Neurofibromatosis type 1 (NF1) is a proteiform genetic condition caused by pathogenic variants in NF1 and characterized by a heterogeneous phenotypic presentation. Relevant genotype–phenotype correlations have recently emerged, but only few pertinent studies are available. We retrospectively reviewed clinical, instrumental, and genetic data from a cohort of 583 individuals meeting at least 1 diagnostic National Institutes of Health (NIH) criterion for NF1. Of these, 365 subjects fulfilled ≥2 NIH criteria, including 235 pediatric patients. Genetic testing was performed through cDNA-based sequencing, Next Generation Sequencing (NGS), and Multiplex Ligation-dependent Probe Amplification (MLPA). Uni- and multivariate statistical analysis was used to investigate genotype–phenotype correlations. Among patients fulfilling ≥ 2 NIH criteria, causative single nucleotide variants (SNVs) and copy number variations (CNVs) were detected in 267/365 (73.2%) and 20/365 (5.5%) cases. Missense variants negatively correlated with neurofibromas (p = 0.005). Skeletal abnormalities were associated with whole gene deletions (p = 0.05) and frameshift variants (p = 0.006). The c.3721C>T; p.(R1241*) variant positively correlated with structural brain alterations (p = 0.031), whereas Lisch nodules (p = 0.05) and endocrinological disorders (p = 0.043) were associated with the c.6855C>A; p.(Y2285*) variant. We identified novel NF1 genotype–phenotype correlations and provided an overview of known associations, supporting their potential relevance in the implementation of patient management.

Assessment of endothelial dysfunction in cancer survivors may have a role in the early identification of non-communicable diseases and cardiovascular late effects. Oncological therapies may impair endothelial function. Therefore, in patients such as childhood cancer survivors who could benefit from early cardioprotective pharmacological interventions, it is essential to monitor endothelial function, even if the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, as well as invasive and non-invasive tools with and without pharmacological stimuli have been studied. Human clinical studies that have examined lifestyle or cancer treatment protocols have yielded evidence showing the involvement of lipid and lipoprotein levels, glycemic control, blood pressure, adiposity, inflammation, and oxidative stress markers on the state of endothelial health and its role as an early indicator of cardiometabolic risk. However, with regards to pharmacological interventions, cautious interpretation of the result attained whilst monitoring the endothelial function is warranted due to methodological limitations and substantial heterogeneity of the results reported in the published studies. In this narrative review, an overview of evidence from human clinical trials examining the effects of cancer therapies on endothelial disease is provided together with a discussion of endothelial function assessment using the different non-invasive techniques available for researchers and clinicians, in recent years.

Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal region. In contrast to the suprasellar region, where biopsy is the standard procedure in case of a suspected germ-cell tumor to avoid mutilation to the endocrine structures, pineal tumors are more accessible to primary resection. We evaluated the perioperative course of patients with pineal germinoma who were diagnosed by primary biopsy or resection in the SIOP CNS GCT 96 trial. Methods: Overall, 235 patients had germinoma, with pineal localization in 113. The relationship between initial symptoms, tumor size, and postoperative complications was analyzed. Results: Of 111 evaluable patients, initial symptoms were headache (n = 98), hydrocephalus (n = 93), double vision (n = 62), Parinaud syndrome (n = 57), and papilledema (n = 44). There was no significant relationship between tumor size and primary symptoms. A total of 57 patients underwent primary resection and 54 underwent biopsy. Postoperative complications were reported in 43.2% of patients after resection and in 11.4% after biopsy (p < 0.008). Biopsy was significantly more commonly performed on larger tumors (p= 0.002). Conclusions: These results support the practice of biopsy over resection for histological confirmation of pineal germinoma.

BRAF inhibitors, in recent years, have played a central role in the disease control of unresectable BRAF-mutated pediatric low-grade gliomas (LGGs). The aim of the study was to investigate the acute and long-term effects of vemurafenib on the lipid metabolism in children treated for an LGG. In our cohort, children treated with vemurafenib (n = 6) exhibited alterations in lipid metabolism a few weeks after starting, as was demonstrated after 1 month (n = 4) by the high plasma levels of the total cholesterol (TC = 221.5 ± 42.1 mg/dL), triglycerides (TG = 107.8 ± 44.4 mg/dL), and low-density lipoprotein (LDL = 139.5 ± 51.5 mg/dL). Despite dietary recommendations, the dyslipidemia persisted over time. The mean lipid levels of the TC (222.3 ± 34.7 mg/dL), TG (134.8 ± 83.6 mg/dL), and LDL (139.8 ± 46.9 mg/dL) were confirmed abnormal at the last follow-up (45 ± 27 months, n = 6). Vemurafenib could be associated with an increased risk of dyslipidemia. An accurate screening strategy in new clinical trials, and a multidisciplinary team, are required for the optimal management of unexpected adverse events, including dyslipidemia.

Background: Gorlin syndrome (GS) is a rare autosomal dominant disorder, associated with pathogenic PTCH1 or SUFU variants, predisposing to tumors such as basal cell carcinoma, medulloblastoma (MB), odontogenic keratocyst, and, rarely, cardiac fibroma (CF). MB occurs in ~5% of GS cases, typically in early childhood, while CF appears in 1–3%. Their coexistence in childhood is extremely rare. This report describes a pediatric GS case with synchronous MB and CF, focusing on the management priorities between oncologic and cardiac interventions. Methods: A 15-year follow-up is reported for a girl diagnosed at 22 months with desmoplastic/nodular MB and left ventricular CF. GS diagnosis was based on clinical features, imaging, and confirmation of a pathogenic PTCH1 variant (c.3306+1G>T). A literature narrative review on CF in GS was also conducted. Results: MB gross total resection was followed by chemotherapy, during which ventricular tachycardia episodes occurred, managed with cardioversion and antiarrhythmics. Given the favorable prognosis of early-treated MB in GS, oncologic therapy was prioritized. Cardiac status was monitored with ECG, Holter, echocardiography, and cardiac MRI. An adapted AIEOP protocol minimized cardiotoxicity. CF was managed conservatively, with no further arrhythmias and preserved ventricular function throughout 15 years. MB has not recurred. Conclusions: In GS patients with concurrent MB and CF, prioritizing MB treatment and adopting a conservative, closely monitored approach to CF can yield excellent long-term outcomes. In children with MB, especially syndromic forms, routine echocardiography is recommended to detect CF. This case underscores the value of multidisciplinary care in managing complex GS presentations.