Purpose of review: This review summarizes the recent clinical and genetic developments in neurofibromatosis type 1 (NF1) and provides an insight into the possible underlying pathomechanisms.
Recent findings: NF1, or von Recklinghausen disease, is one of the most common hereditary neurocutaneous disorders in humans. Clinically, NF1 is characterized by café-au-lait spots, freckling, skin neurofibroma, plexiform neurofibroma, bony defects, Lisch nodules and tumors of the central nervous system. The responsible gene, NF1, encodes a 2818 amino acid protein (neurofibromin). Pathological mutations range from single nucleotide substitutions to large-scale genomic deletions dispersed throughout the gene. In addition to the conventional mutation screening methods, a DNA chip microarray-based technology, combinational sequence-based hybridization, has been introduced to expedite mutation detection. Functional analysis has become more amenable following the development of the following: (1) primary Schwann cell cultures from NF1 patients; (2) mouse models; (3) proteomic technologies; and (4) mRNA silencing by RNA interference. These studies have shown that neurofibromin plays a role in adenylate cyclase and AKT-mTOR mediated pathways. It also appears to affect Ras-GTPase activating protein activity through the phosphorylation of protein kinase C which impacts on cell motility by binding with actin in the cytoskeleton.
Summary: Recent advances in the clinical features and molecular genetics of NF1 will be discussed together with insights into the underlying pathomechanisms of NF1.