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Background: The corrected QT interval (QTc) is affected by changes in autonomic sympathovagal modulation. The aim of this study was to determine whether children with orthostatic dysregulation (OD) have a longer QTc while standing than children without OD. Methods: We retrospectively assessed patients who underwent the Schellong test and electrocardiography between November 2016 and November 2019. Patients who met the criteria of OD subtypes according to the Japanese clinical guidelines for juvenile OD (version 1) were classified as OD positive (the OD‐positive group), and patients who did not meet the criteria were classified as OD negative (the OD‐negative group). Results: There were 73 patients in the OD‐positive group and 52 patients in the OD‐negative group. Baseline heart rate, QT interval, and QTc were comparable between the OD‐positive and OD‐negative groups. Heart rate after standing was significantly higher in the OD‐positive group than in the OD‐negative group (median: 33 bpm vs. 21 bpm, p < 0.001). Further, shortening of QT interval after standing was greater in the OD‐positive group than in the OD‐negative group (median: 19 ms vs. 8 ms, p = 0.015). The QTc significantly increased from baseline to standing in both groups. Changes in the QT interval corrected by Bazett's formula were greater in the OD‐positive group than in the OD‐negative group (median: 73 ms vs. 42 ms, p < 0.001). Conclusions: The QTc increased significantly from baseline to standing in the OD‐positive group. Thus, a high QTc while standing could be considered an auxiliary marker for OD diagnosis. [ABSTRACT FROM AUTHOR]

Early diagnosis of systemic juvenile idiopathic arthritis (s‐JIA) is a prerequisite for therapeutic efficacy. However, it is often challenging because most patients with s‐JIA do not show arthritis at disease onset and are simply diagnosed with fever of unknown origin. Serum ferritin levels have commonly been used to diagnose s‐JIA because they increase in patients with this condition by more than 5 times their normal value. However, there are no definite biomarkers for s‐JIA, which makes the clinical diagnosis of s‐JIA difficult. We report a case of s‐JIA in which interleukin (IL)‐18 elevation was observed before ferritin elevation at the early phase of s‐JIA. We propose serum IL‐18 levels as a more useful biomarker for the early diagnosis of s‐JIA compared to serum ferritin levels. [ABSTRACT FROM AUTHOR]

Abstract Background Myostatin is a negative regulator of skeletal muscle growth. Truncating mutations in the myostatin gene have been reported to result in gross muscle hypertrophy. Duchenne muscular dystrophy (DMD), the most common lethal muscle wasting disease, is a result of an absence of muscle dystrophin. Although this disorder causes a rather uniform pattern of muscle wasting, afflicted patients display phenotypic variability. We hypothesized that genetic variation in myostatin is a modifier of the DMD phenotype. Methods We analyzed 102 Japanese DMD patients for mutations in the myostatin gene. Results Two polymorphisms that are commonly observed in Western countries, p.55A>T and p.153K>R, were not observed in these Japanese patients. An uncommon polymorphism of p.164E>K was uncovered in four cases; each patient was found to be heterozygous for this polymorphism, which had the highest frequency of the polymorphism observed in the Japanese patients. Remarkably, two patients were found to be heterozygous for one of two novel missense mutations (p.95D>H and p.156L>I). One DMD patient carrying a novel missense mutation of p.95D>H was not phenotypically different from the non-carriers. The other DMD patient was found to carry both a novel mutation (p.156L>I) and a known polymorphism (p.164E>K) in one allele, although his phenotype was not significantly modified. Any nucleotide change creating a target site for micro RNAs was not disclosed in the 3' untranslated region. Conclusion Our results indicate that heterozygous missense mutations including two novel mutations did not produce an apparent increase in muscle strength in Japanese DMD cases, even in a patient carrying two missense mutations.

The dystrophin gene, which is mutated in Duchenne and Becker muscular dystrophy, is characterized by its extremely large introns. Seven cryptic exons from the intronic sequences of the dystrophin gene have been shown to be inserted into the processed mRNA. In this study, we have cloned seven novel cryptic exons embedded in dystrophin introns that were amplified from dystrophin mRNA isolated from lymphocytes. All of these sequences, which ranged in size from 27 to 151 bp, were found to be cryptic exons because they were completely homologous to intronic sequences (introns 1, 18, 29, 63, 67, and 77), and possessed consensus sequences for branch points, splice acceptor sites, and splice donor sites. Compared with the 77 authentic dystrophin exons, the 14 cryptic exons were characterized by (1) lower Shapiro’s splicing probability scores for the splice donor and acceptor sites; (2) smaller and larger densities of splicing enhancer and silencer motifs, respectively; (3) a longer distance between the putative branch site and the splice acceptor site; and (4) with one exception, the introduction of premature stop codons into their respective transcripts. These characteristics indicated that the cryptic exons were weaker than the authentic exons. Our results suggested that a mutation deep within an intron that changed these parameters could cause dystrophinopathy. The cryptic exons identified provide areas that should be examined for the detection of mutations in the dystrophin gene, and they may help us to understand the roles of large dystrophin introns. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of topiramate (TPM) for the treatment of children with epilepsies, we introduced TPM to 45 patients whose epilepsy began in childhood and whose ages ranged from 4 months to 30 years old (mean age: 11 years 7 months). Thirteen of these patients had been diagnosed with generalized epilepsy (GE) (1 cryptogenic, 12 symptomatic), 30 with localization-related epilepsy (LRE) (7 idiopathic, 23 symptomatic), and 2 with unclassified epilepsy [1 case of severe myoclonic epilepsy in infancy (SMEI), 1 case of epilepsy with continuous spikes and waves during slow sleep (CSWS)]. The initial dose of TPM was 1.97 +/- 0.45 mg/kg/day, followed by a slow titration to the maximum dose of 7.32 +/- 1.32 mg/kg/day. After a mean treatment period of 13.5 months (range 4-20 months), the rate of reduction in seizure frequency by more than 50% [50% responder rate (50% RR)] and the rate of complete remission (seizure-free) were 53.8% and 23.1%, respectively, in patients with GE, and 73.3% and 23.3%, respectively, in patients with LRE. TPM was significantly effective against many seizure types including tonic, clonic, complex partial, myoclonic, and atypical absence seizures. Adverse effects included sleepiness in 13 cases (28.9%), weight loss in 6 cases (13.3%), and metabolic acidosis in 2 cases (4.4%); all of these effects were both mild and transient. In conclusion, TPM is effective and safe for the treatment of pediatric epilepsies.