neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a multisystem neurocutaneous condition that primarily affects the skin, nervous system, eyes, and bones. It arises when a pathogenic change occurs in the NF1 gene, which encodes neurofibromin, a protein that keeps cell growth signals in check through the RAS pathway. NF1 is usually noticed in childhood and affects people of all sexes. The condition is relatively common among inherited disorders, occurring in roughly 1 in 2,500 to 3,000 births worldwide. Severity and symptoms vary widely between individuals, even within the same family.

The hallmark features of NF1 include six or more café-au-lait macules, freckling in the underarm or groin regions, multiple cutaneous or plexiform neurofibromas, and tiny iris growths called Lisch nodules that are visible with a slit-lamp eye exam. These characteristic findings often guide the initial diagnosis. Early in life, families may notice light-brown skin patches or developmental concerns, such as specific learning disabilities that affect about half of school-aged children with NF1. As children grow, benign nerve-sheath tumors (neurofibromas) can appear on or under the skin, and some individuals develop larger plexiform neurofibromas that may press on vital structures. Optic pathway gliomas, spinal or brain tumors, and skeletal issues such as scoliosis, tibial bowing, or short stature can also emerge over time. Less common but important complications include hypertension related to blood-vessel changes, adrenal gland tumors called pheochromocytomas, and pulmonary valve narrowing. Not all individuals experience all features, and the clinical spectrum ranges from very mild skin findings to complex medical challenges requiring specialized care.

NF1 results from a pathogenic variant in the NF1 gene on chromosome 17. Neurofibromin, the protein product of this gene, normally dampens RAS signaling that drives cell growth. When neurofibromin is missing or not working properly, cells can grow in an uncontrolled way, which underlies the formation of neurofibromas and other tumors seen in this condition. NF1 is inherited in an autosomal dominant manner, meaning one altered copy of the gene is sufficient to cause the condition. Each child of an affected individual has a 50 percent chance of inheriting the variant. Approximately 50 percent of cases arise as new (de novo) variants, so a child may be the first in the family to be diagnosed. Once a person has NF1, they can pass the variant to their children. Even within the same family, the severity and specific symptoms can vary considerably (variable expressivity), so predicting the exact clinical course for any one person is difficult. Genetic counseling is strongly recommended for affected individuals and their relatives.

Currently, management focuses on supportive care, symptom control, and proactive monitoring. Foundational therapies include yearly comprehensive physical examinations that screen the skin for new or changing neurofibromas, blood pressure checks to detect early hypertension, and annual ophthalmologic assessments to monitor vision and identify optic pathway gliomas. MRI is often used to follow complex plexiform neurofibromas or brain tumors, and surgical removal is considered when tumors cause pain, functional impairment, or cosmetic concern. Educational support and individualized learning plans address specific learning disabilities. Targeted approaches are expanding. The MEK inhibitor selumetinib may be offered by specialists for children with inoperable, symptomatic plexiform neurofibromas, and its use requires close supervision for potential side effects. Long-term care is inherently multidisciplinary, typically involving neurologists, dermatologists, ophthalmologists, oncologists, orthopedic surgeons, and developmental pediatricians. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Genetic counseling assists families with inheritance questions and family planning decisions.

Most individuals with NF1 live into adulthood and lead active lives, although the condition may require lifelong medical attention. The risk of tumor growth, learning challenges, and orthopedic complications means health impacts can range from mild to significant. Outcomes described in medical literature continue to evolve as standards of care improve. Early recognition, vigilant surveillance, and access to specialists can reduce complications and enhance quality of life. Because manifestations differ so much from person to person, families often find it helpful to connect with expert centers and genetic counselors who can tailor monitoring and intervention plans to an individual’s needs.

NF1 is an active research area with numerous ongoing clinical trials exploring new therapies. Investigational efforts include additional MEK inhibitors, other targeted drugs aimed at different components of the RAS pathway, and natural-history studies that clarify how tumors grow over time. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.