A Novel Missense Mutation in Fumarate Hydratase in an Italian Patient with a Diffuse Variant of Cutaneous Leiomyomatosis (Reed’s Syndrome)

Abstract

BACKGROUND: The multiple cutaneous and uterine leiomyomatosis syndrome (MCUL) is a rare autosomal dominant condition characterized by cutaneous leiomyomatosis in both sexes and uterine leiomyomas in women. This syndrome overlaps with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. METHODS: We report an Italian family in which the finding of multiple cutaneous leiomyomas in the proband, a 46-year-old woman, led to the diagnosis of Reed's syndrome and to a general and genetic screening. RESULTS: DNA sequencing in the proband disclosed a missense mutation designated p.Asp341Tyr that has not been reported previously. Interestingly, the patient's mother had a clear-cell-type renal cancer removed at the age of 57 years. CONCLUSION: Cutaneous leiomyomas are the clinical and histological clue leading to the diagnosis of MCUL or HLRCC. Dermatologists should be aware that a correct evaluation of a patient with cutaneous leiomyomas involves a complete medical and family history, physical examination and a genetic counseling.