Inherited Tumor Syndromes Involving the Nervous System

Abstract

Abstract The inherited tumor syndromes involving the nervous system are a group of genetically determined disorders with neoplastic or dysplastic lesions in the nervous system and in extraneural tissues. The group includes the conditions discussed in this chapter: neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), von HippelLindau disease (VHL), tuberous sclerosis complex (TSC), and Cowden/Lhermitte-Duclos disease (CLDD). Other syndromes of this type include the Li-Fraumeni syndrome, Turcot’s syndrome, and the nevoid basal cell carcinoma syndrome (Kleihues and Cavenee, 2000). NF1, NF2, VHL, and TSC have also been classified as neurocutaneous diseases (NCDs), or phakomatoses. The two terms are sometimes used synonymously. The NCDs are a collection of familial and spontaneously occurring disorders with lesions involving both the nervous system and the skin that are not necessarily neoplastic or dysplastic. The criteria defining this collection are arbitrary, because some of the conditions classified as NCDs do not include skin lesions—for example, VHL (Gomez, 1987, 1991). Phakomatosis is a term suggested by Van der Hoeve (1923) as a generic designation originally for two of the more common NCDs, NF1 and TSC. It is derived from the Greek word phakos, meaning “motherspot.” The motherspots referred to by Van der Hoeve were the malformative and dysplastic lesions often found in the brain, skin, and viscera of patients with the two diseases. The motherspots were considered similar, except for the absence of neval cells, to cutaneous nevi or birthmarks. The masses or tumors developing from the motherspots were called phakomas. They represented a spectrum of proliferative activity including benign and malignant neoplasms. Later, Van der Hoeve added VHL (1932) and SturgeWeber disease (1936) to the list of phakomatoses.