Central Nervous System (CNS) tumors are the leading solid malignancies in children, 50% of CNS tumors in children are glial tumors, with two-thirds of these gliomas being categorized as low-grade gliomas (LGG). We aimed to review the clinical profile, management, and outcomes of pediatric LGG cases. A retrospective cohort study was conducted at Aga Khan University Hospital between 2013 and 2025 including patients aged ≤ 18 years diagnosed with LGG. A total of 191 patients were identified, with a slight preponderance of male patients (51.3%). Median age was 10 years (IQR 6-14) with the larger age group being 10-18 years (50.3%). Median duration of presenting symptoms was 4 months (IQR 1-18). Headaches (n = 112, 58.6%) and vomiting (n = 93, 48.7%) were the primary presenting complaints. Tumors were predominantly supratentorial (n = 115, 60.2%). The most common histopathology was Pilocytic Astrocytoma (n = 119). Upfront surgery was done in 163 (85.3%) patients; Gross Total Resection (GTR) was achieved in 85 patients (52.1%). Twenty-six (13.7%) patients received Chemotherapy while 9 (4.8%) had radiation therapy. Disease didn't progress in 131 (68.6%) patients while progression and relapse occurred in 36 (18.8%) and 7 (3.7%) patients, respectively. Seventeen (8.9%) patients did not have any follow-op scans. The Overall Survival (OS) was 95.3%, with only 9 deaths recorded. Biopsy was deferred to 28 patients (14.7%), a group primarily comprising Subependymal Giant Cell Astrocytomas (SEGA) (n = 17, 60.7%), Tectal Plate Glioma (n = 3, 10.7%), and Optic Path Glioma (n = 5, 17.8%). Kaplan-Meier analysis estimated a median EFS of 84.2 months (95% CI: 70.9-97.5 months). However, this estimate should be interpreted cautiously given the relatively short median follow-up and substantial right-censoring. Despite heterogeneity in histopathology and location, outcomes were comparable to those reported in the literature, underscoring the effectiveness of current practices while highlighting the need for improved follow-up and comprehensive outcome reporting in resource-limited settings.

Various tumors can involve the orbital space. Although orbital tumors are rare, these sight-threatening and possibly life-threatening disorders consist of a broad disease spectrum. The purpose of the study is to determine the prevalence of orbital tumors presenting in a tertiary eye care centre and evaluate their Demographic pattern and Clinical findings. This cross-sectional descriptive study was conducted in the Department of Oculoplasty, Ispahani Islamia Eye Institute & Hospital from August 2019 to July 2020. 30 patients were selected of all age and sex presented with primary orbital tumors during study period. All patient was examined properly. Their demographic, clinical, radiological and histopathological data was collected. Total 30 patients meet the inclusion criteria. Among them 8 cases were diagnosed by clinical & radiological examinations. Twenty two (22) cases were diagnosed by histopathology. Among 30 diagnosed patients 16 patients were male and 14 patients were female. Age range of 30 patients were 1 months to 60 years. 1-10 years category 13 patients, 11-20 years 4 patients, 21-30 years 1 patients, 31-40 years 3 patients, 41-50 years 0 patients and 50+ years 9 patients. 09 patients were diagnosed as malignant neoplasm and other 21 patients were diagnosed as benign neoplasm. Among 9 malignant neoplasms 8 cases are diagnosed as NHL and rest one was Adenoid cystic carcinoma. Among 21 benign cases 6 were diagnosed as dermoid cyst, 4 cases were diagnosed as orbital lymphangioma, 2 cases were diagnosed as orbital capillary hemangioma, 2 cases Optic nerve glioma and plexiform neurofibroma, optic nerve meningioma, pleomorphic adenoma, schwannoma, glomus tumor, Langerhans cell histiocytoma, cavernous hemangioma one case each. The age distribution of diagnosed 30 patients exhibited two peaks, at 0 to 10 years (13 patients) and 50+ years (9 patients). In the 0- to 9-year-old patients, the most common tumors were dermoid cyst 6 patients and in 50+ years patient age group most common diagnosis was NHL (8 patients). The most common sign and symptom were proptosis (76.66%), palpable mass (73.33%) and restricted ocular movement 46.66%. A wide range of tumors can involve the orbit. The prevalence of malignant tumors increased with age, and in younger age group vascular and cystic tumors are more common. Most common malignancy is NHL occurs in older age group and most common benign orbital tumor is dermoid cyst occurs in younger age group. Among all tumors proptosis, palpable mass and restricted movement was the most common presenting features.

