It is a rare disorder with a birth incidence of 1 in every 3,000 individuals. Although rare, it is the most common autosomal dominant disorder of the nervous system.

NF1 results from mutations in the NF1 gene, which encodes the information necessary for the production of the protein called Neurofibromin. NF1 is what is called a tumor suppressor gene, when it is altered or absent cells divide in an uncontrolled manner leading to tumor formation.

There is a great diversity of symptoms and their degree of manifestation within individuals. These variations are not correlated with a particular alteration of the NF1 gene and there can be extensive variability even in between members of the same family.

Common manifestations of the disease include skin lesions and neurofibromas in both the peripheral and central nervous system. The most frequent skin lesion is the presence of dark areas called café-au-lait spots. These spots are often already present at birth and may grow in size and number during childhood but may eventually vanish in adulthood. Later in childhood NF1 patients can also develop freckles on their underarms and groin. Some individuals can also develop cutaneous and subcatenous neurofibromas in late childhood to adulthood. All these skin lesions can be a source of discomfort and even cause deformity but they are not life threatening.

Later in life, individuals with NF1 can develop neurofibromas in the peripheral nervous system called plexiform neurofibromas. These tumors can grow in any location of the nerve from the spinal root to the distal periphery. Depending on their size and the nerve affected they can compromise the nerve function causing different symptoms. These plexiform neurofibromas are the leading cause of neurological defects and the major cause of morbidity in individuals affected with NF1.

Within the central nervous system, individuals with NF1 are at risk of developing gliomas, being optic pathway gliomas the most common form. The outcome for optic gliomas varies from not causing any symptom to vision loss if the tumor continues to grow.

Another characteristic feature of NF1 is the development of Lisch nodules, benign tumors in the iris that usually do not impair vision. Lisch nodules usually appear in the mid-late childhood.

In addition, there are important nontumor manifestations including cognitive deficits, an increased risk for bone malformations, high blood pressure or nonnervous system cancers. Even though the majority of NF1 diagnosed children will have normal capabilities, they might present some learning difficulties. The degree of these learning impairments is highly variable. One of the most common bone malformations is scoliosis, an abnormal curvature of the spine. There are also usual deformations of the bones in the skull and in the arms and legs.

NF1 is often diagnosed by the presence of dark pigmented patches on the skin called café-au-lait spots and other clinical manifestations or symptoms of the disease.

The criteria for the diagnosis of NF1 is the presence of two of the clinical symptoms described above (café-au-lait spots, freckles in the underarm or groin, neurofibromas, Lisch nodules, optic glioma) and/or a first-degree relative with NF1. Although not routinely, a genetic test looking for NF1 mutations could also be performed.

Due to the heterogeneity of the disease, the treatment varies depending on the clinical manifestations and type of tumor that each patient shows.

Currently, the only treatment available for plexiform neurofibroma is surgery. But tumors can rarely being fully removed frequently leading to regrowth after surgery.

Optic pathway gliomas are left untreated until they cause a decline in vision, then chemotherapy could be considered.

There is a continuous effort for the development of new effective therapies for NF1, with several clinical trials currently ongoing.

Due to the heterogeneity of the disease, the prognosis also varies greatly among individuals. It can range from very mild manifestations to more severe conditions. Up to date, there is no way to predict what would determine the degree of the disease. But more than half of the people diagnosed will only present minor symptoms.

Blakeley, J. O. and S. R. Plotkin (2016). "Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis." Neuro Oncol 18(5): 624-638.

Rad, E. and A. R. Tee (2016). "Neurofibromatosis type 1: Fundamental insights into cell signalling and cancer." Semin Cell Dev Biol 52: 39-46.

The Children´s Tumor Foundation: www.ctf.org