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Background: The switch/sucrose nonfermenting (SWI/SNF) complex is an adenosine triphosphate-dependent chromatin-remodeling complex associated with the regulation of DNA accessibility. Germline mutations in the components of the SWI/SNF complex are related to human developmental disorders, including the Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. These disorders are collectively referred to as SWI/SNF complex-related intellectual disability disorders (SSRIDDs)., Methods: Whole-exome sequencing was performed in 564 Korean patients with neurodevelopmental disorders. Twelve patients with SSRIDDs (2.1%) were identified and their medical records were retrospectively analyzed., Results: ARID1B, found in eight patients, was the most frequently altered gene. Four patients harbored pathogenic variants in SMARCA4, SMARCB1, ARID2, and SMARCA2. Ten patients were diagnosed with CSS, and one patient without a typical phenotype was diagnosed with ARID1B-related nonsyndromic intellectual disability. Another patient harboring the SMARCA2 pathogenic variant was diagnosed with NCBRS. All pathogenic variants in ARID1B were truncating, whereas variants in SMARCA2, SMARCB1, and SMARCA4 were nontruncating (missense). Frequently observed phenotypes were thick eyebrows (10/12), hypertrichosis (8/12), coarse face (8/12), thick lips (8/12), and long eyelashes (8/12). Developmental delay was observed in all patients, and profound speech delay was also characteristic. Agenesis or hypoplasia of the corpus callosum was observed in half of the patients (6/12)., Conclusions: SSRIDDs have a broad disease spectrum, including NCBRS, CSS, and ARID1B-related nonsyndromic intellectual disability. Thus, SSRIDDs should be considered as a small but important cause of human developmental disorders., (© 2021. The Author(s).)

Background: Due to remarkable progress in cancer treatment, endocrine complications are now the major medical issues facing childhood cancer survivors. Although non-central nervous system solid tumors (NCSTs) account for approximately 40% of all pediatric cancers, there have been few studies on endocrine complications associated with NCSTs. This study investigated endocrinopathies following the treatment of pediatric NCSTs., Design and Setting: Retrospective study in a single academic center., Methods: This study analyzed 253 survivors of childhood NCSTs who were diagnosed between January of 2000 and December of 2018. The medical charts were reviewed regarding the frequency of endocrinopathies and treatment modalities. The hazard ratios were assessed by multivariable Cox regression analysis. The final height-SDS were analyzed by multivariable linear regression analysis., Results: There were 76 patients (30%) that developed at least one endocrine complication. Forty-four patients (17.4%) experienced endocrine complications within five years of their cancer diagnosis. The most common endocrine complication was growth failure (n = 35), followed by obesity (n = 18), and primary gonadal failure (n = 16). High cumulative doses of alkylating agents increased the risk of developing at least one endocrine complication. Hematopoietic stem cell transplantation was an important risk factor for primary gonadal failure., Conclusions: This study described the comprehensive endocrine outcomes, including growth failure, obesity, primary gonadal failure, primary hypothyroidism, dyslipidemia, and osteoporosis, following the treatment of childhood NCSTs. As endocrinopathies occurred within five years of primary tumor diagnosis, surveillance for endocrine dysfunction is required for early intervention and management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Shin, Choi, Kim, Koh, Im, Yoo and Choi.)

Background: The prevalence of monogenic diabetes is estimated to be 1.1-6.3% of patients with diabetes mellitus (DM) in Europe. The overlapping clinical features of various forms of diabetes make differential diagnosis challenging. Therefore, this study investigated the etiologic distribution and clinical characteristics of pediatric diabetes, including monogenic diabetes, who presented at a single tertiary center over the last 20 years., Methods: This study included 276 consecutive patients with DM diagnosed before 18 years of age from January 2000 to December 2019 in Korea. Clinical features, biochemical findings, β-cell autoantibodies, and molecular characteristics were reviewed retrospectively., Results: Of the 276 patients, 206 patients (74.6%), 49 patients (17.8%), and 21 patients (7.6%) were diagnosed with type 1 DM, type 2 DM, and clinically suspected monogenic diabetes, respectively. Among 21 patients suspected to have monogenic diabetes, 8 patients had clinical maturity-onset diabetes of the young (MODY), and the remaining 13 patients had other types of monogenic diabetes. Among them, genetic etiologies were identified in 14 patients (5.1%) from 13 families, which included MODY 5, transient neonatal DM, developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, Wolfram syndrome, Donohue syndrome, immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, Fanconi-Bickel syndrome, Wolcott-Rallison syndrome, cystic fibrosis-related diabetes, and maternally inherited diabetes and deafness., Conclusions: Genetically confirmed monogenic diabetes accounted for 5.1% of patients evaluated at a single tertiary center over 20-year period. Based on the findings for our sample, the frequency of mutations in the major genes of MODY appears to be low among pediatric patients in Korea. It is critical to identify the genetic cause of DM to provide appropriate therapeutic options and genetic counseling.

