Diagnostic performance of automated, streamlined, daily updated exome analysis in patients with neurodevelopmental delay.

BACKGROUND: The diagnostic yield of whole-exome sequencing (WES) varies from 30%-50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10-15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses. METHODS: The study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems. RESULTS: At the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period. CONCLUSION: Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information.

Treatment of superimposed preeclampsia on chronic hypertension in a twin pregnancy with automatic continuous positive airway pressure: a case report.

BACKGROUND: Obstructive sleep apnoea (OSA) is related with adverse pregnancy outcomes, including preeclampsia. However, there are small studies about treatment of OSA with automatic continuous positive airway pressure (CPAP) in adverse obstetric outcomes. CASE PRESENTATION: We introduce a case of 34 year old twin pregnant woman diagnosed with superimposed preeclampsia on chronic hypertension at 28 + 1/7 weeks of gestation. A level III polysomnography showed obstructive sleep apnoea, and automatic CPAP was applied. After the CPAP treatment concomitant with an antihypertensive drugs, both blood pressure and urinary protein concentration were reduced. The pregnancy safely continued for 49 days (to 35 + 1/7 weeks), with stable blood pressure, allowing prolongation of gestation of the foetuses. CONCLUSION: This is the first case to report OSA with preeclampsia in a twin pregnancy. Our results suggest that automatic CPAP as an adjunct treatment to antihypertensive drugs may be beneficial in controlling blood pressure in early-onset preeclampsia associated with OSA.

A sibship with duplication of Xq28 inherited from the mother; genomic characterization and clinical outcomes.

BACKGROUND: Loss-of-function mutations in methyl-CpG-binding protein 2 (MECP2; MIM *300005) results in the Rett syndrome, whereas gain-of-function mutations are associated with the MECP2 duplication syndrome. METHODS: We did research on a family with two brothers showing Xq28 duplication syndrome using various molecular cytogenetic techniques such as multiplex ligation-dependent probe amplification and array-based genomic hybridization. RESULTS: The duplicated region had several genes including MECP2 and interleukin-1 receptor associated kinase 1 (IRAK1; MIM *300283). MECP2 and IRAK1 were associated with the neurological phenotypes in dose-sensitive and dose-critical manner. The brothers demonstrated severe intellectual disability, autistic features, generalized hypotonia, recurrent infections, epilepsy, choreiform movements such as hand-wringing movement, and moderate increased spasticity with the lower limbs. The X-inactivation test showed a complete skewed X inactivation pattern of mother. In this reason, the mother had the same loci duplication but showed significantly little neurological manifestation compared to the two sons. CONCLUSIONS: MECP2/IRAK1 duplication at Xq28 is inherited as an X-linked recessive trait and male-specific disorder associated with severe intellectual disability. We tried to analyze the information of the relationship between neuropsychiatric phenotype and the extent of duplication at Xq28 by comparing with previous reports.

My child cannot breathe while sleeping: a report of three cases and review.

BACKGROUND: Sudden breath-holding episodes during sleep in young children are potentially related to sudden infant death syndrome and other life-threatening events. Additionally, these episodes can negatively affect child's growth and development. CASE PRESENTATION: Here, we present 3 cases of preschool children with similar paroxysmal nocturnal waking events associated with choking that had different etiologies (nocturnal frontal lobe epilepsy, nocturnal gastroesophageal reflux disease, and parasomnia, respectively). CONCLUSIONS: It is important to take into consideration the fact that breath spells during sleep can occur as a rare manifestation of parasomnia due to gastroesophageal reflux or as a symptom of nocturnal frontal lobe epilepsy. Full video electroencephalography, polysomnography, and simultaneous gastric pH monitoring should be used for the differential diagnosis of sleep-related disorders, such as breath spells, in children.

Poor sleep quality has an adverse effect on childhood asthma control and lung function measures.

