NF1, Cutaneous & Plexiform Neurofibromas

Neurofibromatosis Type 1 (NF1) is a genetic disorder characterized by distinctive skin abnormalities and a high number of non-cancerous nervous system and non-nervous system tumors that grow throughout the body. It is the most common single gene disorder of the nervous system, affecting roughly 1 in every 3300 people or approximately 100,000 individuals in the US alone. NF1 typically presents at birth or in early childhood with dermatological manifestations (café au lait spots and skin fold freckling).

Multiple non-cancerous tumors (neurofibromas) often form on or underneath the skin or along nerves throughout the body. Cutaneous neurofibromas (cNFs) are the most common tumor in NF1 patients, manifesting as small bumps under the skin that can increase in number and size over time. Cutaneous neurofibromas rarely result in significant medical issues, but cause irritation/sensitivity, cosmetic concerns, and social difficulty.

Plexiform neurofibromas (pNFs) are the next most common type of tumor in individuals with NF1. It is estimated that up to 50% of patients with NF1 will develop a pNF. pNF are histologically benign tumors that are made up of a variety of cell types including neuronal axons, Schwann cells, fibroblasts, mast cells, macrophages, perineural cells and extracellular matrix materials such as collagen. They grow along the nerve sheath and may involve multiple fascicles and branches of nerve. pNFs can occur in any part of the body and can grow throughout a person’s lifetime, often becoming disfiguring, disabling or deadly via compression of vital structures or conversion to a malignant sarcoma, malignant peripheral nerve sheath tumor. There are currently no known therapies that are effective at stopping or reversing their growth or their impact on the lives of patients with NF1.

Other manifestations of NF1 can include:

• Cognitive deficits

• Bone malformations (dysplasias)

• Eye abnormalities

• Cardiovascular issues

• Increased risk of certain malignancies (such as gastrointestingal stromal tumors, leukemias, gliomas, breast cancer in women >50 years and neuroendocrine tumors)