塩浜 直

OBJECTIVES: To investigate the clinical characteristics and management of plexiform neurofibromas (PNs) in Japanese children with neurofibromatosis 1 (NF1) in the beginning of a new era of treatment with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor selumetinib. STUDY DESIGN: Primary and secondary surveys were conducted targeting 1612 departments of pediatrics and dermatology in hospitals with ≥300 beds and children's hospitals, which followed up pediatric patients with NF1-associated PN between April 1, 2022, and April 30, 2024, in Japan. RESULTS: The response rates in the primary and secondary surveys were 40.4 % and 33.8 %, respectively, and 49 patients were followed up in 23 departments. Their ages at the time ranged from 3.3 to 18.8 years and the onset of PN was most frequently recognized during the first year of life. PN was most often observed superficially in the face (39 %), neck (27 %), and head (24 %), followed by the buttocks (20 %), back (18 %), and thighs (18 %). In addition, PNs could be identified radiologically in the spinal/paraspinal regions (18 %) and pelvis (16 %), where they were rarely visible on the corresponding body surfaces. Major morbidities were cosmetic disfigurement (78 %), pain (53 %), and dysfunction (61 %). Selumetinib use was frequent (69 %) and significantly associated with pain (chi-square test, p = 0.014) and dysfunction (p = 0.014). CONCLUSIONS: This retrospective nationwide study revealed early onset, diverse tumor locations, and varying morbidities in children with NF1-PN, underscoring the need for early evaluation and optimal treatment. A prospective multicenter registry system is warranted to attain better management.

Backgroud: Rett syndrome is a neurodevelopmental disorder that affects 1 in 10,000 females. Various treatments have been explored; however, no effective treatments have been reported to date, except for trofinetide, a synthetic analog of glycine-proline-glutamic acid, which was approved by the FDA in 2023. Serological biomarkers that correlate with the disease status of RTT are needed to promote early diagnosis and to develop novel agents. Methods: In this study, we performed a high-depth proteomic analysis of extracellular vesicles containing preparations extracted from patient plasma samples to identify novel biomarkers. Results: We identified 33 upregulated and 17 downregulated candidate proteins among a total of 4273 proteins in RTT compared to the healthy controls. Among these, UBE3B was predominantly increased in patients with Rett syndrome and exhibited a strong correlation with the clinical severity score, indicating the severity of the disease. Conclusions: We demonstrated that the proteomics of high-depth extracellular vesicles containing preparations in rare diseases could be valuable in identifying new disease biomarkers and understanding their pathophysiology.

Down syndrome (DS) is a genetic disorder characterized by intellectual disability whose etiology includes an additional partial or full copy of chromosome 21. Brain surface morphometry analyses can potentially assist in providing a better understanding of structural brain differences, and may help characterize DS-specific neurodevelopment. We performed a retrospective surface morphometry study of 73 magnetic resonance imaging (MRI) examinations of DS patients (aged 1 day to 22 years) and compared them to a large cohort of 993 brain MRI examinations of neurotypical participants, aged 1 day to 32 years. Surface curvature measurements, absolute surface area measurements, and surface areas as a percentage of total brain surface area (%TBSA) were extracted from each brain region in each examination. Results demonstrate broad reductions in surface area and abnormalities of surface curvature measurements across the brain in DS. After adjusting our regional surface area measurements as %TBSA, abnormally increased presentation in DS relative to neurotypical controls was observed in the left precentral, bilateral entorhinal, left parahippocampal, and bilateral perirhinal cortices, as well as Brodmann's area 44 (left), and the right temporal pole. Findings suggest the presence of developmental abnormalities of regional %TBSA in DS that can be characterized from clinical MRI examinations.