Multiple cutaneous and uterine leiomyomatosis (MCUL; OMIM 150800) is an autosomal dominantly inherited disease characterized by
leiomyomas of the skin and uterine
leiomyomas. Recently, association of MCUL with different forms of
renal cancer has been described. This syndrome is referred to as
hereditary leiomyomatosis and renal cell cancer (OMIM 605839). Both disorders result from heterozygous germline mutations in the
fumarate hydratase (FH) gene that may function as a
tumor suppressor. Interestingly, cutaneous
leiomyomas do not only manifest in a diffuse and symmetric fashion. Rather frequently, a segmental or band-like manifestation pattern can be observed, usually following the lines of Blaschko. Here, we sought to elucidate the molecular basis of diffuse and segmental cutaneous
leiomyomatosis in six unrelated Dutch and Spanish patients and their families. We identified six novel FH mutations, including one missense and one
nonsense mutation, two deletions and two splice-site mutations. The segmental phenotype that was observed in various patients with FH mutations most likely reflects a type 2 segmental manifestation of cutaneous
leiomyomatosis as previously also described for other autosomal dominantly inherited
skin diseases. The results presented here extend the current data on the molecular basis of familial cutaneous
leiomyomatosis and comprise, to the best of our knowledge, the first genetic study in Dutch and Spanish patients with this disorder. In addition, we review the clinical and molecular aspects of the disease.