BACKGROUND: It is unclear as to whether sleep respiratory breathing disorder (SRBD) is a risk factor for uncontrolled asthma in children. The aim of this study was therefore to investigate whether SRBD may have an adverse effect on childhood asthma control and lung function measures. METHODS: This was a cross-sectional study of 220 children with well-controlled (n = 108), partly controlled (n = 92), and uncontrolled asthma (n = 20) according to the Global Initiative for Asthma guideline. SRBD was assessed using the Pediatric Sleep Questionnaire (PSQ). The association of SRBD with partly controlled/uncontrolled asthma was investigated on multivariate logistic regression analysis. RESULTS: Of 220 children with asthma, 43 (19.6%) had SRBD: well-controlled, 16.7% (18/108); partly controlled, 21.7% (20/92); and uncontrolled, 25.0% (5/20; P = 0.54). There was a significant difference in forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC; P = 0.007) and childhood asthma control test (C-ACT) score (P < 0.001) according to asthma control status, but not in PSQ score (P = 0.18). Children with obstructive sleep apnea (PSQ >0.33) had a lower C-ACT score compared with controls (PSQ ≤0.33; 19.6 ± 5.1 vs 22.0 ± 4.2, P = 0.002). PSQ score was negatively correlated with FEV1 /FVC (r = -0.16, P = 0.02). On multivariate logistic regression analysis, high PSQ score increased the odds of having partly controlled/uncontrolled asthma by 9.12 (95% CI: 1.04-79.72, P = 0.046) after adjusting for confounding factors. CONCLUSION: SRBD is an independent risk factor for partly controlled/uncontrolled asthma and has an adverse effect on lung function measures in children. Further research is warranted to determine whether the improvement of sleep quality may also enhance level of asthma control and lung function in children.

Effectiveness of Helmet therapy for infants with moderate to severe positional plagiocephaly.

BACKGROUND: The use of helmet treatment for positional plagiocephaly has increased recently; however, its effect is unknown in Korea. PURPOSE: This study aimed to investigate the effectiveness of helmet therapy and identify its influencing factors. METHODS: Ninety pediatric patients diagnosed with moderate to severe positional plagiocephaly received helmet therapy. Severity of moderate to severe positional plagiocephaly was defined as cranial vault asymmetry (CVA) >10 mm or CVA index (CVAI) >6%. Patients were categorized by age, severity, and daily helmet wear. Multiple regression analysis controlled for factors like sex and prematurity. Treatment success was assessed by comparing pre/post-helmet theray CVA and CVAI, considering normalization or decrease to mild plagiocephaly (CVA ≤10 mm or CVAI ≤6%). RESULTS: A total of 90 participants were enrolled (mean age, 5.6±1.6 months; male, 53 [58.9%]). The mean helmet therapy duration was 6.4±2.7 months, while the mean daily wear time was 18.4±2.7 hours. Among the 90 patients, 66 (73.3%) had moderate disease and 24 (26.7%) had severe disease. The mean CVA and CVAI decreased by 6.3±2.7 mm and 4.3%±1.8% after versus before treatment (P<0.001). Treatment was successful in 76 infants (84.4%). The most effective changes in CVA and CVAI were noted in those who began treatment before 9 months of age (6.2±2.5 mm and 5.0%±1.9%, P<0.001), had high compliance (6.2±2.4 mm and 4.9%±1.9%, P<0.001), and had high severity (8.0±2.3 mm and 6.6%±1.7%, P<0.001). CONCLUSION: Starting helmet treatment before 9 months and wearing it over 15 hours daily yielded better outcomes.

Changes in childhood growth after adenotonsillectomy: a population-based cohort study.