Optic nerve gliomas (ONGs) are rare pediatric tumors of the anterior visual pathway, most commonly low-grade pilocytic astrocytomas. While frequently associated with neurofibromatosis type 1 (NF1) , sporadic cases tend to present later in childhood and may demonstrate a more aggressive clinical course. We report a case of a 12-year-old female who presented with sudden onset headache, progressive diminution of vision in the left eye, and unilateral proptosis of one week duration. Ocular examination revealed visual acuity of 6/6 in the right eye and counting fingers at 2 m in the left eye, with Grade 3 relative afferent pupillary defect, total color vision loss and optic disc edema. Hertel’s exophthalmometry confirmed left-sided proptosis. Neuroimaging showed a fusiform enlargement of the left optic nerve with optic canal widening on computed tomography, and T2 hyperintense, T1 hypointense lesion on magnetic resonance imaging without diffusion restriction, consistent with optic nerve glioma. There were no clinical features suggestive of NF1 . The patient was referred for neurosurgical evaluation and underwent 15 cycles of radiotherapy. This case highlights the importance of early recognition of sporadic optic nerve glioma as a cause of unilateral proptosis in children. Prompt ophthalmic assessment and neuroimaging are crucial to prevent irreversible visual loss and intracranial extension. Multidisciplinary management and long-term follow-up remain essential in optimizing outcomes.

Recent advances in molecular pathology have transformed the diagnostic landscape and management of human cancer. Increasingly, integration of genomic and epigenomic data with conventional histopathology has improved tumor classification, refined prognostic assessment, and revealed previously unsuspected therapeutic targets. High-throughput techniques such as next-generation sequencing, gene fusion panels, and methylation arrays have expanded applicability to formalin-fixed tissue and enabled simultaneous evaluation of multiple cancer-defining alterations/genetic drivers. In optic nerve gliomas, MAPK pathway activation through BRAF or FGFR1 alterations, or NF1 inactivation, is a basic biological feature with diagnostic implications, while MEK inhibitors may be of clinical benefit in selected patients. Optic nerve sheath/orbital meningiomas demonstrate divergent molecular landscapes depending on location, with NF2-driven and non-NF2-driven pathways informing recurrence risk and behavior. In the orbit, characteristic genetic drivers facilitate diagnosis of mesenchymal tumors such as solitary fibrous tumor (NAB2::STAT6) and alveolar rhabdomyosarcoma (PAX3/7::FOXO1), while molecular profiling assists in distinguishing challenging peripheral nerve and melanocytic lesions. Similarly, lacrimal gland neoplasms parallel salivary gland counterparts, with recurrent fusions such as PLAG1, HMGA2, and MYB::NFIB of great diagnostic utility. These advances underscore the growing role of molecular diagnostics in improving accuracy, guiding prognostication, and refining the classification of rare ocular tumors. As high-throughput techniques continue to mature, integration with evolving spatial and single-cell-based approaches promises to expand our understanding and further personalize diagnostic and therapeutic strategies.

Endoscopic Endonasal Approach for Optic Nerve Sheath Fenestration and Bony Decompression of the Optic Canal for Treatment of Optic Nerve Glioma in an 11-Year-Old Boy

Surgical Management of Optic Pathway-Hypothalamic Gliomas: Institutional Experience and Systematic Review

