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Vascular anomalies are congenital localized abnormalities that result from improper development and maintenance of the vasculature. The lesions of vascular anomalies vary in location, type, and clinical severity of the phenotype, and the current treatment options are often unsatisfactory. Most vascular anomalies are sporadic, but patterns of inheritance have been noted in some cases, making genetic analysis relevant. Developments in the field of genomics, including next-generation sequencing, have provided novel insights into the genetic and molecular pathophysiological mechanisms underlying vascular anomalies. These insights may pave the way for new approaches to molecular diagnosis and potential disease-specific therapies. This article provides an introduction to genetic testing for vascular anomalies and presents a brief summary of the etiology and genetics of vascular anomalies. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder characterized by multiple symptoms including neuropsychological deficits such as seizures, intellectual disability, and autism. TSC is inherited in an autosomal dominant pattern and is caused by mutations in either the TSC1 or TSC2 genes, which enhance activation of the mammalian target of rapamycin (mTOR) signaling pathway. Recent studies have suggested that mTOR inhibitors such as rapamycin can reverse TSC-associated deficits in rodent models of TSC. In addition, clinical trials are ongoing to test the efficacy of mTOR inhibitors toward the psychiatric symptoms associated with TSC. Here, we report a case study of a Korean patient with TSC, who exhibited multiple symptoms including frequent seizures, intellectual disability, language delays, and social problems. We performed whole exome sequencing and identified a novel small deletion mutation in TSC2. Expressing the novel deletion mutant in HEK293T cells significantly increased mTOR pathway activation. Furthermore, everolimus treatment showed not only reduction in SEGA size, but dramatically improved behavioral deficits including autism related behaviors in the patient. In summary, we identified a novel small deletion mutation in TSC2 associated with severe TSC in a Korean family that enhances the activation of mTOR signaling in vitro. Everolimus treatment improved behavioral deficits in the patient. [ABSTRACT FROM AUTHOR]

Most craniosynostoses are sporadic, but may have an underlying genetic basis. Secondary and syndromic craniosynostosis accompanies various systemic diseases or associated anomalies. Early detection of an associated disease may facilitate the interdisciplinary management of patients and improve outcomes. For that reason, systematic evaluation of craniosynostosis is mandatory. The authors reviewed systematic evaluation of craniosynostosis with an emphasis on genetic analysis. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the clinical features of children who have survived a water submersion incident, and to identify risk factors for prognosis. Methods: We retrospectively reviewed the medical records of patients who experienced submersion between January 2005 and December 2014. The patients were classified into 2 groups, according to complications, and prognostic factors were evaluated. Results: During the study period, 29 children experienced submersion (20 boys and 9 girls; mean age, 83.8±46.4 months). Submersion occurred most commonly in the summer, with the peak incidence in August. The most frequent Szpilman clinical score was grade 5 (13 patients; 44.8%), followed by grade 6 (7 patients; 24.1%), and grades 1 or 2 (3 patients; 10.3%). Five children (17.2%) in the poor prognosis group died or had hypoxic ischemic encephalopathy, and the overall mortality rate was 6.9%. Poor prognosis after submersion was associated with lower consciousness levels (P=0.003), higher Szpilman scores (P=0.007), greater need for intubation and mechanical ventilator support (P=0.001), and longer duration of oxygen therapy (P=0.015). Poor prognosis was also associated with lower bicarbonate levels (P=0.038), as well as higher sodium, aspartate transaminase (AST), and alanine transaminase (ALT) levels (P=0.034, P=0.006, and P=0.005, respectively). Szpilman clinical scores were positively correlated with consciousness levels (r=0.489, P=0.002) and serum liver enzyme levels (AST and ALT; r=0.521, P=0.004). Conclusion: We characterized the prognostic factors associated with submersion outcomes, using the Szpilman clinical score, which is comparable to consciousness level for predicting mortality. [ABSTRACT FROM AUTHOR]

