神経線維腫症

Neurofibromatosis type 1 (NF1) is the most prevalent neurocutaneous syndrome, affecting approximately 1 in 3000 individuals. This genetic disorder involves multiple organ systems and exhibits marked variability in clinical presentation, with characteristic cutaneous, ophthalmological, neurological, cardiovascular, skeletal, and neurodevelopmental features. It may also be associated with multiple neoplasms. Timely and accurate diagnosis is essential to ensure optimal patient care. A lifelong, multidisciplinary management approach is recommended. The objective of this consensus is to summarize the clinical manifestations and provide evidence-based recommendations for the diagnosis and management of NF1.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that rarely demonstrate heterologous differentiation from angiosarcomatous components. These lesions can be hard to accurately diagnose. OBSERVATIONS: A 25-year-old man with neurofibromatosis type 1 and a history of a left lumbar subcutaneous MPNST developed a lung metastasis of only the angiosarcoma component of the MPNST. Prior to H3K27me3 staining of the lung mass, there was no association of the angiosarcoma with the MPNST. Reinterpretation of the lumbar subcutaneous MPNST led to the identification of a previously unrecognized angiosarcomatous portion in that tumor as well. LESSONS: This case highlights the importance of using H327me3 staining for accurate diagnosis of biopsies only capturing the heterologous components of MPNST. https://thejns.org/doi/10.3171/CASE251012.

RASopathies comprise a group of congenital malformation syndromes with predominant neuro-cardio-facial-cutaneous involvement resulting from pathogenic variants in RAS/mitogen-activated protein kinase (MAPK) signaling pathway genes. In this study 33 patients are presented with their clinical and molecular findings as an RASopathy cohort including a family with an AMMECR1-related disorder. The diagnostic distribution of the cohort included Noonan syndrome (n = 18), neurofibromatosis type 1 (n = 8), and single cases of cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis-Noonan syndrome, NF1 microdeletion syndrome, Noonan syndrome-like disorder with loose anagen hair, Noonan syndrome with multiple lentigines and AMMECR1-related midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis (MIM# 300990). The most prevalent clinical manifestations were dermatological findings (90.9%), skeletal features (84.4%), cardiovascular involvement (75.8%), and typical craniofacial dysmorphism suggestive of RASopathy (72.7%). Variants were most frequently identified in PTPN11 and NF1, followed by single cases involving the BRAF, HRAS, LZTR1, RAF1, RIT1, SHOC2, and SOS1. Notably, one patient harbored a variant in AMMECR1, which is not involved in the RAS/MAPK pathway. Overall, this study delineates the clinical and molecular landscape of a cohort from Türkiye and underscores that the AMMECR1-related phenotype represents a distinct entity that closely mimics Noonan syndrome.

This mixed methods study examined mental health concerns and alienation among U.S. adults with neurofibromatosis type 1 (NF1) and parents of children with NF1. Qualitative interviews with six adult patients and six parents revealed 14 mental health triggers related to NF1 symptoms and care. Alienation was identified as a focal response to triggers during thematic analysis, and participants shared desired resources to cope with alienation and navigate care. A follow-up survey with 313 participants confirmed these triggers were commonly experienced. Survey respondents facing more triggers experienced greater alienation (Pearson's r = 0.513 for patients, r = 0.396 for parents, p < 0.0001) and lower flourishing (Pearson's r = -0.378 for patients, r = -0.371 for parents, p < 0.0001). Multiple linear regression accounting for sociodemographics confirmed these relationships as significant (p < 0.01). Targeting triggers of alienation requires greater development of educational, emotional, and social support resources; provider awareness and engagement in offering these supports; and promoting positive online content about living with NF1.

BACKGROUND: Plexiform neurofibromas (PN) represent a significant cause of morbidity among patients diagnosed with neurofibromatosis type 1 (NF1). MEK inhibitors continue to be developed as targeted therapies by inhibiting the mitogen-activated protein kinase pathway to treat PN; nonetheless to this day, therapeutic responses have varied across different patient populations and clinical contexts, and the overall efficacy and tolerability of these agents remain incompletely characterized. OBJECTIVE: We aimed to systematically evaluate the efficacy and safety of MEK inhibitor therapy in patients with NF1-associated PN and to evaluate differences among key subgroups based on the most contemporary metadata. METHODS: A comprehensive search was performed across electronic databases to identify studies that reported outcomes related to MEK inhibitor therapy in NF1-associated PN. Pooled proportions were calculated using a random-effects meta-analysis with logit transformation. Outcomes assessed included objective response rate, disease control rate, disease progression rate, and grade ≥ 3 adverse events. RESULTS: A total of 23 studies comprising 769 patients were included. The pooled objective response rate was estimated at 56% (95% confidence interval [CI] 46-65; I2 = 79.2%), with significantly higher response rates observed in clinical trials (61%) compared with real-world cohorts (44%) [p = 0.035], while no statistically significant difference was observed between pediatric (58%) versus adult populations (51%) [p = 0.407]. The pooled disease control rate was 96% (95% CI 91-98; I2 = 17%) and the pooled disease progression rate was estimated at 2% (95% CI 1-5; I2 = 0%), both reflecting on-treatment outcomes. Grade ≥ 3 adverse events occurred in 13% of patients (95% CI 6-25; I2 = 51.9%). Subgroup analyses revealed comparable disease control across study settings, with moderate variability in response and toxicity estimates. CONCLUSIONS: The use of MEK inhibitors is associated with high rates of disease control and minimal tumor progression in patients with NF1-related PN, with consistent effects observed across clinical trial and real-world environments. Although tumor reduction occurs in some patients, the predominant therapeutic benefit appears to be sustained disease stabilization, with response variability noted among different age groups and study designs.