NF1

About NF1

NF1 Neurofibromatosis type 1 on chromosome 17q11.2 encodes neurofibromin, a large GTPase activating protein that switches off RAS by accelerating GTP hydrolysis, restraining growth signaling. It is one of the largest human genes and has a high new mutation rate. Pathogenic variants cause neurofibromatosis type 1, historically called von Recklinghausen disease after the German pathologist Friedrich von Recklinghausen, who described it in 1882. It is one of the most common autosomal dominant disorders, affecting about 1 in 3,000 people, and about half of cases arise from new variants. Features include multiple cafe au lait spots, freckling in the armpits or groin, cutaneous neurofibromas, which are benign nerve sheath tumors, Lisch nodules of the iris, optic pathway gliomas, bone abnormalities, and learning difficulties. Plexiform neurofibromas can be large and disfiguring, and a significant minority of affected people develop malignant peripheral nerve sheath tumors. The gene was identified in 1990. The MEK inhibitors selumetinib and mirdametinib are approved for symptomatic inoperable plexiform neurofibromas. NF1 belongs to the RASopathies, which also include Noonan, Costello, Legius, and cardiofaciocutaneous syndromes. Genetic testing identifies a pathogenic variant in most people meeting clinical criteria.