From the Guidelines
Pediatric optic pathway gliomas are primarily driven by genetic factors, with neurofibromatosis type 1 (NF1) being the most significant contributor, accounting for approximately 20-30% of all cases, as noted in studies such as 1. The development of these tumors involves a complex interplay of genetic and environmental factors. Children with NF1 have a 15-20% lifetime risk of developing optic pathway gliomas, which are typically benign pilocytic astrocytomas (PAs; World Health Organization grade I astrocytomas) that can arise anywhere along the optic pathway, including the optic nerves, optic chiasm, optic tracts, and optic radiations 1. Other genetic alterations commonly found in sporadic (non-NF1) optic pathway gliomas include BRAF gene fusions or mutations, particularly the KIAA1549-BRAF fusion and the BRAFV600E mutation, which lead to constitutive activation of the MAPK pathway and promote tumor growth. Some key points to consider in the development and treatment of pediatric optic pathway gliomas include:
- The role of NF1 in the development of optic pathway gliomas, with approximately 75-85% of NF1-associated OPGs located within the optic nerve and chiasm 1
- The importance of early diagnosis and treatment, as vision loss is a significant risk factor for these tumors, particularly in young children under the age of 2 years and in females 1
- The potential for molecularly targeted therapies, including inhibitors of the RAS effectors MEK and mTOR, to provide alternative treatment options for patients with NF1-OPG, as discussed in studies such as 1
- The need for further research into the molecular and cellular determinants of human NF1-OPG, including the development of patient-derived xenograft models and the study of microglia recruitment and activation in the tumor microenvironment 1. In terms of treatment, chemotherapy is often the primary approach, but molecularly targeted therapies and ecological therapies that target the tumor microenvironment, such as microglia/macrophages, may offer promising alternatives for preventing or reducing vision loss from NF1-OPG, as noted in studies such as 1.
From the Research
Genetic Factors
- Neurofibromatosis type 1 (NF1) is a genetic disorder that increases the risk of developing optic pathway gliomas (OPGs) 2, 3, 4
- NF1 is associated with a 15-20% risk of developing OPGs 2, 4
- Genetic predisposition plays a significant role in the development of OPGs, particularly in children with NF1 5
Environmental Factors
- There is limited evidence on the environmental factors that contribute to the development of OPGs
- However, it is suggested that early detection and monitoring of OPGs can improve treatment outcomes 5, 4
Interaction between Genetic and Environmental Factors
- A multidisciplinary approach to diagnosis and management of OPGs is crucial, particularly in children with NF1 2, 6
- Regular follow-up and monitoring by a team of specialists, including pediatricians, ophthalmologists, and neuro-oncologists, can help identify children at risk of OPGs and improve treatment outcomes 2, 4
- The role of environmental factors in the development of OPGs is not well understood, but it is clear that genetic factors, such as NF1, play a significant role in increasing the risk of developing OPGs 3, 5
Treatment and Management
- Treatment of OPGs depends on various factors, including the size and location of the tumor, as well as the presence of NF1 3, 6
- A comprehensive treatment plan may include observation, surgery, chemotherapy, and radiation therapy 3, 6
- Multidisciplinary management of OPGs can improve treatment outcomes and reduce the risk of vision loss and other complications 2, 6