Neurofibromatosis type 1

Abstract

Neurofibromatosis type 1 is a complex autosomal dominant disorder caused by germline mutations in the NF1 tumour suppressor gene. Nearly all individuals with neurofibromatosis type 1 develop pigmentary lesions (café-au-lait macules, skinfold freckling and Lisch nodules) and dermal neurofibromas. Some individuals develop skeletal abnormalities (scoliosis, tibial pseudarthrosis and orbital dysplasia), brain tumours (optic pathway gliomas and glioblastoma), peripheral nerve tumours (spinal neurofibromas, plexiform neurofibromas and malignant peripheral nerve sheath tumours), learning disabilities, attention deficits, and social and behavioural problems, which can negatively affect quality of life. With the identification of NF1 and the generation of accurate preclinical mouse strains that model some of these clinical features, therapies that target the underlying molecular and cellular pathophysiology for neurofibromatosis type 1 are becoming available. Although no single treatment exists, current clinical management strategies include early detection of disease phenotypes (risk assessment) and biologically targeted therapies. Similarly, new medical and behavioural interventions are emerging to improve the quality of life of patients. Although considerable progress has been made in understanding this condition, numerous challenges remain; a collaborative and interdisciplinary approach is required to manage individuals with neurofibromatosis type1 and to develop effective treatments.

Programmed death ligand 1 expression and tumor infiltrating lymphocytes in neurofibromatosis type 1 and 2 associated tumors

“…The diagnosis of NF1 or NF2 in all patients was made using currently established clinical diagnostic criteria [1-2]. Two NF1 patients concurrently had a malignant nerve sheath tumor (MPNST) in a different anatomical location.…”

“…While the majority of NF-related tumors are histologically benign, they are a leading cause of morbidity and mortality in NF patients. Standard therapies have traditionally included surgery and radiation therapy, and molecular targeted therapies have recently emerged with some success in subsets of NF-related tumors [1-4]. Despite these advances, there remains an urgent need for novel, more effective and less toxic therapies for NF patients, especially those with large tumor burden.…”

“…These elevated cytokines and amplified signaling pathways may provide a potential mechanism for upregulation of PD-L1 expression in tumor cells [1, 3, 14]. Therefore, we hypothesized that PD-1/PD-L1 axis-mediated immune escape mechanisms might also exist in NF related tumors.…”

The Relationship Between Heart Rate Variability, Psychological Flexibility, and Pain in Neurofibromatosis Type 1

“…1 It is associated with a high risk for chronic pain due to multiple morbidities, including plexiform neurofibromas (PNs; benign tumors composed of a proliferation of cells in the nerve sheath), chronic headaches, pseudoarthrosis, scoliosis, and gastrointestinal complications. 2 In particular, PN-related pain is neuropathic in nature, occurring in about 30% to 50% of patients, 3,4 and is associated with worse everyday functioning and quality of life. 5–7 Despite this, there has been limited research into factors related to pain in this population.…”

Neurofibromatosis type 1 and optic pathway glioma: Molecular interplay and therapeutic insights

“…Nearly15–20% of children with NF1 will develop CNS tumors before adulthood, and the majority of these are low‐grade optic pathway gliomas (OPGs) . While pilocytic astrocytoma (PA) is the most commonly encountered histological type, other pathological subtypes of NF1–low‐grade glioma (LGG) include diffuse astrocytoma, which, although rare, are more frequent in children with NF1 …”