into osmotic and secretory diarrhea. Congenital tufting enteropathy (CTE), also known as intestinal epithelial dysplasia, is a type of secretory CDD. CTE is a rare autosomal recessive enteropathy that presents with intractable neonatal-onset diarrhea, intestinal failure, severe malnutrition, and parenteral nutrition dependence. Villous atrophy of the intestinal epithelium, crypt hyperplasia, and irregularity of surface enterocytes are the specific pathological findings of CTE. The small intestine and occasionally the colonic mucosa include focal epithelial tufts. In 2008, Sivagnanam et al. discovered that mutations in the epithelial cell adhesion molecule (EpCAM, MIM# 185535) were the genetic cause of CTE (MIM# 613217). More than a hundred mutations have been reported to date. Furthermore, mutations in the serine peptidase inhibitor Kunitz type 2 (SPINT2, MIM# 605124) have been linked to syndromic CTE. In this study, we report the case of a 17-month-old male infant with congenital diarrhea. Despite extensive etiological workup, no etiology could be established before admission to our center. The patient died 15 hours after being admitted to our center in a metabolically decompensated state, probably due to a delay in admission and diagnosis. Molecular autopsy with exome sequencing revealed a previously reported homozygous missense variant, c.757G>A, in EpCAM, which was confirmed by histopathological examination.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.20 no.2
• /
• pp.114-123
• /
• 2017

Purpose: The goal of this study was the early diagnosis of ABCB11 spectrum liver disorders, especially those focused on benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis. Methods: Fifty patients presenting neonatal cholestasis were evaluated to identify underlying etiologies. Genetic analysis was performed on patients suspected to have syndromic diseases or ABCB11 spectrum liver disorders. Two families with proven ABCB11 spectrum liver disorders were subjected to genetic analyses to confirm the diagnosis and were provided genetic counseling. Whole exome sequencing and Sanger sequencing were performed on the patients and the family members. Results: Idiopathic or viral hepatitis was diagnosed in 34%, metabolic disease in 20%, total parenteral nutrition induced cholestasis in 16%, extrahepatic biliary atresia in 14%, genetic disease in 10%, neonatal lupus in 2%, congenital syphilis in 2%, and choledochal cyst in 2% of the patients. The patient with progressive familial intrahepatic cholestasis had novel heterozygous mutations of ABCB11 c.11C>G (p.Ser4*) and c.1543A>G (p.Asn515Asp). The patient with benign recurrent intrahepatic cholestasis had homozygous mutations of ABCB11 c.1331T>C (p.Val444Ala) and heterozygous, c.3084A>G (p.Ala1028Ala). Genetic confirmation of ABCB11 spectrum liver disorder led to early liver transplantation in the progressive familial intrahepatic cholestasis patient. In addition, the atypically severe benign recurrent intrahepatic cholestasis patient was able to avoid unnecessary liver transplantation after genetic analysis. Conclusion: ABCB11 spectrum liver disorders can be clinically indistinguishable as they share similar characteristics related to acute episodes. A comprehensive genetic analysis will facilitate optimal diagnosis and treatment.

• Korean Journal of Cleft Lip And Palate
• /
• v.7 no.1
• /
• pp.35-46
• /
• 2004

The frequency of abnormality at birth is average 1-1.5%, and of these, cleft lip & palate is known to be the most frequent congenital abnormality, Cleft is considered to be due to multi-factorial heredity correlated with genetic and environmental factors, Cleft patients require the collaborative treatment with several medical departments, Clinics for Maxillo-Oral Disorders of Tohoku University Dental Hospital performs the total managements related to such as occlusion and language for the patients with congenital maxilla-facial abnormality, This study examined the patients with cleft lip and/or palate who came to the Clinics for Maxilla-Oral Disorders of Tohoku University Dental Hospital for the past 17 years from Jan. 1987 to Dec, 2002, and had the results as follows, 1. Annual mean number of patients The annual mean number of the patients for 17 years from Jan, 1987 to Dec, 2002 was 91 patients, ranging from 63 minimum to 116 maximum, 2, Gender and types of cleft There were 747(51%) males and 709(49%) females, with a male to female ratio 1,05:1. CLP was the most frequent cleft type as shown in 616 patients, and other patients manifested different complaints such as CL, CP, SMCP and MC in order. 3. The laterality in cleft type The lip cleft was frequently expressed orderly on left, right and both sides of CL patients while orderly being shown on left, both and right sides of CLP patients. Accordingly, lip cleft was most commonly found on the left side. 4. Address at first visit Of 1,456 subjects, 850(58.4%) patients were residing in Miyagi Prefecture, where this hospital is located. 5. Age at first visit 615(42.2%) patients came to the hospital at their age younger than 1 year old, comprising 282(19.4%) patients age younger than 2 months old and 333(22.9%) patients age between 2 month old and 1 year old. 6. Mother's age at birth For the mother's age at birth, 526(39.9%) patients were at the age of 25 to 30 years old, and 17(1.3%) patients were over 40 years old. 7. Birth weight 34.3%(443 patients) had a birth weight of 2500-3000gm and 56.0%(724 patients) had a 3000-4000gm. It was also found that 7.9%(102 patients) had a birth weight of less than 2500gm. 8. Familial expression The frequency of familial expression was 6.5%(94 patients).