OBJECTIVES: This study aimed to investigate the association between adenotonsillectomy (T&A) and serial changes in growth in children through a population-based nationwide study as well as the national health insurance service (NHIS) database. METHODS: Propensity score (PS) matched children with and without T&A were selected in NHIS database, which includes all individuals born in Korea in 2008-2009. Serial changes of BMI and height were compared in children with and without T&A, and growth changes depending on the time of operation were also considered. The outcomes were differences in age-/sex-standardized BMI (BMI-z) and height (height-z) between the groups. Changes in BMI-z and height-z were further analyzed according to the timing of operation. RESULTS: Of 919,707 individuals born in Korea in 2008-2009, 3172 children were included in the operation group and 31,663 PS-matched children were included in the control group. T&A was related to increased weight and height in the operation group than in the control group. At 66-71 months of age, BMI-z and height-z were 0.41 (0.02) and 0.42 (0.02), respectively, in the operation group and 0.18 (0.01) and 0.35 (0.01), respectively, in the control group. On adjustment with preoperative BMI-z, more weight gain was noted in the operation group (p < 0.001). Shortly after T&A, BMI-z increased significantly in the operation group; a significant increase in height-z was observed more than 1 year after T&A. CONCLUSIONS: Children who underwent T&A tended to experience a growth spurt; when surgical intervention such as T&A is required, care should be taken to minimize or reverse the anticipated weight gain.

Neurodevelopmental outcomes and comorbidities of children with congenital muscular torticollis: evaluation using the National Health Screening Program for Infants and Children database.

BACKGROUND: Congenital muscular torticollis (CMT) is a common musculoskeletal disorder occurring at birth or in infancy. PURPOSE: This study aimed to investigate the risk of comorbidities in CMT and explore the differences in neurodevelopmental outcomes between children who received physical therapy and those who did not. METHODS: Children with CMT born in 2008 and 2009 in Korea were included. CMT was defined as a primary diagnosis of congenital deformity of sternocleidomastoid muscle according to the International Classification of Diseases 10th revision. Here we investigated the associated neurological/musculoskeletal comorbidities of children with CMT versus those of the general population. We divided those with torticollis into treatment and nontreatment groups and assessed their developmental outcomes within both groups of children using the Korean-Ages and Stages Questionnaire (K-ASQ). RESULTS: Of the 917,707 children, 0.2% (n=1,719) were diagnosed with CMT. In children with torticollis, the prevalence of congenital hip deformities significantly increased to 4.5% (n=78). The prevalence of congenital head/spine deformities and other congenital malformations of the skull and facial bones increased to 2.6% (n=44), while the prevalence of congenital foot deformities was 2.4% (n=42). The risk ratio (RR) for delayed development based on the K-ASQ was higher for the total assessment (adjusted RR=0.97; 95% confidence interval, 0.93-0.99) in the CMT patients without physical therapy than in those with therapy. There was no significant intergroup difference in the assessment of each developmental area. CONCLUSION: The prevalence of comorbid musculoskeletal deformities was higher in children with CMT than in the control group. The risk of developmental delay was higher in children who did not receive physical therapy than in those who did.

Cohort profile: National Investigation of Birth Cohort in Korea study 2008 (NICKs-2008).

BACKGROUND: An adequate large-scale pediatric cohort based on nationwide administrative data is lacking in Korea. PURPOSE: This study established the National Investigation of Birth Cohort in Korea study 2008 (NICKs-2008) based on data from a nationwide population-based health screening program and data on healthcare utilization for children. METHODS: The NICKs-2008 study consisted of the Korean National Health Insurance System (NHIS) and the National Health Screening Program for Infants and Children (NHSPIC) databases comprising children born in 2008 (n=469,248) and 2009 (n=448,459) in the Republic of Korea. The NHIS database contains data on age, sex, residential area, income, healthcare utilization (International Classification of Diseases-10 codes, procedure codes, and drug classification codes), and healthcare providers. The NHSPIC consists of 7 screening rounds. These screening sessions comprised physical examination, developmental screening (rounds 2-7), a general health questionnaire, and age-specific anticipatory guidance. RESULTS: During the 10-year follow-up, 2,718 children (0.3%) died, including more boys than girls (hazard ratio, 1.145; P<0.001). A total of 848,048 children participated in at least 1 of the 7 rounds of the NHSPIC, while 96,046 participated in all 7 screening programs. A total of 823 infants (0.1%) weighed less than 1,000 g, 3,177 (0.4%) weighed 1,000-1,499 g, 37,166 (4.4%) weighed 1,500-2,499 g, 773,081 (91.4%) weighed 2,500-4,000 g, and 32,016 (5.1%) weighed over 4,000 g. There were 23,404 premature babies (5.5%) in 2008 compared to 23,368 (5.6%) in 2009. The developmental screening test indicated appropriate development in 95%-98% of children, follow-up requirements for 1%-4% of children, and recommendations for further evaluation for 1% of children. CONCLUSION: The NICKs-2008, which integrates data from the NHIS and NHSPIC databases, can be used to analyze disease onset prior to hospitalization based on information such as lifestyle, eating habits, and risk factors.

