Neurofibromatosis (NF) is a group of chronic genetic disorders that cause tumors to grow on nerve tissue throughout the body. The condition is chronic and highly variable, meaning its effects differ significantly from person to person. Neurofibromatosis Type 1 (NF1) and Neurofibromatosis Type 2 (NF2) are the two main forms, each following a distinct clinical course. Generally, NF is progressive, with new symptoms often appearing and existing lesions growing larger. This progression is frequently accelerated by hormonal changes, such as those occurring during puberty.
Childhood Indicators of Neurofibromatosis Type 1
The initial signs of Neurofibromatosis Type 1 (NF1), the most common form, typically manifest in infancy or early childhood, often leading to diagnosis by age eight. The most recognizable markers are flat, light brown patches on the skin known as café-au-lait spots (CALs); having six or more is a strong diagnostic indicator, and they are usually present at birth or appear within the first few years of life. Children may also present with Lisch nodules, which are small, benign tumors located on the iris of the eye that do not typically affect vision and are considered a stable diagnostic feature. Skeletal issues, such as bowing of the lower leg bones, or an abnormal curvature of the spine called scoliosis, are also common indicators. A serious concern is the possible development of an optic pathway glioma (OPG), a tumor on the nerve connecting the eye to the brain, which usually appears before age eight and can affect vision, although many remain asymptomatic.
Tumor Development and Progression Across Adulthood
The progression of NF1 often accelerates with age, driven by the proliferation and growth of neurofibromas, frequently triggered by hormonal shifts like puberty or pregnancy. The most visible change is the increasing number and size of cutaneous neurofibromas, which are soft, pea-sized, benign tumors that grow on or just under the skin and are present in almost all adults with NF1, appearing during the teenage years and accumulating throughout life. Progression also involves plexiform neurofibromas, benign tumors involving multiple nerve branches that occur in about half of patients; these can increase in size and become invasive, causing pain, disfigurement, or neurological issues at any age. A major progressive complication is the lifetime risk (8-13%) of developing a malignant peripheral nerve sheath tumor (MPNST), an aggressive cancer that typically arises from pre-existing plexiform neurofibromas in adolescence or adulthood. Rapid growth, new pain, or a change in tumor consistency can signal this malignant transformation, alongside other internal manifestations that may appear later in life, such as vascular issues and hypertension.
Tracking and Managing Disease Progression
Managing NF1 progression requires consistent and comprehensive clinical surveillance throughout life, with the focus shifting as the patient ages. Regular annual check-ups are necessary to monitor for new symptoms, including a full skin and soft tissue examination to track neurofibroma development, and blood pressure measurement to screen for hypertension. Neurological assessments are also conducted yearly to check for internal tumor growth or changes in function. Magnetic resonance imaging (MRI) is the preferred modality for tracking internal tumor growth, particularly plexiform neurofibromas, and is used when new clinical symptoms arise, such as new pain or rapid tumor growth. Advanced imaging techniques, like FDG-PET/CT scans, are increasingly used to monitor for potential malignant transformation in high-risk individuals, allowing for timely intervention such as surgical removal of symptomatic tumors or targeted pharmacological treatments.
The Distinct Course of Neurofibromatosis Type 2
Neurofibromatosis Type 2 (NF2) follows a different progressive path than NF1, defined by the near-universal development of bilateral vestibular schwannomas. These benign tumors grow on the eighth cranial nerve, responsible for hearing and balance, and typically cause progressive hearing loss, tinnitus, and balance dysfunction starting in late adolescence or early adulthood. NF2 patients also frequently develop schwannomas on other cranial and peripheral nerves, meningiomas, and spinal tumors, which can lead to a range of neurological issues and management challenges. Unlike the cutaneous tumor burden of NF1, the main progressive concern in NF2 is the impact of these internal nerve sheath tumors on function and quality of life. Treatment focuses on controlling the growth of vestibular schwannomas through surgery or radiation, with the goal of delaying total deafness, requiring specialized, ongoing neurological and audiological care.