Neurodevelopmental Outcomes Prediction in Newborns with Seizures Caused by KCNQ2 Gene Defects.

INTRODUCTION: Pathogenic variant in the KCNQ2 gene is a common genetic etiology of neonatal convulsion. However, it remains a question in KCNQ2-related disorders that who will develop into atypical developmental outcomes. METHODS: We established a prediction model for the neurodevelopmental outcomes of newborns with seizures caused by KCNQ2 gene defects based on the Gradient Boosting Machine (GBM) model with a training set obtained from the Human Gene Mutation Database (HGMD, public training dataset). The features used in the prediction model were, respectively, based on clinical features only and optimized features. The validation set was obtained from the China Neonatal Genomes Project (CNGP, internal validation dataset). RESULTS: With the HGMD training set, the prediction results showed that the area under the receiver-operating characteristic curve (AUC) for predicting atypical developmental outcomes was 0.723 when using clinical features only and was improved to 0.986 when using optimized features, respectively. In feature importance ranking, both variants pathogenicity and protein functional/structural features played an important role in the prediction model. For the CNGP validation set, the AUC was 0.596 when using clinical features only and was improved to 0.736 when using optimized features. CONCLUSION: In our study, functional/structural features and variant pathogenicity have higher feature importance compared with clinical information. This prediction model for the neurodevelopmental outcomes of newborns with seizures caused by KCNQ2 gene defects is a promising alternative that could prove to be valuable in clinical practice.

Genetic Spectrum of Congenital Anomalies of the Kidney and Urinary Tract in Chinese Newborn Genome Project.

Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) corresponds to a spectrum of defects. Several large-cohort studies have used high-throughput sequencing to investigate the genetic risk of CAKUT during antenatal, childhood, and adulthood period. However, our knowledge of newborns with CAKUT is limited. Methods: This multicenter retrospective cohort study explored the genetic spectrum of CAKUT in a Chinese neonatal cohort. Clinical data and whole exome sequencing (WES) data of 330 newborns clinically diagnosed with CAKUT were collected. WES data were analyzed for putative deleterious single nucleotide variants (SNVs) and potential disease-associated copy number variants (CNVs). Results: In this study, pathogenic variants were identified in 61 newborns (18.5%, 61/330), including 35 patients (57.4%) with SNVs, 25 patients (41%) with CNVs, and 1 patient with both an SNV and a CNV. Genetic diagnosis rates were significantly higher in patients with extrarenal manifestations (P＜0.001), especially in those with cardiovascular malformations (P＜0.05). SNVs in genes related to syndromic disorders (CAKUT with extrarenal manifestations) were common, affecting 20 patients (57.1%, 20/35). KMT2D was the most common gene (5 patients) and 17q12 deletion was the most common CNV (4 patients). Patient 110 was detected with both a CNV (17q12 deletion) and an SNV (a homozygous variant of SLC25A13). Among the newborns with positive genetic results, 22 (36.1%, 22/61) patients may benefit from a molecular diagnosis and change in clinical management (including early multidisciplinary treatment, disease-specific follow-up, and familial genetic counseling). Conclusion: This study shows the heterogeneous genetic etiologies in a Chinese CAKUT neonatal cohort by using WES. Patients with CAKUT who have extrarenal manifestations are more likely to harbor genetic diagnoses. Kabuki syndrome and 17q12 deletion syndrome were the most common genetic findings. Approximately 36.1% of the patients may benefit from molecular diagnoses and a change in clinical management.

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Leukodystrophy (LD) is a group of genetic heterogeneous diseases characterized by primary abnormalities in glial cells and myelin sheath, and it is a common nervous system disease in children and has significant genotype-phenotype correlation. In recent years, the improvement in high-throughput sequencing has changed the diagnostic and therapeutic mode of LD, and elaborative phenotype analysis, such as the collection of natural history and multimodal neuroimaging evaluation during development, also provides important information for subsequent genetic diagnosis. This article reviews LD from the perspective of clinical genetics, in order to improve the awareness of this disease among pediatricians in China.

Altruistic sharing behavior in children: Role of theory of mind and inhibitory control.

This study aimed to assess altruistic sharing behavior in children aged 3 to 5, 6 to 8, and 9 to 11 years and to explore the involvement of potential cognitive mechanisms, namely theory of mind (ToM) and inhibitory control. A total of 158 children completed a dictator game with stickers as incentives. ToM was evaluated using a false belief task in preschoolers and the Strange Story Test in school-age children. Inhibitory control was assessed in preschoolers with the Day-Night task and in older children with the Stroop Color-Word Test. The result was that 48.10% of children aged 3 to 5 years decided to share, and the percentage rose significantly with increasing age. The difference in altruism level in children who decided to share among the three age groups was nonsignificant. These results suggest that mechanisms underlying the decision to share or not and altruistic behavior may be different. No significant linear relations were found between cognitive processes (i.e., ToM and inhibitory control) and sharing behavior. Surprisingly, 9- to 11-year-olds who shared 3 of 10 stickers performed worse in inhibitory control than did those who shared any other number of stickers. In conclusion, the proportion of children who decided to share, but not the level of altruism, increased with age. ToM was not involved in altruistic sharing, whereas inhibitory control may play a role when deciding how much to share.