Assessment of vitamin D, exercise, and lipid profile associated with excessive daytime sleepiness in school children.

Previous research reported associations of excessive daytime sleepiness (EDS) with a low vitamin D level, obesity, and sexual maturity. The aim of this study was to identify the association and rank the importance of these with EDS. This study examined 618 children who were 10-12 year-old. The pediatric daytime sleepiness scale (PDSS) was used to evaluate EDS and sleep patterns. EDS was defined as a total PDSS score above 17. We ranked the importance of the relationship of these factors with EDS using random forest analysis. EDS (n = 111, 18%) was positively associated with more advanced pubertal stage in girls, chronic cough, urticaria, and allergic rhinitis. Multivariable analysis with adjustment for confounding indicated that children with low level of 25-hydroxyvitaminD3 (25(OH)D3 (<20 ng/mL) and high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) levels had an increased risk of EDS (25(OH)D3:adjusted odds ratio [aOR] = 1.73; 95% confidence interval [CI]: 1.06 to 2.81; P = 0.028; HDL-C: aOR = 2.84; 95% CI: 1.05 to 7.68; P = 0.039). Random forest analysis indicated that 25(OH)D3 level, exercise, and body mass index (BMI) were over three. This study indicated high levels of 25-(OH)D3 and HDL-C and performing regular exercise decreased the risk of EDS.

Characteristics and Treatment of Anaphylaxis in Children Visiting a Pediatric Emergency Department in Korea.

Anaphylaxis is a serious life-threatening allergic disease in children. This study is aimed at determining the characteristics of pediatric patients who experienced anaphylaxis along with treatments administered in order to determine the usefulness of tryptase level assessment as a marker of anaphylaxis in Korean children. A total of 107 patients who were diagnosed with anaphylaxis in a single pediatric emergency center over a 3-year period were included in the study. Patient clinical characteristics, symptoms, signs, allergy history, trigger factors, treatments, and laboratory findings, including serum tryptase levels, were included in the analysis. Food allergies (39.3%) were the most commonly reported patient allergic history, and 58 patients (54.2%) were triggered by food. Among this group, nuts and milk exposure were the most common, affecting 15 patients (25.9%). History of anaphylaxis and asthma were more common in severe anaphylaxis compared to mild or moderate anaphylaxis cases. Epinephrine intramuscular injection was administrated to 76 patients (71.0%), and a self-injectable epinephrine was prescribed to 18 patients (16.8%). The median tryptase level was 4.80 ng/mL (range: 2.70-10.40) which was lower than the 11.4 ng/mL value commonly documented for standard evaluation in adults with anaphylaxis. The most common cause of pediatric anaphylaxis was food including nuts and milk. The rate of epinephrine injection was relatively high in our pediatric emergency department. The median tryptase level associated with anaphylaxis reactions in children was lower than 11.4 ng/mL. Further studies are needed to help improve diagnostic times and treatment accuracy in pediatric patients who develop anaphylaxis.

Effects of school time on sleep duration and sleepiness in adolescents.

