Epidemiology of Genetic Diseases with Peripheral Nerve Tumors

Neoplasms of the peripheral nerve sheath may arise de novo, by spontaneous mutations involving a variety of genetic syndromes, but there appears to be a strong association between some inherited genetic syndromes and the development of peripheral nerve tumors. Most notably, neurofibromatosis type I (NF 1) and type II (NF 2) and schwannomatosis are syndromes that predispose individuals to developing peripheral nerve sheath tumors. Manifestations display a wide spectrum, such that even affected individuals in the same family may demonstrate different symptoms and tumor burden. The peripheral nerve tumors in affected individuals can be benign or malignant. Tumors associated with NF1 include cutaneous neurofibromas, intraneural neurofibromas, or the disease-defining plexiform neurofibromas. Malignant peripheral nerve sheath tumors are the only primary cancer of peripheral nerves and are the leading cause of death in NF1 individuals. Bilateral vestibular schwannomas are a hallmark of NF2, but affected individuals also have a high predisposition for peripheral nerve schwannomas, multiple meningiomas, and ependymomas. Schwannomatosis is a recently recognized addition to the neurofibromatoses that demonstrates a high propensity toward the development of multiple schwannomas. Besides the neurofibromatosis group, some genetically inherited endocrinopathies such as Carney complex and multiple endocrine neoplasia type 2B may predispose individuals toward developing peripheral nerve sheath tumors.