Neurofibromatosis Type 1 : A General Review.

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal-dominant genetic disorder caused by pathogenic variants in the NF1 gene. Its clinical phenotype is heterogeneous and evolves across the lifespan; approximately 1 in 3,000 individuals worldwide are affected. Cardinal features comprise café-au-lait macules, axillary/inguinal freckling, cutaneous neurofibromas, plexiform neurofibromas, and optic-pathway gliomas. Advanced molecular diagnostics-including next-generation sequencing (NGS) and RNA sequencing-have markedly improved mutation detection rates and facilitate definitive diagnosis. Therapeutic progress has also accelerated: the U.S. FDA has approved the MEK inhibitors selumetinib and mirdametinib for the treatment of plexiform neurofibromas, and these agents may offer benefit for additional NF1-related manifestations. The disorder further compromises skeletal integrity, neurocognitive function, and confers an increased risk of malignancy. This review highlights the necessity for multidisciplinary care of individuals with NF1, with emphasis on early diagnosis, age-stratified health-surveillance suggestion from infancy through adulthood, cancer-prevention strategies, and comprehensive genetic counseling, all aimed at mitigating complications and enhancing quality of life.