Delaying the time of start of school allows for longer sleep duration, better mood, and better school performance. In South Korea, a campaign was launched in 2014 to delay the school start time to 9 a.m. We analyzed the campaign's effects on adolescents' total sleep duration, sleepiness (presented as weekend catch-up sleep), emotions, and school performance. Based on data from 2013, changes of sleep patterns, emotions, and academic achievement in adolescents were evaluated using the 2012-2016 Korea Youth Risk Behavior Web-based survey from two educational districts: Gyeonggi (fully participated in the delayed school start time campaign; intervention group) and Daegu/Gyeongbuk/Ulsan (DGU, never participated; control group). The primary outcomes were sleep duration, time of sleep onset, and difference in sleep duration between weekdays and the weekend. Secondary outcomes were the proportional changes of mood, stress, and school performance. The sleep duration of students in the intervention group temporarily increased in 2015. However, because there was a simultaneous delay in time of sleep onset, sleep duration returned to pre-campaign levels in 2016. Although sleep duration did not increase, weekend catch-up sleep decreased by approximately 19 minutes for students in the intervention group. Meanwhile, in the control group sleep duration tended to decrease over the same period. The impact of the campaign on students' emotions and school performance could not be confirmed. This study demonstrated that delaying the school start time to 9 a.m. reduced duration of weekend catch-up sleep with a transient increase in sleep duration in adolescents.

Sleep-wake cycle on amplitude-integrated EEG and neuroimage outcomes in newborns.

BACKGROUND: The aim of this study was to evaluate the results of sleep-wake cycle monitoring using amplitude-integrated EEG (aEEG) and neuroimaging in newborn infants with a possible perinatal hypoxic insult, investigate the correlation between the findings, and determine the relevance of the findings to reasonably predict neurological outcome. METHODS: aEEG was recorded among newborn infants suspected of perinatal asphyxia between November, 2014 and June, 2015 in one neonatal intensive care unit facility. Brain imaging with serial ultrasonography and MRI when available were performed, and the infants were divided into two groups according to findings and potential neurological outcome: Group I (favorable findings) and Group II (severe findings such as high grade intraventricular hemorrhage, cerebral infarction or white matter injury). Established sleep-wake cycle times after birth was compared between the two groups. RESULTS: Among 107 newborn infants, 85 subjects were classified as Group I and the remaining 22 subjects as Group II. The total number of aEEG sessions was 207 and recording time was 2,796 h with a mean of 14.43 ± 13.40 h per study. Estimated times of cyclicity were earlier in Group I (113.34 h, 95 % CI 82.31-144.37) as compared to Group II (504.39 h, 95 % CI 319.91-688.88; p < 0.001). CONCLUSIONS: Delayed cyclicity on aEEG has a strong correlation with unfavorable brain neuroimages in newborns with possible perinatal asphyxia. If sleep-wake cycles do not appear during initial period after birth, follow-up aEEG studies are recommended. TRIAL REGISTRATION: Retrospectively registered Registration number: BD 2015-148 Name of registry: amplitude integrated EEG in neonate Date of registration: September 9, 2015.

Distinct pH modulation for dual function of Galphah (transglutaminase II).

Galpha(h), also known as transglutaminase II, has GTPase as well as transglutaminase activities. To better understand the factors affecting these dual enzymatic activities, we examined the optimal pH (at 25 degrees C) and thermal stability (at 37 degrees C) of the activities using membranous Galpha(h) from mouse heart. The optimum pH for the GTPase activity of Galpha(h) is approximately 7.0. As well, the GTP binding activity of Galpha(h) is more thermostable at pH 7.0 than that at pH 9.0. Consistent with these observations on the GTPase function of Galpha(h), both the phospholipase C-delta1 activity and the yield of co-immunoprecipitation of Galpha(h)-coupled phospholipase C-delta1 in alpha(1)-adrenoceptor/Galpha(h)/phospholipase C-delta1 complex preparations were enhanced by incubation with an alpha(1)-agonist, phenylephrine, at pH 7.0. On the other hand, the transglutaminase activity of Galpha(h) is higher in the basic pH range with an optimum activity at pH approximately 9.0. Also, the transglutaminase activity of Galpha(h) is more thermostable at pH 9.0 than that at pH 7.0. These results indicate not only pH as a modulator for the dual functions of Galpha(h), but also provide direct evidence for the involvement of pH in the Galpha(h)-mediated alpha(1)-adrenoceptor signaling system in vitro.

