NF1

NF1, also known as neurofibromatosis type 1 or von Recklinghausen disease, is a genetic disorder characterized by multiple café-au-lait spots, neurofibromas, and various other clinical features. It results from mutations in the NF1 gene on chromosome 17, which encodes neurofibromin, a tumor suppressor that downregulates Ras signaling. NF1 is inherited in an autosomal dominant pattern with complete penetrance but variable expressivity; about half of cases arise from new mutations.

Clinical features include multiple café-au-lait macules, axillary and inguinal freckling (Crowe sign), Lisch nodules on the iris, and cutaneous or plexiform neurofibromas. Optic glioma, sphenoid wing dysplasia, tibial bowing, short stature, and skeletal abnormalities are common. Learning disabilities and attention problems occur in a substantial minority. Plexiform neurofibromas can be extensive and may transform into malignant peripheral nerve sheath tumors (MPNST).

Diagnosis relies on NIH criteria: two or more of the following: six or more café-au-lait macules; two or more neurofibromas or one plexiform neurofibroma; axillary or inguinal freckling; optic glioma; two or more Lisch nodules; distinctive osseous lesions; a first-degree relative with NF1. Genetic testing can confirm the diagnosis, especially in uncertain cases.

Management requires lifelong multidisciplinary care. Regular surveillance for tumor burden, vision and learning issues, and blood pressure is recommended. Imaging is guided by symptoms. Treatment focuses on symptom relief and tumor management; solitary neurofibromas can be removed surgically. In the 2010s–2020s, MEK inhibitors such as selumetinib have been approved for children with inoperable symptomatic plexiform neurofibromas, offering tumor shrinkage in many cases.

Prognosis varies widely. NF1 is associated with increased risks of MPNST and pheochromocytoma; overall life expectancy may be somewhat reduced, but many individuals lead active lives with appropriate care.