Abstract: Schaaf-Yang syndrome (SYS) is a recently identified disorder caused by a loss-of-function mutation in a maternally imprinted gene, MAGEL2, at 15q11.2q13. Due to its extreme rarity and wide range of clinical severity, clinical suspicion is difficult for a physician. In the current study, its frequency among the Korean pediatric patients with developmental delay (DD) or intellectual disability (ID) was assessed. As the first report of Korean patients with SYS, our study aims to increase the awareness of this condition among the physicians taking care of the pediatric patients with DD/ID and hypotonia.The patients diagnosed with SYS by whole-exome sequencing (WES) among the 460 Korean pediatric patients with DD/ID were included, and their clinical and molecular features were reviewed.Four patients (0.9%) were diagnosed with SYS. Profound DD (4 patients), multiple anomalies including joint contractures and facial dysmorphism (4 patients), generalized hypotonia (3 patients), and severe respiratory difficulty requiring mechanical ventilation (3 patients) were noted in most cases, similar to those in previous reports. Sleep apnea (2 patients), autistic features (2 patients), a high grade of gastroesophageal reflux (1 patient), and seizures (1 patient) were found as well. A total of 3 different truncating MAGEL2 mutations were identified. A previously-reported mutation, to be the most common one, c.1996dupC, was found in 2 patients. The other 2 mutations, c.2217delC and c.3449_3450delTT were novel mutations. As MAGEL2 is maternally imprinted, 2 patients had inherited the MAGEL2 mutation from their respective healthy fathers.SYS is an extremely rare cause of DD/ID. However, hypotonia, joint contractures, profound DD/ID and facial dysmorphism are the suggestive clinical features for SYS. As a maternally imprinted disorder, it should be reminded that SYS may be inherited in form of a mutation from a healthy father., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Inadequate sleep is associated with increased risk of cardiovascular events; however, the associations between sleep duration or quality and cardiac function or structure are not well understood. This cross-sectional study was conducted to investigate to what extent sleep duration and quality are associated with left ventricular (LV) diastolic dysfunction or structural deterioration., Methods: A total of 31,598 healthy Korean adults who received echocardiography and completed the Pittsburg Sleep Quality Index were enrolled in this study. Participants were stratified into three groups by self-reported sleep duration (i.e., <7, 7-9, >9 hours) and into two groups by subjective sleep quality. Sleep duration was also assessed as a continuous variable. The odds ratios for impaired LV diastolic function, increased relative wall thickness, and LV hypertrophy (LVH) were compared between groups using multivariable logistic regression analyses., Results: After adjustment for confounding variables (e.g., age, smoking, body mass index), there was a statistically significant association between short sleep duration (<7 hours) and greater LVH (fully adjusted odds ratio = 1.32 [95% confidence interval {CI} = 1.02-1.73]). Short sleep duration was also significantly associated with greater LVH (0.87 per hour [95% CI = 0.78-0.98]) and increased relative wall thickness (0.92 [95% CI = 0.86-0.99]), but there was no significant association between sleep and LV diastolic function. Among individuals with normal sleep duration, poor quality of sleep was not associated with adverse cardiac measures., Conclusions: These results indicate that short sleep duration (<7 hours) is associated with unfavorable LV structural characteristics. The association of insufficient sleep with adverse cardiovascular health outcomes may be mediated in part by adverse changes in cardiac structure and function.