Novel nonsense GNAS mutation in a 14-month-old boy with plate-like osteoma cutis and medulloblastoma.

Plate-like osteoma cutis (PLOC) is a dermatological disorder characterized by superficial ossification and rarely occurs without any underlying tissue abnormalities or pre-existing calcification. The hereditary form of PLOC is mainly due to inactivating mutation in the GNAS gene. Inactivating mutation of the GNAS gene is associated with several diseases, which commonly manifest heterotopic ossification and hormonal resistance; however, the development of malignant neoplasm has never been reported. Herein, we report a case of a patient with a novel nonsense mutation in the GNAS gene, who presented with concurrent PLOC and medulloblastoma.

Depression and marital intimacy level in parents of infants with sleep onset association disorder: a preliminary study on the effect of sleep education.

PURPOSE: Sleep onset association disorder (SOAD) is a form of behavioral insomnia observed in children that is caused by inappropriate sleep training. SOAD typically disturbs the sleep of not only infants and children but also their parents. We investigated levels of depression and marital intimacy among parents of infants with typical SOAD, to understand the influence of SOAD on family dynamics, as well as examine ways for improving depression and marital intimacy through behavioral training. METHODS: Depression and marital intimacy were assessed using the Beck Depression Inventory (BDI) and Waring Intimacy Questionnaire (WIQ). These measures were administered to 65 parents of infants (n=50) diagnosed with SOAD. We conducted sleep education and behavioral training for the parents and compared levels of depression and marital intimacy after 2-6 weeks of training. RESULTS: The 65 parents consisted of 50 mothers and 15 fathers. Depressive symptoms were higher among mothers than fathers (P =0.007). Marital intimacy was negatively correlated with depressive symptoms. Twenty-six parents were assessed again after sleep training. We found that mothers' depressive symptoms and marital intimacy improved post training. CONCLUSION: SOAD can be detrimental to both infants and parents, especially for parents who sleep with their infants. For instance, disruption of sleep patterns in such parents can reduce marital intimacy. However, behavioral modification is an effective treatment for infants with frequent nighttime waking, as well as for diminishing the depressive symptoms of sleep-deprived parents.

Neuroprotective effect of human placental extract on hypoxic-ischemic brain injury in neonatal rats.

We investigated the neuroprotective effects of human placental extracts (HPE) and the effects of HPE on recovery of cognitive and behavioral function on hypoxic-ischemic brain injury in the newborn rat. The right common carotid arteries of 7-day-old rats were coagulated, and rats were then exposed to 8% oxygen. Immediately before and again at three times after the hypoxia-ischemia (pre-treatment group), and immediately after and three times again after hypoxia-ischemia (post-treatment group), the rats were intraperitoneally injected with HPE (0.1, 0.25, or 0.5 mL/10 g/dose). No-treatment rats received saline only. On postnatal day 12, brains were removed and gross morphological damage was evaluated. To quantify the severity of brain injury, bilateral cross-sectional areas of the anterior commissural and posterior hippocampal levels were analyzed with NIH Image. Assessments of the open field activity levels at 2, 4, 6 and 8 week and, the Morris water maze test at 8 weeks after hypoxia-ischemia were carried out according to standard methods. HPE pre-treatment decreased the incidence of liquefactive cerebral infarction, at an optimally neuroprotective dose of 0.5 mL/10 g/dose (P<0.05). In the Morris water maze test, the group injected with HPE at 0.5 mL/10 g/dose concentration showed shorter escape latencies than the no-treatment group (P<0.05). These findings support a protective effect of the HPE treatment on neuronal integrity and cognitive function following hypoxic-ischemic brain injury. Injected at an appropriate dose prior to exposure, HPE may significantly reduce or prevent hypoxic-ischemic injury in the immature brain.