Because of the proximity of optic pathway-hypothalamic gliomas (OPHGs) to critical neuroanatomical structures and their unpredictable natural history, the role of resection in their treatment is often debated. We present our institutional surgical experience and a systematic review of outcomes in patients with surgically treated OPHG. The health records of patients with OPHGs who underwent surgery at our institution were retrospectively reviewed. A systematic review of the literature was also performed to extract surgically treated OPHG cases. Clinical presentation, surgical approach, extent of resection, complications, and outcomes were analyzed. A total of 9 adult patients from our institution were included (mean age 32.3 ± 17.3 years; 5 women [56%]), and we identified 15 studies that met inclusion criteria with a total of 50 patients (mean age 14.4 ± 11.2 years; 24 women [48%]). Visual disturbance was the most common presenting symptom (56% of our patients and 76% of patients from the literature). The most common pathology was pilocytic astrocytoma (67% in our cohort, 62% of patients in the literature). In our cohort, tumors involved the hypothalamus (67%), optic chiasm (67%), and optic nerve (56%), and 33% of patients had gross total resection. In the historical cases, tumors involved the hypothalamus (94%), optic chiasm (42%), and optic nerve (16%), and 12% of patients had gross total resection. Complications in our series included diabetes insipidus (11%), anterior choroidal infarct (11%), and ptosis (11%), and in the literature, new endocrine dysfunction (28%) and visual disturbance (16%) were reported. Three patients (33%) had tumor recurrence at a mean of 27.3 ± 7.6 months, whereas 11 patients (22%) reported in the literature had tumor recurrence at a mean of 55.7 ± 44.3 months. Surgery can be performed with reasonable risk and can play a key role in the multidisciplinary management of select patients with OPHG.

Optic glioma, a slow-growing tumor, is associated with Neurofibromatosis type 1 (NF1) mutations and increased midkine (MDK) production. A connection between asthma and optic glioma has previously been observed, but the mechanisms are unclear. To elucidate the role of asthma in the regulation of glioma formation, we investigated the role of T cells and the subsequent pathways in the regulation of microglia, a key player in the glioma tumor microenvironment (TME). While asthma is often linked to chronic inflammation, our mathematical analysis and experimental evidence suggest that inflammation can play a key role in suppressing the proliferation of optic glioma cells via immune reprogramming of T cells and the delicate control of signaling networks in microglia. Our mathematical model unveils the complex interactions between tumor and immune cells in optic glioma. Our results indicate that asthma-induced T cell reprogramming inhibits tumor growth by promoting the release of decorin and a subsequent suppression of CCR8 and the intercellular binding kinetics in microglia, followed by blocking of CCL5 production in TME via suppression of NFκB. We developed anti-cancer strategies by leveraging this asthma-induced immune regulation.

Optic nerve gliomas which are a part of a broader category of optic pathway gliomas, are low grade astrocytic tumours arising along the optic nerve, chiasm or tract. They represent approximately 1.5% to 4% of all orbital tumours and constitute a significant proportion of primary optic nerve neoplasms. Histologically, most optic nerve gliomas are classified as a pilocytic astrocytoma, with generally idle behaviours, although rare malignant forms exist.

Background . Neurofibromatosis type 1 (NF1) is a genetic disorder that is characterized by multiple light brown patches of skin (café-au-lait spots) and neurofibromas. It can lead to an increased risk of malignant tumors, cognitive impairment, and skeletal abnormalities. NF1 is caused by heterozygous mutations in the NF1 gene, and identifying the specific mutation can form the basis for pathogenetic treatment of tumor syndrome. Several studies indicate that patients with the NF1 in-frame deletions tend to have a milder form of the disease that is characterized by the absence of neurofibromas. the purpose of the study was to identify in-frame deletions in the NF1 gene in patients from the Republic of Bashkortostan as well as to characterize the clinical symptoms of NF1 in this group of patients. Material and Methods . An analysis of outpatient records of NF1 patients from the Republic of Bashkortostan was conducted, along with an objective clinical examination of the patients and DNA sequencing to identify in-frame deletions in the NF1 gene. Twenty-six patients (12 females and 14 males) aged 3 to 69 years were studied. Results . The retrospective analysis of outpatient records and examination of NF1 patients showed the NF1 incidence of 1:7403.6 people. Two in-frame deletions in the NF1 gene were identified in 6 patients with NF1 from 3 unrelated families: NF1:NM_000267.3:exon21:c.2674_2679del:p. S892_K893del; NF1:NM_000267.3:exon27:c.3526_3528delAGA:p.Arg1176del. The clinical manifestations of NF1 in patients with identified mutations and their comparative characteristics with all NF1 patients in the Republic were described. In the general group of NF1 patients from the Republic, a rarer detection of neurofibromas and malignant tumors, optic nerve gliomas, and cognitive impairment was revealed. Conclusion . In patients with NF1 from the Republic of Bashkortostan with in-frame deletions in the NF1 gene, no brain cysts or tumors, plexiform neurofibromas, and optic nerve gliomas were detected. Although the mutations we identified have not previously been described in the scientific literature, our analysis of clinical features is consistent with the findings of other authors regarding the presence of phenotypic correlations with in-frame deletions.

