Leiomyomas are benign, smooth muscle Tumours with some connective tissue elements. They are very common, occurring in about 20 % of women over the age of 35 years, and the incidence increases with advancing age. They occur more frequently in women of Afro-Caribbean origin. Uterine leiomyomas are probably more common in first-degree relatives of index cases than in the general population. Uterine leiomyomas are component neoplasias of at least two heritable neoplasia syndromes: hereditary leiomyoma–renal cell carcinoma syndrome (HLRCC), which is also known as multiple cutaneous uterine leiomyomatosis (MCUL), and Cowden syndrome. HLRCC/MCUL is caused by germline heterozygous mutations in the gene encoding fumarate hydratase (FH) (Alam et al. 2001; Tomlinson et al. 2002). FH is a nuclear gene encoding a mitochondrial enzyme involved in electron transport and the Krebs cycle (Eng et al. 2003). While germline heterozygous FH mutations cause HLRCC, germline homozygous mutations cause severe neurodegeneration (Eng et al. 2003). Although searching for germline FH mutations in women with isolated leiomyomas is not justified, FH sequencing should be offered in rare cases where familial uterine leiomyomatosis is present, even in the absence of other features associated with FH mutations (Tolvanen et al. 2012). Although few somatic intragenic mutations in FH have been found in sporadic uterine leiomyomas, biallelic inactivation by both genetic and nongenetic mechanisms occur with some frequency in these sporadic Tumours (Kiuru et al. 2002; Lehtonen et al. 2004).
Uterine leiomyomas are common in the general population which makes it difficult to establish that they are true components of Cowden syndrome, but have been associated in some studies (http://www.nccn.org/professionals/ physician_gls/pdf/genetics_screening.pdf). Uterine leiomyomas were reported in a woman carrying heterozygous mutations in both PTEN and SDHC (Zbuk et al. 2007).