- What is the diagnosis?
Neurofibromatosis type I.
- What is the natural history of this process?
Neurofibromatosis type I (NF1) mainly involves the skin with neurofibromas and cafe-au-lait spots (von Recklinghausen disease) but there can also be neurofibromas involving visceral organs, and there is also a greater risk for other benign and malignant neoplasms including meningiomas, gliomas, and pheochromocytomas. This is an autosomal dominant disorder in which half of cases are due to spontaneous new mutations.
- What is the genetic basis for this lesion?
The NF1 gene contains approximately 250,000 base pairs (explaining the high spontaneous number of mutations seen with this very large gene) and encodes a polypeptide of 2818 amino acids. The NF1 protein is found in many tissues and cell lines (human, rat and mouse) studied so far.
The NF1 sequence has significant similarity to the catalytic domain of the GTPase-activating protein GAP. The NF1 protein is therefore thought to affect signal transduction by stimulating the conversion of the Ras protein from a GTP-bound active form to a GDP-bound inactive form. Ras function plays a key role in cellular growth and differentiation and altered NF1 control of ras may explain the neurofibromatosis phenotype.