A 16-year-old boy presented with blurring of vision in both eyes for 6 months. On evaluation, OU best-corrected visual acuity was 6/6 partial, the anterior segment was normal, intraocular pressure (IOP) was 14 mmHg in both eyes, and fundus examination showed OU elevated disc margins with a lumpy appearance, Cup disc ratio (CDR) 0.1, with the rest of the fundus within normal limits. Ultrasonography revealed well-defined echogenic foci at the optic nerve head. Optical coherence tomography (OCT) showed a hyporeflective core with a hyperreflective cap. Perimetry revealed enlargement of the blind spot with depression of the temporal field in the right eye and enlargement of the blind spot with generalized constriction of fields in the left eye as shown in Figures 1 and 2.Figure 1: Right eye showing optic nerve head drusen: (a) color photo, (b) EDI optical coherence tomography, (c) ultrasound, (d) 24-2 Humphrey visual field grayscale, (e) pattern deviation mapFigure 2: Left eye showing optic nerve head drusen: (a) color photo, (b) EDI optical coherence tomography, (c) ultrasound, (d) 24-2 Humphrey visual field grayscale, (e) pattern deviation mapOptic nerve head drusen (ONHD) derives its name from the German word “geodes” which are benign acellular calcium concretions deposited anterior to the lamina cribrosa. Optic nerve drusen are benign acellular calcium concretions deposited anterior to the lamina cribrosa. ONHD imply disruption of axoplasmic flow in the orthograde direction. Electron microscopy suggests intra-axonal calcium phosphate accumulation with rupture of axons and release of calcium into the interstitium.[1] ONHD are closely associated with retinitis pigmentosa, angioid streaks, and Alagille syndrome. IOP should be closely monitored, as preexisting field defects due to ONHD can confuse the diagnosis of glaucoma.[2] ONHD can cause peripapillary hemorrhage secondary to a compressive effect on peripapillary vessels. However, it is benign and tends to resolve on its own. A more serious complication is Choroidal Neovascular Membrane (CNVM). While OCT and OCT angiography are commonly used for diagnosis, Fundus auto fluorescence (FAF) can be a reasonable option. Subretinal fluid from active CNVM usually presents as hypoautofluorescence, while disciform scarring or fibrosis presents as uneven autofluorescence of the lesion surrounded by hyperautofluorescence. Intravitreal antivascular endothelial growth factor agents are used for the treatment.[3] Patients with ONHD can develop resultant Non-arteritic anterior ischemic optic neuropathy (NAION) as the ONHD crowd the disc even more, leading to a further decline in perfusion pressure. Such NAION is more common in young patients with favorable outcomes compared to traditional NAION. Differential diagnoses include optic disc edema, meningioma, glioma, or astrocytic hamartoma. Although most cases are benign with no visual sequelae, clinicians should be aware of the potential complications that can arise, including vision and field loss, and promote frequent examinations. Multimodal imaging, such as OCT and FAF in addition to standard visual field testing, is strongly suggested in the management of patients with ONHD and ONHD-associated complications. Data availability statement Data will be made available on reasonable request to the corresponding authors. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Combined Transcranial-Orbital Approach for Resection of a Pediatric Optic Nerve Glioma With Preservation of the Annulus of Zinn: 2-Dimensional Operative Video.