The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF -2578, -1154, -634, and 936) and kinase insert domain containing receptor (KDR -604, 1192, and 1719) polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A) or poor (collateral grade B and C) groups. The frequencies and distributions of four VEGF (-2578, -1154, -634, and 936) and KDR (-604, 1192, and 1719) polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF -2578, -1154, -634, and 936 or KDR -604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the -634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040) whereas the KDR -604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024). Patients with the CC genotype of VEGF -634 had better collateral vessel formation after surgery. Our results suggest that the VEGF -634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation.

Sleep patterns and school performance of Korean adolescents assessed using a Korean version of the pediatric daytime sleepiness scale.

PURPOSE: Korean adolescents have severe nighttime sleep deprivation and daytime sleepiness because of their competitive educational environment. However, daytime sleep patterns and sleepiness have never been studied using age-specific methods, such as the pediatric daytime sleepiness scale (PDSS). We surveyed the daytime sleepiness of Korean adolescents using a Korean translation of the PDSS. METHODS: We distributed the 27-item questionnaire, including the PDSS and questions related to sleep pattern, sleep satisfaction, and emotional state, to 3,370 students in grades 5-12. RESULTS: The amount of nighttime sleep decreased significantly with increasing age. During weekday nights, 5-6(th) graders slept for 7.95±1.05 h, 7-9(th) graders for 7.57±1.05 h, and 10-12(th) graders for 5.78±1.13 h. However, the total amounts of combined daytime and nighttime sleep during weekdays were somewhat greater, 8.15±1.12 h for 5-6(th) graders, 8.17±1.20 h for 7-9(th) graders, and 6.87±1.40 h for 10-12(th) graders. PDSS scores increased with age, 11.89±5.56 for 5-6(th) graders, 16.57±5.57 for 7-9(th) graders, and 17.71±5.24 for 10-12(th) graders. Higher PDSS scores were positively correlated with poor school performance and emotional instability. CONCLUSION: Korean teenagers sleep to an unusual extent during the day because of nighttime sleep deprivation. This negatively affects school performance and emotional stability. A Korean translation of the PDSS was effective in evaluating the severity of daytime sleepiness and assessing the emotional state and school performance of Korean teenagers.

Obstructive sleep apnea syndrome in children: Epidemiology, pathophysiology, diagnosis and sequelae.

The prevalence of pediatric obstructive sleep apnea syndrome (OSAS) is approximately 3% in children. Adenotonsillar hypertrophy is the most common cause of OSAS in children, and obesity, hypotonic neuromuscular diseases, and craniofacial anomalies are other major risk factors. Snoring is the most common presenting complaint in children with OSAS, but the clinical presentation varies according to age. Agitated sleep with frequent postural changes, excessive sweating, or abnormal sleep positions such as hyperextension of neck or abnormal prone position may suggest a sleep-disordered breathing. Night terror, sleepwalking, and enuresis are frequently associated, during slow-wave sleep, with sleep-disordered breathing. Excessive daytime sleepiness becomes apparent in older children, whereas hyperactivity or inattention is usually predominant in younger children. Morning headache and poor appetite may also be present. As the cortical arousal threshold is higher in children, arousals are not easily developed and their sleep architectures are usually more conserved than those of adults. Untreated OSAS in children may result in various problems such as cognitive deficits, attention deficit/hyperactivity disorder, poor academic achievement, and emotional instability. Mild pulmonary hypertension is not uncommon. Rarely, cardiovascular complications such as cor pulmonale, heart failure, and systemic hypertension may develop in untreated cases. Failure to thrive and delayed development are serious problems in younger children with OSAS. Diagnosis of pediatric OSAS should be based on snoring, relevant history of sleep disruption, findings of any narrow or collapsible portions of upper airway, and confirmed by polysomnography. Early diagnosis of pediatric OSAS is critical to prevent complications with appropriate interventions.