Neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic disorders. While individuals with NF1 typically come to medical attention with characteristic pigmentary abnormalities (café-au-lait macules, skinfold freckling, Lisch nodules), they are also prone to the development of numerous other clinical problems, including bone defects (tibial bowing and pseudarthrosis, sphenoid wing dysplasia), cognitive, behavioral, and specific learning difficulties, and benign and malignant nervous system tumors (neurofibromas, malignant peripheral nerve sheath tumors, optic pathway gliomas). Since the identification of the NF1 gene and its encoded protein product, neurofibromin, converging data from laboratory and clinical studies have led to new insights into the mechanisms that underlie disease pathogenesis and progression and have revealed new targets for therapeutic intervention. While the mainstay of NF1 management remains age-specific surveillance and anticipatory guidance, recent research has begun to identify prognostic risk factors for specific NF1 clinical features and disease severity that may lead to future precision medicine approaches.