Identification of a de novo variant in the ASXL2 gene related to Shashi-Pena syndrome.

BACKGROUND: ASXL2 encodes proteins involved in epigenetic regulation and the assembly of transcription factors at specific genomic loci. Germline de novo truncating variants in ASXL2 have been implicated in Shashi-Pena syndrome, which results in features of developmental delay (DD), glabellar nevus flammeus, hypotonia, and cardiac disorders. However, the variants are rare, and the clinical spectrum may be incomplete. METHODS: The clinical data such as brain MRI were collect. The whole exome sequencing was performed for genetic etiology analysis. RESULTS: Here, we report a patient with DD, hypotonia, early atrial septal defect, and abnormal white matter signal. She presented with Shashi-Pena syndrome with a truncated variant in ASXL2 (NM_018263.6, c.2142_2152del, p.Ser714Argfs*5). She died of a digestive tract infection when she was 1 year and 6 months old. CONCLUSIONS: Our study further expanded the spectrum of phenotypes and genetic variations of the syndrome, and we believe that it is necessary to screen the ASXL2 gene in patients with DD and cardiac and bone disorders.

Multi-dimensional influence of pediatric epilepsy on children and their families: A cross-sectional study.

OBJECTIVE: In this study, we aimed to evaluate the effects of pediatric epilepsy on family burden, parental anxiety, depression states, and quality of life of both parents and children. METHODS: The study was undertaken between March and December 2021 using an online questionnaire that included the Family Burden Scale of Disease, the 7-item Generalized Anxiety Disorder scale, the 9-item Patient Health Questionnaire, the WHO Quality of Life Scale (WHOQOL-BREF), and the PedsQL 4.0 Generic Core Scales (parent-proxy report). RESULTS: A total of 288 parents of children aged 2-18 years were included. Overall, 94.8% of the participating families experienced high levels of disease burden, 67.0% of parents suffered from anxiety states, 57.0% suffered from depression states, and 56.2% of children with epilepsy suffered from comorbid neuropsychiatric symptoms. The mean WHOQOL-BREF score for parental quality of life was 53.7 ± 12.8, while the median PedsQL score for children's quality of life was 65.4 (49.6-81.7). Parental depression states contributed the most to family burden and parental quality of life, whereas comorbidities of epilepsy contributed the most to children's quality of life. Seizure frequency significantly influenced parental anxiety states, and family burden was the most significant predictor of parental depression states. CONCLUSION: Heavy disease burden, anxiety states, and depression states are prevalent in families with children suffering from epilepsy, and most have a poor quality of life. There is a need for greater focus on the quality of life of this patient population and their caregivers, as well as increased resources to help combat anxiety, depression, and poor quality of life.

Inpatient medical cost of status epilepticus in children: A national-wide, multicenter study from China.

OBJECTIVES: To describe the inpatient medical cost during hospitalization in children with status epilepticus (SE) and identify factors associated with the cost by a nationwide, multicenter study in China. MATERIALS & METHODS: We retrospectively identified pediatric inpatients with SE form Hospital Information System (HIS) of 44 hospitals in 27 provinces in China between 2013 and 2015. Inpatient medical cost and factors associated with the cost were analyzed. RESULTS: A total of 4041 children diagnosed with SE with inpatient medical cost were enrolled in the present study. The median age at admission was 2.9 (range 0.1-18) years, and 2271 patients were male (56.2%). The median inpatient medical cost of children with SE was $1175.5 (665.1-2320.6). The median inpatient medical cost was $3865.6 (1837.4-8210.4) in children with SRSE and $1048.6 (619.8-1865.4) in those with N-SRSE (p < 0.0001). Children with length of hospital stay (LOS) > 7 showed a much higher inpatient medical cost than those with LOS ≤ 7 day ($2300.7 vs. $767.2, p < 0.0001). Regarding different etiologies, children with acute symptomatic etiology showed the highest median inpatient medical cost of $1681.1 (901.0-3699.6), in which children with central nervous system (CNS) infection reported $2606.0 (1380.0-5016.1) and prolonged febrile seizures (PFS) reported $909.8 (649.3-1322.0). Additionally, children with idiopathic/cryptogenic etiology reported a medical cost of $923.2 (548.9-1534.5). Multiple linear regression analysis of cost-driving factors revealed LOS > 7, examinations, treatment equipment and procedures, and treatment medicines were independently associated with a higher inpatient medical cost (R2 = 60.91). In addition, PFS and idiopathic/cryptogenic epilepsy etiology were independently associated with a lower cost. CONCLUSIONS: SE in children was a cost intensive disease in China with a median inpatient medical cost of $1175.5. LOS, etiology and examinations, treatment equipment and procedures, and treatment medicines were significantly associated with inpatient medical cost.

Assessment of tuberous sclerosis-associated neuropsychiatric disorders using the MINI-KID tool: a pediatric case-control study.

