Multiple Cutaneous and Uterine Leiomyomatosis

Multiple cutaneous and uterine leiomyomatosis (MCUL: OMIM 150800), which is also known as Reed syndrome, is an autosomal dominant disorder in which benign skin tumors arising from the arrector pili muscle and uterine fibroids typically develop in the third and fourth decades [1, 2]. Reed et al first reported on two families in which members of successive generations demonstrated cutaneous leiomyomas, uterine leiomyomas, and/or leiomyosarcomas in 1973 [3]. A small population of families with MCUL has also been reported to demonstrate clusters of renal cancer, either manifesting as type 2 papillary renal cell carcinoma or renal collecting duct cancer. This latter disease variant is referred to as hereditary leiomyomatosis and renal cell cancer (HLRCC: OMIM 605839) [4, 5]. Heterozygous germline mutations in the fumarate hydratase (FH, fumarase) gene (MIM 136850) mapped on chromosome 1q42.3-q43 are detected in both MCUL and HLRCC and many different mutations have been reported in the FH gene [6, 7]. The FH gene encodes the fumarate hydratase (FH) enzyme, that catalyzes the conversion of fumarate to malate as part of the TCA cycle in the mitochondrial matrix. This chapter will initially explain the clinical manifestations and etiology of MCUL/HLRCC based on the data from previous reports. The structure and fundamental function of the FH protein, FH gene mutation and the relation between alteration of FH protein and tumorigenesis in MCUL/HLRCC will be addressed. Finally, the diagnosis and treatments of MCUL/HLRCC is also explained.