Low-grade gliomas (LGG), both sporadic and neurofibromatosis type 1 (NF1)-associated, are the most common pediatric brain tumors. When unresectable, progressive, or symptomatic, they require treatment. Bevacizumab (BVZ), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has shown efficacy for progressive LGG, especially optic pathway gliomas. Reported toxicities include hypertension (HTN) and proteinuria. Children with NF1 are predisposed to HTN and vasculopathy, but data on BVZ safety in this group are lacking. We compared the incidence of BVZ-associated toxicity in children with LGG with and without NF1. Retrospective study of all BVZ-treated LGG patients (2010-2023) at a single center. Seventeen children with LGG were treated with BVZ: 8 NF1, 82% optic glioma, 18% other. All received BVZ as second- or third-line therapy combined with chemotherapy. In the non-NF1 group, 77% patients developed grade 1-2 HTN; none received antihypertensives. Six developed grade 1 proteinuria. In the NF1 group, 62.5% developed grade 1-2 HTN, including one with aortic coarctation who had worsening of previous HTN, 2 required antihypertensive therapy (p nonsignificant HTN non-NF1 vs. NF1). Only 1 NF1 patient developed proteinuria. No patients in either group stopped BVZ prematurely for toxicity. HTN was reversible after BVZ cessation in all except the coarctation of the aorta patient. HTN is more common than previously reported in both NF1 and non-NF1 patients treated with BVZ for LGG, but reversible. Blood pressure should be monitored and treated appropriately. BVZ appears to be a safe and efficacious therapeutic option for young patients with NF1-related optic glioma.

Abstract We describe a 46-year-old male with Neurofibromatosis type 1 (NF1) and a previously known parenchymal medullary mass identified in 2022, initially managed with surveillance. In late 2023, he developed a progressive brainstem syndrome prompting presentation to our center. MRI showed a T2/FLAIR hyperintense, heterogeneously enhancing ventral medullary mass with leptomeningeal involvement, a non-enhancing right pontine lesion, right optic nerve glioma, and nodular leptomeningeal foci at T4 and L4–L5. He received IMRT to the brainstem prior to tissue diagnosis with good local response. Due to progression at T4, biopsy revealed a hypercellular, mitotically active glioma without necrosis or microvascular proliferation. Molecular profiling demonstrated IDH1/2-wildtype, H3K27M-negative, retained ATRX, intact 1p/19q, and CDKN2A/B homozygous deletion. DNA methylation profiling classified the tumor as high-grade astrocytoma with piloid features (HGAP). Spinal lesions responded to proton therapy, but new metastatic foci emerged in the subependymal lateral ventricles, leptomeninges, and cervical spinal cord. He underwent whole-brain radiation, oral temozolomide, and intrathecal cytarabine/etoposide. In June 2024, cell-free DNA analysis showed a similar molecular profile with newly identified 1p/19q codeletion, diverging from tissue findings. The patient remains alive >3 years from initial presentation. HGAP is a novel molecular class of IDH-wildtype gliomas defined by DNA methylation profiling and MAPK pathway alterations (commonly NF1, BRAF, FGFR1), CDKN2A/B codeletion, and ATRX alterations. These tumors often resemble glioblastoma or diffuse midline gliomas on imaging and are typically infratentorial or spinal, complicating biopsy. Prognostic data are limited, with <50% 5-year overall survival and no clear prognostic value of MGMT promoter methylation. This case illustrates multifocal HGAP in a patient with NF1 with favorable survival. The acquired 1p/19q codeletion raises questions about tumor mosaicism, subclonal evolution, and prognostic implications.

Abstract Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by café au lait macules, intertriginous freckling, Lisch nodules, central nervous system, and peripheral nerve tumors such as plexiform neurofibromas (PNs). Additionally, some patients experience learning disabilities and cognitive deficits. Although there was an FDA-approved drug for pediatric populations with inoperable PNs (selumetinib), there were no FDA-approved drugs for adults until February 2025, when Mirdametinib, a highly selective, allosteric, central nervous system-penetrant, MEK 1/2 inhibitor, was approved. It was evaluated in the ReNeu study, a phase 2b single-arm study, with 114 participants, including 58 adult and 56 pediatric patients. 41% of adults and 52% of children achieved a confirmed objective response. The most commonly reported adverse events were acneiform rash, diarrhea, and vomiting, all of which affected more than 50% of the participants. More severe side effects included left ventricular dysfunction and ocular toxicity, such as retinal vein occlusion and retinal pigment epithelium detachment. The median time to response in adults was 7.8 months. We report the case of a 39-year-old female patient with NF1, right optic glioma, and multiple cutaneous and plexiform neurofibromas. In 2021, she underwent a partial resection of a plexiform neurofibroma located on her right frontal scalp and eyelid. Despite the surgery, she continued to experience significant discomfort and disfigurement. She is the first adult patient to start treatment with Mirdametinib following its FDA approval. After three months of treatment, she has tolerated the medication well. She developed an acneiform rash on her face and trunk shortly after beginning treatment, which resolved with doxycycline and topical corticosteroids. To ensure her safety, she is closely monitored with echocardiograms and ophthalmological evaluations every three months.