BACKGROUND: The tuberous sclerosis-associated neuropsychiatric disorders (TAND) have not previously been studied in China. We aimed to assess the psychiatric level of individuals with TAND using the Mini International Neuropsychiatric Interview for Children (MINI-KID) in China. RESULTS: A total of 83.16% of individuals (79/95) had at least one TAND, and 70.53% (67/95) had an intellectual disability. The MINI-KID tool diagnosed 16 neuropsychiatric diseases, the most common of which were attention-deficit/hyperactivity disorder (ADHD) (51.58%, 49/95) and social anxiety disorder (30.53%, 29/95). The number of children with psychiatric diseases in the tuberous sclerosis complex (TSC) group was significantly greater than the number in the typically developing group (P < 0.0001). Notably, 69.47% (66/95) had two or more psychiatric disorders. Pervasive developmental disorder (PDD) was often co-morbid with other psychiatric disorders. CONCLUSIONS: This study used the structured and systematic MINI-KID scale to determine the diagnosis of psychiatric co-morbidities in a relatively large sample, suggesting a higher rate. By comparing the status of individuals with TSC with typically developing children, the results suggests that neuropsychiatric co-morbidities are significantly higher in individuals with TSC. Research has revealed the frequent presence of two, three or more neuropsychiatric diseases in individuals with TSC.

Clinical characteristics and prognosis in a large paediatric cohort with status epilepticus.

PURPOSE: To describe the aetiology, clinical features, and short-term outcomes of children with status epilepticus (SE), in particular super-refractory SE (SRSE), by a nationwide multicentre study in China. METHODS: In this retrospective study, inpatient children with SE were identified from neurology departments and paediatric intensive care units from 44 hospitals in 27 provinces of China between 2013 and 2015. Clinical data were exported from the Hospital Information System. RESULTS: Clinical records from children with SE (n = 4255) aged 1 month to 18 years were enrolled; 13.1 % were diagnosed with SRSE. The most common known SE aetiology was acute symptomatic aetiology (42.8 %) and 50.2 % of SE was caused by epilepsy of unknown aetiology. Acute central nervous system (CNS) infections (38.8 %) were associated with SRSE (P < 0.001). The overall SE in-hospital mortality rate was 3.0 %, which was significantly higher in the children with SRSE than in those with non-SRSE (15.2 % versus 1.4 %, respectively; P < 0.001). Fourteen percent of the children with SE had various levels of neurological dysfunction at discharge. SRSE was a risk factor for in-hospital mortality (hazard ratio = 4.14; 95 % confidence interval [CI]: 2.34-7.32; P < 0.001) and neurological dysfunction at discharge (odds ratio = 2.85; 95 % CI: 1.90-4.27; P < 0.001). CONCLUSION: Acute symptomatic aetiology was the most common known cause of paediatric SE. Aetiology was associated with progression to SRSE and short-term neurological dysfunction at discharge. Furthermore, SRSE was considered a risk factor for in-hospital mortality and short-term neurological dysfunction.

Assessment of the neuropsychiatric comorbidities in Chinese children with epilepsy using the MINI-KID tool.

This study aimed to assess neuropsychiatric comorbidities and analyze risk factors in Chinese children with epilepsy. Children with epilepsy aged between 6 and 16 years from the Children's Hospital of Fudan University were included. Children with asthma and typically developing children were matched for age and gender, and served as control groups. Neuropsychiatric disorders were assessed by interviewing the parents or guardians using the Mini International Neuropsychiatric Interview for children (MINI-KID) (parent version). Basic information and clinical data were also collected using an author designed questionnaire. Multiple logistic regression analysis was done to identify the risk factors associated with neuropsychiatric comorbidities. In this study, 140 children with epilepsy, 70 children with asthma and 70 typically developing children were recruited. Neuropsychiatric disorders were significantly more common in children with epilepsy (41.4%) as compared with the asthma group (15.7%) and the control group (10.0%). Of the 58 children with epilepsy who had neuropsychiatric comorbidities, only 29.3% had been diagnosed before our study. Multivariate analysis revealed that a younger age at seizure onset (OR=0.877, 95%CI: 0.773∼0.996), seizures occurring more than once monthly during the past year (OR=3.526, 95%CI: 1.177∼10.562), polytherapy (OR=2.632, 95%Cl: 1.066∼6.501) were all significantly associated with neuropsychiatric comorbidities in children with epilepsy. In conclusion, children with epilepsy are more likely to have neuropsychiatric comorbidities, and up to 70% of them were undiagnosed. Early screening, diagnosis and treatment of neuropsychiatric comorbidities in children with epilepsy may improve the long-term prognosis.

Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation.

Cyanine-based 1-amino-1-deoxyglucose as fluorescent probes for glucose transporter mediated bioimaging.

Two novel cyanine-based 1-amino-1-deoxy-ß-glucose conjugates (Glu-1N-Cy3 and Glu-1N-Cy5) were designed, synthesized and their fluorescence characteristics were studied. Both Glu-1N-Cy3 and Glu-1N-Cy5 accumulate in living HT29 human colon cancer cells, which overexpress glucose transporters (GLUTs). The cellular uptake of the bioprobes was inhibited by natural GLUT substrate d-glucose and 2-deoxy-d-glucose. The GLUT specificity of the probes was validated with quercetin, which is both a permeant substrate via GLUTs and a high-affinity inhibitor of GLUT-mediated glucose transport. Competitive fluorometric assay for GLUT substrate cell uptake revealed that Glu-1N-Cy3 and Glu-1N-Cy5 are 5 and 10 times more sensitive than 2-NBDG, a leading fluorescent glucose bioprobe. This study provides fundamental data supporting the potential of these two conjugates as new powerful tools for GLUT-mediated theranostics, in vitro and in vivo molecular bioimaging and drug R&D.