Type 1 neurofibromatosis

Type 1 neurofibromatosis (NF1) is an autosomal-dominant genetic tumor predisposition disorder with the defining features of café au lait spots, multiple neurofibromas, and iris Lisch nodules.

Diagnosis is made clinically; RNA-based NF1 mutation molecular testing can help to confirm the diagnosis.

The disorder is progressive, though clinically variable.

Multiple organ systems are involved: skin, central nervous system, peripheral nerves, eyes, bones, gastrointestinal tract, and vascular and endocrine systems.

Presentation in a young child may be subtle.

Regular follow-up, especially during childhood and adolescence and in complex cases, is recommended to identify lesions early, especially malignant peripheral nerve sheath tumors.

NF1 is an autosomal-dominant genetic disorder caused by pathogenic variants in the gene encoding the neurofibromin protein. Neurofibromin normally acts as a tumor suppressor; therefore, people with NF1 are predisposed to abnormal cell growth and development of benign and malignant tumors. The defining features of NF1 are café au lait spots, multiple neurofibromas, and iris Lisch nodules. Additional manifestations are almost always present, but vary in their combination and severity. They can involve the skin, central nervous system, peripheral nerves, eyes, bones, gastrointestinal tract, and vascular and endocrine systems. The most common additional manifestations are intertriginous freckling; choroidal abnormalities; learning disabilities; behavior issues; diffuse, occasionally massive plexiform neurofibromas; optic pathway gliomas; and renovascular hypertension.[1]Friedman JM. Neurofibromatosis 1. In: Adam MP, Bick S, Mirzaa GM, et al., eds. GeneReviews®​ [Internet]. Seattle, WA: University of Washington; 1993-2025.​​ Additional manifestations that are less common but characteristic include malignant peripheral nerve sheath tumors, dystrophic scoliosis, and sphenoid wing dysplasia.