Early-onset epileptic encephalopathies are one of the most severe early onset epilepsies that can lead to progressive psychomotor impairment. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects, and an increasing number of novel genetic causes continue to be uncovered. A typical diagnostic approach includes documentation of anamnesis, determination of seizure semiology, electroencephalography, and neuroimaging. If primary biochemical investigations exclude precipitating conditions, a trial with the administration of a vitaminic compound (pyridoxine, pyridoxal-5-phosphate, or folinic acid) can then be initiated regardless of presumptive seizure causes. Patients with unclear etiologies should be considered for a further workup, which should include an evaluation for inherited metabolic defects and genetic analyses. Targeted next-generation sequencing panels showed a high diagnostic yield in patients with epileptic encephalopathy. Mutations associated with the emergence of epileptic encephalopathies can be identified in a targeted fashion by sequencing the most likely candidate genes. Next-generation sequencing technologies offer hope to a large number of patients with cryptogenic encephalopathies and will eventually lead to new therapeutic strategies and more favorable long-term outcomes. [ABSTRACT FROM AUTHOR]

KCNQ2 mutations induce a neonatal-onset epileptic encephalopathy of widely varying severity, ranging from benign familial neonatal epilepsy to severe refractory epileptic encephalopathy. Refractory seizures with KCNQ2 mutations have a positive response to sodium-channel blockers. Recently, a distinctive ictal pattern has been reported during amplitude-integrated electroencephalographic (aEEG) monitoring in infants with KCNQ2 encephalopathy. Herein, we describe a case of KCNQ2 encephalopathy with this distinctive ictal aEEG pattern, which was confirmed using conventional electroencephalography (EEG). A 3-day-old female infant presented with neonatal seizures accompanied by cyanosis and desaturation. Her seizure semiology was tonic and focal clonic. Her ictal aEEG demonstrated a sudden rise in amplitude followed by a suppressed background pattern. This pattern was also confirmed on conventional EEG. Her seizures were refractory despite the administration of multiple conventional antiepileptic drugs. Finally, c.794C>T; p. (Ala265Val) mutation was observed in the KCNQ2 gene on genetic testing, and she was diagnosed with KCNQ2 encephalopathy. Identifying this distinctive ictal pattern on aEEG monitoring facilitates the early detection of KCNQ2 encephalopathy and timely targeted treatment in patients with refractory seizures. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is one of the most significant postoperative complications of pediatric cardiac surgery. Because serum creatinine has limitations as a diagnostic marker of AKI, new biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are being evaluated to overcome these limitations and detect AKI at an early stage after cardiac surgery. Purpose: This study aimed to investigate the clinical usefulness of these biomarkers in young children. Methods: Thirty patients with congenital heart diseases who underwent cardiac surgery using cardiopulmonary bypass (CPB) were selected, and their urine and blood samples were collected at baseline and 6, 24, and 48 hours after surgery. Serum creatinine and blood urea nitrogen levels as well as NGAL, KIM-1, and IL-18 levels in urine samples were measured, and clinical parameters were evaluated. Results: Of the 30 patients, 12 developed AKI within 48 hours after cardiac surgery. In the AKI group, 8 of 12 (66.6%) met AKI criteria after 24 hours, and urine KIM-1/creatinine (Cr) level (with adjustment of urine creatinine) peaked at 24 hours with significant difference from baseline level. Additionally, urine KIM-1/Cr level in the AKI group was significantly higher than in the non-AKI group at 6 hours. However, urine NGAL/Cr and IL-18/Cr levels showed no specific trend with time for 48 hours after cardiac surgery. Conclusion: It is suggested that urine KIM-1/Cr concentration could be considered a good biomarker for early AKI prediction after open cardiac surgery using CPB in young children with congenital heart diseases. [ABSTRACT FROM AUTHOR]