Abstract Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder that predisposes individuals to a range of neoplasms, including optic gliomas, astrocytomas, neurofibromas, breast carcinomas, and leukemias. The condition affects approximately 1 in 3,000 individuals and results from mutations in the NF1 gene on chromosome 17q11.2. This gene encodes neurofibromin, a tumor suppressor protein that regulates cell growth through the RAS/MAPK pathway. High-grade astrocytoma with piloid features (HGAP) is a rare tumor, with only 42 reported NF1-associated cases. It is a recently recognized primary brain tumor entity. Histologically, it has overlapping features of pilocytic astrocytoma and glioblastoma. Definitive diagnosis is primarily dependent on its global DNA methylation signature or epigenetic profile. The average age of onset is 44 years, and median survival is 15 months. We report two additional NF-1 associated HGAP cases. Patient 1, a 34-year-old woman with an unresectable left basal ganglia tumor, underwent biopsy, radiation, and chemotherapy. Molecular analysis showed NF1 and ATRX mutations, CDKN2A loss, and a methylation profile consistent with HGAP. Patient 2, a 51-year-old man with a right pontine tumor, had 70% resection followed by adjuvant therapy. Pathology revealed NF1 and ATRX mutations, CDKN2A and p16 loss, and methylation profiling consistent with HGAP. Both patients received selumetinib, a MEK inhibitor which targets the RAS/MAPK pathway. Patient 1 has stable disease at 15 months; patient 2 remained stable for 18 months before passing of pneumonia. He survived 5 years after diagnosis of HGAP. Of prior HGAP cases, none received selumetinib, though one was treated with trametinib, another MEK inhibitor, with 8.5 months survival. Given the rarity of NF1-associated HGAP, large scale studies are difficult. These cases suggest MEK inhibitors may offer therapeutic benefit. Collaborative research is needed to better understand the disease’s molecular profile and optimize treatment strategies.

Neurofibromatosis (NF) is characterised by multiple skin lesions distributed across the body and follows an autosomal dominant inheritance pattern. There are two main subtypes: NF type 1 (NF1) and NF type 2 (NF2), each with distinct clinical features. NF1 typically presents with numerous cutaneous neurofibromas, café-au-lait spots, plexiform neurofibromas, Lisch nodules, freckling in the axillary or inguinal regions, and optic gliomas. In contrast, NF2 is marked by bilateral vestibular schwannomas and central nervous system tumours such as meningiomas and ependymomas. A 69-year-old male presented with a swelling on his back. He had a malignant tumour that had transformed from plexiform NF to neurofibrosarcoma. A wide-excision biopsy of the swelling was done and a Malignant Peripheral Nerve Sheath Tumour (MPNST) was given as a diagnosis on Histopathological Examination (HPE). He underwent surgery for excision of the swelling. The patient had undergone Contrast-Enhanced Computed Tomography (CECT) of the thorax, abdomen and pelvis, showing cystic bronchial changes in the lower lobe and minimal in the posterior segment of the right lower lobe. Also, there was evidence of a large heterogeneous enhancing lobulated soft tissue density lesion in the subcutaneous plane of the neck and upper back. NF can be prevented from progressing if the malignant change is identified early. Surgical excision is the primary therapy; nevertheless, there is a greater chance of local recurrence, particularly in those suffering from NF1. The patient had undergone wide local excision with vacuum-assisted closure, which was followed by skin grafting.

Objective: Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome with multisystemic involvement that facilitates tumour formation. The aim of this study was to evaluate the demographic and clinical characteristics as well as genetic results of pediatric patients diagnosed with neurofibromatosis type 1. Materials and Methods: This retrospective, cross-sectional descriptive study included 23 patients. Main disease criteria, clinical features, and genetic results obtained using next-generation sequencing and multiple-ligation probe amplification techniques were recorded. Information on zygosity, mutation types, variant positions, ACMG classification and inheritance models were analysed. Results: Café-au-lait spots were present in all patients. Inguinal/axillary freckling was the second most common finding seen in 60.9% of patients. Lisch nodules were observed in patients older than six years, whereas choroidal abnormalities were common in younger patients. Optic glioma was found in 13% of patients and cutaneous neurofibromas in 21.7% of patients, which is lower than that observed in adult patients. Focal signal intensity image was more common in patients with cognitive impairment (OR: 4.50, CI 95% 0.659-30.715, p=0.02). Epilepsy was diagnosed in two patients and treated with a single drug. Macrocephaly (30.4%) was the most common cranial deformity. Missense mutations (43.5%) were the most common, while one frameshift novel mutation (c.6771del. K2257Nfs*8) was identified. Conclusion: The emergence of new genetic technologies and advances in health care may facilitate earlier diagnosis of neurofibromatosis and the prediction and treatment of complications that may develop.

