Progressive encephalomyelitis with rigidity and myoclonus: a pediatric case report and literature review.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study. CASE PRESENTATION: We report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab. CONCLUSIONS: We summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.

DNA index as prognostic factor in childhood acute lymphoblastic leukemia in the COG-TARGET database.

BACKGROUND: This study was aimed to evaluate the value of DNA index(DI) among pediatric acute lymphoblastic leukemia (ALL) treated on Children's Oncology Group (COG) protocols between 2000 and 2015. METHODS: Retrospective study were analysis among pediatric ALL patients from the TARGET dataset. RESULT: Totally, 1668 eligible pediatric patients were enrolled in this study. Of them, 993 are male and 675 are female with a median age of 7.6 years old. The median follow-up for those patients was 7.7 years (range 0.1-15.7 years). The probability of 15-year EFS and OS were reported to be 67.5 ± 3.1% and 78.3 ± 2.5%, respectively. BCR/ABL1 fusion gene affected the early treatment response and the survival of childhood ALL. Moreover, those patients with ETV6/RUNX1 fusion gene were also significantly associated with better EFS (HR = 0.6, 95% CI 0.4-0.8, P = 0.003) and OS (HR = 0.3, 95%CI 0.2-0.5, P < 0.001) compared to patients with no ETV6/RUNX1. On the contrary, BM NR on Day+ 29 showed a significant decrease in EFS (HR = 3.1, 95%CI 2.1-4.5, P < 0.001) and OS (HR = 1.7, 95%CI 1.1-2.8, P = 0.026). Multivariate analysis showed that DI was significantly associated with better EFS and OS. The threshold effect of DI on poor outcome was significant after adjusting for potential confounders. The adjusted regression coefficient (Log RR) was 0.7 (95%CI 0.1-3.2, P = 0.597) for DI < 1.1 while 8.8 (95%CI 1.4-56.0, P = 0.021) for DI ≥ 1.2 and 0.0 (95%CI 0.0-0.8, P = 0.041) for 1.1 ≤ DI < 1.2. Generalized additive models revealed that the lowest rates of the adverse outcomes estimated to occur among DI between 1.1 and 1.2. CONCLUSION: For those childhood ALL treated on COG protocols between 2000 and 2015, ETV6/RUNX1 and BM NR were closely related to the prognosis. Moreover, the DI between 1.1 and 1.2 can serve as a significant cut-point discriminating the risk group, which indicated a favourable prognostic factor.

[Clinical phenotypes and copy number variations in children with microdeletion and microduplication syndromes: an analysis of 50 cases].

OBJECTIVE: To investigate the association between genotype and phenotype of microdeletion and microduplication syndromes (MMSs) and the pathogenesis of pathogenic copy number variations (CNVs). METHODS: A total of 50 children with MMSs diagnosed by chromosomal microarray analysis (CMA) from June 2013 to September 2015 were enrolled, and the clinical manifestations and features of pathogenic CNVs were analyzed. RESULTS: The main clinical manifestations of children with MMSs included mental retardation, developmental delay, short stature, and unusual facies, with the presence of abnormalities in multiple systems. There were 54 pathogenic CNVs in total, consisting of 36 microdeletion segments and 18 microduplication segments, with sizes ranging from 28 kb to 48.5 Mb (mean 13.86 Mb). Pathogenic CNVs often occurred in chromosomes X, 15, and 1. CONCLUSIONS: The clinical manifestations of MMSs are not specific, and a genotype-first approach can be used for diagnosis. Mode of inheritance, type of recombination (deletion or duplication), size of segment, and functional genes included helps with the interpretation of CNVs of de novo mutations, and in-depth research on rare pathogenesis may become breakthrough points for the identification of new MMSs.

Identification of novel CSNK2A1 variants and the genotype-phenotype relationship in patients with Okur-Chung neurodevelopmental syndrome: a case report and systematic literature review.

De novo germline variants of the casein kinase 2α subunit (CK2α) gene (CSNK2A1) have been reported in individuals with the congenital neuropsychiatric disorder Okur-Chung neurodevelopmental syndrome (OCNS). Here, we report on two unrelated children with OCNS and review the literature to explore the genotype-phenotype relationship in OCNS. Both children showed facial dysmorphism, growth retardation, and neuropsychiatric disorders. Using whole-exome sequencing, we identified two novel de novo CSNK2A1 variants: c.479A>G p.(H160R) and c.238C>T p.(R80C). A search of the literature identified 12 studies that provided information on 35 CSNK2A1 variants in various protein-coding regions of CK2α. By quantitatively analyzing data related to these CSNK2A1 variants and their corresponding phenotypes, we showed for the first time that mutations in protein-coding CK2α regions appear to influence the phenotypic spectrum of OCNS. Mutations altering the ATP/GTP-binding loop were more likely to cause the widest range of phenotypes. Therefore, any assessment of clinical spectra for this disorder should be extremely thorough. This study not only expands the mutational spectrum of OCNS, but also provides a comprehensive overview to improve our understanding of the genotype-phenotype relationship in OCNS.