Purpose: There is limited data on the use of perampanel in children under 12 years of age. We evaluated the efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy. Methods: This retrospective observational study was performed in Kyungpook National University Hospital from July 2016 to March 2018. A responder was defined as a patient with =50% reduction in monthly seizure frequency compared with the baseline. Adverse events and discontinuation data were obtained to evaluate tolerability. Results: Twenty-two patients (8 males, 14 females) aged 3.1-11.4 years (mean, 8.0±2.5 years) were included in this study. After an average of 9.2 months (range, 0.5-19 months) of follow-up, 15 patients (68%) showed a reduction in seizure frequency, including 5 patients (23%) with seizure freedom. The age at epilepsy onset was significantly lower (P=0.048), and the duration of epilepsy was significantly longer (P=0.019) in responders than in nonresponders. Nine patients (41%) experienced adverse events, including somnolence (23%), respiratory depression (9%), violence (4.5%), and seizure aggravation (4.5%). The most serious adverse event was respiratory depression, which required mechanical ventilation in 2 patients (9%). Eight patients (36%) discontinued perampanel due to lack of efficacy or adverse events. Three out of 4 patients (75%) who discontinued perampanel due to adverse events had an underlying medical condition. Conclusion: Perampanel offers a treatment option for refractory epilepsy in children. Adjunctive treatment with perampanel requires special consideration in those with underlying medical conditions to prevent serious adverse events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Major advances in genetics allow us to uncover genetic causes of epilepsy and influence therapeutic decisions. As precision medicine becomes a focus for biohealth industry, laws related to next generation sequencing are improving and its application will continue to expand. Although genetic testing can be considered for anyone who is suspected to have a genetic cause, the most suitable indication is drug-resistant epilepsy. Epileptic patients who have genetic testing can be classified into three groups: (1) patients with defined phenotypes suggesting monogenic epilepsy syndrome; (2) patients with neuropsychiatric comorbidities or dysmorphic features; and (3) patients with undefined phenotypes with multiple candidate genes. Applicable genetic testing methods for epilepsy are as follows: Sanger sequencing, chromosome microarray, targeted gene panels, whole exome sequencing, and whole genome sequencing. Sanger sequencing is indicated for patients with defined phenotypes by a single gene mutation. Chromosome microarray is recommended as part of the initial evaluation of unexplained epilepsy, particularly among patients with associated neuropsychiatric comorbidities or dysmorphic features. Next generation sequencing can be informative in patients with undefined phenotypes with multiple candidate genes. Targeted gene panels are a cost-effective alternative to both Sanger sequencing and whole exome sequencing for the genetic diagnosis of epilepsy. There are, however, social, ethical and even financial hurdles to overcome in the transition of next generation sequencing technology into the clinic. This review focuses on recent transformation of epilepsy genetics and suggests a strategy for actual clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: A limited number of studies have examined the link between F-wave abnormalities and clinical presentation in pediatric Guillain-Barré syndrome (GBS). Therefore, this study examined the importance of F-wave abnormalities as a prognostic factor in pediatric GBS patients. Methods: The records and electrodiagnostic studies (EDS) of 70 GBS patients were retrospectively evaluated, and divided into 2 groups according to the results of EDS. Group A (n=33) presented with F-wave abnormalities, and group B (n=26) exhibited normal findings. We compared laboratory reports, clinical features, response to treatment, and prognosis between the 2 groups. Results: Motor weakness was the most frequently observed symptom for either group. Clinically, the incidence of fever and upper respiratory symptoms differed between the 2 groups, while the prevalence of abnormal deep tendon reflex (DTR) was significantly higher in group A than B (P<0.05). Patients diagnosed with GBS had received intravenous immunoglobulin treatment: 94% in group A and 58% in group B. Furthermore, significantly greater numbers of patients in group A showed H-reflex abnormalities and poor prognosis compared with group B (P<0.05). Conclusion: This study demonstrated that F-waves are a clinically important prognostic factor in GBS. F-wave abnormalities were associated with abnormal DTR and poor prognosis in patients. Limited studies have examined the link between F-wave abnormalities and clinical results; therefore, further randomized controlled studies are needed to confirm the clinical characteristics and efficacy of treatments. [ABSTRACT FROM AUTHOR]