PurposeEvaluation of the incidence and variability of ocular manifestations in children with neurofibromatosis type 1.MethodsIn this study, the files of 71 children aged 0-18 years with neurofibromatosis type 1 were retrospectively analyzed. Child age groups were categorized as 0-6, 7-12, and 13-18 years. In cycloplegic refractive examination, ≥-0.50 Diopter (D) values in spherical equivalents were recorded as myopia, ≥+2.0 D as hypermetropia, and ≥±1.0 D cylindrical values as astigmatism. Patients with a difference of ≥1 D in spherical or cylindrical equivalents between the 2 eyes were considered anisometropic. Amblyopia was defined as a best-corrected visual acuity ≤0.8 with Snellen chart and a difference of at least 2 lines between both eyes. The presence of 2 or more iris Lisch nodules (iris hamartoma) was considered positive.ResultsOf the 71 patients whose ocular findings were evaluated, 32 (45.1%) were boys and 39 (54.9%) were girls. According to age and gender, myopia (P = .878), hypermetropia (P = .329), myopia astigmatism (P = .761), hypermetropia astigmatism (P = .457), mixed astigmatism, anisometropia (P = .836), amblyopia (P = .551), emmetropia (P = .234), optic glioma (P = .598), strabismus (P = .219), and ptosis (P = .099) showed no significant difference (P > .05). A statistically significant difference was observed in the Lisch nodule, one of the ocular examination findings, according to age and gender (P < .05).ConclusionsPediatric patients with neurofibromatosis type 1, with common ocular manifestations, should undergo a comprehensive ophthalmologic examination. Early diagnosis and treatment are crucial for improving the clinical course of the disease and preserving vision.

BackgroundAuthenticated preclinical brain tumor models provide unprecedented opportunities to evaluate next-generation treatments. However, some therapies with robust anti-tumor activity in mice fail in human trials, highlighting the need to better prioritize candidates for clinical translation. Herein, we implemented a head-to-head preclinical strategy using a well-characterized murine model of NF1-optic pathway glioma (Nf1OPG).MethodsNf1OPG mice were treated with standard of care (SOC; carboplatin), clinically evaluated (everolimus, mirdametinib), and investigational (pexidartinib, HBS-101, lamotrigine) drugs during the period of most rapid tumor growth (6-12 weeks of age). Anti-tumoral efficacy was assessed by proliferation (%Ki67+ cells) and optic nerve (ON) volume, while vision-related outcomes were measured using retinal nerve fiber layer (RNFL) thickness and retinal ganglion cell (RGC) determinations. Tumor microenvironment (TME) soluble mediator (Ccl2, Ccl3, Ccl4, Ccl5) and tumor cell marker (NeuN, Gpr17) RNA expression was quantitated by qRT-PCR. Outcomes were compared to carboplatin-treated Nf1OPG, untreated Nf1OPG, and Nf1+/- mice.ResultsWhile all agents restored normal tissue architecture, reduced ON proliferation, and decreased TME soluble mediator and tumor cell marker RNA expression, only lamotrigine and mirdametinib also reduced ON volume. Everolimus, lamotrigine, and HBS-101 restored RNFL thickness to wild-type levels, whereas carboplatin showed a trend towards normalization.ConclusionsThis referential preclinical study design affords direct head-to-head comparisons of investigational therapies relative to SOC treatment using clinically meaningful outcomes (OPG growth and RNFL thickness). Using this strategy, lamotrigine emerged as the most promising therapy for limiting tumor progression and vision loss in Nf1-OPG mice, relevant to clinical translation for children with NF1-OPG.